Association of Early Postoperative Regional Oxygen Saturation Measures and Development of Necrotizing Enterocolitis in Neonates Following Cardiac Surgery.

Necrotizing enterocolitis (NEC) is a relatively common complication in neonates with single ventricle physiology following heart surgery. Near-infrared spectroscopy (NIRS) is used to measure regional oxygen saturations in neonates in the postoperative period. We sought to investigate the association of somatic regional oxygen saturation (srSO2) and cerebral regional oxygen saturation (crSO2) in the early postoperative period and the subsequent development of NEC. We performed a retrospective cohort study of neonates who underwent cardiac surgery with cardiopulmonary bypass from October 2017 to September 2021 at the University of Virginia Children's Hospital. Values of srSO2 and crSO2 were captured over the first 48 h following surgery. 166 neonates were included and the median age at time of surgery was 8 days. NEC was diagnosed in 18 neonates following heart surgery with a median interval from surgery to diagnosis of 7 days. Neonates with single ventricle physiology had lower average crSO2 (62% vs 78%, p < 0.001), average srSO2 (72% vs 86%, p < 0.001), average crSO2 to srSO2 ratio (0.874 vs 0.913, p < 0.001), and an increased average srSO2-crSO2 difference (10% vs 8%, p = 0.03). Adjusting for single ventricle physiology, lower average crSO2 was associated with the development of definite NEC (modified Bell's criteria stage IIa and higher) (OR = 0.86, 95% CI 0.78-0.96, p = 0.007). Lower crSO2 values in the early postoperative period in neonates following cardiac surgery was associated with an increased risk in the subsequent development of NEC.

Targeting the complexity of ERBB2 biology in gastroesophageal carcinoma.

ERBB2 is the most prominent therapeutic target in gastroesophageal adenocarcinoma (GEA). For two decades, trastuzumab was the only treatment available for GEA overexpressing ERBB2. Several drugs showing evidence of efficacy over or in complement to trastuzumab in breast cancer failed to show clinical benefit in GEA. This resistance to anti-ERBB2 therapy is peculiarly recurrent in GEA and is mostly due to tumor heterogeneity with the existence of low expressing ERBB2 tumor clones and loss of ERBB2 over time. The development of new ERBB2 testing strategies and the use of antibody-drug conjugates having a bystander effect are providing new tools to fight heterogeneity in ERBB2-positive GEA. Co-amplifications of tyrosine kinase receptors, alterations in mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K) signaling pathways and in proteins controlling cell cycle are well known to contribute resistance to anti-ERBB2 therapy, and they can be targeted by dual therapy. Recently described, NF1 mutations are responsible for Ras phosphorylation and activation and can also be targeted by MEK/ERK inhibition along with anti-ERBB2 therapy. Multiple lines of evidence suggest that immune mechanisms involving antibody-dependent cell-mediated cytotoxicity are preponderant over intracellular signaling in anti-ERBB2 therapy action. A better comprehension of these mechanisms could leverage immune action of anti-ERBB2 therapy and elucidate efficacy of combinations associating immunotherapy and anti-ERBB2 therapy, as suggested by the recent intermediate positive results of the KEYNOTE-811 trial.

An observational epidemiological study to analyze intracerebral hemorrhage across the United States: Incidence and mortality trends from 1990 to 2017.

OBJECTIVES: Intracerebral Hemorrhage (ICH) accounts for 10% of strokes annually in the United States (US). Up-to-date trends in disease burden and regional variations remain unknown. Our study reports updated trends of ICH incidence, mortality, and mortality to incidence ratio (MIR) across the US. MATERIALS AND METHODS: Observational study to evaluate the incidence and mortality from ICH across the US. Data was obtained from Global Burden of Disease (GBD) database. Age-Standardized Incidence (ASIRs) and Death (ASDRs) Rates, as well as the Mortality- to-Incidence ratios (MIRs) for ICH in the US overall and state-wise from 1990-2017. Joinpoint regression analysis was used, with presentation of estimated annual percentage changes (EAPCs). RESULTS: Overall decrease in ASIRs, ASDRs, and MIRs in the US for both sexes. The 2017 mean ASIR was 25.67/100,000 for men and 19.17/100,000 for women, whereas mean ASDR was 13.96/100,000 for men and 11.35/100,000 for women. District of Columbia had greatest decreases in ASIR EAPCs for both men and women at -41.25% and -40.58%, respectively, and greatest decreases in ASDR EAPCs for men and women at -55.38% and -48.51%, respectively. MIR between 1990-2017 decreased in men by -12.12% and women by -7.43%. MIR increased in men from 2014-2017 (EAPC +2.2%) and in women from 2011-2017 (EAPC +1.0%). CONCLUSION: Decreasing trends in incidence, mortality, and MIR. No significant trends in mortality were found in the last 6 years of the study period. MIR worsened in males from 2014-2017 and females from 2011-2017, suggesting decreased ICH-related survival lately.

[Access to health care throughout the country]. / Zugang zur Gesundheitsversorgung in der Fläche.

The legal basis for describing the regional care situation is based on the adjusted supply rate of the 'demand planning guideline'. However, it provides only limited information about the accessibility of medical care which is crucial for the reality of patients' lives. The aim of this review is to present geographic approaches that spatially measure access to dermatological care in its physical and digital dimension. Here, on the one hand, the classical geographic parameter 'accessibility' is addressed, and on the other hand, data from the Federal Ministry of Transport and Digital Infrastructure (BMVI) on broadband coverage are presented as access parameters of teledermatological applications. In addition to the methodological approach, limitations and potentials in the interpretation of the results, minimum standards are also considered. The access parameters presented here make it possible to investigate spatial disparities and to present them clearly via cartographic representations. While the example of accessibility with a car shows almost area-wide access to the nearest dermatology practice (≤ 30 min), investigations on public transport accessibility reveal rather heterogeneous accessibility. Particularly in the identification of 'dual care gaps', sub-areas with poor physical and digital accessibility, these approaches could support and advance the application of alternative care models. However, the approaches presented here focus on potential accessibility. Further dimensions on actual physician utilisation or availability-also with regard to minimum standards-should be the subject of future research.

[Methods for analysing spatial data : Using the example of skin cancer prevalence in Germany]. / Methoden zur Analyse räumlicher Daten : Beispiel der regionalen Hautkrebsprävalenz in Deutschland.

BACKGROUND: Studies show a spatial variation in skin cancer frequencies, but the causes have not been fully understood. When analysing spatial patterns and correlations, different approaches need to be considered, as the data have special features due to their spatial structure. AIM OF THE STUDY: Why the spatial consideration of skin cancer frequencies is important at all, and which methods of analysis are useful is considered in more detail in this article. The article provides an introduction and overview of statistical methods that are important for the spatial analysis of skin cancer frequencies. MATERIALS AND METHODS: At first it is shown which descriptive methods, such as statistical smoothing, can be applied. Next, spatial cluster and regression analyses will be discussed. Testing for spatial autocorrelation will be considered. RESULTS: In particular, the spatial dependence of the data on neighbouring regions, which if ignored can lead to biased estimates, is of particular importance in the analysis of spatial data and requires special spatial analysis methods. DISCUSSION: This article provides an introduction and overview of statistical methods relevant to the spatial analysis of skin cancers.

[Relevance of health geographic research for dermatology]. / Bedeutung der gesundheitsgeografischen Forschung für die Dermatologie.

The association between geographic and medical aspects is a well-known phenomenon, which also occurs in dermatological research. This article reviews the field of health geography, the history of the association between spatial location and health, and focuses on current areas of research. Research focusing on explaining regional variations in health refer to individual aspects and needs, population factors, environmental factors, and health care delivery structures in specific regions, as well as the interaction between them. Regional healthcare research is primarily concerned with access to health services and on the utilisation of those services. Methodologically, the analysis of geodata and the application of geographic information systems (GIS) and spatial modelling play a major role in this field. Dermatological research and dermatological practice can benefit from the findings of the regional analysis of access, utilisation, and variations in order to obtain a more detailed picture of care and thus to optimise care.

[Analysis of the skin cancer incidence in Hamburg]. / Untersuchung der Hautkrebshäufigkeit in Hamburg.

BACKGROUND: The aim of health geographical research is to identify regional variations in health and care and their causes. Regional differences are also evident in skin cancer incidence, but knowledge about small-scale, inner-city variations is not yet available. OBJECTIVES: How can the inner-city variations in skin cancer incidence in Hamburg, Germany, be described and how can initial indications of their causes be identified? METHODS: The study area is the city of Hamburg and the data source is the Hamburg City Health Study with N = 10,000 persons aged 45-74 years. Descriptive methods are used to characterise the regional variation in skin cancer prevalence adjusted for age and sex. A correlation analysis provides information on possible associations with sociodemographic conditions in the city districts and district clusters. RESULTS: Skin cancer prevalence varies within the urban area with high prevalences (maximum 13.8%) in the north-east and south-west of Hamburg. Weak to medium correlations with selected sociodemographic variables are found. For example, the higher the living space per inhabitant (r = 0.35), the higher the skin cancer prevalence in the district. CONCLUSIONS: The Hamburg City Health Study shows regional and inner-city disparities and possible associations between skin cancer prevalence and local sociodemographic conditions. However, further and methodologically more extensive studies are necessary in order to make detailed statements.

[Regional variations in healthcare for patients with psoriasis and atopic dermatitis in Germany]. / Regionale Variationen in der Versorgung von Patienten mit Psoriasis und atopischer Dermatitis in Deutschland.

BACKGROUND: Psoriasis (Pso) and atopic dermatitis (AD) are chronic skin diseases that result in significant physical and psychological impairment, financial burden, and loss of quality of life. According to previous data, there are regional differences in healthcare. OBJECTIVES: The aim was to analyse the epidemiology as well as the treatment of insured people with Pso and AD in Germany in a regional comparison. METHODS: Data of the insurance company Techniker Krankenkasse for the year 2019 regarding treatment prevalences as well as drug prescriptions on the regional level for all physicians were examined. RESULTS: In 2019 the overall prevalence of Pso was 2.5% (about 2 million insured people in Germany) and AD was 4.2% (about 3.6 million insured people). In Pso, new guideline-compliant drugs were frequently utilised, yet systemic glucocorticosteroids (GCS) were still disproportionally prescribed. Regionally, there were pronounced disparities with higher prescription rates of the new drugs in the north and east. Insured people with AD most frequently received topical GCS (approx. 88%), of which most were class III (66%), and significantly less frequently calcineurin inhibitors (< 10%), which also conform to guidelines. Systemically, GCS were by far most commonly used (about 25% of all insured people with drug prescriptions). Dupilumab, the only long-term drug approved in 2019, was very rarely prescribed, accounting for less than 1%. Again, large regional differences similar to Pso were found. CONCLUSION: Pso and AD show relevant disparities and gaps in drug care in the regional comparison despite uniform national guidelines and patient needs. The barriers to appropriate modern pharmaceuticals need to be clarified and mitigated.

A transcriptomic signature to predict adjuvant gemcitabine sensitivity in pancreatic adenocarcinoma.

BACKGROUND: Chemotherapy is the only systemic treatment approved for pancreatic ductal adenocarcinoma (PDAC), with a selection of regimens based on patients' performance status and expected efficacy. The establishment of a potent stratification associated with chemotherapeutic efficacy could potentially improve prognosis by tailoring treatments. PATIENTS AND METHODS: Concomitant chemosensitivity and genome-wide RNA profiles were carried out on preclinical models (primary cell cultures and patient-derived xenografts) derived from patients with PDAC included in the PaCaOmics program (NCT01692873). The RNA-based stratification was tested in a monocentric cohort and validated in a multicentric cohort, both retrospectively collected from resected PDAC samples (67 and 368 patients, respectively). Forty-three (65%) and 203 (55%) patients received adjuvant gemcitabine in the monocentric and the multicentric cohorts, respectively. The relationships between predicted gemcitabine sensitivity and patients' overall survival (OS) and disease-free survival were investigated. RESULTS: The GemPred RNA signature was derived from preclinical models, defining gemcitabine sensitive PDAC as GemPred+. Among the patients who received gemcitabine in the test and validation cohorts, the GemPred+ patients had a higher OS than GemPred- (P = 0.046 and P = 0.00216). In both cohorts, the GemPred stratification was not associated with OS among patients who did not receive gemcitabine. Among gemcitabine-treated patients, GemPred+ patients had significantly higher OS than the GemPred-: 91.3 months [95% confidence interval (CI): 61.2-not reached] versus 33 months (95% CI: 24-35.2); hazard ratio 0.403 (95% CI: 0.221-0.735, P = 0.00216). The interaction test for gemcitabine and GemPred+ stratification was significant (P = 0.0245). Multivariate analysis in the gemcitabine-treated population retained an independent predictive value. CONCLUSION: The RNA-based GemPred stratification predicts the benefit of adjuvant gemcitabine in PDAC patients.

Regional variations in the use of statutory skin cancer screenings in Germany: population-based spatial multisource analysis.

BACKGROUND: Due to the increasing incidence of skin cancer, programmes for the prevention of skin cancer have been developed and implemented in Germany. However, utilization of skin cancer screenings shows marked regional differences. Reasons and predictors of such variations are unclear. OBJECTIVES: The objective of the study is to identify predictors for regional use of skin cancer screening variations in Germany. METHODS: Analysis of the population set of ambulatory claims data (2009-2015) of the statutory health insurances (SHI) in Germany (70.2 million people in 2015). Skin cancer screening utilization rate was determined on county level. Descriptive, cluster and multivariate analyses were performed to identify spatial patterns in skin cancer screening utilization. RESULTS: Overall, 6.5-7.9 million people participated in skin cancer screenings. Utilization rates of people ≥35 years of age were 9.74% (2009) and 10.96% (2015). Marked regional variations were identified between the counties. Dermatologists in Saxony and Westphalia-Lippe as well as general practitioners in Lower Saxony and North Rhine showed particularly high utilization rates. Multiple regression analyses demonstrated e.g. positive associations between the skin cancer screening utilization rates and employees with higher vocational qualifications and shorter travel time by car to the nearest major urban centre. CONCLUSION: Utilization rates of skin cancer screening vary largely in Germany with specific spatial patterns. Multivariate analyses demonstrate associations with socio-economic and geographical determinants. The results indicate the importance of health policy measures. These should be used in a more targeted manner in the regions in order to increase utilization of skin cancer screening.

[Network Analyses in Regional Health Care Research: Example of Dermatological Care in the Metropolitan Region of Hamburg]. / Netzwerkanalysen in der regionalen Versorgungsforschung: Das Beispiel der dermatologischen Versorgung in der Metropolregion Hamburg.

BACKGROUND: One of the overall objectives of the legislator is to ensure an overall "homogeneous", and easily accessible medical care for the population. The physician-patient ratio can be used to describe the regional health care situation. But this method does not provide information concerning the availability of, for instance, the nearest doctor. Therefore, further parameters such as accessibility must be taken into consideration. For this purpose, network analyses are an appropriate method. The objective of this study is to present methodological tools to evaluate the healthcare situation in the metropolitan region of Hamburg, primarily focusing on accessibility using dermatologists as an example. METHODS: Analyzing data of 20 counties, the geographical distribution of N=357 dermatologists and the physician-patient ratio were calculated. In a second step, a network analysis regarding accessibility was performed. In order to calculate accessibility, address data (physicians) were transformed into coordinates, consisting of defined places (N=303) and restrictions (e. g. speed, turn restrictions) of the network. The calculation of population-based accessibility is based on grid cells for the population density. RESULTS: Despite adequacy of the overall medical situation, differences in the availability of the nearest dermatologists in the metropolitan region are remarkable, particularly when use of public transport is taken into consideration. In some counties, over 60% of the population require at least one hour to get to the nearest dermatologist using public transportation. In rural regions within the metropolitan area are particularly affected. CONCLUSION: The network analysis has shown that the choice and availability of transportation in combination with the location (rural/urban) is essential for health care access. Especially elderly people in rural areas with restricted mobility are at a disadvantage. Therefore, modern health care approaches (e. g. telemedicine) are necessary to optimize the health care situation in rural areas. Network analyses can make a valuable methodological contribution to the analysis of regional health care disparities.

[Real world data sources for health services research on skin cancer]. / Real-world-Datenquellen für die Versorgungsforschung zum Hautkrebs.

Health services research in dermatology with the objective to improve prevention, efficient diagnostics and treatment of skin cancer requires real world data from all sectors. This article provides an overview of currently available relevant real world data sources and the utilization potential. It lists exemplary results of existing studies: secondary data analyses based on billing data from statutory health insurance funds were used among other things to estimate the participation rate in the statutory skin cancer screening. This was approximately 31% in the 2­year period and was higher in the western German federal states than in the eastern ones. Furthermore, participation was higher for women than for men. Regional data in combination with sociostructural and sociodemographic indicators are available for planning of dermatological care and the analysis points to an association with the prevalence of skin cancer. Primary data are available and necessary for recording patient reported endpoints and evaluating the treatment of skin cancer patients by dermatologists. Extensive histopathological databases record not only clinical markers of skin cancer but also sociodemographic characteristics of the patients and indicate a correlation between the time of diagnosis or therapy and the insurance status and place of residence. In addition to the utilization potential, specific limitations of the data sources are listed.

Epidemiology of skin cancer in the German population: impact of socioeconomic and geographic factors.

BACKGROUND: Skin cancer being the most common cancer in Germany has shown increasing incidence in the past decade. Since mostly caused by excessive UV exposure, skin cancer is largely related to behaviour. So far, the impact of regional and sociodemographic factors on the development of skin cancer in Germany is unclear. OBJECTIVES: This study aimed to investigate the association of potential predictive factors with the prevalence of skin cancers in Germany. METHODS: Nationwide ambulatory care claims data from persons insured in statutory health insurances (SHI) with malignant melanoma (MM, ICD-10 C43) and non-melanocytic skin cancer (NMSC, ICD-10 C44) in the years 2009-2015 were analysed. In addition, sociodemographic population data and satellite-based UV and solar radiation data were associated. Descriptive and multivariate (spatial) statistical analyses (e.g. Bayes' smoothing) were conducted on county level. RESULTS: Data from 70.1 million insured persons were analysed. Age-standardized prevalences per 100 000 SHI insured persons for MM and NMSC were 284.7 and 1126.9 in 2009 and 378.5 and 1708.2 in 2015. Marked regional variations were observed with prevalences between 32.9% and 51.6%. Multivariate analysis shows among others statistically significant positive correlations between higher income and education, and MM/NMSC prevalence. CONCLUSION: Prevalence of MM and NMSC in Germany shows spatio-temporal dynamics. Our results demonstrate that regional UV radiation, sunshine hours and sociodemographic factors have significant impact on skin cancer prevalence in Germany. Individual behaviour obviously is a major determinant which should be subject to preventive interventions.

Modulation of autoimmune arthritis severity in mice by apolipoprotein E (ApoE) and cholesterol.

Apolipoprotein E (ApoE) deficiency promoted an exacerbation of autoimmune arthritis in mice by inducing proinflammatory immune responses. In this study we analysed the contribution of hypercholesterolaemia and/or the absence of ApoE anti-inflammatory properties, unrelated to its function in the control of cholesterol metabolism, towards the acceleration of arthritis in these mutant animals. The induction and severity of collagen type II-induced arthritis (CIA) were compared for B10.RIII wild-type (WT), B10.RIII.ApoE+/- , B10.RIII.ApoE-/- and B10.RIII.low-density lipoprotein receptor (LDLR-/- ) mice with different concentrations of circulating ApoE and cholesterol. A 50-70% reduction in serum levels of ApoE was observed in heterozygous B10.RIII.ApoE+/- mice in comparison to B10.RIII.WT, although both strains of mice exhibited similar circulating lipid profiles. This ApoE reduction was associated with an increased CIA severity that remained lower than in homozygous B10.RIII.ApoE-/- mice. An important rise in circulating ApoE concentration was observed in hypercholesterolaemic B10.RIII.LDLR-/- mice fed with a normal chow diet, and both parameters increased further with an atherogenic hypercholesterolaemic diet. However, the severity of CIA in B10.RIII.LDLR-/- mice was similar to that of B10.RIII.WT controls. In conclusion, by comparing the evolution of CIA between several strains of mutant mice with different levels of serum ApoE and cholesterol, our results demonstrate that both hypercholesterolaemia and ApoE regulate the intensity of in-vivo systemic autoimmune responses.

[Risk characteristics and survival rates of malignant melanoma in Germany and the Netherlands]. / Risikomerkmale und Überlebensrate des malignen Melanoms in Deutschland und den Niederlanden.

BACKGROUND: Mortality and lethality of malignant melanoma (MM) show marked variations throughout Europe, thereunder a higher risk within the Netherlands (NL) when compared to Germany (D). GOAL AND METHODS: Comparison of systems and exploration of possible causal factors that could explain the difference between D and NL. Comparative healthcare research analysis using published international literature, as well as publicly accessible databases, and a subsequent hypothesis-generating analysis. RESULTS: The higher rate of excised MM less than 1 mm in diameter in D (65 % vs. 45 %) confirms the clinical reports of the cancer registries. The biological factors for the emergence of MM, such as skin type, do not seem to significantly differ from each other. Among the further potential predictors there are no relevant differences within, for example, geographical conditions and the qualifications of the treating physicians. Primary prevention has a longer continual tradition in D. Here, secondary prevention is characterized by population-based extensive screening, which does not occur within the NL. In addition, distinct differences are found regarding access to dermatologists. CONCLUSION: System access to a medical specialist and the prevention of skin cancer are currently the most distinctive potential determinants of more favorable MM survival rate in Germany.

[Regional differences in the health care of basal cell carcinoma]. / Regionale Unterschiede in der Versorgung des Basalzellkarzinoms.

BACKGROUND: Basal cell carcinoma (BCC) is the most common type of skin cancer in Germany. So far, it is unclear whether regional variations exist in the health care of the BCC. OBJECTIVES: Analysis of regional variations in health care (e. g., skin cancer screening) and their causes using the example of BCC. MATERIALS AND METHODS: Qualitative and quantitative analysis of the regional health care situation of BCC based on three studies was undertaken. These studies include the analysis of n = 7015 histopathological indications whose average tumor thickness is regarded as a characteristic of the quality of care, and a secondary data analysis of GK insured (n = 6.1 million DAK-insured persons), and a nationwide survey (FORSA) of n = 1004 participants focusing on the use of skin cancer screening. RESULTS: Analysis of the histopathological examination showed regional variations in average tumor depth of penetration. These are associated with the rural/urban characteristics of the region and individual sociodemographic indicators (e. g., employment sector or education). The results for age- and gender-specific use (DAK data) showed higher participation rates regarding skin cancer screening in western than in eastern federal states (Bundesländer). Moreover, it was revealed that the trend for using skin cancer screening was higher in urban than in rural areas. The results of population-related surveys confirm this trend. CONCLUSION: Although it is not possible to compare the studies directly, all three showed an association between city/state and the use of skin cancer screenings. In addition, sociodemographic characteristics that are related to the quality of health care were identified.

Sex-based prognostic implications of nonobstructive coronary artery disease: results from the international multicenter CONFIRM study.

PURPOSE: To determine the clinical outcomes of women and men with nonobstructive coronary artery disease ( CAD coronary artery disease ) with coronary computed tomographic (CT) angiography data in patients who were similar in terms of CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution. MATERIALS AND METHODS: Institutional review board approval was obtained for all participating sites, with either informed consent or waiver of informed consent. In a prospective international multicenter cohort study of 27 125 patients undergoing coronary CT angiography at 12 centers, 18 158 patients with no CAD coronary artery disease or nonobstructive (<50% stenosis) CAD coronary artery disease were examined. Men and women were propensity matched for age, CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution, which resulted in a final cohort of 11 462 subjects. Nonobstructive CAD coronary artery disease presence and extent were related to incident major adverse cardiovascular events ( MACE major adverse cardiovascular events ), which were inclusive of death and myocardial infarction and were estimated by using multivariable Cox proportional hazards models. RESULTS: At a mean follow-up ± standard deviation of 2.3 years ± 1.1, MACE major adverse cardiovascular events occurred in 164 patients (0.6% annual event rate). After matching, women and men experienced identical annualized rates of myocardial infarction (0.2% vs 0.2%, P = .72), death (0.5% vs 0.5%, P = .98), and MACE major adverse cardiovascular events (0.6% vs 0.6%, P = .94). In multivariable analysis, nonobstructive CAD coronary artery disease was associated with similarly increased MACE major adverse cardiovascular events for both women (hazard ratio: 1.96 [95% confidence interval { CI confidence interval }: 1.17, 3.28], P = .01) and men (hazard ratio: 1.77 [95% CI confidence interval : 1.07, 2.93], P = .03). CONCLUSION: When matched for age, CAD coronary artery disease risk factors, angina typicality, and nonobstructive CAD coronary artery disease extent, women and men experience comparable rates of incident mortality and myocardial infarction.

Prognostic significance of calcified plaque among symptomatic patients with nonobstructive coronary artery disease.

BACKGROUND: Coronary artery calcium (CAC) is a well-established predictor of clinical outcomes for population screening. Limited evidence is available as to its predictive value in symptomatic patients without obstructive coronary artery disease (CAD). The aim of the current study was to assess the prognostic value of CAC scores among symptomatic patients with nonobstructive CAD. METHODS: From the COronary Computed Tomographic Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 7,200 symptomatic patients with nonobstructive CAD (<50% coronary stenosis) on coronary-computed tomographic angiography were prospectively enrolled and followed for a median of 2.1 years. Patients were categorized as without (0% stenosis) or with (>0% but <50% coronary stenosis) a luminal stenosis. CAC scores were calculated using the Agatston method. Univariable and multivariable Cox proportional hazard models were employed to estimate all-cause mortality and/or myocardial infarction (MI). Four-year death and death or MI rates were 1.9% and 3.3%. RESULTS: Of the 4,380 patients with no luminal stenosis, 86% had CAC scores of <10 while those with a luminal stenosis had more prevalent and extensive CAC with 31.9% having a CAC score of ≥100. Among patients with no luminal stenosis, CAC was not predictive of all-cause mortality (P = .44). However, among patients with a luminal stenosis, 4-year mortality rates ranged from 0.8% to 9.8% for CAC scores of 0 to ≥400 (P < .0001). The mortality hazard was 6.0 (P = .004) and 13.3 (P < .0001) for patients with a CAC score of 100-399 and ≥400. In patients with a luminal stenosis, CAC remained independently predictive in all-cause mortality (P < .0001) and death or MI (P < .0001) in multivariable models containing CAD risk factors and presenting symptoms. CONCLUSIONS: CAC allows for the identification of those at an increased hazard for death or MI in symptomatic patients with nonobstructive disease. From the CONFIRM registry, the extent of CAC was an independent estimator of long-term prognosis among symptomatic patients with luminal stenosis and may further define risk and guide preventive strategies in patients with nonobstructive CAD.