Publications by authors named "Andrew Y Chang"

14 Publications

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The impact of novel coronavirus COVID-19 on noncommunicable disease patients and health systems: a review.

J Intern Med 2021 04 27;289(4):450-462. Epub 2020 Oct 27.

Department of Medicine, Stanford University, Stanford, CA, USA.

Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic affecting all levels of health systems. This includes the care of patients with noncommunicable diseases (NCDs) who bear a disproportionate burden of both COVID-19 itself and the public health measures enacted to combat it. In this review, we summarize major COVID-19-related considerations for NCD patients and their care providers, focusing on cardiovascular, pulmonary, renal, haematologic, oncologic, traumatic, obstetric/gynaecologic, operative, psychiatric, rheumatologic/immunologic, neurologic, gastrointestinal, ophthalmologic and endocrine disorders. Additionally, we offer a general framework for categorizing the pandemic's disruptions by disease-specific factors, direct health system factors and indirect health system factors. We also provide references to major NCD medical specialty professional society statements and guidelines on COVID-19. COVID-19 and its control policies have already resulted in major disruptions to the screening, treatment and surveillance of NCD patients. In addition, it differentially impacts those with pre-existing NCDs and may lead to de novo NCD sequelae. Likely, there will be long-term effects from this pandemic that will continue to affect practitioners and patients in this field for years to come.
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http://dx.doi.org/10.1111/joim.13184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675448PMC
April 2021

Outcomes and Care Quality Metrics for Women of Reproductive Age Living With Rheumatic Heart Disease in Uganda.

J Am Heart Assoc 2020 04 16;9(8):e015562. Epub 2020 Apr 16.

University Hospitals Harrington Heart & Vascular Institute Case Western Reserve University Cleveland OH.

Background Rheumatic heart disease disproportionately affects women of reproductive age, as it increases the risk of cardiovascular complications and death during pregnancy and childbirth. In sub-Saharan Africa, clinical outcomes and adherence to guideline-based therapies are not well characterized for this population. Methods and Results In a retrospective cohort study of the Uganda rheumatic heart disease registry between June 2009 and May 2018, we used multivariable regression and Cox proportional hazards models to compare comorbidities, mortality, anticoagulation use, and treatment cascade metrics among women versus men aged 15 to 44 with clinical rheumatic heart disease. We included 575 women and 252 men with a median age of 27 years. Twenty percent had New York Heart Association Class III-IV heart failure. Among patients who had an indication for anticoagulation, women were less likely than men to receive a prescription of warfarin (66% versus 81%; adjusted odds ratio, 0.37; 95% CI, 0.14-0.96). Retention in care (defined as a clinic visit within the preceding year) was poor among both sexes in this age group (27% for men, 24% for women), but penicillin adherence rates were high among those retained (89% for men, 92% for women). Mortality was higher in men than women (26% versus 19% over a median follow-up of 2.7 years; adjusted hazard ratio, 1.66; 95% CI, 1.18-2.33). Conclusions Compared with men, women of reproductive age with rheumatic heart disease in Uganda have lower rates of appropriate anticoagulant prescription but also lower mortality rates. Retention in care is poor among both men and women in this age range, representing a key target for improvement.
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http://dx.doi.org/10.1161/JAHA.119.015562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428530PMC
April 2020

Breast cancer induces systemic immune changes on cytokine signaling in peripheral blood monocytes and lymphocytes.

EBioMedicine 2020 Feb 22;52:102631. Epub 2020 Jan 22.

Department of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA 91010, USA. Electronic address:

Background: It is increasingly recognized that cancer progression induces systemic immune changes in the host. Alterations in number and function of immune cells have been identified in cancer patients' peripheral blood and lymphoid organs. Recently, we found dysregulated cytokine signaling in peripheral blood T cells from breast cancer (BC) patients, even those with localized disease.

Methods: We used phosphoflow cytometry to determine the clinical significance of cytokine signaling responsiveness in peripheral blood monocytes from non-metastatic BC patients at diagnosis. We also examined the correlation between cytokine signaling in peripheral monocytes and the number of tumor-infiltrating macrophages in paired breast tumors.

Findings: Our results show that cytokine (IFNγ) signaling may also be dysregulated in peripheral blood monocytes at diagnosis, specifically in BC patients who later relapsed. Some patients exhibited concurrent cytokine signaling defects in monocytes and lymphocytes at diagnosis, which predict the risk of future relapse in two independent cohorts of BC patients. Moreover, IFNγ signaling negatively correlates with expression of CSF1R on monocytes, thus modulating their ability to infiltrate into tumors.

Interpretation: Our results demonstrate that tumor-induced systemic immune changes are evident in peripheral blood immune cells for both myeloid and lymphoid lineages, and point to cytokine signaling responsiveness as important biomarkers to evaluate the overall immune status of BC patients.

Funding: This study was supported by the Department of Defense Breast Cancer Research Program (BCRP), The V Foundation, Stand Up to Cancer (SU2C), and Breast Cancer Research Foundation (BCRF).
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http://dx.doi.org/10.1016/j.ebiom.2020.102631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992943PMC
February 2020

Interventions to Reduce Ethnic and Racial Disparities in Dyslipidemia Management.

Curr Treat Options Cardiovasc Med 2019 May 7;21(5):24. Epub 2019 May 7.

Division of Cardiovascular Medicine, Stanford University School of Medicine, Falk Cardiovascular Research Building, 870 Quarry Rd, Room CV2C87, Stanford, CA, 94305, USA.

Purpose Of Review: Race and ethnicity are associated with disparities in risk assessment, screening, patient awareness, treatment, and control of dyslipidemia and can contribute to worsened cardiovascular outcomes. This review summarizes these gaps in care and highlights recent interventions aimed at reducing them.

Recent Findings: Disparities in dyslipidemia diagnosis and treatment are well documented among certain racial and ethnic minority groups. Less is known about dyslipidemia among Hispanics, Asians, and Native Americans/Pacific Islanders, who have significant heterogeneity in cardiovascular risk and outcomes. Programs to reduce inequalities have focused on targeted risk assessment, improved screening practices, statin adherence-enhancing policies, culturally inclusive risk factor modification campaigns, and multidisciplinary treatment teams, with variable success. Interventions to reduce racial/ethnic disparities in dyslipidemia are important at all phases of care. Nevertheless, initiatives concentrating on single elements of the lipid treatment cascade were generally less effective at improving clinical endpoints than those that comprehensively addressed multiple phases. Moreover, there was a disproportionately greater number of published studies analyzing patient-facing lifestyle-based risk factor modifications than other types of interventions. Future investigations should focus on understudied populations such as disaggregated Hispanic, Asian, and Native American populations. Additionally, innovative strategies utilizing information technology and provider-facing programs are needed.
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http://dx.doi.org/10.1007/s11936-019-0725-4DOI Listing
May 2019

Patient and facility variation in costs of catheter ablation for atrial fibrillation.

J Cardiovasc Electrophysiol 2018 08 22;29(8):1081-1088. Epub 2018 Jun 22.

Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.

Background: Cost-effectiveness or value of cardiovascular therapies may be undermined by unwarranted cost variation, particularly for heterogeneous procedures such as catheter ablation for atrial fibrillation (AF). We sought to characterize cost variation of AF ablation in the US healthcare system and the relationship between cost and outcomes.

Methods And Results: We performed a retrospective cohort study using data from the MarketScan commercial claims and Medicare supplemental databases including patients who received an AF ablation from 2007 to 2011. We aggregated encounter cost, reflecting total payments received for the encounter, to the facility level to calculate median facility cost. We classified procedures as outpatient or inpatient and assessed for association between cost and 30-day and 1-year outcomes. The analysis cohort included 9,415 AF ablations (59±11 years; 28% female; 52% outpatient) occurring at 327 facilities, with large cost variation across facilities (median: $25,100; 25th percentile: $18,900, 75th percentile: $35,600, 95th percentile: $57,800). Among outpatient procedures, there was reduced healthcare utilization in higher cost quintiles with reductions in rehospitalization at 30-days (Quintile 1: 16.1%, Quintile 5: 8.8%, P < 0.001) and 1-year (Quintile 1: 34.8%, Quintile 5: 25.6%, P < 0.001), which remained significant in multivariate analysis.

Conclusions: Although median costs of AF ablation are below amounts used in prior cost-effectiveness studies that demonstrated good value, large facility variation in cost suggests opportunities for cost reduction. However, for outpatient encounters, association of cost to modestly improved outcomes suggests cost containment strategies could have variable effects.
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http://dx.doi.org/10.1111/jce.13655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469652PMC
August 2018

Motivations of women in Uganda living with rheumatic heart disease: A mixed methods study of experiences in stigma, childbearing, anticoagulation, and contraception.

PLoS One 2018 28;13(3):e0194030. Epub 2018 Mar 28.

Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, Ohio, United States of America.

Background: Rheumatic heart disease (RHD) is a leading cause of premature mortality in low- and middle-income countries (LMICs). Women of reproductive age are a unique and vulnerable group of RHD patients, due to increased risk of cardiovascular complications and death during pregnancy. Yet, less than 5% of women of childbearing age with RHD in LMICs use contraceptives, and one in five pregnant women with RHD take warfarin despite known teratogenicity. It is unclear whether this suboptimal contraception and anticoagulant use during pregnancy is due to lack of health system resources, limited health literacy, or social pressure to bear children.

Methods: We conducted a mixed methods study of 75 women living with RHD in Uganda. Questionnaires were administered to 50 patients. Transcripts from three focus groups with 25 participants were analyzed using qualitative description methodology.

Results: Several themes emerged from the focus groups, including pregnancy as a calculated risk; misconceptions about side-effects of contraceptives and anticoagulation; reproductive decision-making control by male partners, in-laws, or physicians; abandonment of patients by male partners; and considerable stigma against heart disease patients for both their reproductive and financial limitations (often worse than that directed against HIV patients). All questionnaire respondents were told by physicians that their hearts were not strong enough to support a pregnancy. Only 14% used contraception while taking warfarin. All participants felt that society would look poorly on a woman who cannot have children due to a heart condition.

Conclusions: To our knowledge, this is the first qualitative study of female RHD patients and their attitudes toward cardiovascular disorders and reproduction. Our results suggest that health programs targeting heart disease in LMICs must pay special attention to the needs of women of childbearing age. There are opportunities for improved family/societal education programs and community engagement, leading to better outcomes and patient empowerment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194030PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874006PMC
June 2018

IL6 Signaling in Peripheral Blood T Cells Predicts Clinical Outcome in Breast Cancer.

Cancer Res 2017 03 22;77(5):1119-1126. Epub 2016 Nov 22.

Department of Immuno-Oncology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, California.

IL6 is a pleiotropic cytokine with both pro- and anti-inflammatory properties, which acts directly on cancer cells to promote their survival and proliferation. Elevated serum IL6 levels negatively correlate with survival of cancer patients, which is generally attributed to the direct effects of IL6 on cancer cells. How IL6 modulates the host immune response in cancer patients is unclear. Here, we show the IL6 signaling response in peripheral blood T cells is impaired in breast cancer patients and is associated with blunted Th17 differentiation. The mechanism identified involved downregulation of gp130 and IL6Rα in breast cancer patients and was independent of plasma IL6 levels. Importantly, defective IL6 signaling in peripheral blood T cells at diagnosis correlated with worse relapse-free survival. These results indicate that intact IL6 signaling in T cells is important for controlling cancer progression. Furthermore, they highlight a potential for IL6 signaling response in peripheral blood T cells at diagnosis as a predictive biomarker for clinical outcome of breast cancer patients. .
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http://dx.doi.org/10.1158/0008-5472.CAN-16-1373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334262PMC
March 2017

Regenerative Medicine: Potential Mechanisms of Cardiac Recovery in Takotsubo Cardiomyopathy.

Curr Treat Options Cardiovasc Med 2016 Mar;18(3):20

Division of Cardiology, Department of Medicine, Stanford University Medical Center, Room G1120A Lokey Stem Cell Research Building, 265 Campus Drive, Stanford, CA, 94305, USA.

Opinion Statement: Takotsubo cardiomyopathy is an increasingly reported cause of acute chest pain and acute heart failure and is often associated with significant hemodynamic compromise. The illness is remarkable for the reversibility in systolic dysfunction seen in the disease course. While the pathophysiology of takotsubo syndrome is not completely elucidated, research suggests the presence of a cytoprotective process that allows the myocardium to recover following the inciting insult. Here, we summarize molecular and histologic studies exploring the response to injury in takotsubo disease and provide some discussion on how they may contribute to further investigations in cardiac recovery and regeneration.
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http://dx.doi.org/10.1007/s11936-016-0443-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957545PMC
March 2016

The Global Health Implications of e-Cigarettes.

JAMA 2015 Aug;314(7):663-4

Department of Medicine, Stanford University School of Medicine, Stanford, California2Center for Innovation in Global Health, Stanford University, Stanford, California.

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http://dx.doi.org/10.1001/jama.2015.8676DOI Listing
August 2015

Evaluating the Cost-effectiveness of Catheter Ablation of Atrial Fibrillation.

Arrhythm Electrophysiol Rev 2014 Nov 29;3(3):177-83. Epub 2014 Nov 29.

Department of Medicine, Stanford University School of Medicine, Stanford, California; Veterans Affairs Palo Alto Health Care System, California, US.

Atrial fibrillation (AF) is one of the most common cardiac conditions treated in primary care and specialty cardiology settings, and is associated with considerable morbidity, mortality and cost. Catheter ablation, typically by electrically isolating the pulmonary veins and surrounding tissue, is more effective at maintaining sinus rhythm than conventional antiarrhythmic drug therapy and is now recommended as first-line therapy. From a value standpoint, the cost-effectiveness of ablation must incorporate the upfront procedural costs and risks with the benefits of longer term improvements in quality of life (QOL) and healthcare utilisation. Here, we present a primer on cost-effectiveness analysis (CEA), review the data on cost-effectiveness of AF ablation and outline key areas for further investigation.
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http://dx.doi.org/10.15420/aer.2014.3.3.177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711535PMC
November 2014

Spatial organization of dendritic cells within tumor draining lymph nodes impacts clinical outcome in breast cancer patients.

J Transl Med 2013 Oct 2;11:242. Epub 2013 Oct 2.

Department of Medicine, Stanford University, 269 Campus Drive, 94305 Stanford, CA, USA.

Background: Dendritic cells (DCs) are important mediators of anti-tumor immune responses. We hypothesized that an in-depth analysis of dendritic cells and their spatial relationships to each other as well as to other immune cells within tumor draining lymph nodes (TDLNs) could provide a better understanding of immune function and dysregulation in cancer.

Methods: We analyzed immune cells within TDLNs from 59 breast cancer patients with at least 5 years of clinical follow-up using immunohistochemical staining with a novel quantitative image analysis system. We developed algorithms to analyze spatial distribution patterns of immune cells in cancer versus healthy intra-mammary lymph nodes (HLNs) to derive information about possible mechanisms underlying immune-dysregulation in breast cancer. We used the non-parametric Mann-Whitney test for inter-group comparisons, Wilcoxon Matched-Pairs Signed Ranks test for intra-group comparisons and log-rank (Mantel-Cox) test for Kaplan Maier analyses.

Results: Degree of clustering of DCs (in terms of spatial proximity of the cells to each other) was reduced in TDLNs compared to HLNs. While there were more numerous DC clusters in TDLNs compared to HLNs,DC clusters within TDLNs tended to have fewer member DCs and also consisted of fewer cells displaying the DC maturity marker CD83. The average number of T cells within a standardized radius of a clustered DC was increased compared to that of an unclustered DC, suggesting that DC clustering was associated with T cell interaction. Furthermore, the number of T cells within the radius of a clustered DC was reduced in tumor-positive TDLNs compared to HLNs. Importantly, clinical outcome analysis revealed that DC clustering in tumor-positive TDLNs correlated with the duration of disease-free survival in breast cancer patients.

Conclusions: These findings are the first to describe the spatial organization of DCs within TDLNs and their association with survival outcome. In addition, we characterized specific changes in number, size, maturity, and T cell co-localization of such clusters. Strategies to enhance DC function in-vivo, including maturation and clustering, may provide additional tools for developing more efficacious DC cancer vaccines.
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http://dx.doi.org/10.1186/1479-5876-11-242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852260PMC
October 2013

Center-surround vs. distance-independent lateral connectivity in the olfactory bulb.

Front Neural Circuits 2012 31;6:34. Epub 2012 May 31.

Department of Neurobiology, Yale University School of Medicine, New Haven CT, USA.

Lateral neuronal interactions are known to play important roles in sensory information processing. A center-on surround-off local circuit arrangement has been shown to play a role in mediating contrast enhancement in the visual, auditory, and somatosensory systems. The lateral connectivity and the influence of those connections have been less clear for the olfactory system. A critical question is whether the synaptic connections between the primary projection neurons, mitral and tufted (M/T) cells, and their main inhibitory interneurons, the granule cells (GCs), can support a center-surround motif. Here, we study this question by injecting a "center" in the glomerular layer of the olfactory bulb (OB) with a marker of synaptic connectivity, the pseudorabies virus (PRV), then examines the distribution of labeling in the "surround" of GCs. We use a novel method to score the degree to which the data fits a center-surround model vs. distance-independent connectivity. Data from 22 injections show that M/T cells generally form lateral connections with GCs in patterns that lie between the two extremes.
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http://dx.doi.org/10.3389/fncir.2012.00034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364486PMC
October 2012

Learning to live together: harnessing regulatory T cells to induce organ transplant tolerance.

Yale J Biol Med 2011 Dec;84(4):345-51

Stanford University School of Medicine, Stanford, California, USA.

The discovery of immune cells with regulatory effects has created considerable excitement for their potential use in inducing tolerance to transplanted tissues. Despite the fact that these cells possess essential functions in vivo, attempts to translate them into effective clinical therapies has proved challenging due to a number of unanticipated complexities in their behavior. This article provides a broad summary of research done to understand the largest of the regulatory cell subtypes, namely CD4+Foxp3+ Regulatory T cells (T(Regs)). Special attention will be paid to current and future difficulties in using T(Regs) clinically, as well as room for improvement and innovation in this field.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3238321PMC
December 2011

Lateral Connectivity in the Olfactory Bulb is Sparse and Segregated.

Front Neural Circuits 2011 25;5. Epub 2011 Apr 25.

Department of Neurobiology, Yale University School of Medicine New Haven, CT, USA.

Lateral connections in the olfactory bulb were previously thought to be organized for center-surround inhibition. However, recent anatomical and physiological studies showed sparse and distributed interactions of inhibitory granule cells (GCs) which tended to be organized in columnar clusters. Little is known about how these distributed clusters are interconnected. In this study, we use transsynaptic tracing viruses bearing green or red fluorescent proteins to further elucidate mitral- and tufted-to-GC connectivity. Separate sites in the glomerular layer were injected with each virus. Columns with labeling from both viruses after transsynaptic spread show sparse red or green GCs which tended to be segregated. However, there was a higher incidence of co-labeled cells than chance would predict. Similar segregation of labeling is observed from dual injections into olfactory cortex. Collectively, these results suggest that neighboring mitral and tufted cells receive inhibitory inputs from segregated subsets of GCs, enabling inhibition of a center by specific and discontinuous lateral elements.
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http://dx.doi.org/10.3389/fncir.2011.00005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084525PMC
July 2011