The changing microRNA landscape by color and cloudiness: a cautionary tale for nipple aspirate fluid biomarker analysis

Abstract Purpose Investigation of nipple aspirate fluid (NAF)-based microRNAs (miRNAs) as a potential screening tool for women at increased risk of developing breast cancer is the scope of our research. While aiming to identify discriminating NAF-miRNAs between women with different mammographic densities, we were confronted with an unexpected confounder: NAF sample appearance. Here we report and alert for the impact of NAF color and cloudiness on miRNA assessment. Methods Seven classes of NAF colors coupled with cloudiness appearance were established. Using 173 NAF samples from 154 healthy women (19 samples were bilaterally collected), the expression of 14 target and 2 candidate endogenous control (EC) miRNAs was investigated using Taqman Advanced miRNA assays to identify significant differential expression patterns between color-cloudiness classes. Inter- and intra-individual variation of miRNA expression was analyzed using the coefficient of variation (CV). Results We found that between the seven NAF classes, fold change miRNA expression differences ranged between 2.4 and 19.6 depending on the interrogated miRNA. Clear NAF samples exhibited higher miRNA expression levels compared to cloudy NAF samples with fold change differences ranging between 1.1 and 6.2. Inter-individual and intra-individual miRNA expression was fairly stable (CV < 15 %), but nevertheless impacted by NAF sample appearance. Within NAF classes, inter-individual variation was largest for green samples (CV 6-15 %) and smallest for bloody samples (CV 2-6 %). Conclusions Our data indicate that NAF color and cloudiness influence miRNA expression and should, therefore, be systematically registered using an objective color classification system. Given that sample appearance is an inherent feature of NAF, these variables should be statistically controlled for in multivariate data analyses. This cautionary note and recommendations could be of value beyond the field of NAF-miRNAs, given that variability in sample color and cloudiness is likewise observed in liquid biopsies such as urine, cerebrospinal fluid and sputum, and could thereby influence the levels of miRNAs and other biomarkers.

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The Predominant microRNAs in β-cell Clusters for Insulin Regulation and Diabetic Control

Current Drug Targets ◽

10.2174/1389450121666191230145848 ◽

2020 ◽

Vol 21 (7) ◽

pp. 722-734

Author(s):

Adele Soltani ◽

Arefeh Jafarian ◽

Abdolamir Allameh

Keyword(s):

Mirna Expression ◽

Expression Profiles ◽

Expression Patterns ◽

Diabetic Control ◽

In Vitro Proliferation ◽

Cell Functions ◽

Mirna Expression Profiles ◽

Multiple Processes ◽

The Impact

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic β-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in β-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of β-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into β-cells, resulting in enhanced β-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of β-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived β-cells to therapeutically relevant outputs will be discussed as well.

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miRNAs Expression Pattern in Essential Thrombocythemia and Polycythemia Vera Patients.

Blood ◽

10.1182/blood.v114.22.1912.1912 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1912-1912

Author(s):

Aina Pons ◽

Carlos Besses ◽

Luz Martínez-Avilés ◽

Alberto Alvarez-Larran ◽

Raquel Longaron ◽

...

Keyword(s):

Polycythemia Vera ◽

Expression Pattern ◽

Essential Thrombocythemia ◽

Mirna Expression ◽

Fold Change ◽

Differentially Expressed ◽

Hematopoietic Stem ◽

Mutational Status ◽

Increased Risk ◽

Normal Controls

Abstract Abstract 1912 Poster Board I-935 Background: Essential Thrombocythemia (ET) and Polycythemia Vera (PV) are myeloproliferative neoplasms (MPN) arising from a multipotent hematopoietic stem cell characterized by an unregulated production of platelets, red cells and white cells alone or in combination, a tendency to clonal evolution and an increased risk of thrombohemorrhagic complications. MicroRNAs (miRNA) are negative regulators of genes involved in cellular proliferation, apoptosis and/or carcinogenesis. Aim: To analyze the expression pattern of miRNA between PV and ET patients and to find distinctive signatures in ET patients according to JAK2V617F and c-MPL mutational status. Material and Methods: Total RNA was extracted from peripheral blood granulocytes of 50 ET patients, 10 PV patients and 10 controls. Median age of patients was 57 years (range, 20-88); males 36%. The JAK2V617F mutation was present in 23 (46%) of 50 ET patients and in all PV patients. MPL mutations were present in 5 (18%) of 27 JAK2V617F negative cases (3 cases MPLW515L, 1 case MPLW515K and 1 case MPLS505N). miRNA expression was profiled in 384 miRNA via Taqman Low Density Array in ABI PRISM 7900. Expression data was normalized with RNU48 and relative quantification was calculated with the 2–σσCt method. The data were presented as log10 of relative quantity of target miRNA. Median of normal controls was used as calibrator for all samples. Data were analyzed by means of Significant Analysis of MicroArrays (SAM), Prediction Analysis of MicroArrays (PAM) and Class Comparison methods using BRB array tools version 3.7.0 and TIGR multiexperiment viewer version 4.3. Results: We found a general downregulation of miRNA in ET and PV patients respect to normal controls. A set of 29 miRNA allowed us to discriminate between ET and PV versus normal controls; three of these miRNA were up-regulated and 16 down-regulated in PV and ET vs. normal controls with a >2 fold change and p value <0.01. A distinctive signature of 79 miRNAs differentiated ET, PV and controls and a hierarchical clustering analysis defined miRNA expression profiles of the three particular groups. When we compared miRNA differentially expressed between PV and ET patients, we found nine miRNA, 4 up-regulated and 5 down-regulated in ET with respect to PV patients (p<0.01). Statistical comparisons between ET JAK2V617F-positive and ET JAK2V617F-negative cases showed a distinctive signature of 13 miRNA that allowed us to discriminate between the two groups. In addition, we also found in JAK2V617F cases 19 miRNA differentially expressed between MPL positive and MPL negative patients, with a >2 fold change and p<0.01. Finally, an increased expression of miR-142-5p correlated with JAK2V617F allele burden in ET patients Conclusions: Our study demonstrates that ET and PV can be defined by specific signatures of miRNA. In ET, some miRNA allow us to discriminate cases according to JAK2V617F mutational status and also between MPL-positive and MPL-negative JAK2V617F-negative patients. Research Funding: FIS EC07/90791 Disclosures: No relevant conflicts of interest to declare.

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The effects of drought stress and western corn rootworm feeding on maize root biology

10.32469/10355/64002 ◽

2010 ◽

Author(s):

◽

Kristen A. Leach

Keyword(s):

Gene Expression ◽

Mirna Expression ◽

Expression Patterns ◽

Primary Root ◽

Diabrotica Virgifera Virgifera ◽

Western Corn Rootworm ◽

Specific Response ◽

Corn Rootworm ◽

Defense Genes ◽

The Impact

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Drought and western corn rootworm (WCR), Diabrotica virgifera virgifera, can have substantial impacts on the potential yield of maize, Zea may L. Maize lines were selected to survey the level of diversity available for primary root elongation maintenance under water stress and three WCR-related traits: WCR damage, root size, and root regrowth. Data analysis suggests that lines belonging to the Tropical/Semi-tropical population structure group are a significant source of alleles which would improve resistance/tolerance to these stressors. Further analysis of the WCR trait data found significant correlations with agronomically important traits related to plant maturity, confirming the impact of maize phenology on WCR damage. This indicates that phase change or changes in biochemical pathways as the plant matures may serve as additional criteria to effectively select germplasm that is resistant/tolerant to WCR feeding. In an effort to identify maize genes responsible for defense against WCR herbivory, a transcriptome analysis discovered that the presence of an endosymbiont, Wolbachia, down-regulated the expression of defense genes. Gene expression time courses suggest WCR elicits a response to herbivory by WCR+wb which was confirmed by a more extensive analysis of the microarray data. Maize defense genes were found to be down-regulated in agreement with the previous study. Transcriptional down-regulation may be the result of transposable element interference or post-transcriptional regulation by small RNAs, i.e. siRNAs or miRNAs. Three classes of miRNA were identified based on their response to WCR+wb, WCR-wb, and control treatments in the CRW3 germplasm; WCR-specific response, Wolbachia-specific response, and generalized defense response. Models based on the miRNA expression patterns along with information from the literature about their targets and downstream effects enabled us to predict phenotypes based on miRNA mediated-changes in gene expression. Results of the GO term enrichment analysis together with miRNA expression analysis support miRNA-mediated post-translational modification as one mechanism underlying the Wolbachia-associated changes in maize gene expression.

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The Physiological MicroRNA Landscape in Nipple Aspirate Fluid: Differences and Similarities with Breast Tissue, Breast Milk, Plasma and Serum

International Journal of Molecular Sciences ◽

10.3390/ijms21228466 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8466

Author(s):

Susana I. S. Patuleia ◽

Carla H. van Gils ◽

Angie M. Oneto Cao ◽

Marije F. Bakker ◽

Paul J. van Diest ◽

...

Keyword(s):

Breast Milk ◽

Mirna Expression ◽

Breast Tissue ◽

Expression Profiles ◽

Expression Patterns ◽

Nipple Aspirate Fluid ◽

Sample Type ◽

Messenger Rnas ◽

Tumor Diagnostics ◽

Profiling Techniques

Background: MicroRNAs (miRNAs) target 60% of human messenger RNAs and can be detected in tissues and biofluids without loss of stability during sample processing, making them highly appraised upcoming biomarkers for evaluation of disease. However, reporting of the abundantly expressed miRNAs in healthy samples is often surpassed. Here, we characterized for the first time the physiological miRNA landscape in a biofluid of the healthy breast: nipple aspirate fluid (NAF), and compared NAF miRNA expression patterns with publically available miRNA expression profiles of healthy breast tissue, breast milk, plasma and serum. Methods: MiRNA RT-qPCR profiling of NAF (n = 41) and serum (n = 23) samples from two healthy female cohorts was performed using the TaqMan OpenArray Human Advanced MicroRNA 754-Panel. MiRNA quantification data based on non-targeted or multi-targeted profiling techniques for breast tissue, breast milk, plasma and serum were retrieved from the literature by means of a systematic search. MiRNAs from each individual study were orderly ranked between 1 and 50, combined into an overall ranking per sample type and compared. Results: NAF expressed 11 unique miRNAs and shared 21/50 miRNAs with breast tissue. Seven miRNAs were shared between the five sample types. Overlap between sample types varied between 42% and 62%. Highly ranked NAF miRNAs have established roles in breast carcinogenesis. Conclusion: This is the first study to characterize and compare the unique physiological NAF-derived miRNA landscape with the physiological expression pattern in breast tissue, breast milk, plasma and serum. Breast-specific sources did not mutually overlap more than with systemic sources. Given their established role in carcinogenesis, NAF miRNA assessment could be a valuable tool in breast tumor diagnostics.

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PSVI-14 Differentially expressed microRNAs with potential regulatory roles in ileum of Holstein cows with subclinical Johne’s disease

Journal of Animal Science ◽

10.1093/jas/skz258.425 ◽

2019 ◽

Vol 97 (Supplement_3) ◽

pp. 206-207

Author(s):

Mengqi Wang ◽

Nathalie Bissonnette ◽

Philip Griebel ◽

Pier-Luc Dudemaine ◽

Duy N Do ◽

...

Keyword(s):

Mirna Expression ◽

Johne's Disease ◽

Fold Change ◽

Johne’S Disease ◽

Functional Enrichment ◽

Holstein Cows ◽

Inflammatory Disorder ◽

Receptor Signaling ◽

Immune System Development ◽

The Impact

Abstract Paratuberculosis or Johne’s disease (JD), caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic inflammatory disorder of the intestinal tract of ruminants. The mechanisms of JD pathogenesis remain unclear but MAP can cause chronic inflammatory lesions in the terminal small intestine of cattle. Using microRNA (miRNA) transcriptome analysis, this study investigated the impact of MAP infection on miRNA expression and their potential regulatory roles in JD progression. Ileal tissues were collected from MAP infected Holstein cows (n = 5) and healthy cows (n = 5). Purified total RNA were used to construct libraries followed by next generation sequencing, bioinformatic processing using a standard pipeline, differential miRNA expression analysis with DESeq2 software, and functional enrichment with ClueGo app in Cytoscape. A total of 269 miRNAs were expressed in ileal tissue including three abundantly expressed miRNAs (Bta-miR-143; 54.05% of total read counts), bta-miR-145 (11.54%) and bta-miR-192 (4.31%)). Twenty miRNAs were significantly (P < 0.05) differently expressed (DE) when comparing ileal tissues from MAP infected and uninfected cows. Bta-miR-383 (fold change = -12.93) and bta-miR-1842 (fold-change = 8.17) were the most down- and up-regulated miRNAs, respectively. Amongst the DE miRNAs, bta-miR-146a, bta-miR-146b and bta-miR-393 are inflammation-related miRNAs and considered potential biomarkers of bovine mastitis and other diseases, while bta-miR-370 and bta-miR-383 are associated with lipid metabolism. The predicted target genes of DE miRNAs were enriched (P < 0.05) for gene ontology terms related to regulation of metabolic, cell and developmental processes, and immune system development. KEGG pathway analysis revealed potential involvement in immune regulation (e.g. T-cell receptor signaling and C-type lectin receptor signaling pathways) and pathways in cancer were also enriched (P < 0.05). Our results indicate that some DE miRNAs play important roles by regulating metabolism and immune processes during JD and provide DE miRNAs that might form targets for future development of intervention measures.

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Perturbation of Hypothalamic MicroRNA Expression Patterns in Male Rats After Metabolic Distress: Impact of Obesity and Conditions of Negative Energy Balance

Endocrinology ◽

10.1210/en.2013-1770 ◽

2014 ◽

Vol 155 (5) ◽

pp. 1838-1850 ◽

Cited By ~ 39

Author(s):

Susana Sangiao-Alvarellos ◽

Lara Pena-Bello ◽

María Manfredi-Lozano ◽

Manuel Tena-Sempere ◽

Fernando Cordido

Keyword(s):

Energy Balance ◽

Caloric Restriction ◽

Mirna Expression ◽

High Fat Diet ◽

Expression Profiles ◽

Expression Patterns ◽

Male Rats ◽

High Fat ◽

Peripheral Tissues ◽

The Impact

The hypothalamus plays a crucial role in body weight homeostasis through an intricate network of neuronal circuits that are under the precise regulation of peripheral hormones and central transmitters. Although deregulated function of such circuits might be a major contributing factor in obesity, the molecular mechanisms responsible for the hypothalamic control of energy balance remain partially unknown. MicroRNAs (miRNAs) have been recognized as key regulators of different biological processes, including insulin sensitivity and glucose metabolism. However, the roles of miRNA pathways in the control of metabolism have been mostly addressed in peripheral tissues, whereas the potential deregulation of miRNA expression in the hypothalamus in conditions of metabolic distress remains as yet unexplored. In this work, we used high-throughput screening to define to what extent the hypothalamic profiles of miRNA expression are perturbed in two extreme conditions of nutritional stress in male rats, namely chronic caloric restriction and high-fat diet–induced obesity. Our analyses allowed the identification of sets of miRNAs, including let-7a, mir-9*, mir-30e, mir-132, mir-145, mir-200a, and mir-218, whose expression patterns in the hypothalamus were jointly altered by caloric restriction and/or a high-fat diet. The predicted targets of these miRNAs include several elements of key inflammatory and metabolic pathways, including insulin and leptin. Our study is the first to disclose the impact of nutritional challenges on the hypothalamic miRNA expression profiles. These data will help to characterize the molecular miRNA signature of the hypothalamus in extreme metabolic conditions and pave the way for targeted mechanistic analyses of the involvement of deregulated central miRNAs pathways in the pathogenesis of obesity and related disorders.

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RNAseq studies reveal distinct transcriptional response to vitamin A deficiency in small intestine versus colon, uncovering novel vitamin A-regulated genes

10.1101/798504 ◽

2019 ◽

Author(s):

Zhi Chai ◽

Yafei Lyu ◽

Qiuyan Chen ◽

Cheng-Hsin Wei ◽

Lindsay M. Snyder ◽

...

Keyword(s):

Small Intestine ◽

Vitamin A ◽

Target Genes ◽

Vitamin A Deficiency ◽

Expression Patterns ◽

Differentially Expressed Gene ◽

Intestinal Barrier ◽

Intestinal Barrier Function ◽

Increased Risk ◽

The Impact

AbstractVitamin A (VA) deficiency remains prevalent in resource limited countries, affecting over 250 million preschool aged children. Vitamin A deficiency is associated with reduced intestinal barrier function and increased risk of mortality due to mucosal infection. Using Citrobacter rodentium (C. rodentium) infection in mice as a model for diarrheal diseases in humans, previous reports showed reduced pathogen clearance and survival in vitamin A deficient (VAD) mice compared to their vitamin A sufficient (VAS) counterparts.ObjectivesTo characterize and compare the impact of preexisting VA deficiency on gene expression patterns in the small intestine (SI) and the colon, and to discover novel target genes in VA-related biological pathways.MethodsVAD mice were generated by feeding VAD diet to pregnant C57/BL6 dams and their post-weaning offspring. RNAseq were performed using the total mRNAs extracted from SI and colon. Differentially Expressed Gene (DEG), Gene Ontology (GO) enrichment, and Weighted Gene Co-expression Network Analysis (WGCNA) were performed to characterize expression and co-expression patterns.ResultsDEGs compared between VAS and VAD groups detected 49 SI and 94 colon genes. By GO information, SI DEGs were significantly enriched in categories relevant to retinoid metabolic process, molecule binding, and immune function. Immunity related pathways, including “humoral immune response” and “complement activation” were positively associated with VA in SI. Three co-expression modules showed significant correlation with VA status in SI; these modules contained four known retinoic acid targets. In addition, other SI genes of interest (e.g. Mbl2, Cxcl14, and Nr0b2) in these modules were suggested as new candidate genes regulated by VA. Furthermore, our analysis showed that markers of two cell types in SI, mast cells and Tuft cells, were significantly altered by VA status. In colon, “cell division” was the only enriched category and was negatively associated with VA. Thus, comparison of co-expression modules between SI and colon indicated distinct networks under the regulation of dietary VA and suggest that preexisting VAD could have a significant impact on the host response to a variety of disease conditions.

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Zinc Depletion Increases Readmission in Older Patients: An Example of Interactions Between Nutrition and Disease

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000275 ◽

2017 ◽

Vol 87 (1-2) ◽

pp. 10-16 ◽

Cited By ~ 1

Author(s):

Salah Gariballa ◽

Awad Alessa

Keyword(s):

Nutritional Status ◽

Inductively Coupled Plasma ◽

Older Patients ◽

Controlled Trial ◽

Prognostic Indicators ◽

Hospitalised Patients ◽

Increased Risk ◽

Co Morbidity ◽

The Impact ◽

Poor Nutrition

Abstract. Background: ill health may lead to poor nutrition and poor nutrition to ill health, so identifying priorities for management still remains a challenge. The aim of this report is to present data on the impact of plasma zinc (Zn) depletion on important health outcomes after adjusting for other poor prognostic indicators in hospitalised patients. Methods: Hospitalised acutely ill older patients who were part of a large randomised controlled trial had their nutritional status assessed using anthropometric, hematological and biochemical data. Plasma Zn concentrations were measured at baseline, 6 weeks and at 6 months using inductively- coupled plasma spectroscopy method. Other clinical outcome measures of health were also measured. Results: A total of 345 patients assessed at baseline, 133 at 6 weeks and 163 at 6 months. At baseline 254 (74%) patients had a plasma Zn concentration below 10.71 μmol/L indicating biochemical depletion. The figures at 6 weeks and 6 months were 86 (65%) and 114 (70%) patients respectively. After adjusting for age, co-morbidity, nutritional status and tissue inflammation measured using CRP, only muscle mass and serum albumin showed significant and independent effects on plasma Zn concentrations. The risk of non-elective readmission in the 6-months follow up period was significantly lower in patients with normal Zn concentrations compared with those diagnosed with Zn depletion (adjusted hazard ratio 0.62 (95% CI: 0.38 to 0.99), p = 0.047. Conclusions: Zn depletion is common and associated with increased risk of readmission in acutely-ill older patients, however, the influence of underlying comorbidity on these results can not excluded.

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Thrombophilia and risk of VTE recurrence according to the age at the time of first VTE manifestation

VASA ◽

10.1024/0301-1526/a000447 ◽

2015 ◽

Vol 44 (4) ◽

pp. 313-323 ◽

Cited By ~ 6

Author(s):

Lea Weingarz ◽

Marc Schindewolf ◽

Jan Schwonberg ◽

Carola Hecking ◽

Zsuzsanna Wolf ◽

...

Keyword(s):

Factor V Leiden ◽

Cox Proportional Hazards ◽

First Episode ◽

Factor V ◽

Factor V Leiden Mutation ◽

Younger Patients ◽

Risk Of Recurrence ◽

G20210a Mutation ◽

Increased Risk ◽

The Impact

Abstract. Background: Whether screening for thrombophilia is useful for patients after a first episode of venous thromboembolism (VTE) is a controversial issue. However, the impact of thrombophilia on the risk of recurrence may vary depending on the patient’s age at the time of the first VTE. Patients and methods: Of 1221 VTE patients (42 % males) registered in the MAISTHRO (MAin-ISar-THROmbosis) registry, 261 experienced VTE recurrence during a 5-year follow-up after the discontinuation of anticoagulant therapy. Results: Thrombophilia was more common among patients with VTE recurrence than those without (58.6 % vs. 50.3 %; p = 0.017). Stratifying patients by the age at the time of their initial VTE, Cox proportional hazards analyses adjusted for age, sex and the presence or absence of established risk factors revealed a heterozygous prothrombin (PT) G20210A mutation (hazard ratio (HR) 2.65; 95 %-confidence interval (CI) 1.71 - 4.12; p < 0.001), homozygosity/double heterozygosity for the factor V Leiden and/or PT mutation (HR 2.35; 95 %-CI 1.09 - 5.07, p = 0.030), and an antithrombin deficiency (HR 2.12; 95 %-CI 1.12 - 4.10; p = 0.021) to predict recurrent VTE in patients aged 40 years or older, whereas lupus anticoagulants (HR 3.05; 95%-CI 1.40 - 6.66; p = 0.005) increased the risk of recurrence in younger patients. Subgroup analyses revealed an increased risk of recurrence for a heterozygous factor V Leiden mutation only in young females without hormonal treatment whereas the predictive value of a heterozygous PT mutation was restricted to males over the age of 40 years. Conclusions: Our data do not support a preference of younger patients for thrombophilia testing after a first venous thromboembolic event.

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Percutaneous Coronary Intervention in Patients with Diabetes and Multivessel or Left Main Disease – a Review

Interventional Cardiology Review ◽

10.15420/icr.2012.7.1.37 ◽

2012 ◽

Vol 7 (1) ◽

pp. 37

Author(s):

Donald E Cutlip ◽

Keyword(s):

Percutaneous Coronary Intervention ◽

Coronary Artery ◽

Statistical Significance ◽

Bare Metal Stents ◽

Coronary Intervention ◽

Metal Stents ◽

Increased Risk ◽

Percutaneous Coronary ◽

Patients With Diabetes ◽

The Impact

Coronary artery disease in patients with diabetes is frequently a diffuse process with multivessel involvement and is associated with increased risk for myocardial infarction and death. The role of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with diabetes and multivessel disease who require revascularisation has been debated and remains uncertain. The debate has been continued mainly because of the question to what degree an increased risk for in-stent restenosis among patients with diabetes contributes to other late adverse outcomes. This article reviews outcomes from early trials of balloon angioplasty versus CABG through later trials of bare-metal stents versus CABG and more recent data with drug-eluting stents as the comparator. Although not all studies have been powered to show statistical significance, the results have been generally consistent with a mortality benefit for CABG versus PCI, despite differential risks for restenosis with the various PCI approaches. The review also considers the impact of mammary artery grafting of the left anterior descending artery and individual case selection on these results, and proposes an algorithm for selection of patients in whom PCI remains a reasonable strategy.

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