Four-Compartment Diffusion Model of Cortisol Disposition: Comparison With 3 Alternative Models in Current Clinical Use.

Context: Estimated rates of cortisol elimination and appearance vary according to the model used to obtain them. Generalizability of current models of cortisol disposition in healthy humans is limited. Objective: Development and validation of a realistic, mechanistic model of cortisol disposition that accounts for the major factors influencing plasma cortisol concentrations in vivo (Model 4), and comparison to previously described models of cortisol disposition in current clinical use (Models 1-3). Methods: The 4 models were independently applied to cortisol concentration data obtained for the hydrocortisone bolus experiment (20 mg) in 2 clinical groups: healthy volunteers (HVs, n = 6) and corticosteroid binding globulin (CBG)-deficient (n = 2). Model 4 used Fick's first law of diffusion to model free cortisol flux between vascular and extravascular compartments. Pharmacokinetic parameter solutions for Models 1-4 were optimized by numerical methods, and model-specific parameter solutions were compared by repeated measures analysis of variance. Models and respective parameter solutions were compared by mathematical and simulation analyses, and an assessment tool was used to compare performance characteristics of the four models evaluated herein. Results: Cortisol half-lives differed significantly between models (all P < .001) with significant model-group interaction (P = .02). In comparative analysis, Model 4 solutions yielded significantly reduced free cortisol half-life, improved fit to experimental data (both P < .01), and superior model performance. Conclusion: The proposed 4-compartment diffusion model (Model 4) is consistent with relevant experimental observations and met the greatest number of empiric validation criteria. Cortisol half-life solutions obtained using Model 4 were generalizable between HV and CBG-deficient groups and bolus and continuous modes of hydrocortisone infusion.

Decreased maximal cortisol secretion rate in patients with cirrhosis: Relation to disease severity.

BACKGROUND & AIMS: Hepatic enzymes play a major role in the metabolic elimination of cortisol, and reduced rates of cortisol clearance have been consistently observed in patients with chronic liver disease. It is less clear whether there are concomitant abnormalities of adrenocortical function in patients with cirrhosis. In the present study, we sought to assess adrenocortical function in patients with cirrhosis using measures of free cortisol appearance and elimination rates that are independent of serum concentrations of cortisol binding proteins. METHODS: Post hoc analysis used computer-assisted numerical and modelling methods with serial total and free cortisol concentration data to obtain rates of free cortisol appearance and elimination. Rate parameters were obtained in 114 patients with chronic liver disease, including Child-Pugh (CP) ≤8 (n = 53) and CP >8 (n = 61). RESULTS: Maximal cortisol secretion rate (CSRmax) was significantly decreased (p = 0.01) in patients with cirrhosis with CP >8 (0.28 nM/s; 95% CI 0.24-0.34) compared with those with CP ≤8 (0.39 nM/s; 95% CI 0.33-0.46), and CSRmax was negatively correlated with CP score (r = -0.19, p = 0.01). Free cortisol elimination rate was significantly (p = 0.04) decreased in the CP >8 group (0.16 ± 0.20 min-1) compared with that in the CP ≤8 group (0.21 ± 0.21 min-1), and free cortisol elimination rates were negatively correlated with CP score (r = -0.23, p = 0.01). A significant correlation between CSRmax and free cortisol elimination rate (r = 0.88, p <0.001) was observed. CONCLUSIONS: CSRmax and free cortisol elimination rates were significantly reduced according to severity of cirrhosis. In contrast to stimulated total cortisol concentrations, CSRmax estimates were independent of cortisol-binding protein concentrations. Results provide additional evidence of subnormal adrenocortical function in patients with cirrhosis. LAY SUMMARY: We applied numerical analytic methods to characterise adrenocortical function in patients with varying stages of chronic liver disease. We found that patients with more severe cirrhosis have decreased rate of free cortisol elimination and decreased maximal cortisol secretion rate, which is a measure of adrenocortical function. In contrast to conventional measures of adrenocortical function, those obtained using numerical methods were not affected by variation in corticosteroid binding globulin and albumin concentrations. We conclude that patients with cirrhosis demonstrate measurable abnormalities of adrenocortical function, evidence of which supports aspects of the hepatoadrenal syndrome hypothesis.

Libman-Sacks endocarditis and associated cerebrovascular disease: The role of medical therapy.

BACKGROUND: Libman-Sacks endocarditis in patients with systemic lupus erythematosus (SLE) is commonly complicated with embolic cerebrovascular disease (CVD) or valve dysfunction for which high-risk valve surgery is frequently performed. However, the role of medical therapy alone for Libman-Sacks endocarditis and associated acute CVD remains undefined. OBJECTIVE: To determine in this cross-sectional and longitudinal study if conventional anti-inflammatory and anti-thrombotic therapy may be an effective therapy in SLE patients with Libman-Sacks endocarditis and associated acute CVD. METHODS AND MATERIALS: 17 SLE patients with Libman-Sacks endocarditis detected by two-and-three-dimensional transesophageal echocardiography (TEE) and complicated with acute CVD [stroke/TIA, focal brain injury on MRI, or cognitive dysfunction] were treated with conventional anti-inflammatory and anti-thrombotic therapy for a median of 6 months and then underwent repeat TEE, transcranial Doppler, brain MRI, and neurocognitive testing for re-assessment of Libman-Sacks endocarditis and CVD. RESULTS: Valve vegetations decreased in number, diameter, and area (all p ≤0.01); associated valve regurgitation significantly improved (p = 0.04), and valve thickening did not progress (p = 0.56). In 13 (76%) patients, valve vegetations or valve regurgitation resolved or improved in number and size or by ≥1 degree, respectively, as compared to 4 (24%) patients in whom vegetations or valve regurgitation persisted unchanged or increased in size or by ≥1 degree (p = 0.03). Also, cerebromicroembolism, lobar and global gray and white matter cerebral perfusion, ischemic brain lesion load, and neurocognitive dysfunction resolved or significantly improved (all p ≤0.04). CONCLUSION: These preliminary data suggest that combined conventional anti-inflammatory and antithrombotic therapy may be an effective treatment for Libman-Sacks endocarditis and its associated CVD and may obviate the need for high-risk valve surgery.

Prevalence and Treatment of Postpartum Stress Urinary Incontinence: A Systematic Review.

OBJECTIVES: Many women present for treatment of stress urinary incontinence (SUI) after childbirth. This systematic review describes the efficacy of treatment options for SUI initiated during the 12 months after delivery. METHODS: We conducted a systematic review to identify studies comparing treatment options for SUI initiated in the 12 months after parturition. We searched MEDLINE from inception to February 2019, using Medical Subject Heading terms related to pregnancy and urinary incontinence. Preintervention and postintervention populations were compared using analysis of variance with Fisher least significant difference method used to determine efficacy between groups. Grades for Recommendation, Assessment, Development and Evaluation system was used to categorize quality of evidence as high, moderate, low, or very low. RESULTS: We double screened 4548 abstracts, identifying 98 articles for full-text review. Seven studies met the eligibility criteria and were included. Compared with a control group, the 4 interventions identified outperformed the control group (P < 0.001) using Fisher (with effect sizes noted): (1) supervised pelvic floor physical therapy (0.76), (2) electrical stimulation (0.77), (3) home physical therapy (PT) (0.44), and (4) surgery (not applicable). Based on Grades for Recommendation, Assessment, Development and Evaluation assessment, there was moderate evidence to support PT and electrical stimulation, with insufficient evidence for surgery. There were no significant differences in parity, age, or body mass index via analysis of variance. The overall strength of evidence is poor for the treatment of postpartum SUI; more data are needed to fully evaluate other treatment options. CONCLUSIONS: All identified interventions demonstrated greater improvement for postpartum SUI over no treatment. Supervised PT ± electrostimulation was the most effective nonsurgical intervention.

Aortic adventitial thickness as a marker of aortic atherosclerosis, vascular stiffness, and vessel remodeling in systemic lupus erythematosus.

INTRODUCTION: There is limited human imaging data on the association of adventitial thickness (AT) with arterial disease. Systemic lupus erythematosus (SLE) is a prototypical disease model for studying markers of premature arterial disease. OBJECTIVE: To determine if increased aortic AT is associated with aortic atherosclerosis [increased intima media thickness (IMT) or plaques], stiffness [increased pressure-strain elastic modulus (PSEM)], and vessel remodeling. METHODS: In total, 70 SLE patients and 26 age- and sex-matched controls underwent transesophageal echocardiography (TEE). Two-dimensional guided M-mode images were obtained to assess AT, IMT, and plaques, and PSEM at the proximal, mid, and distal thoracic aorta. Images were interpreted by 3 observers unaware of the subjects' clinical data and each other's measurements. Abnormal aortic AT, IMT, and PSEM were defined as > 2SD above the overall mean values in controls and corresponded to > 1 mm, > 1 mm, and > 10.6 Pascal units, respectively. Plaques were defined as focal-protruding IMT > 50% of the surrounding vessel wall. RESULTS: Abnormal aortic AT, atherosclerosis, and abnormal stiffness were more frequent in SLE patients than in controls (all p ≤ 0.02). In SLE patients, abnormal AT combined with atherosclerosis was associated with larger aortic end-diastolic diameters than in controls (p ≤ 0.05). In SLE patients, aortic AT was greater in patients with atherosclerosis and in those with abnormal stiffness than in patients without these abnormalities (all p ≤ 0.02). In patients with abnormal AT, the degree of aortic stiffness was similar to those with atherosclerosis (p = 0.22). CONCLUSION: In patients with SLE, increased aortic AT is associated with aortic atherosclerosis, abnormal stiffness, and eccentric vessel remodeling. Key Points • In patients with SLE, abnormal aortic adventitial thickness is associated with aortic atherosclerosis, abnormal stiffness, and eccentric vessel remodeling. • In patients with SLE, aortic adventitial thickening may contribute to the extent of aortic atherosclerosis, abnormal aortic stiffness, and vessel remodeling. • To our knowledge, this is the first human imaging study to characterize the aortic adventitial layer and delineate its association with aortic disease.

Transesophageal Versus Transthoracic Echocardiography for Assessment of Left Ventricular Diastolic Function.

Background: Transesophageal echocardiography (TEE) has not been compared to transthoracic echocardiography (TTE) for assessment of left ventricular diastolic function (LVDF). Left ventricular diastolic dysfunction is common in systemic lupus erythematosus (SLE), a disease model of premature myocardial disease. Methods: 66 patients with SLE (mean age 36±12 years, 91% women) and 26 age-and-sex matched healthy volunteers (mean age 34±11 years, 85% women) underwent TEE immediately followed by TTE. From basal four-chamber views, mitral inflow E and A velocities, E/A ratio, E deceleration time, isovolumic relaxation time, septal and lateral mitral E' and A' velocities, septal E'/A' ratio, mitral E to septal and lateral E' ratios, and pulmonary veins systolic to diastolic peak velocities ratio were measured. Measurements were averaged over 3 cardiac cycles and performed by 2 independent observers. Results: LVDF parameters were worse in patients than in controls by TEE and TTE (all p≤0.03). Most LVDF parameters were similar within each group by TEE and TTE (all p≥0.17). By both techniques, mitral E and A, mitral and septal E/A ratios, septal and lateral E', septal and lateral E/E' ratios, and average E/E' ratio were highly correlated (r=0.64-0.96, all p≤0.003); E deceleration time, isovolumic relaxation time, and septal A' velocities were moderately correlated (r=0.43-0.54, all p≤0.03); and pulmonary veins systolic to diastolic ratio showed the lowest correlation (r=0.27, p=0.04). Conclusion: By TEE and TTE, LVDF parameters were worse in SLE patients than in controls; and in both groups, LVDF parameters assessed by TEE and TTE were similar and significantly correlated.

Progression of atherosclerosis versus arterial stiffness with age within and between arteries in systemic lupus erythematosus.

The progression of atherosclerosis versus arterial stiffness with age within and between arteries has not been defined. Systemic lupus erythematosus (SLE) is a human model of accelerated arterial disease that may permit this determination. 76 SLE patients (69 women, age 37 ± 12 years) and 26 age-and-sex-matched controls (22 women, age 34 ± 11 years) underwent transesophageal echocardiography and carotid ultrasonography for assessment of atherosclerosis [plaques and intima-media thickening (IMT)] and arterial stiffness [increased pressure-strain elastic modulus (PSEM)] of the descending thoracic aorta and carotid arteries. Since IMT is highly associated with plaques, IMT was used as a marker of atherosclerosis to assess its progression in relation with age and PSEM. Aortic and carotid plaques, IMT, and PSEM were greater in patients than in controls (all p ≤ 0.05). Within the aorta and within the carotid arteries, the average percent increases per decade of age for IMT versus PSEM were similar in patients (8.55% versus 9.33% and 3.39% versus 2.46%, respectively) and controls (5.53% versus 6.60% and 4.75% versus 3.49%, respectively) (all p ≥ 0.58). However, in SLE patients, the average percent increases per decade of age for IMT and PSEM were higher in the aorta than in the carotid arteries (8.55% and 9.33% versus 3.39% and 2.46%, respectively, both p ≤ 0.03). In patients with SLE, atherosclerosis and arterial stiffness progress with age parallel to each other within arteries, but divergently between arteries with different anatomy and hemodynamics.

Impact of Health Care and Socioeconomic Needs on Health Care Utilization and Disease Management: The University of New Mexico Hospital Care One Program.

Understanding how unmet basic needs impact health care in patients with complex conditions is vital to improve health outcomes and reduce health care costs. The purpose of this observational study was to explore the association between health care and socioeconomic needs and health care utilization and disease management among patients with chronic conditions at an intensive, patient-centered, office-based program. The study used a cross-sectional design and a convenience sampling approach. Data were collected through a patient questionnaire and medical records. Analysis included descriptive and inferential statistics. Data from 48 established patients were analyzed. Financial and lack of transportation were the 2 most frequently reported unmet needs. More than 65% of participants had their chronic condition(s) under control. Sex and ethnicity were the only 2 demographic variables that yielded significant differences (P ≤ 0.01) on visits to the emergency room and having chronic condition(s) under control. Those who reported having unmet transportation needs were more likely to have a condition uncontrolled and to have lost medical appointments compared to those who had this social need met (P ≤ 0.05). Statistically significant differences in terms of missing medical appointments also were found between those whose overall financial and housing needs were unmet and those who had those needs met (P ≤ 0.05). Results indicate that participating patients generally had good control of their conditions. The study adds evidence in support of the call for health care to address patients' socioeconomic needs, and the health care benefits of intensive case management programs. The model may be considered for adoption throughout New Mexico, and nationally.

Army and Navy ECHO Pain Telementoring Improves Clinician Opioid Prescribing for Military Patients: an Observational Cohort Study.

BACKGROUND: Opioid overdose deaths occur in civilian and military populations and are the leading cause of accidental death in the USA. OBJECTIVE: To determine whether ECHO Pain telementoring regarding best practices in pain management and safe opioid prescribing yielded significant declines in opioid prescribing. DESIGN: A 4-year observational cohort study at military medical treatment facilities worldwide. PARTICIPANTS: Patients included 54.6% females and 46.4% males whose primary care clinicians (PCCs) opted to participate in ECHO Pain; the comparison group included 39.9% females and 60.1% males whose PCCs opted not to participate in ECHO Pain. INTERVENTION: PCCs attended 2-h weekly Chronic Pain and Opioid Management TeleECHO Clinic (ECHO Pain), which included pain and addiction didactics, case-based learning, and evidence-based recommendations. ECHO Pain sessions were offered 46 weeks per year. Attendance ranged from 1 to 3 sessions (47.7%), 4-19 (32.1%, or > 20 (20.2%). MAIN MEASURES: This study assessed whether clinician participation in Army and Navy Chronic Pain and Opioid Management TeleECHO Clinic (ECHO Pain) resulted in decreased prescription rates of opioid analgesics and co-prescribing of opioids and benzodiazepines. Measures included opioid prescriptions, morphine milligram equivalents (MME), and days of opioid and benzodiazepine co-prescribing per patient per year. KEY RESULTS: PCCs participating in ECHO Pain had greater percent declines than the comparison group in (a) annual opioid prescriptions per patient (- 23% vs. - 9%, P < 0.001), (b) average MME prescribed per patient/year (-28% vs. -7%, p < .02), (c) days of co-prescribed opioid and benzodiazepine per opioid user per year (-53% vs. -1%, p < .001), and (d) the number of opioid users (-20.2% vs. -8%, p < .001). Propensity scoring transformation-adjusted results were consistent with the opioid prescribing and MME results. CONCLUSIONS: Patients treated by PCCs who opted to participate in ECHO Pain had greater declines in opioid-related prescriptions than patients whose PCCs opted not to participate.

Correlation of neurocognitive function and brain lesion load on magnetic resonance imaging in systemic lupus erythematosus.

Neurocognitive dysfunction and brain injury on magnetic resonance imaging (MRI) are common in patients with systemic lupus erythematosus (SLE) and are associated with increased morbidity and mortality. However, brain MRI is expensive, is restricted by payers, and requires high expertise. Neurocognitive assessment is an easily available, safe, and inexpensive clinical tool that may select patients needing brain MRI. In this cross-sectional and controlled study, 76 SLE patients (69 women, age 37 ± 12 years) and 26 age and gender-matched healthy subjects (22 women, age 34 ± 11 years) underwent assessment of attention, memory, processing speed, executive function, motor function, and global neurocognitive function. All subjects underwent brain MRI with T1-weighted, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging. Hemispheric and whole brain lesion load in cm3 were determined using semi-automated methods. Neurocognitive z-scores in all clinical domains were significantly lower and whole brain and right and left hemispheres brain lesion load were significantly greater in patients than in controls (all p ≤ 0.02). There was significant correlation between neurocognitive z-scores in all domains and whole brain lesion load: processing speed (r = - 0.46; p < 0.0001), attention (r = - 0.42; p < 0.001), memory (r = - 0.40; p = 0.0004), executive function (r = - 0.25; p = 0.03), motor function (r = - 0.25; p = 0.05), and global neurocognitive function (r = - 0.38; p = 0.006). Similar correlations were found for brain hemisphere lesion loads (all p ≤ 0.05). These correlations were strengthened when adjusted for glucocorticoid therapy and SLE disease activity index. Finally, global neurocognitive z-score and erythrosedimentation rate were the only independent predictors of whole brain lesion load (both p ≤ 0.007). Neurocognitive measures and brain lesion load are worse in SLE patients than in controls. In SLE patients, neurocognitive z-scores correlate negatively with and independently predict brain lesion load. Therefore, neurocognitive testing may be an effective clinical tool to select patients needing brain MRI.

ENDO ECHO IMPROVES PRIMARY CARE PROVIDER AND COMMUNITY HEALTH WORKER SELF-EFFICACY IN COMPLEX DIABETES MANAGEMENT IN MEDICALLY UNDERSERVED COMMUNITIES.

OBJECTIVE: To determine whether participation in a multidisciplinary telementorship model of healthcare delivery improves primary care provider (PCP) and community health worker (CHW) confidence in managing patients with complex diabetes in medically underserved regions. METHODS: We applied a well-established healthcare delivery model, Project ECHO (Extension for Community Healthcare Outcomes), to the management of complex diabetes (Endo ECHO) in medically underserved communities. A multidisciplinary team at Project ECHO connected with PCPs and CHWs at 10 health centers across New Mexico for weekly videoconferencing virtual clinics. Participating PCPs and CHWs presented de-identified patients and received best practice guidance and mentor-ship from Project ECHO specialists and network peers. A robust curriculum was developed around clinical practice guidelines and presented by weekly didactics over the ECHO network. After 2 years of participation in Endo ECHO, PCPs and CHWs completed self-efficacy surveys comparing confidence in complex diabetes management to baseline. RESULTS: PCPs and CHWs in rural New Mexico reported significant improvement in self-efficacy in all measures of complex diabetes management, including PCP ability to serve as a local resource for other healthcare providers seeking assistance in diabetes care. Overall self-efficacy improved by 130% in CHWs ( P<.0001) and by 60% in PCPs ( P<.0001), with an overall large Cohen's effect size. CONCLUSION: Among PCPs and CHWS in rural, medically underserved communities, participation in Endo ECHO for 2 years significantly improved confidence in complex diabetes management. Application of the ECHO model to complex diabetes care may be useful in resource-poor communities with limited access to diabetes specialist services. ABBREVIATIONS: CHW = community health worker; CME = Continuing Medical Education; ECHO = Extension for Community Healthcare Outcomes; FQHC = federally qualified health center; PCP = primary care provider.

Characterization of Cortisol Secretion Rate in Secondary Adrenal Insufficiency.

CONTEXT: In secondary adrenal insufficiency (SAI), chronic deficiency of adrenocorticotropin (ACTH) is believed to result in secondary changes in adrenocortical function, causing an altered dose-response relationship between ACTH concentration and cortisol secretion rate (CSR). OBJECTIVE: We sought to characterize maximal cortisol secretion rate (CSRmax) and free cortisol half-life in patients with SAI, compare results with those of age-matched healthy controls, and examine the influence of predictor variables on ACTH-stimulated cortisol concentrations. DESIGN: CSRmax was estimated from ACTH1-24 (250 µg)-stimulated cortisol time-concentration data. Estimates for CSRmax and free cortisol half-life were obtained for both dexamethasone (DEX) and placebo pretreatment conditions for all subjects. SETTING: Single academic medical center. PATIENTS: Patients with SAI (n = 10) compared with age-matched healthy controls (n = 21). INTERVENTIONS: The order of DEX vs placebo pretreatment was randomized and double-blind. Cortisol concentrations were obtained at baseline and at intervals for 120 minutes after ACTH1-24. MAIN OUTCOME MEASURES: CSRmax and free cortisol half-life were obtained by numerical modeling analysis. Predictors of stimulated cortisol concentrations were evaluated using a multivariate model. RESULTS: CSRmax was significantly (P < 0.001) reduced in patients with SAI compared with controls for both placebo (0.17 ± 0.09 vs 0.46 ± 0.14 nM/s) and DEX (0.18 ± 0.13 vs 0.43 ± 0.13 nM/s) conditions. Significant predictors of ACTH1-24-stimulated total cortisol concentrations included CSRmax, free cortisol half-life, and baseline total cortisol, corticosteroid-binding globulin, and albumin concentrations (all P < 0.05). CONCLUSIONS: Our finding of significantly decreased CSRmax confirms that SAI is associated with alterations in the CSR-ACTH dose-response curve. Decreased CSRmax contributes importantly to the laboratory diagnosis of SAI.

A model for conditional male trimorphisms.

Conditional dimorphisms are widespread in color, morphology, behavior, and life history. Such traits have been successfully modeled in game theory as conditional strategies, and in quantitative genetics as threshold traits. Conditional trimorphisms have recently been unveiled, and here we combine the rock-paper-scissors (RPS) model of game theory and the environmental threshold (ET) model of quantitative genetics to model trimorphisms that are environmentally induced and result from the expression of two thresholds. We investigated the tactic fitness structure for maintenance of alternative reproductive tactics in scarab dung beetles that constitute the first known examples of conditional male trimorphism. We parameterized a novel ternary fitness landscape that explains how conditional male trimorphism in these beetles can be maintained. We tracked changes in tactic frequencies in a wild population of Phanaeus triangularis and detected fitness intransitivity consistent with RPS dynamics. Quantitative predictions of our model compare favorably with corresponding observed parameters. The ternary landscape further reveals how geographic populations of these beetles can evolve between conditional trimorphism and dimorphism. The ternary model also suggests that polyphenic systems could potentially evolve between conditional and purely genetic mediation.

Cycling Versus Continuous Mode In Neuromodulator Programming: A Crossover, Randomized, Controlled Trial.

This is a randomized, controlled, blind, crossover trial comparing cycling versus continuous programming of a sacral neuromodulator in women diagnosed with overactive bladder (OAB). At 6 months, treatment order significantly affected Overactive Bladder Questionnaire - Short Form (OABq-SF) symptom scores. The cycling followed by continuous stimulation group had superior OABq-SF scores (p > 0.02).

Distal tibia allograft for glenohumeral instability: does radius of curvature match?

BACKGROUND: A distal tibia osteochondral allograft is a potential graft option for glenoid reconstruction because the distal tibia may have a similar radius of curvature (ROC) as the glenoid. This study evaluated ROC mismatch as measured on computed tomography (CT) scans between the glenoid, distal tibia, and humeral head. METHODS: Bilateral CT images were formatted for 10 decedents from the Office of the Medical Investigator database, giving 20 specimens per anatomic location. The ROCs of the glenoid, distal tibia, and humeral head were measured. A statistical model was generated to assess ROC mismatch of randomly paired distal tibias and glenoids. RESULTS: The mean ± standard deviation ROC was 2.9 ± 0.25 cm for the glenoid, 2.3 ± 0.21 cm for the distal tibia, and 2.5 ± 0.12 cm for the humeral head. No differences were found in laterality, intraobserver, or interobserver measurements. The least-squares difference in the ROC between the glenoid and tibia was 0.57 cm, glenoid and humerus was 0.40 cm, and humerus and tibia was 0.17 cm. Only 22% of randomly paired distal tibias and glenoids had a difference in ROC of 0.3 cm or less. CONCLUSION: CT measurement of the ROC of the glenoid, distal tibia, and humeral head is reliable and reproducible. The probability of obtaining a random distal tibia allograft with a similar ROC to the glenoid is low. Obtaining ROC measurements of the injured glenoid and the distal tibia allograft specimen before use for glenoid reconstruction may be useful.

Long-Term Blood-Brain Barrier Permeability Changes in Binswanger Disease.

BACKGROUND AND PURPOSE: The blood-brain barrier (BBB) is disrupted in small vessel disease patients with lacunes and white matter hyperintensities (WMHs). The relationship of WMHs and regional BBB permeability changes has not been studied. We hypothesized that BBB disruption occurs in normal appearing WM and regions near the WMHs. To test the hypothesis, we repeated BBB permeability measurements in patients with extensive WMHs related to Binswanger disease. METHODS: We selected a subset of 22 Binswanger disease subjects from a well-characterized larger prospective vascular cognitive impairment cohort. We used 16 age-matched controls for comparison. The abnormal WM permeability (WMP) was measured twice for several years using dynamic contrast-enhanced magnetic resonance imaging. WMP maps were constructed from voxels above a predetermined threshold. Scans from first and second visits were coregistered. WM was divided into 3 regions: normal appearing WM, WMH ring, and WMH core. The ring was defined as 2 mm on each side of the WMH border. WMP was calculated in each of the 3 specific regions. We used paired t test, ANOVA, and Fisher exact test to compare individual changes. RESULTS: WMP was significantly higher in subjects than in controls (P<0.001). There was no correlation between WMH load and WMP. High permeability regions had minimal overlap between first and second scans. Nine percent of WMP was within the WMHs, 49% within the normal appearing WM, and 52% within the WMH ring (P<0.001; ANOVA). CONCLUSIONS: Increased BBB permeability in normal appearing WM and close to the WMH borders supports a relationship between BBB disruption and the development of WMHs.

Lambl's Excrescences: Association with Cerebrovascular Disease and Pathogenesis.

BACKGROUND: Lambl's excrescences (LEx) are detected by transesophageal echocardiography (TEE) and are characterized as thin, elongated, and hypermobile structures located at the leaflets' coaptation point of the heart valves. The association of LEx with cerebrovascular disease (CVD) is still undefined and yet patients with LEx and suspected CVD receive unproven effective antiplatelet or anticoagulant therapy or even undergo valve surgery. Also, the association of LEx with aging and atherogenic, inflammatory, or thrombogenic parameters has not been reported. METHODS: Seventy-seven patients with systemic lupus erythematosus (SLE) (71 women, age 37 ± 12 years) and 26 age- and sex-matched healthy controls (22 women, age 34 ± 11 years) prospectively underwent routine history and physical exam, transcranial Doppler, brain MRI, TEE, carotid duplex, and clinical and laboratory evaluations of atherogenesis, inflammation, platelet activity, coagulation, and fibrinolysis. Subjects without stroke/TIA on enrollment (with and without LEx) had a median follow-up of 57 months. RESULTS: On enrollment, 33 (43%) of 77 patients had CVD manifested as acute stroke/TIA (23 patients), cerebromicroembolism by transcranial Doppler (17 patients), or cerebral infarcts by MRI (14 patients). Mitral or aortic valve LEx were equally frequent in healthy controls (46%) as in patients with and without any CVD (39 and 43%), stroke/TIA (35 and 43%), cerebromicroembolism (41 and 42%), or cerebral infarcts (36 and 43%) (all p ≥ 0.72). Also, other mechanisms for CVD other than LEx such as Libman-Sacks vegetations, patent foramen ovale or interatrial septal aneurysm, aortic or carotid atherosclerosis, or thrombogenesis were found in ≥94% of patients with CVD. In addition, 36 subjects with and 44 without LEx had similar low incidence of stroke/TIA (1 (1.3%) and 2 (2.5%), respectively, p = 1.0) during follow-up. Finally, LEx were not associated with aging, atherogenic risk factors, atherosclerosis, inflammation, or thrombogenesis. CONCLUSIONS: In this study, LEx are similarly prevalent in healthy controls and SLE patients, are not associated with CVD, and are not associated with pathogenic risk factors. Therefore, the study findings suggest that LEx may not be cardioembolic substrates, may not represent pathologic valve structures, and may not require therapy.