Whether cardiovascular (CV) disease is associated with clinical outcomes in cancer patients receiving immunotherapy is unknown. We reviewed the Mayo Clinic database for all cancer patients who ...received an immune checkpoint inhibitor (ICI). Multivariate logistic regression analysis, survival analyses, and Cox proportional-hazards models were formulated. Between March, 2010 and July, 2019, 3,326 patients received ICI. Mean patient age was 63.5 years (range: 16 to 96 years). In a Cox proportional-hazards model, obesity (hazard ratio HR 0.65, 95% confidence level CI 0.55 to 0.77, p < 0.001) and hypercholesterolemia (HR 0.80, 95% CI 0.72 to 0.89, p < 0.001) were associated with lower all-cause mortality while hypertension (HR 1.32, 95% CI 1.17 to 1.49, p < 0.001) and smoking (HR 1.17, 95% CI 1.06 to 1.29, p = 0.002) were associated with higher overall mortality. Among patients with lung cancer, multivariable-adjusted hazard ratios for death from any cause for beta blocker users, as compared with patients who had never used a beta blocker, were 1.39 (95% CI 1.10 to 1.76, p = 0.006). A total of 80 patients (2.4%) experienced CV immune-related adverse events. Event-related morality for ICI-induced myocarditis was 41.7% (5/12). Multivariable-adjusted hazard ratios for ICI-induced myocarditis were 5.2 (95% CI 1.4 to 18.7, p = 0.01) for history of heart failure, 4.06 (95% CI 1.15 to 14.3, p = 0.03) for history of acute coronary syndrome, and 1.07 (per each 1-year increase, 95% CI 1.01 to 1.14, p = 0.02) for age. In conclusion, our study shows that CV factors are associated with clinical outcomes in cancer patients receiving ICI and could be used to predict mortality. In patients with lung cancer, pretreatment beta blocker use is associated with higher all-cause mortality. Three clinical factors—history of heart failure, history of acute coronary syndrome, and age greater than 80 years—help identify patients at higher risk of ICI-induced myocarditis who might benefit from more intensive cardiac surveillance.
Preeclampsia and cognitive impairment later in life Fields, Julie A., PhD; Garovic, Vesna D., MD; Mielke, Michelle M., PhD ...
American journal of obstetrics and gynecology,
07/2017, Letnik:
217, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Background Hypertension is a risk factor for cerebrovascular disease and cognitive impairment. Women with hypertensive episodes during pregnancy report variable neurocognitive changes within the ...first decade following the affected pregnancy. However, long-term follow-up of these women into their postmenopausal years has not been conducted. Objective The aim of this study was to examine whether women with a history of preeclampsia were at increased risk of cognitive decline 35-40 years after the affected pregnancy. Study Design Women were identified and recruited through the medical linkage, population-based Rochester Epidemiologic Project. Forty women with a history of preeclampsia were age- and parity-matched to 40 women with a history of normotensive pregnancy. All women underwent comprehensive neuropsychological assessment and completed self-report inventories measuring mood, ie, depression, anxiety, and other symptoms related to emotional state. Scores were compared between groups. In addition, individual cognitive scores were examined by neuropsychologists and a neurologist blinded to pregnancy status, and a clinical consensus diagnosis of normal, mild cognitive impairment, or dementia for each participant was conferred. Results Age at time of consent did not differ between preeclampsia (59.2 range 50.9-71.5 years) and normotensive (59.6 range 52.1-72.2 years) groups, nor did time from index pregnancy (34.9 range 32.0-47.2 vs 34.5 range 32.0-46.4 years, respectively). There were no statistically significant differences in raw scores on tests of cognition and mood between women with histories of preeclampsia compared to women with histories of normotensive pregnancy. However, a consensus diagnosis of mild cognitive impairment or dementia trended toward greater frequency in women with histories of preeclampsia compared to those with normotensive pregnancies (20% vs 8%, P = .10) and affected more domains among the preeclampsia group ( P = .03), most strongly related to executive dysfunction ( d = 1.96) and verbal list learning impairment ( d = 1.93). Conclusion These findings suggest a trend for women with a history of preeclampsia to exhibit more cognitive impairment later in life than those with a history of normotensive pregnancy. Furthermore, the pattern of cognitive changes is consistent with that observed with vascular disease/white matter pathology.
Active cancer is the major predictor of venous thromboembolism (VTE) recurrence, but further stratification of recurrence risk is uncertain. In a population-based cohort study of all Olmsted County, ...Minnesota, residents with active cancer-related incident VTE during the 35-year period from 1966 to 2000 who survived 1 day or longer, we estimated VTE recurrence, bleeding on anticoagulant therapy, and survival and tested cancer and noncancer characteristics and secondary prophylaxis as predictors of VTE recurrence and bleeding, using Cox proportional hazards modeling. Of 477 patients, 139 developed recurrent VTE over the course of 1533 person-years of follow-up. The adjusted 10-year cumulative VTE recurrence rate was 28.6%. The adjusted 90-day cumulative incidence of major bleeding on anticoagulation was 1.9%. Survival was significantly worse for patients with cancer who had recurrent VTE (particularly pulmonary embolism) and with bleeding on anticoagulation. In a multivariable model, brain, lung, and ovarian cancer; myeloproliferative or myelodysplastic disorders; stage IV pancreatic cancer; other stage IV cancer; cancer stage progression; and leg paresis were associated with an increased hazard, and warfarin therapy was associated with a reduced hazard, of recurrent VTE. Recurrence rates were significantly higher for cancer patients with 1 or more vs no predictors of recurrence, suggesting these predictors may be useful for stratifying recurrence risk.
•VTE recurrence risk in patients with cancer can be stratified by cancer type, stage, stage progression, and presence of leg paresis.•Patients with cancer at high VTE recurrence risk should be considered for secondary prophylaxis.
Studies of the impact of systemic lupus erythematosus (SLE) and its pregnancy complications have yielded conflicting results. Major limitations of these studies relate to their small numbers of ...patients and retrospective designs. The aim of this study was to perform a systematic literature review of pregnancy outcomes in women with SLE and a meta-analysis of the association of lupus nephritis with adverse pregnancy outcomes.
We searched electronic databases from 1980 to 2009 and reviewed papers with validity criteria. Random-effects analytical methods were used to evaluate pregnancy complications rates.
Thirty-seven studies with 1842 patients and 2751 pregnancies were included. Maternal complications included lupus flare (25.6%), hypertension (16.3%), nephritis (16.1%), pre-eclampsia (7.6%), and eclampsia (0.8%). The induced abortion rate was 5.9%, and when excluded, fetal complications included spontaneous abortion (16.0%), stillbirth (3.6%), neonatal deaths (2.5%), and intrauterine growth retardation (12.7%). The unsuccessful pregnancy rate was 23.4%, and the premature birth rate was 39.4%. Meta-regression analysis showed statistically significant positive associations between premature birth rate and active nephritis and increased hypertension rates in subjects with active nephritis or a history of nephritis. History of nephritis was also associated with pre-eclampsia. Anti-phospholipid antibodies were associated with hypertension, premature birth, and an increased rate of induced abortion.
In patients with SLE, both lupus nephritis and anti-phospholipid antibodies increase the risks for maternal hypertension and premature births. The presented evidence further supports timing of pregnancy relative to SLE activity and multispecialty care of these patients.
The measurement of multiple protein biomarkers may refine risk stratification in clinical settings. This concept has stimulated development of multiplexed immunoassay platforms that provide multiple, ...parallel protein measurements on the same specimen.
We provide an overview of antibody-based multiplexed immunoassay platforms and discuss technical and operational challenges. Multiplexed immunoassays use traditional immunoassay principles in which high-affinity capture ligands are immobilized in parallel arrays in either planar format or on microspheres in suspension. Development of multiplexed immunoassays requires rigorous validation of assay configuration and analytical performance to minimize assay imprecision and inaccuracy. Challenges associated with multiplex configuration include selection and immobilization of capture ligands, calibration, interference between antibodies and proteins and assay diluents, and compatibility of assay limits of quantification. We discuss potential solutions to these challenges. Criteria for assessing analytical multiplex assay performance include the range of linearity, analytical specificity, recovery, and comparison to a quality reference method. Quality control materials are not well developed for multiplexed protein immunoassays, and algorithms for interpreting multiplex quality control data are needed.
Technical and operational challenges have hindered implementation of multiplexed assays in clinical settings. Formal procedures that guide multiplex assay configuration, analytical validation, and quality control are needed before broad application of multiplexed arrays can occur in the in vitro diagnostic market.
Summary
Reasons for trends in venous thromboembolism (VTE) incidence are uncertain. It was our objective to determine VTE incidence trends and risk factor prevalence, and estimate ...population-attributable risk (PAR) trends for each risk factor. In a population-based cohort study of all residents of Olmsted County, Minnesota from 1981–2010, annual incidence rates were calculated using incident VTE cases as the numerator and age- and sex-specific Olmsted County population estimates as the denominator. Poisson regression models were used to assess the relationship of crude incidence rates to year of diagnosis, age at diagnosis, and sex. Trends in annual prevalence of major VTE risk factors were estimated using linear regression. Poisson regression with time-dependent risk factors (person-years approach) was used to model the entire population of Olmsted County and derive the PAR. The age- and sex-adjusted annual VTE incidence, 1981–2010, did not change significantly. Over the time period, 1988–2010, the prevalence of obesity, surgery, active cancer and leg paresis increased. Patient age, hospitalisation, surgery, cancer, trauma, leg paresis and nursing home confinement jointly accounted for 79 % of incident VTE; obesity accounted for 33 % of incident idiopathic VTE. The increasing prevalence of obesity, cancer and surgery accounted in part for the persistent VTE incidence. The PAR of active cancer and surgery, 1981–2010, significantly increased. In conclusion, almost 80 % of incident VTE events are attributable to known major VTE risk factors and one-third of incident idiopathic VTE events are attributable to obesity. Increasing surgery PAR suggests that concurrent efforts to prevent VTE may have been insufficient.
Supplementary Material to this article is available online at www.thrombosis-online.com.
Background Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery. Data are lacking on the long-term prognostic implications of POAF. We hypothesized that POAF, which ...reflects underlying cardiovascular pathophysiologic substrate, is a predictive marker of late AF and long-term mortality. Methods We identified 603 Olmsted County, Minnesota, residents without prior documented history of AF who underwent coronary artery bypass graft and/or valve surgery from 2000 to 2005. Patients were monitored for first documentation of late AF or death at >30 days postoperatively. Multivariate Cox regression models were used to assess the independent association of POAF with late AF and long-term mortality. Results After a mean follow-up of 8.3 ± 4.2 years, freedom from late AF was less with POAF than no POAF (57.4% vs 88.9%, P < .001). The risk of late AF was highest within the first year at 18%. Univariate analysis demonstrated that POAF was associated with significantly increased risk of late AF hazard ratio (HR), 5.09; 95% CI, 3.65-7.22 and long-term mortality (HR, 1.79; 95% CI, 1.38-2.22). After adjustment for age, sex, and clinical and surgical risk factors, POAF remained independently associated with development of late AF (HR, 3.52; 95% CI, 2.42-5.13) but not long-term mortality (HR, 1.16; 95% CI, 0.87-1.55). Conversely, late AF was independently predictive of long-term mortality (HR, 3.25; 95% CI, 2.42-4.35). Diastolic dysfunction independently influenced the risk of late AF and long-term mortality. Conclusions Postoperative atrial fibrillation was an independent predictive marker of late AF, whereas late AF, but not POAF, was independently associated with long-term mortality. Patients who develop new-onset POAF should be considered for continuous anticoagulation at least during the first year following cardiac surgery.
Limited data exist on trends in incidence of atrial fibrillation (AF). We assessed the community-based trends in AF incidence for 1980 to 2000 and provided prevalence projections to 2050.
The adult ...residents of Olmsted County, Minnesota, who had ECG-confirmed first AF in the period 1980 to 2000 (n=4618) were identified. Trends in age-adjusted incidence were determined and used to construct model-based prevalence estimates. The age- and sex-adjusted incidence of AF per 1000 person-years was 3.04 (95% CI, 2.78 to 3.31) in 1980 and 3.68 (95% CI, 3.42 to 3.95) in 2000. According to Poisson regression with adjustment for age and sex, incidence of AF increased significantly (P=0.014), with a relative increase of 12.6% (95% CI, 2.1 to 23.1) over 21 years. The increase in age-adjusted AF incidence did not differ between men and women (P=0.84). According to the US population projections by the US Census Bureau, the number of persons with AF is projected to be 12.1 million by 2050, assuming no further increase in age-adjusted incidence of AF, but 15.9 million if the increase in incidence continues.
The age-adjusted incidence of AF increased significantly in Olmsted County during 1980 to 2000. Whether or not this rate of increase continues, the projected number of persons with AF for the United States will exceed 10 million by 2050, underscoring the urgent need for primary prevention strategies against AF development.
The risk for venous thromboembolism during pregnancy or postpartum is uncertain.
To estimate the relative and absolute risk for deep venous thrombosis and pulmonary embolism during pregnancy and ...postpartum and to describe trends in incidence.
Population-based inception cohort study using the resources of the Rochester Epidemiology Project.
Olmsted County, Minnesota.
Women with deep venous thrombosis or pulmonary embolism first diagnosed between 1966 and 1995, including women with venous thromboembolism during pregnancy or the postpartum period (defined as delivery of a newborn no more than 3 months before the deep venous thrombosis or pulmonary embolism event date, including delivery of a stillborn infant after the first trimester).
The authors obtained yearly counts of live births in Olmsted County between 1966 and 1995 from the Minnesota Department of Health.
The relative risk (standardized incidence ratio) for venous thromboembolism among pregnant or postpartum women was 4.29 (95% CI, 3.49 to 5.22;P < 0.001), and the overall incidence of venous thromboembolism (absolute risk) was 199.7 per 100,000 woman-years. The annual incidence was 5 times higher among postpartum women than pregnant women (511.2 vs. 95.8 per 100,000), and the incidence of deep venous thrombosis was 3 times higher than that of pulmonary embolism (151.8 vs. 47.9 per 100,000). Pulmonary embolism was relatively uncommon during pregnancy versus the postpartum period (10.6 vs. 159.7 per 100,000). Over the 30-year study period, the incidence of venous thromboembolism during pregnancy remained relatively constant whereas the postpartum incidence of pulmonary embolism decreased more than 2-fold.
Because the Olmsted County population was 98% white and of non-Hispanic ethnicity, the results may not be generalizable to other ethnicities.
Among pregnant women, the highest risk period for venous thromboembolism and pulmonary embolism in particular is during the postpartum period. Any prophylaxis against these events should be particularly targeted to postpartum women. Although the incidence of pulmonary embolism has decreased over time, the incidence of deep venous thrombosis remains unchanged, indicating the need to better identify pregnant women at increased risk.
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