Kidney tubule health scores and their associations with incident CKD in women living with HIV.

OBJECTIVES: Individual kidney tubule biomarkers are associated with chronic kidney disease (CKD) risk in people living with HIV (PLWH). Whether a combination of kidney biomarkers can be integrated into informative summary scores for PLWH is unknown. METHODS: We measured eight urine biomarkers of kidney tubule health at two visits over a 3-year period in 647 women living with HIV in the Women's Interagency Health Study. We integrated biomarkers into factor scores using exploratory factor analysis. We evaluated associations between CKD risk factors and factor scores, and used generalized estimating equations to determine associations between factor scores and risk of incident CKD. RESULTS: Factor analysis identified two unique factor scores: a tubule reabsorption score comprising alpha-1-microglobulin, beta-2-microglobulin and trefoil factor-3; and a tubule injury score comprising interleukin-18 and kidney injury molecule-1. We modelled the two factor scores in combination with urine epidermal growth factor (EGF) and urine albumin. Predominantly HIV-related CKD risk factors were independently associated with worsening tubule reabsorption scores and tubule injury scores. During a median follow-up of 7 years, 9.7% (63/647) developed CKD. In multivariable time-updated models that adjusted for other factor scores and biomarkers simultaneously, higher tubule reabsorption scores [risk ratio (RR) = 1.27, 95% confidence interval (CI): 1.01-1.59 per 1 SD higher time-updated score], higher tubule injury scores (RR = 1.36, 95% CI: 1.05-1.76), lower urine EGF (RR = 0.75, 95% CI: 0.64-0.87), and higher urine albumin (RR = 1.20, 95% CI: 1.02-1.40) were jointly associated with risk of incident CKD. CONCLUSIONS: We identified two novel and distinct dimensions of kidney tubule health that appear to quantify informative metrics of CKD risk in PLWH.

3 T MRI uterine peristalsis: comparison of symptomatic fibroid patients versus controls.

AIM: To compare uterine peristalsis between symptomatic fibroid patients and normal subjects and to determine the possible effect of fibroid characteristics on uterine peristalsis at high-field magnetic resonance imaging (MRI). MATERIALS AND METHODS: The present study included 20 symptomatic fibroid patients (age range 39-53 years) and 20 normal subjects (age range 19-46 years). MRI images were obtained during the peri-ovulatory phase using 3 T MRI using a sagittal T2 turbo spin-echo sequence and a half-Fourier acquisition single-shot turbo spin-echo sequence for display on cine mode. Two radiologists independently evaluated the images for the presence of uterine peristalsis by confidence level. In cases where peristalsis was present, the images were also evaluated for peristalsis frequency and direction. For fibroid patients, uterine and index fibroid volume, fibroid burden and index fibroid location were also recorded. RESULTS: Uterine peristalsis was significantly decreased in symptomatic fibroid patients compared with normal controls (p < 0.01). Peristalsis frequency in fibroid patients was also lower than in normal subjects. Direction of peristalsis was cervix-to-fundus for the majority of fibroid patients and controls. There was no significant relationship between fibroid characteristics, such as uterine volume, index fibroid volume, index fibroid location, and fibroid number in fibroid patients with, and fibroid patients without peristalsis. CONCLUSION: In women with symptomatic fibroids, the presence of uterine peristalsis is significantly decreased compared to normal controls on 3 T cine MRI. The presence of fibroids appears to disturb the normal conduction of uterine peristalsis and may interfere with fluid (e.g., menses, sperm) transport.

Sepsis in young infants with congenital heart disease.

BACKGROUND: We sought to describe the incidence, pathogen distribution, and mortality associated with blood culture-proven sepsis in young infants with congenital heart disease (CHD) admitted to a neonatal intensive care unit (NICU). METHODS: Cohort study of all blood cultures obtained from infants with CHD between 4 and 120 days of age cared for in 250 NICUs managed by the Pediatrix Medical Group in the United States between 1996 and 2007. RESULTS: Of 11,638 infants with CHD, 656 (6%) had 821 episodes of sepsis: a cumulative incidence of 71/1000 admissions. Gram-positive organisms were the most common cause (64%), and coagulase-negative Staphylococcus and Staphylococcus aureus were the most frequently isolated species. On multivariable regression, infants with sepsis were more likely to die compared to infants with sterile blood cultures (odds ratio [OR] = 1.53 [95% confidence interval: 1.09, 2.13]). Infants with Gram-negative bacteraemia and candidaemia were more likely to die than infants with sterile blood cultures (OR = 2.01 [1.20, 3.37], and OR = 3.18 [1.60, 6.34], respectively). CONCLUSION: Infants with CHD have a high incidence of culture-proven sepsis, especially with staphylococcal organisms. Gram-negative bacteraemia and candidaemia are strongly associated with increased mortality in this group of young infants.

Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse.

Chronic migraine has been linked to the excessive use of acute headache medications. Medication overuse (MO) is commonly considered the most significant risk factor for the progression of migraine from an episodic to a chronic condition. Managing MO is a challenge. Discontinuation of the acute medication can result in withdrawal headache, nausea, vomiting and sleep disturbances. This review summarizes the results from two similarly designed, randomized, placebo-controlled, multicentre studies of chronic migraine conducted in the USA and European Union. Both studies demonstrate the efficacy and safety of the migraine preventive medication, topiramate, for the treatment of chronic migraine in patient populations both with and without MO. These studies may have important implications for the future of chronic migraine management, suggesting that detoxification prior to initiating prophylactic therapy may not be required in all patients if MO is present.

Time course of adverse events most commonly associated with topiramate for migraine prevention.

The efficacy, safety and tolerability of topiramate has been demonstrated in three large multicenter, randomized, double-blind, placebo-controlled trials. To characterize the time course of adverse events (AEs) that led to treatment discontinuation in >/=2% of patients who received topiramate 100 mg/day during three pivotal, multicenter, randomized, double-blind, placebo-controlled, and 26-week trials. The pooled population comprised all randomized patients who reported safety data during the double-blind phase (topiramate 100 mg/day, n = 386; placebo n = 372), which consisted of a 4-week titration period and a 22-week maintenance period. Incidence, time to onset, and cumulative mean rate of AEs were assessed. Overall, AEs led to treatment discontinuation in 24.9% of patients receiving topiramate 100 mg/day and 11.0% receiving placebo (P < 0.001). AEs leading to discontinuation during the double-blind phase in > or =2% of patients included paresthesia (8.0% discontinued), any cognitive symptoms (7.3% discontinued), fatigue (4.7% discontinued), insomnia (3.4% discontinued), nausea (2.3% discontinued), loss of appetite, anxiety, and dizziness (2.1% discontinued because each AE). Most AEs began during the titration period. Paresthesia, any cognitive symptoms, nausea, and loss of appetite occurred at a higher rate in the topiramate group than in the placebo group (P < 0.01). AEs leading to discontinuation of topiramate are probably to occur during dose titration. If a patient has not experienced one of these AEs within the first 6 weeks of initiating topiramate 100 mg/day, these AEs are unlikely to occur.

Borderline Brenner tumor of the ovary: MRI findings.

Ovarian Brenner tumor is an uncommon epithelial tumor that accounts for 1.5% to 2.5% of all ovarian neoplasms. These tumors are usually benign. Whereas the magnetic resonance imaging features of benign Brenner tumors have been described, reports of malignant findings are limited. We report a case of borderline malignant Brenner tumor that imaged as a cystic lesion with papillary projections and solid elements.

Uterine artery embolization for leiomyomata.

OBJECTIVE: To determine whether uterine artery embolization is safe and effective for treating uterine leiomyomata. METHODS: We analyzed 200 consecutive patients (61 reported previously) undergoing uterine artery embolization for the treatment of uterine leiomyomata at a single institution. After treatment, follow-up data were obtained by written questionnaire mailed to the patients at intervals of 2 weeks, 3 months, 6 months, and 12 months after treatment. Follow-up imaging was obtained at 3 months and 12 months after therapy. All complications and subsequent gynecologic interventions were recorded prospectively, obtained using the patient questionnaires and physician contact. The percentages and their 95% confidence intervals (CI) were calculated to compare the symptoms at follow-up. Proportional odds models for repeated ordinal responses were used to assess the stability of symptom improvement over time. RESULTS: The mean follow-up was 21 months (minimum 12). Heavy menstrual bleeding improved in 87% (95% CI 82%, 92%) of patients at 3 months and in 90% (95% CI 86%, 95%) at 1 year after therapy. Bulk symptoms improved in 93% of patients (95% CI 88%, 96%) at 3 months and in 91% (95% CI 86%, 95%) at 1 year after treatment. Only one major periprocedural complication occurred (pulmonary embolus), which resolved with anticoagulant therapy. Subsequent gynecologic interventions occurred in 10.5% of the patients (95% CI 7.0%, 15.0%) during the follow-up period. CONCLUSION: Uterine artery embolization is safe and controls the symptoms caused by leiomyomata in most patients.

The fetus at term: in utero volume-selected proton MR spectroscopy with a breath-hold technique--a feasibility study.

In three healthy gravidas at 38 and 39 weeks gestation, fetal MR spectroscopy was performed with a breath-hold technique by using the following pulse sequences: single voxel point-resolved spectroscopy, or PRESS, for liver and heart studies and stimulated-echo acquisition mode, or STEAM, for brain studies. Signal peaks of lipid from heart and liver were detected, as were the signal peaks of choline, creatine, and N-acetylaspartate from fetal brain. Findings demonstrated the feasibility of performing proton MR spectroscopy to assess mobile fetal structures.

Staging of gynecologic malignancies.

Magnetic resonance imaging (MRI) is gaining momentum for staging gynecologic malignancies. MRI staging is an adjunct to clinical and surgical staging in women with cervical or endometrial cancer, respectively. For women with possible adnexal pathology, MRI is useful for lesion characterization. In patients with ovarian cancer, MRI determination of disease extent helps treatment planning, either as a surgical roadmap or to identify nonresectable patients.

Symptomatic fibroleiomyomata: MR imaging of the uterus before and after uterine arterial embolization.

PURPOSE: To determine the magnetic resonance (MR) imaging features of uterine fibroleiomyomata after uterine arterial embolization (UAE) and identify pretreatment MR imaging features that may be predictive of successful UAE. MATERIALS AND METHODS: T1- and T2-weighted and dynamic gadolinium-enhanced T1-weighted images were obtained before and 3 months after UAE in 31 patients. Up to five fibroleiomyomata (total of 125) were evaluated for volume, location, signal intensity characteristics, and vascularity. Region-of-interest curves were used to assess the vascular enhancement pattern of each fibroleiomyoma and adjacent myometrium. Each patient completed a questionnaire on symptoms 3 months after UAE. RESULTS: UAE resulted in significant reductions in mean uterine volume (from 588.6 to 393.1 cm(3)) and mean fibroleiomyoma volume (from 69.4 to 41.4 cm(3)) (P <.005). After UAE, lesions showed signal intensity changes consistent with hemorrhagic infarction. The vascularity of fibroleiomyomata was decreased (P <.001), with no significant change in myometrial vascularity. Submucosal location was a strong positive predictor of fibroleiomyoma volume reduction (P < 001). When a reduction in vascularity was the measure of success, hypervascularity was a strong indicator of success (P <. 005). CONCLUSION: MR imaging is useful for quantitative assessment of signal intensity and morphologic changes before and after UAE. Pretreatment MR imaging findings may help predict the success of the procedure.

Diagnostic value of radiological tests in chronic pelvic pain.

Chronic pelvic pain (CPP) presents a diagnostic as well as a therapeutic challenge to many clinicians. This chapter briefly describes the most frequent identifiable causes for CPP amenable to imaging; explains the most widely-used and widely available radiological tests for CPP; and compares/contrasts each test's utility and accuracy for a given causality. Examples of each imaging modality are included for demonstration purposes, and a summation table cross-references the best diagnostic methods with corresponding disease processes. References from the literature of both radiology and gynaecology were used in preparing this review.

Magnetic resonance spectroscopy to detect lecithin in amniotic fluid and fetal lung.

BACKGROUND: Proton magnetic resonance spectroscopy is a noninvasive technique that detects molecules within a specified region in vivo. Lecithin, the major component of surfactant, has a characteristic magnetic resonance signal, but to our knowledge, it has never been reported in fetal lung or amniotic fluid (AF). The objective of this study was to characterize the lecithin signal in utero, which could lead to a noninvasive fetal lung maturity test. METHOD: Human fetal lung and AF pockets can be identified and studied with magnetic resonance spectroscopy with the use of a 1.5-tesla Vision whole-body magnetic resonance scanner (Siemens Medical Systems; Erlangen, Germany). Spectroscopy data are collected with a single-voxel-point-resolved spectroscopy sequence. After identification of fetal anatomy with the use of scout magnetic resonance images, magnetic resonance spectroscopy of human fetal lung and AF identifies a lecithin peak. EXPERIENCE: Three healthy gravidas near term were studied and lecithin peaks were identified in all. CONCLUSION: Lecithin can be identified in vivo with the use of volume-selected proton magnetic resonance spectroscopy. Patient comfort and extremely short scan times suggest that refined magnetic resonance spectroscopy might be a safe, quick, and comfortable test of fetal lung maturity.

Tamoxifen-induced uterine abnormalities: the role of imaging.

Tamoxifen citrate is an orally administered, nonsteroidal antiestrogen agent that is widely used for the treatment of breast cancer and that has recently been found to prevent breast cancer in some high-risk populations. Tamoxifen may, however, cause adverse effects at the uterine level. In this article, the authors review (a) the histopathologic uterine changes associated with tamoxifen therapy, (b) the spectrum of uterine imaging findings in women treated with tamoxifen, and (c) the recommendations of the American College of Obstetrics and Gynecology for women treated with tamoxifen. An algorithm for imaging evaluation of the uterus in women treated with tamoxifen is presented.

MR hysterosalpingography: protocol development and refinement for simulating normal and abnormal fallopian tube patency--feasibility study with a phantom.

PURPOSE: To develop and refine a pulse sequence and protocol for testing the feasibility of magnetic resonance (MR) hysterosalpingography in a phantom model. MATERIALS AND METHODS: A phantom simulating the uterus, fallopian tubes, and surrounding pelvic cavity was constructed. T2-weighted acquisition strategies-breath-hold fast spin-echo, rapid acquisition with relaxation enhancement (RARE), and haff-Fourier RARE-were refined to acquire sequential 70-mm coronal imaging volumes. Contrast agent was injected into the introducing catheter entering the os of the simulated uterus. Interacquisition interval, type of contrast agent (eg, sterile saline solution or water), and quantity of contrast agent (eg, 1-5 mL per acquisition) were varied. Digital image subtraction was used to enhance image quality. Images were qualitatively analyzed and rated good, fair, or poor for temporal resolution, spatial resolution, fallopian tube conspicuity, and free spill conspicuity. Once the technique was refine, the phantom was reconfigured to simulate unilateral and bilateral hydrosalpinx. RESULTS: The RARE sequence with an 8-second interacquisition interval and a 5-mL interacquisition of sterile water produced good images of the simulated fallopian tubes and free spill. Depiction of unilateral and bilateral hydrosalpinx was also reliably demonstrated. CONCLUSION: This study with a phantom model demonstrates the feasibility of MR hysterosalpingography to depict normal and diseased fallopian tubes.

Initial results from uterine fibroid embolization for symptomatic leiomyomata.

PURPOSE: To evaluate the safety and short-term efficacy of uterine fibroid embolization (UFE) in patients with symptomatic uterine fibroids. MATERIALS AND METHODS: Bilateral UFE was performed in 61 patients with symptomatic uterine leiomyomata during a 16-month period. Imaging was performed before the procedure and at 3 months and 1 year after the procedure. Questionnaires were obtained at regular intervals after the procedure to assess patient outcome. RESULTS: All procedures but one were technically successful. Mean clinical follow-up was 8.7 months. Minor complications occurred in five patients during the follow-up period. All were treated without permanent sequelae. Menstrual bleeding was improved in 89%, with 81% of patients moderately to markedly improved. Pelvic pain and pressure was improved in 96% of patients, with moderate to marked improvement in 79%. At initial imaging follow-up (mean, 4.4 months postprocedure), median uterine volume decreased 34% (P = .0001) and the median dominant fibroid volume decreased 50% (P = .0001). Imaging at 1 year (mean, 12.3 months) after the procedure showed continued reduction with a median uterine volume reduction of 48% (P = .0002) and median dominant fibroid volume decrease of 78% (P = .0002). CONCLUSION: In the authors' initial clinical experience, UFE appears effective in controlling symptoms and substantially reducing fibroid volume with few complications.

Acute and subacute liver-related hemorrhage: MRI findings.

We retrospectively reviewed the MR studies on all patients with liver-related fluid collections compatible with acute or early subacute hemorrhage, who underwent MR imaging at our center between June 1994 and January 1998. All patients had a clinical history of an underlying liver lesion or injury with a duration of symptomatology of less than 5 days. In three patients with only 2-3 days of symptoms, the liver-related hemorrhagic fluid was hypointense on T1-weighted images and markedly hypointense on T2-weighted images relative to liver, consistent with intracellular deoxyhemoglobin. The fluid was relatively homogeneous in signal intensity. In three patients with 3-5 days of symptoms, the majority of liver-related fluid was hyperintense on T1-weighted images and hypointense on T2-weighted images relative to liver, consistent with intracellular methemoglobin. Three of these latter four patients also had fluid collections of varying T1-and T2-weighted signal intensity consistent with blood breakdown products of varying ages. Clinical findings matched the MR findings of acute/early subacute blood in all cases. Our results describe the findings of acute and early subacute liver hemorrhage. The most helpful MR feature of bleeding of recent origin is very low signal intensity of the fluid on T2-weighted imaging.

T2-weighted MRI of the uterus: fast spin echo vs. breath-hold fast spin echo.

This study compared one routine T2-weighted fast spin echo (T2FSE) sequence with a breath-hold T2FSE (BH T2FSE) sequence of the female pelvis for image quality, uterine anatomy, lesion detection, and signal intensity measurements. Thirty-two consecutive women (mean age 41.7 years) were imaged at 1.5 T with one high-resolution routine T2FSE sequence and one BH T2FSE sequence in the sagittal plane as part of comprehensive pelvic magnetic resonance imaging. The different image sets were rated separately for imaging characteristics (overall image quality, uterine anatomy definition, lesion detection, and free fluid conspicuity) and then compared side by side. The image sets were also compared for artifacts (ghosting, blurring, pulsatility, and chemical shift misregistration). Signal-to-noise (S/N) and signal difference-to-noise (SD/N) ratios were calculated for the different uterine zones, uterine abnormalities, free fluid, rectus abdominis muscle, and bladder. Contrast-to-noise ratios (CNRs) were calculated for uterine abnormalities. Twenty-eight uterine abnormalities were detected in 20 patients and included leiomyomata (13 patients), adenomyosis (7 patients), benign endometrial polyps (6 patients), endometrial carcinoma (1 patient), and pregnancy (1 patient). BH T2FSE was superior or equivalent to T2FSE for overall image quality in 23/32 patients (71.8%), uterine anatomy definition in 19/32 patients (59.3%), and lesion detection in 13/20 patients (65%). BH T2FSE performed less well than T2FSE for free fluid conspicuity in 5/5 (100%) patients. BH T2FSE was equivalent to or less affected than T2FSE for ghosting artifact in 24/32 patients (75%) and blurring artifact in 29/32 patients (90.6%). Pulsatility and chemical shift artifacts were not problematic for either image set. S/N and SD/N were higher for all BH T2FSE determinations compared with T2FSE. For the endometrium, junctional zone, myometrium, and bladder, these differences were statistically significant. There were no statistically significant differences for CNR between the two image sets, although BH T2FSE values for leiomyomata, adenomyosis, and abnormal endometria were higher than those calculated for T2FSE. All pathology detected with T2FSE was detected on BH T2FSE despite the breath-hold sequence's inherently poorer spatial resolution compared with the non-breath-hold sequence. BH T2FSE may be able to replace T2FSE for some uterine applications with a substantial time savings.

Serendipity in diagnostic imaging: magnetic resonance imaging of the breast.

BACKGROUND: Magnetic resonance imaging (MRI) of the breast has been proposed as a noninvasive diagnostic test for evaluation of suspicious ("index") lesions noted on mammography and/or clinical breast examination (CBE). However, women may have incidental ("serendipitous") lesions detected by MRI that are not found on mammography or CBE. To understand better whether or not biopsy procedures should be performed to evaluate serendipitous lesions, we estimated the breast cancer risk for women with this type of lesion. METHODS: A decision analysis model was used to estimate the positive predictive value (i.e., the chance that a woman with a serendipitous lesion has cancer) of MRI for serendipitous lesions in women who had an abnormal mammogram and/or CBE suspicious for cancer (where a biopsy procedure is recommended). We restricted the analysis to data from women whose index lesions were noncancerous and used meta-analysis of published medical literature to determine the likelihood ratios (measures of how test results change the probability of having cancer) for MRI and the combination of CBE and mammography. The positive predictive value of MRI was calculated using the U.S. population prevalence of cancer (derived from registry data) and the likelihood ratios of the diagnostic tests. RESULTS: Under a wide variety of assumptions, the positive predictive value of MRI was extremely low for serendipitous lesions. For instance, assuming sensitivity and specificity values for MRI of 95.6% and 68.6%, respectively, approximately four of 1000 55- to 59-year-old women with serendipitous lesions would be expected to have cancer (positive predictive value = 0.44%, 95% confidence interval = 0.24%-0.67%). CONCLUSION: In women with a suspicious lesion discovered by mammography and/or CBE that is found to be benign, serendipitous breast lesions detected by MRI are extremely unlikely to represent invasive breast cancer. Immediate biopsy of such serendipitous lesions may, therefore, not be required.