Systematic review of deep learning image analyses for the diagnosis and monitoring of skin disease.

Skin diseases affect one-third of the global population, posing a major healthcare burden. Deep learning may optimise healthcare workflows through processing skin images via neural networks to make predictions. A focus of deep learning research is skin lesion triage to detect cancer, but this may not translate to the wider scope of >2000 other skin diseases. We searched for studies applying deep learning to skin images, excluding benign/malignant lesions (1/1/2000-23/6/2022, PROSPERO CRD42022309935). The primary outcome was accuracy of deep learning algorithms in disease diagnosis or severity assessment. We modified QUADAS-2 for quality assessment. Of 13,857 references identified, 64 were included. The most studied diseases were acne, psoriasis, eczema, rosacea, vitiligo, urticaria. Deep learning algorithms had high specificity and variable sensitivity in diagnosing these conditions. Accuracy of algorithms in diagnosing acne (median 94%, IQR 86-98; n = 11), rosacea (94%, 90-97; n = 4), eczema (93%, 90-99; n = 9) and psoriasis (89%, 78-92; n = 8) was high. Accuracy for grading severity was highest for psoriasis (range 93-100%, n = 2), eczema (88%, n = 1), and acne (67-86%, n = 4). However, 59 (92%) studies had high risk-of-bias judgements and 62 (97%) had high-level applicability concerns. Only 12 (19%) reported participant ethnicity/skin type. Twenty-four (37.5%) evaluated the algorithm in an independent dataset, clinical setting or prospectively. These data indicate potential of deep learning image analysis in diagnosing and monitoring common skin diseases. Current research has important methodological/reporting limitations. Real-world, prospectively-acquired image datasets with external validation/testing will advance deep learning beyond the current experimental phase towards clinically-useful tools to mitigate rising health and cost impacts of skin disease.

Real-World Implementation and Outcomes of Adalimumab Therapeutic Drug Monitoring in Psoriasis: A National Specialized Center Experience.

Serum adalimumab concentration is a biomarker of treatment response but therapeutic drug monitoring (TDM) is yet to be implemented in routine psoriasis care. We incorporated adalimumab TDM in a national specialized psoriasis service and evaluated it using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) implementation science framework. We undertook pre-implementation planning (validating local assays) and implementation interventions targeted to patients (pragmatic sampling at routine reviews), clinicians (introduction of a TDM protocol), and healthcare systems (adalimumab TDM as a key performance indicator). Over 5 months, 170 of 229 (74%) individuals treated with adalimumab received TDM. Clinical improvement after TDM-guided dose escalation occurred in 13 of 15 (87%) nonresponders with serum drug concentrations <8.3 µg/ml (median PASI reduction of 3.2 [interquartile range = 2.2-8.2] after 23.4 weeks) and in all nonresponders who had TDM-guided switch in biologic due to supratherapeutic drug concentrations (>8.3 µg/ml; n = 2) or positive antidrug antibody (n = 2) (PASI reduction of 7.8 [interquartile range = 7.5-12.9] after 20.0 weeks). Proactive TDM led to dose reduction in five individuals with clear skin and subtherapeutic or supratherapeutic drug concentrations; four (80%) sustained clear skin after 50 weeks (range = 42-52). Adalimumab TDM based on pragmatic serum sampling is clinically viable and may lead to patient benefit. Context-specific implementation interventions and systematic implementation assessment may bridge the biomarker research-to-practice gap.

Nonadherence to systemic immune-modifying therapy in people with psoriasis during the COVID-19 pandemic: findings from a global cross-sectional survey.

BACKGROUND: Nonadherence to immune-modifying therapy is a complex behaviour which, before the COVID-19 pandemic, was shown to be associated with mental health disorders in people with immune-mediated diseases. The COVID-19 pandemic has led to a rise in the global prevalence of anxiety and depression, and limited data exist on the association between mental health and nonadherence to immune-modifying therapy during the pandemic. OBJECTIVES: To assess the extent of and reasons underlying nonadherence to systemic immune-modifying therapy during the COVID-19 pandemic in individuals with psoriasis, and the association between mental health and nonadherence. METHODS: Online self-report surveys (PsoProtectMe), including validated screens for anxiety and depression, were completed globally during the first year of the pandemic. We assessed the association between anxiety or depression and nonadherence to systemic immune-modifying therapy using binomial logistic regression, adjusting for potential cofounders (age, sex, ethnicity, comorbidity) and country of residence. RESULTS: Of 3980 participants from 77 countries, 1611 (40.5%) were prescribed a systemic immune-modifying therapy. Of these, 408 (25.3%) reported nonadherence during the pandemic, most commonly due to concerns about their immunity. In the unadjusted model, a positive anxiety screen was associated with nonadherence to systemic immune-modifying therapy [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.07-1.76]. Specifically, anxiety was associated with nonadherence to targeted therapy (OR 1.41, 95% CI 1.01-1.96) but not standard systemic therapy (OR 1.16, 95% CI 0.81-1.67). In the adjusted model, although the directions of the effects remained, anxiety was not significantly associated with nonadherence to overall systemic (OR 1.20, 95% CI 0.92-1.56) or targeted (OR 1.33, 95% CI 0.94-1.89) immune-modifying therapy. A positive depression screen was not strongly associated with nonadherence to systemic immune-modifying therapy in the unadjusted (OR 1.22, 95% CI 0.94-1.57) or adjusted models (OR 1.14, 95% CI 0.87-1.49). CONCLUSIONS: These data indicate substantial nonadherence to immune-modifying therapy in people with psoriasis during the pandemic, with attenuation of the association with mental health after adjusting for confounders. Future research in larger populations should further explore pandemic-specific drivers of treatment nonadherence. Clear communication of the reassuring findings from population-based research regarding immune-modifying therapy-associated adverse COVID-19 risks to people with psoriasis is essential, to optimize adherence and disease outcomes.

Development of antidrug antibodies against adalimumab maps to variation within the HLA-DR peptide-binding groove.

Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6-36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.

Factors associated with adverse COVID-19 outcomes in patients with psoriasis-insights from a global registry-based study.

BACKGROUND: The multimorbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse outcomes of coronavirus disease 2019 (COVID-19), but the data are limited. OBJECTIVE: Our aim was to characterize the course of COVID-19 in patients with psoriasis and identify factors associated with hospitalization. METHODS: Clinicians reported patients with psoriasis with confirmed/suspected COVID-19 via an international registry, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection. Multiple logistic regression was used to assess the association between clinical and/or demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviors. RESULTS: Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% were receiving a nonbiologic, and 10% were not receiving any systemic treatment for psoriasis. In all, 348 patients (93%) were fully recovered from COVID-19, 77 (21%) were hospitalized, and 9 (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted odds ratio [OR] = 1.59 per 10 years; 95% CI = 1.19-2.13), male sex (OR = 2.51; 95% CI = 1.23-5.12), nonwhite ethnicity (OR = 3.15; 95% CI = 1.24-8.03), and comorbid chronic lung disease (OR = 3.87; 95% CI = 1.52-9.83). Hospitalization was more frequent in patients using nonbiologic systemic therapy than in those using biologics (OR = 2.84; 95% CI = 1.31-6.18). No significant differences were found between classes of biologics. Independent patient-reported data (n = 1626 across 48 countries) suggested lower levels of social isolation in individuals receiving nonbiologic systemic therapy than in those receiving biologics (OR = 0.68; 95% CI = 0.50-0.94). CONCLUSION: In this international case series of patients with moderate-to-severe psoriasis, biologic use was associated with lower risk of COVID-19-related hospitalization than with use of nonbiologic systemic therapies; however, further investigation is warranted on account of potential selection bias and unmeasured confounding. Established risk factors (being older, being male, being of nonwhite ethnicity, and having comorbidities) were associated with higher hospitalization rates.

Clinical Impact of Antibodies against Ustekinumab in Psoriasis: An Observational, Cross-Sectional, Multicenter Study.

Ustekinumab is an effective treatment for psoriasis, but response varies between patients. The formation of anti-drug antibodies (ADAs) may explain part of this variation by reducing the free ustekinumab level. Currently, published analyses of the clinical impact of ADAs are incomplete. In this observational cross-sectional multicenter study of 340 patients, we evaluated the impact of ADAs on ustekinumab level and clinical response as assessed by the PASI. Circulating ADA levels were measured using two assays: a drug-sensitive radioimmunoassay and a drug-tolerant ELISA. Circulating ustekinumab levels were measured using an ELISA. ADAs were detected in 3.8% (95% confidence interval [CI] = 3.2-4.2) and in 10.6% (95% CI = 7.9-13.9) of patients using the radioimmunoassay and drug-tolerant ELISA, respectively. At least 85% of the ADAs were neutralizing. Compared with patients negative for ADAs, ADA positivity in the radioimmunoassay and drug-tolerant ELISA were associated with lower median ustekinumab levels (-0.62 µg/ml [95% CI = -1.190 to -0.30] and -0.74 µg/ml [95% CI = -1.09 to -0.47], respectively) and higher absolute PASI (6.6 [95% CI = 3.0-9.9] and 1.9 [95% CI = 0.4-4.0], respectively). Absence of detectable ustekinumab regardless of ADA status correlated with poor clinical outcome (median sample PASI 10.1, 6.5 [95% CI = 3.9-8.8] compared with patients positive for ustekinumab). In conclusion, substantially reduced drug exposure resulting from ADAs formation is associated with impaired clinical response.

Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes.

Association of Serum Ustekinumab Levels With Clinical Response in Psoriasis.

IMPORTANCE: High-cost biologic therapies have transformed the management of immune-mediated inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by measurement of circulating drug levels has been shown to be effective in various settings. However, limited evidence exists for this approach with the interleukin 12 and interleukin 23 inhibitor ustekinumab. OBJECTIVE: To evaluate clinical utility of therapeutic drug monitoring for ustekinumab in patients with psoriasis. DESIGN, SETTING, AND PARTICIPANTS: A prospective observational cohort of 491 adults with psoriasis was recruited to the multicenter Biomarkers of Systemic Treatment Outcomes in Psoriasis study within the British Association of Dermatologists Biologic and Immunomodulators Register from June 2009 to December 2017; samples from some patients were taken between 2009 and 2011 as part of a pilot study with the same inclusion criteria. EXPOSURE: Serum ustekinumab level measured at any point during the dosing cycle using an enzyme-linked immunosorbent assay. MAIN OUTCOMES AND MEASURES: Disease activity measured using the Psoriasis Area and Severity Index (PASI) score. Treatment response outcomes were PASI75 (75% reduction in PASI score from baseline [primary outcome]), PASI90 (90% reduction of PASI score from baseline), and absolute PASI score of 1.5 or less. RESULTS: A total of 491 patients (171 women and 320 men; mean [SD] age, 45.7 [12.8] years) had 1 or more serum samples (total, 853 samples obtained 0-56 weeks from start of treatment) and 1 or more PASI scores within the first year of treatment. Antidrug antibodies were detected in only 17 of 490 patients (3.5%). Early measured drug levels (1-12 weeks after starting treatment) were associated with PASI75 response 6 months after starting treatment (odds ratio, 1.38; 95% CI, 1.11-1.71) when adjusted for baseline PASI score, age, and ustekinumab dose. However, this finding was not consistent across the other PASI outcomes (PASI90 and PASI score of ≤1.5). CONCLUSIONS AND RELEVANCE: This real-world study provides evidence that measurement of early serum ustekinumab levels could be useful to direct the treatment strategy for psoriasis. Adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome.

Defining the Therapeutic Range for Adalimumab and Predicting Response in Psoriasis: A Multicenter Prospective Observational Cohort Study.

Biologics have transformed management of inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by circulating drug levels has been proposed. We aimed to determine the real-world clinical utility of therapeutic drug monitoring in psoriasis. Within a multicenter (n = 60) prospective observational cohort, 544 psoriasis patients were included who were receiving adalimumab monotherapy and had at least one serum sample and Psoriasis Area and Severity Index (PASI) score available within the first year. We present models giving individualized probabilities of response for any given drug level: a minimally effective drug level of 3.2 µg/ml discriminates responders (PASI75 indicates 75% improvement in baseline PASI) from nonresponders, and gives an estimated PASI75 probability of 65% (95% confidence interval = 60-71). At 7 µg/ml, PASI75 probability is 81% (95% CI = 76-86); beyond 7 µg/ml, the drug level/response curve plateaus. Crucially, drug levels are predictive of response 6 months later, whether sampled early or at steady state. We confirm serum drug level to be the most important factor determining treatment response, highlighting the need to take drug levels into account when searching for biomarkers of response. This real-world study with pragmatic drug level sampling provides evidence to support the proactive measurement of adalimumab levels in psoriasis to direct treatment strategy, and is relevant to other inflammatory diseases.

Prevention of food allergy.

The past few decades have witnessed an increase in the prevalence of IgE-mediated food allergy (FA). For prevention strategies to be effective, we need to understand the causative factors underpinning this rise. Genetic factors are clearly important in the development of FA, but given the dramatic increase in prevalence over a short period of human evolution, it is unlikely that FA arises through germline genetic changes alone. A plausible hypothesis is that 1 or more environmental exposures, or lack thereof, induce epigenetic changes that result in interruption of the default immunologic state of tolerance. Strategies for the prevention of FA might include primary prevention, which seeks to prevent the onset of IgE sensitization; secondary prevention, which seeks to interrupt the development of FA in IgE-sensitized children; and tertiary prevention, which seeks to reduce the expression of end-organ allergic disease in children with established FA. This review emphasizes the prevention of IgE-mediated FA through dietary manipulation, among other strategies; in particular, we focus on recent interventional studies in this field.

Does atopic dermatitis cause food allergy? A systematic review.

BACKGROUND: The association between atopic dermatitis (AD) and food allergy (FA) is not fully understood, although a causal relationship has been suggested. This has important implications for prevention and treatment. OBJECTIVE: We aimed to review the association between AD and FA, the effect of FA on AD severity, chronicity, and age of onset, and the temporal relationship between the two. METHODS: Medline and Embase were systematically searched from inception to November 2014 for studies investigating both AD and FA. RESULTS: Sixty-six studies were identified. Eighteen were population-based, 8 used high-risk cohorts, and the rest comprised patients with either established AD or FA. In population-based studies, the likelihood of food sensitization was up to 6 times higher in patients with AD versus healthy control subjects at 3 months of age (odds ratio, 6.18; 95% CI, 2.94-12.98; P < .001). Other population-based studies reported that up to 53% of subjects with AD were food sensitized, and up to 15% demonstrated signs of FA on challenge. Meanwhile, studies including only patients with established AD have reported food sensitization prevalences up to 66%, with challenge-proven FA prevalences reaching up to 81%. Sixteen studies suggested that FA is associated with a more severe AD phenotype. Six studies indicated that AD of earlier onset or increased persistence is particularly associated with FA. Finally, one study found that AD preceded the development of FA. CONCLUSIONS: This systematic review confirms a strong and dose-dependent association between AD, food sensitization, and FA. AD of increased severity and chronicity is particularly associated with FA. There is also evidence that AD precedes the development of food sensitization and allergy, in keeping with a causal relationship.

Eczema and indoor environment: lessons from the International Study of Asthma and Allergies in Childhood (ISAAC) Phase 2.

BACKGROUND: Numerous studies have reported a positive association between damp housing conditions and asthma, but little is known about indoor environmental exposures in relation to childhood eczema. We aimed to specifically investigate the effect of indoor mould and dampness on eczema risk in the International Study of Asthma and Allergies in Childhood (ISAAC). METHODS: ISAAC Phase 2 is a cross-sectional study of 46 051 children aged 8-12 years from 20 countries. Information on demographics, eczema symptoms, and dampness was gathered with parental questionnaires. Children were examined for eczema and underwent skin prick testing. In a stratified subgroup, dust samples were collected to measure house dust mite exposure. Sex, maternal education, parental allergy, pet ownership, maternal smoking, having an older sibling, bedroom sharing, and cooking with fuels were explored as potential confounders or effect modifiers in logistic regression analysis. FINDINGS: Current residential exposure to dampness and mould was significantly associated with flexural eczema in the previous year, with a stronger association seen in non-affluent than in affluent countries (adjusted odds ratio [OR] 1·96, 95% CI 1·62-2·37, vs 1·34, 1·18-1·51). Dampness and mould in the first year of life was also significantly associated with parent-reported eczema ever (1·94, 1·40-2·68, vs 1·43, 1·28-1·60). However, the association with flexural eczema on examination was not significant (0·93, 0·76-1·13). Risk estimates were similar in children positive and negative on skin prick testing, and were not appreciably altered by the effect modifiers, apart from parental allergic disease (parental allergies OR 1·35, 95% CI 1·18-1·54, vs no parental allergies 1·61, 1·37-1·90). INTERPRETATION: These data suggest an association between damp housing conditions and childhood eczema symptoms, which may be causal. Further work is needed to elucidate possible mechanisms. Modification to home environment to reduce dampness and mould could be harnessed to improve or even prevent this common and debilitating condition. FUNDING: None.

Prevention of food allergy.

Despite a trend towards delayed weaning, food allergies (FAs) have increased in the past few decades and are now considered a public health concern, resulting in significant morbidity as well as occasional mortality. Whilst genetic factors are clearly important in the development of FA, a rise in FAs has occurred over a short period of time and is therefore unlikely to be due to germ-line genetic changes alone. Thus, it seems plausible that one or more environmental exposures may, via epigenetic changes, result in the interruption of the 'default immunologic state' of tolerance to foods. Strategies are therefore required for the prevention of FA: primary prevention seeks to prevent the onset of IgE-sensitisation; secondary prevention seeks to interrupt the development of FA in IgE-sensitised children; and tertiary prevention seeks to reduce the expression of 'end-organ' allergic disease in children with established FA. This chapter will outline the major findings in this field, with the aim of equipping the clinician with an evidence-based approach to a burgeoning yet poorly understood clinical problem. We also highlight the methodological challenges hindering the interpretation of existing FA studies. Fortunately, there are now robust studies underway, the results of which are expected to guide public health recommendations with respect to how and when to introduce major allergenic foods to children, regardless of allergic risk.

The association between atopic dermatitis and food allergy in adults.

PURPOSE OF REVIEW: We conducted a systematic literature search for studies investigating the link between atopic dermatitis and food sensitization or clinically significant allergy (FA) in adults, to assess the strength of the association between the two diseases in both general and selected populations. RECENT FINDINGS: Around 10% of adults with FA have concomitant atopic dermatitis at the population level. Adult atopic dermatitis patients show much higher rates of sensitization to foods than healthy individuals, in particular to food proteins cross-reactive with airborne allergens, rather than the food allergens that typically predominate amongst children with atopic dermatitis. When food challenges have been performed, rather than relying on questionnaire information and specific IgE testing alone, they often do not confirm eczematous reactions. Only half of patients who have challenge-proven FA improve on a strict elimination diet. SUMMARY: Challenge-proven FA in adults with atopic dermatitis is uncommon. The incidence of new-onset FA in adult atopic dermatitis patients is currently unknown, as are the main routes of sensitization. There is increasing evidence from studies in infants that sensitization to food protein can occur across the skin barrier, in particular in the presence of eczematous skin inflammation. Carefully conducted large longitudinal studies amongst adults that take into account skin barrier function and genetics are required.

Lentigo maligna mimicking invasive melanoma in Mohs surgery: a case report.

Lentigo maligna is a lentiginous proliferation of atypical melanocytes confined to the epidermis, typically on chronically sun-damaged skin. Following biopsy and exclusion of invasive disease, therapy may involve Mohs surgery, topical treatment or radiotherapy. However, lentigo maligna often involves adnexal structures, creating histological difficulty in distinguishing these foci from invasive melanoma. We present a case in which, during Mohs excision, a nodule of severely atypical melanocytes appeared to lie within the dermis, potentially altering treatment and prognosis. The use of laminin-5 provided a means of resolving this diagnostic dilemma, facilitating continuation of Mohs surgery until tumour clearance was achieved.

Pediatric urticaria.

Although urticaria is not a life-threatening disease, its impact on quality of life in children should not be overlooked. A systematic search of online databases, including Medline, was performed to inform a review aiming to equip clinicians with an evidence-based approach to all aspects of pediatric urticaria. This review hinges on an illustrative case and includes a summary table of studies pertaining to disease management in children. The multiple issues faced by patients, their families, and treating clinicians are highlighted, and the current literature on the presentation, natural history, investigation, and management of this poorly understood condition is assessed.

Radial artery for coronary artery bypass grafting: does proximal anastomosis to the aorta or left internal mammary artery achieve better patency?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'in coronary artery bypass grafting using radial artery grafts, does proximal anastomosis to the aorta or left internal mammary artery achieve better patency'. Altogether >183 papers were found using the reported search, of which 9 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Radial artery grafts typically have a narrower lumen than vein grafts, and as such there is some concern that anastomosing them directly to the aorta during coronary artery bypass grafting (CABG) may impair graft patency. As such, some surgeons prefer to anastomose radial artery grafts to a second-order vessel such as the left internal mammary artery (LIMA). We sought to assess the evidence for this. A handful of papers directly addressing the issue of the effect of the site of proximal anastomosis on graft patency were found, with three showing no significant difference. One such study reported an insignificant difference in angiographic patency at 32 months postoperatively, with 94.1% of off-aorta grafts remaining patent vs 87.2% of off-LIMA grafts (p = 0.123). However, a large-scale well-designed study was able to demonstrate a statistically significant difference at five years postoperatively, with 74.3% of off-aorta grafts patent, compared with 65.2% of off-LIMA (p = 0.004). Nonetheless, a number of papers that report patency for either off-aorta or off-LIMA grafts give comparable figures for each technique. Additionally, different centres and investigators report very different patency results for grafts that have the same site of proximal anastomosis. One centre was able to achieve patency rates for off-LIMA grafts of 88% up to a mean of 7.7 years postoperatively while another centre reported a patency rate of only 78.6% at three years. Given this, and the plethora of other factors influencing graft patency, we conclude that the best evidence suggests that the site of proximal anastomosis has little or no effect on radial artery graft patency following CABG.