Search

BACKGROUND:Uterine leiomyomas (fibroid tumors) cause considerable symptoms in 30-50% of women and are the leading cause of hysterectomy in the United States. Women with uterine fibroid tumors often seek uterine-preserving treatments, but comparative effectiveness trials are lacking. OBJECTIVE:The purpose of this study was to report treatment effectiveness and ovarian function after uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery from the Fibroid Interventions: Reducing Symptoms Today and Tomorrow study. STUDY DESIGN:The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study, which is a randomized controlled trial of uterine artery embolization vs magnetic resonance imaging-guided focused ultrasound surgery, enrolled premenopausal women with symptomatic uterine fibroid tumors; women who declined randomization were enrolled in a parallel observational cohort. A comprehensive cohort design was used for outcomes analysis. Our target enrollment was 220 women, of which we achieved 41% (n=91) in the randomized and parallel arms of the trial. Primary outcome was reintervention for uterine fibroid tumors within 36 months. Secondary outcomes were change in serum anti-Müllerian hormone levels and standardized measures of fibroid symptoms, quality of life, pain, and sexual function. RESULTS:From 2010-2014, 83 women (mean age, 44.4 years) were treated in the comprehensive cohort design (43 for magnetic resonance imaging-guided focused ultrasound surgery [27 randomized]; 40 for uterine artery embolization [22 randomized]); baseline clinical and uterine characteristics were similar between treatment arms, except for higher fibroid load in the uterine artery embolization arm. The risk of reintervention was higher with magnetic resonance imaging-guided focused ultrasound surgery than uterine artery embolization (hazard ratio, 2.81; 95% confidence interval, 1.01-7.79). Uterine artery embolization showed a significantly greater absolute decrease in anti-Müllerian hormone levels at 24 months compared with magnetic resonance imaging-guided focused ultrasound surgery. Quality of life and pain scores improved in both arms but to a greater extent in the uterine artery embolization arm. Higher pretreatment anti-Müllerian hormone level and younger age at treatment increased the overall risk of reintervention. CONCLUSION:Our study demonstrates a lower reintervention rate and greater improvement in symptoms after uterine artery embolization, although some of the effectiveness may come through impairment of ovarian reserve. Both pretreatment anti-Müllerian hormone level and age are associated with risk of reintervention. CLINICAL TRIAL REGISTRATION NUMBER:NCT00995878, clinicaltrials.gov.

Angiographic evidence of the anatomy of coronary arteries and the type of coronary artery lesions in women with a history of hypertensive disorders of pregnancy (HDP) are poorly documented. This study sought to determine the role of a history of HDP as a unique risk factor for early coronary artery disease (CAD) and type of acute coronary syndrome (ACS) (ie, atherosclerotic vs myocardial infarction with nonobstructive coronary arteries [MINOCA]) in women who underwent coronary angiography. This study used a population-based cohort of parous female patients with incident CAD who underwent coronary angiography and age-matched control subjects. The SYNTAX (Synergy between PCI [percutaneous coronary intervention] with TAXUS [Boston Scientific] and Cardiac Surgery) score was assessed to determine the complexity and degree of CAD; MINOCA was diagnosed in the presence of clinical acute myocardial infarction in the absence of obstructive coronary disease. A total of 506 parous female Olmsted County, Minnesota (USA) residents had incident CAD and angiographic data from November 7, 2002 to December 31, 2016. Women with HDP were younger than normotensive women at the time of the event (median: 64.8 years vs 71.8 years; P = 0.030). There was a strong association between HDP and ACS (unadjusted P = 0.018). Women with HDP compared with women with normotensive pregnancies were more likely to have a higher SYNTAX score (OR: 2.28; 95% CI: 1.02-5.12; P = 0.046), and MINOCA (OR: 2.08; 95% CI: 1.02-4.25; P = 0.044). A history of HDP is associated with CAD earlier in life and with a future risk for myocardial infarction with both obstructive and nonobstructive coronary arteries. This study underscores the need for timely detection and treatment of nonobstructive disease, in addition to traditional risk factors. [Display omitted] [ABSTRACT FROM AUTHOR]

BackgroundUterine fibroids are a common problem for reproductive-aged women, yet little comparative effectiveness research is available to guide treatment choice. Uterine artery embolization and magnetic resonance imaging-guided focused ultrasound surgery are minimally invasive therapies approved by the US Food and Drug Administration for treating symptomatic uterine fibroids. The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study is the first randomized controlled trial to compare these 2 fibroid treatments.ObjectiveThe objective of the study was to summarize treatment parameters and compare recovery trajectory and adverse events in the first 6 weeks after treatment.Study designPremenopausal women with symptomatic uterine fibroids seen at 3 US academic medical centers were enrolled in the randomized controlled trial (n = 57). Women meeting identical criteria who declined randomization but agreed to study participation were enrolled in a nonrandomized parallel cohort (n = 34). The 2 treatment groups were analyzed by using a comprehensive cohort design. All women undergoing focused ultrasound and uterine artery embolization received the same postprocedure prescriptions, instructions, and symptom diaries for comparison of recovery in the first 6 weeks. Return to work and normal activities, medication use, symptoms, and adverse events were captured with postprocedure diaries. Data were analyzed using the Wilcoxon rank sum test or χ2 test. Multivariable regression was used to adjust for baseline pain levels and fibroid load when comparing opioid medication, adverse events, and recovery time between treatment groups because these factors varied at baseline between groups and could affect outcomes. Adverse events were also collected.ResultsOf 83 women in the comprehensive cohort design who underwent treatment, 75 completed postprocedure diaries. Focused ultrasound surgery was a longer procedure than embolization (mean [SD], 405 [146] vs 139 [44] min; P

BACKGROUND: Senescence, a mechanism of cellular aging, which is characterized by irreversible proliferation arrest and a proinflammatory secretory phenotype, has been documented in women with preeclampsia. As cellular senescence can persist and progress, we postulated that it is associated with accelerated aging phenotype and accumulation of comorbidities in women with a history of preeclampsia. METHODS: We included a cohort of women with a history of preeclampsia (n=40) age- and parity-matched to a group of referent women with normotensive pregnancies (n=40). Women with prior major cardiovascular events, neurological, or autoimmune conditions were excluded. We collected urine and blood samples to study markers of aging, data on multimorbidity at the time of enrollment, and prospectively followed them for events over the course of 6 years, on average. RESULTS: Women with a history of preeclampsia exhibited unfavorable aging profiles compared with referent women, including decreased urinary α-Klotho (P=0.018); increased leptin (P=0.016) and leptin/adiponectin ratio (P=0.027), and increased extracellular vesicles positive for tissue factor (P=0.025). Women with a history of preeclampsia likewise had a higher rate of comorbidities at the time of enrollment (P=0.003) and had a 4× higher risk of developing major cardiovascular events compared with referent women (P=0.003). CONCLUSIONS: Our data suggest that a history of preeclampsia is associated with accelerated aging as indicated by senescence marker differences and the accumulation of multimorbidity later in life. Targeting cellular senescence may offer novel, mechanism-based approaches for the diagnosis and treatment of adverse health outcomes in women with a history of preeclampsia. [ABSTRACT FROM AUTHOR]

BackgroundUterine fibroids are an important source of morbidity for reproductive-aged women. Despite an increasing number of alternatives, hysterectomies account for about 75% of all fibroid interventional treatments. Evidence is lacking to help women and their health care providers decide among alternatives to hysterectomy. Fibroid Interventions: Reducing Symptoms Today and Tomorrow (NCT00995878, clinicaltrials.gov) is a randomized controlled trial to compare the safety, efficacy, and economics of 2 minimally invasive alternatives to hysterectomy: uterine artery embolization and magnetic resonance imaging-guided focused ultrasound surgery. Although randomized trials provide the highest level of evidence, they have been difficult to conduct in the United States for interventional fibroid treatments. Thus, contemporaneously recruiting women declining randomization may have value as an alternative strategy for comparative effectiveness research.ObjectiveWe sought to compare baseline characteristics of randomized participants with nonrandomized participants meeting the same enrollment criteria and to determine whether combining the 2 cohorts in a comprehensive cohort design would be useful for analysis.Study designPremenopausal women with symptomatic uterine fibroids seeking interventional therapy at 3 US academic medical centers were randomized (1:1) in 2 strata based on calculated uterine volume (

Background: Time-dependent Cox proportional hazards regression is a popular statistical method used in kidney disease research to evaluate associations between biomarkers collected serially over time with progression to kidney failure. Typically, biomarkers of interest are considered time-dependent covariates being updated at each new measurement using last observation carried forward (LOCF). Recently, joint modeling has emerged as a flexible alternative for multivariate longitudinal and time-to-event data. This study describes and demonstrates multivariate joint modeling using as an example the association of serial biomarkers (plasma oxalate [POX] and urinary oxalate [UOX]) and kidney function among patients with primary hyperoxaluria in the Rare Kidney Stone Consortium Registry. Methods: Time-to-kidney failure was regressed on serially measured biomarkers in two ways: time-dependent LOCF Cox proportional hazards regression and multivariate joint models. Results: In time-dependent LOCF Cox regression, higher POX was associated with increased risk of kidney failure (HR = 2.20 per doubling, 95% CI = [1.38-3.51], p < 0.001) whereas UOX was not (HR = 1.08 per doubling, [0.66–1.77], p = 0.77). In multivariate joint models, estimates suggest higher UOX may be associated with lower risk of kidney failure (HR = 0.42 per doubling [0.15–1.04], p = 0.066), though not statistically significant, since impaired urinary excretion of oxalate may reflect worsening kidney function. Conclusions: Multivariate joint modeling is more flexible than LOCF and may better reflect biological plausibility since biomarkers are not steady-state values between measurements. While LOCF is preferred to naïve methods not accounting for changes in biomarkers over time, results may not accurately reflect flexible relationships that can be captured with multivariate joint modeling. [ABSTRACT FROM AUTHOR]

Background: Women with uterine fibroids often seek uterine-preserving treatments, rather than hysterectomy. Imaging-defined endpoints following nonsurgical treatments for fibroids are limited. Materials and Methods: Fibroid Interventions: Reducing Symptoms Today and Tomorrow (FIRSTT), a randomized controlled trial of uterine artery embolization (UAE) versus magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS), enrolled premenopausal women with symptomatic uterine fibroids. In this subanalysis, we report imaging results up to 36 months after UAE or MRgFUS. Magnetic resonance imaging (MRI) was performed at baseline for all women and during the 36 months after treatment if they did not meet other study endpoints. The main outcome of this subanalysis was fibroid volume reduction (defined both in terms of total fibroid load and volume of the largest fibroid), uterine volume reduction, and nonperfused volume. Results: During 2010–2014, 25 of the 37 women who were randomized and treated at Mayo Clinic had a 24-month follow-up MRI (11 UAE; 14 MRgFUS); among these women, 15 (7 UAE and 8 MRgFUS) had a 36-month follow-up MRI. Average age for the cohort was 44.1 (standard deviation, SD = 4.4) years. Nine patients had a second fibroid procedure by 36 months (seven in the MRgFUS arm and two in UAE arm). Median total fibroid load reduction was ∼50% in both treatment arms at both 24- and 36-month follow-up. Volume of the largest fibroid decreased more in the MRgFUS arm, whereas uterine volume decreased more in the UAE arm (neither reached statistical significance). At 24 months, median nonperfused volume was higher in the UAE arm (92%) than the MRgFUS arm (10%). Conclusions: Similar fibroid volume reduction was seen for the MRgFUS and UAE treatments in this comparative effectiveness study. Nonperfused volume 24 months after the procedure was higher in the UAE arm than in the MRgFUS arm. Clinical Trial Registration Number: NCT00995878, clinicaltrials.gov [ABSTRACT FROM AUTHOR]