Globe Axial Length Growth at Age 10.5 Years in the Infant Aphakia Treatment Study.

PURPOSE: To report the change in globe axial length (AL) from the time of unilateral cataract surgery at age 1-7 months to age 10.5 years for infants enrolled in the Infant Aphakia Treatment Study, and to compare AL growth of operated eyes with that of fellow unoperated eyes. DESIGN: Comparative case series. METHODS: AL growth was analyzed relative to treated vs fellow eye, contact lens (CL) vs intraocular lens (IOL), visual acuity (VA) outcome, and the need for surgery for visual axis opacification. Eyes with glaucoma or glaucoma suspect were excluded from the primary analysis but reported separately. RESULTS: Fifty-seven patients have reliable AL data available at both visits. AL was shorter in treated eyes preoperatively (P < .0001) and at 10.5 years of age (P = .021) but AL growth was not different (4.7 mm, P = .99). The growth (70.2% up to age 5 and 29.8% from age 5 to 10.5) was similar in the CL and the IOL group (P = .79). Eyes grew 4.4 mm when visual acuity (VA) was better than 20/200, and 5.2 mm when VA was 20/200 or worse (P = .076). Eyes receiving additional surgery grew more than eyes not receiving additional surgery (P = .052). Patients with glaucoma showed significantly more eye growth (7.3 mm) than those without glaucoma (4.7 mm) and glaucoma suspects (5.1 mm) (P < .05). CONCLUSIONS: Eyes with glaucoma or poor VA often grew longer than the fellow eye. Overall, treated eyes grew similarly in the IOL and CL groups and also kept pace with the growth of the fellow eyes.

Imaging Patterns of Recurrent Infarction in the Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) Study.

Introduction: While much is known about recurrent clinical events in patients with intracranial atherosclerotic disease (ICAD), there is limited data on characteristics of recurrent infarcts. Methods: The NIH-funded MyRIAD prospective, observational study was designed to identify mechanisms of ischemia and predictors of recurrence in ICAD. Recurrent infarction was assessed on MRI at 6-8 weeks. We reviewed the DWI/ADC and FLAIR sequences in patients with recurrent stroke and characterized the number of infarcts, infarct location, size, and patterns based on whether they were borderzone (BZ), perforator (SC/P), cortical or territorial (C/T), and mixed. Temporal characteristics were delineated by ADC/FLAIR correlation. Results: Of the 89 patients with 6-8 weeks MRI, 22 (24.7%) had recurrent infarcts in the territory of the symptomatic artery. Recurrent infarcts were evident on DWI in 63.6% and single infarcts in 54.5%. The median recurrent infarct volume was 2.0 cm3 compared to median index infarct volumes of 2.5 cm3. A mixed infarct pattern was most common (40.9%), followed by borderzone (22.7%), cortical or territorial (27.3%), while only 9.1% were in a perforator artery distribution. Amongst those with a mixed pattern, 8/9 had a borderzone distribution infarct as part of their mixed infarct pattern. Conclusion: These findings provide novel data on the characteristics of early recurrent infarcts in patients with symptomatic ICAD.

Hemodynamic Markers in the Anterior Circulation as Predictors of Recurrent Stroke in Patients With Intracranial Stenosis.

Background and Purpose- Although aggressive medical therapy was superior to stenting in the SAMMPRIS trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis), the stroke rate in the medical arm was still high. The aim of this study was to determine the association between hemodynamic markers (borderzone infarct pattern and impaired collateral flow on baseline imaging) and rates of recurrent stroke in patients treated medically in SAMMPRIS. Methods- This was a post hoc analysis of patients whose qualifying event for SAMMPRIS was an infarct in the territory of a stenotic middle cerebral artery or intracranial carotid artery. Infarcts were adjudicated as involving primarily internal or cortical borderzone territories, the core middle cerebral artery territory, or perforator territories, and collateral flow was assessed according to a standard scale (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology). Log-rank tests and χ2 tests were performed to assess associations of infarct patterns and collateral flow with rates of recurrent stroke. Results- Of 101 patients who qualified, 14 of 53 (26.4%) with borderzone infarcts, 2 of 24 (8.3%) with core middle cerebral artery infarcts, and 3 of 24 (12.5%) with perforator infarcts had a recurrent stroke in the territory (P=0.14 for comparing the 3 groups, P=0.052 for borderzone versus nonborderzone). Of 82 patients with collateral flow assessment, 30 of 43 (70%) with borderzone infarcts, 7 of 19 (37%) with core middle cerebral artery infarcts, and 11 of 20 (55%) with perforator infarcts had impaired collateral flow distal to the stenosis (P=0.049). Patients with borderzone infarcts and impaired collateral flow had the highest risk of recurrent stroke (37%). Conclusions- Borderzone infarcts and impaired collateral flow identify a subgroup of patients with intracranial stenosis who are at particularly high risk of recurrent stroke on medical treatment. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00576693.

Return to Play After Shoulder Instability Surgery in National Collegiate Athletic Association Division I Intercollegiate Football Athletes.

BACKGROUND: Recent attention has focused on the optimal surgical treatment for recurrent shoulder instability in young athletes. Collision athletes are at a higher risk for recurrent instability after surgery. PURPOSE: To evaluate variables affecting return-to-play (RTP) rates in Division I intercollegiate football athletes after shoulder instability surgery. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Invitations to participate were made to select sports medicine programs that care for athletes in Division I football conferences (Pac-12 Conference, Southeastern Conference [SEC], Atlantic Coast Conference [ACC]). After gaining institutional review board approval, 7 programs qualified and participated. Data on direction of instability, type of surgery, time to resume participation, and quality and level of play before and after surgery were collected. RESULTS: There were 168 of 177 procedures that were arthroscopic surgery, with a mean 3.3-year follow-up. Overall, 85.4% of players who underwent arthroscopic surgery without concomitant procedures returned to play. Moreover, 15.6% of athletes who returned to play sustained subsequent shoulder injuries, and 10.3% sustained recurrent instability, resulting in reduction/revision surgery. No differences were noted in RTP rates in athletes who underwent anterior labral repair (82.4%), posterior labral repair (92.9%), combined anterior-posterior repair (84.8%; P = .2945), or open repair (88.9%; P = .9362). Also, 93.3% of starters, 95.4% of utilized players, and 75.7% of rarely used players returned to play. The percentage of games played before the injury was 49.9% and rose to 71.5% after surgery ( P < .0001). Athletes who played in a higher percentage of games before the injury were more likely to return to play; 91% of athletes who were starters before the injury returned as starters after surgery. Scholarship status significantly correlated with RTP after surgery ( P = .0003). CONCLUSION: The majority of surgical interventions were isolated arthroscopic stabilization procedures, with no statistically significant difference in RTP rates when concomitant arthroscopic procedures or open stabilization procedures were performed. Athletes who returned to play often played in a higher percentage of games after surgery than before the injury, and many played at the same or a higher level after surgery.

Nonprocedural Symptomatic Infarction and In-Stent Restenosis After Intracranial Angioplasty and Stenting in the SAMMPRIS Trial (Stenting and Aggressive Medical Management for the Prevention of Recurrent Stroke in Intracranial Stenosis).

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the frequency of symptomatic in-stent restenosis (ISR) and its contribution to nonprocedural symptomatic infarction in the SAMMPRIS trial (Stenting and Aggressive Medical Management for the Prevention of Recurrent Stroke in Intracranial Stenosis). METHODS: Patients without a periprocedural primary end point were followed up to determine the occurrence of any of the following events: ischemic stroke, cerebral infarct with temporary signs, or transient ischemic attack in the territory of the stented artery. Vascular imaging performed after these events was reviewed for ISR. Annual rates for symptomatic ISR were calculated using Kaplan-Meier estimates. RESULTS: Of 183 patients in the stenting group without a periprocedural primary end point, 27 (14.8%) had a symptomatic infarction (stroke or cerebral infarct with temporary signs) and 16 (8.7%) had transient ischemic attack alone in the territory during a median follow-up of 35.0 months. Of the 27 patients with infarctions, 17 (9.3%) had an ischemic stroke and 10 (5.5%) had a cerebral infarct with temporary signs alone. Adequate vascular imaging to evaluate ISR was available in 24 patients with infarctions (showing ISR in 16 [66.7%]) and in 10 patients with transient ischemic attack alone (showing ISR in 8 [80%]). The 1-, 2-, and 3-year rates (with 95% confidence limits) for symptomatic ISR in the SAMMPRIS stent cohort were 9.6% (6.1%-14.9%), 11.3% (7.5%-17.0%), and 14.0% (9.6%-20.2%), respectively. CONCLUSIONS: Symptomatic ISR occurred in at least 1 of 7 patients in SAMMPRIS by 3 years of follow-up and was likely responsible for the majority of nonprocedural cerebral infarctions. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT00576693.

Globe Axial Length Growth at Age 5 Years in the Infant Aphakia Treatment Study.

PURPOSE: To report the longitudinal change in axial length (AL) from the time of unilateral cataract surgery at age 1 to 7 months to age 5 years, and to compare AL growth of operated eyes with that of fellow unoperated eyes. DESIGN: Comparative case series. PARTICIPANTS: Infants enrolled in the Infant Aphakia Treatment Study (IATS). METHODS: The AL at baseline and age 5 years and change in AL were analyzed relative to treated versus fellow eye, visual outcome, and treatment modality (contact lens [CL] vs. intraocular lens [IOL]). Eyes with glaucoma or glaucoma suspect were excluded from primary analysis but reported separately. MAIN OUTCOME MEASURES: The AL growth from preoperative to age 5 years. RESULTS: Seventy patients were eligible; however, AL data for both eyes were available for 64 patients at baseline and 69 patients at age 5 years. The AL was significantly different between treated and fellow eyes preoperatively (18.1 vs. 18.7 mm, P < 0.0001) and at the final follow-up (21.4 vs. 22.1 mm, P = 0.0004). The difference in AL growth between treated and fellow eyes was not significant (3.3 vs. 3.5 mm, P = 0.31). The change in AL in eyes was similar with both treatments (CL 3.2 mm and IOL 3.4 mm, P = 0.53) and did not correlate with visual outcomes (P = 0.85). Eyes receiving additional surgery to clear the visual axis opacification grew significantly more compared with eyes not receiving surgery to clear the visual axis (3.8 vs. 2.7 mm, P = 0.013). Patients with glaucoma showed significantly more eye growth (5.7 mm) than those without glaucoma (3.3 mm) and glaucoma suspects (4.3 mm). CONCLUSIONS: Eyes treated for monocular cataract in infancy have axial growth similar to that of fellow eyes, despite having a shorter AL at the time of surgery. The change in AL in eyes was similar with both treatments (CL and IOL), did not correlate with visual outcomes, and was higher in eyes receiving additional surgery to clear the visual axis or eyes diagnosed with glaucoma.

Behaviors of children with unilateral vision impairment in the Infant Aphakia Treatment Study.

PURPOSE: To determine whether behavioral functioning of 4.5-year-olds differs between two treatments for unilateral cataract and whether behavioral functioning is predicted by visual acuity in the treated eye. METHODS: The Infant Aphakia Treatment Study is a multicenter clinical trial in which 114 infants with unilateral congenital cataracts were randomized to undergo cataract extraction with contact lens correction or implantation of an intraocular lens. Patching data were collected during the year preceding a visit at age 4.5 years, when both visual acuity and caregiver-reported behavioral functioning were assessed for 109 participants. Caregiver stress was assessed with the Parenting Stress Index at 4.25 years. RESULTS: There were no treatment group differences in behavioral functioning as measured by the Child Behavior Checklist. Poorer visual acuity was associated with more externalizing behavior problems (attention problems and aggressive behavior) and total behavior problems in regression models that did not include caregiver stress. Both caregiver stress and dichotomized visual acuity significantly predicted externalizing problems. CONCLUSIONS: Treatment assignment did not affect caregiver-reported behavior. Poor visual acuity may confer risk for problems with attention and aggressive behavior in preschoolers treated for unilateral cataract.

Effect of Electronic Health Record Implementation in Critical Care on Survival and Medication Errors.

BACKGROUND: Electronic health records (EHR) with computerized physician order entry have become exceedingly common and government incentives have urged implementation. The purpose of this study was to ascertain the effect of EHR implementation on medical intensive care unit (MICU) mortality, length of stay (LOS), hospital LOS and medication errors. MATERIALS AND METHODS: Prospective, observational study from July 2010-June 2011 in MICU at an urban teaching hospital in Atlanta, Georgia of 797 patients admitted to the MICU; 281 patients before the EHR implementation and 516 patients post-EHR implementation. RESULTS: Compared with the preimplementation period (N = 43 per 281), the mortality risk at 4 months post-EHR implementation (N = 41 per 247) and at 8 months post-EHR implementation (N = 26 per 269) significantly decreased (P < 0.001). In addition, the mean MICU LOS statistically decreased from 4.03 ± 1.06 days pre-EHR to 3.26 ± 1.06 days 4 months post-EHR and to 3.12 ± 1.05 days 8 months post-EHR (P = 0.002). However, the mean hospital LOS was not statistically decreased. Although medication errors increased after implementation (P = 0.002), this was attributable to less severe errors and there was actually a decrease in the number of severe medication errors (both P < 0.001). CONCLUSIONS: We report a survival benefit following the implementation of EHR with computerized physician order entry in a critical care setting and a concomitant decrease in the number of severe medication errors. Although overall hospital LOS was not shortened, this study proposes that EHR implementation in a busy urban hospital was associated with improved ICU outcomes.

Efficacy and Safety of Glutamine-supplemented Parenteral Nutrition in Surgical ICU Patients: An American Multicenter Randomized Controlled Trial.

OBJECTIVE: To determine whether glutamine (GLN)-supplemented parenteral nutrition (PN) improves clinical outcomes in surgical intensive care unit (SICU) patients. SUMMARY BACKGROUND DATA: GLN requirements may increase with critical illness. GLN-supplemented PN may improve clinical outcomes in SICU patients. METHODS: A parallel-group, multicenter, double-blind, randomized, controlled clinical trial in 150 adults after gastrointestinal, vascular, or cardiac surgery requiring PN and SICU care. Patients were without significant renal or hepatic failure or shock at entry. All received isonitrogenous, isocaloric PN [1.5 g/kg/d amino acids (AAs) and energy at 1.3× estimated basal energy expenditure]. Controls (n = 75) received standard GLN-free PN (STD-PN); the GLN group (n = 75) received PN containing alanyl-GLN dipeptide (0.5 g/kg/d), proportionally replacing AA in PN (GLN-PN). Enteral nutrition (EN) was advanced and PN weaned as indicated. Hospital mortality and infections were primary endpoints. RESULTS: Baseline characteristics, days on study PN and daily macronutrient intakes via PN and EN, were similar between groups. There were 11 hospital deaths (14.7%) in the GLN-PN group and 13 deaths in the STD-PN group (17.3%; difference, -2.6%; 95% confidence interval, -14.6% to 9.3%; P = 0.66). The 6-month cumulative mortality was 31.4% in the GLN-PN group and 29.7% in the STD-PN group (P = 0.88). Incident bloodstream infection rate was 9.6 and 8.4 per 1000 hospital days in the GLN-PN and STD-PN groups, respectively (P = 0.73). Other clinical outcomes and adverse events were similar. CONCLUSIONS: PN supplemented with GLN dipeptide was safe, but did not alter clinical outcomes among SICU patients.

Does the Stenting Versus Aggressive Medical Therapy Trial Support Stenting for Subgroups With Intracranial Stenosis?

BACKGROUND AND PURPOSE: Although the Stenting Versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) trial showed that medical therapy alone was superior to stenting plus medical therapy for preventing recurrent strokes in patients with symptomatic intracranial stenosis, we determined whether SAMMPRIS supported the use of stenting in any subpopulations of patients with symptomatic intracranial arterial stenosis. METHODS: The primary outcome, 30-day stroke and death and later strokes in the territory of the qualifying artery, was compared in those with and without baseline factors in the 2 treatment arms, percutaneous transluminal angioplasty and stenting (PTAS) plus aggressive medical therapy versus aggressive medical therapy alone. Baseline factors included sex, age, race, diabetes mellitus, hypertension, lipid disorder, smoking status, type of qualifying event, qualifying event hypoperfusion symptoms, use of antithrombotic or proton pump inhibitor at baseline, days to enrollment, old infarcts in the same territory, percent stenosis, other artery stenosis, and location of the symptomatic artery. RESULTS: A total of 451 patients were enrolled, 227 randomized to aggressive medical therapy and 224 to PTAS. Of all variables evaluated, the observed 2-year event rates were higher with PTAS than with aggressive medical therapy in the vast majority and the interaction with treatment was not statistically significant for any of the factors. CONCLUSIONS: The SAMMPRIS results do not provide evidence to support the use of PTAS using the Wingspan stent system compared with medical treatment in any examined subpopulation of patients with symptomatic intracranial stenosis, including those with qualifying event hypoperfusion symptoms. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00576693.

Evaluating Simulation-Based ACLS Education on Patient Outcomes: A Randomized, Controlled Pilot Study.

BACKGROUND: Simulation training is widely accepted as an effective teaching tool, especially for dealing with high-risk situations. OBJECTIVE: We assessed whether standardized, simulation-based advanced cardiac life support (ACLS) training improved performance in managing simulated and actual cardiac arrests. METHODS: A total of 103 second- and third-year internal medicine residents were randomized to 2 groups. The first group underwent conventional ACLS training. The second group underwent two 2 1/2-hour sessions of standardized simulation ACLS teaching. The groups were assessed by evaluators blinded to their assignment during in-hospital monthly mock codes and actual inpatient code sheets at 3 large academic hospitals. Primary outcomes were time to initiation of cardiopulmonary resuscitation, time to administration of first epinephrine/vasopressin, time to delivery of first defibrillation, and adherence to American Heart Association guidelines. RESULTS: There were no differences in primary outcomes among the study arms and hospital sites. During 21 mock codes, the most common error was misidentification of the initial rhythm (67% [6 of 9] and 58% [7 of 12] control and simulation arms, respectively, P  =  .70). There were no differences in primary outcome among groups in 147 actual inpatient codes. CONCLUSIONS: This blinded, randomized study found no effect on primary outcomes. A notable finding was the percentage of internal medicine residents who misidentified cardiac arrest rhythms.

Infarct patterns, collaterals and likely causative mechanisms of stroke in symptomatic intracranial atherosclerosis.

BACKGROUND: There are limited data on the specific mechanisms of stroke in patients with intracranial atherosclerotic stenosis (ICAS). We undertook this study to describe infarct patterns and likely mechanisms of stroke in a large cohort of patients with ICAS, and to evaluate the relationship of these infarct patterns to angiographic features (collaterals, stenosis location and stenosis severity). METHODS: We evaluated infarct patterns in the territory of a stenotic intracranial artery on neuroimaging performed at baseline and during follow-up if a recurrent stroke occurred in patients enrolled in the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial. We defined the likely mechanism of stroke (artery-to-artery embolism, perforator occlusion, hypoperfusion or mixed) according to the site of ICAS and based on the infarct patterns on neuroimaging. Collaterals were assessed using American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grades, and stenosis severity using the WASID trial's measurement technique. We evaluated the association of infarct patterns with angiographic features using χ(2) tests. RESULTS: The likely mechanisms of stroke based on the infarct patterns at baseline in the 136 patients included in the study were artery-to-artery embolism (n = 69; 50.7%), perforator occlusion (n = 34; 25%), hypoperfusion (n = 12; 8.8%) and mixed (n = 21; 15.5%). Perforator-occlusive infarcts were more frequent in the posterior circulation, and mixed patterns were more prevalent in the anterior circulation (both p < 0.01). Most of the mixed patterns in the anterior circulation combined small pial or scattered multiple cortical infarcts with infarcts in border-zone regions, especially the cortical ones. Isolated border-zone infarcts were not significantly associated with a poor grading for collaterals or the severity of stenosis. Among 47 patients with a recurrent infarct during follow-up, the infarct patterns suggested an artery-to-artery embolic mechanism in 29 (61.7%). CONCLUSIONS: Artery-to-artery embolism is probably the most common mechanism of stroke in both the anterior and the posterior circulations in patients with ICAS. An extension of intracranial atherosclerosis at the site of stenosis into adjacent perforators also appears to be a common mechanism of stroke, particularly in the posterior circulation, whereas hypoperfusion as the sole mechanism is relatively uncommon. Further research is important to accurately establish the specific mechanisms of stroke in patients with ICAS, since preliminary data suggest that the underlying mechanism of stroke is an important determinant of prognosis.

Axial elongation following cataract surgery during the first year of life in the infant Aphakia Treatment Study.

PURPOSE: To compare ocular axial elongation in infants after unilateral cataract surgery corrected with a contact lens (CL) or primary intraocular lens (IOL) implantation. METHODS: Baseline axial length (AL) was measured at the time of cataract surgery (1-6 months) and at age 1 year. AL at baseline and age 1 year and the change in length/mo were analyzed in relation to treatment modality, cataractous versus fellow eye, and age at surgery using linear mixed models. RESULTS: Mean baseline AL did not differ between the CL and IOL groups for either cataractous or fellow eyes. Eyes with cataracts were shorter than fellow eyes by an average of 0.6 mm (95% confidence interval [CI], 0.4-0.8 mm; P < 0.0001). For the operated eyes, the mean change in AL/mo was smaller in the CL group (0.17 mm/mo) than in the IOL group (0.24 mm/mo) (P = 0.0006) and was independent of age at surgery (P = 0.19). In contrast, the change in AL/mo for fellow eyes decreased with older age at surgery (P < 0.0001). At age 1 year, operated eyes treated with a CL were 0.6 mm shorter on average than operated eyes treated with an IOL (P = 0.009). CONCLUSIONS: At baseline, eyes with cataracts were shorter than fellow eyes. The change in AL/mo was smaller in operated eyes treated with a CL than in operated eyes treated with an IOL, but was not significantly related to age at surgery. (ClinicalTrials.gov number, NCT00212134.).

Collaterals dramatically alter stroke risk in intracranial atherosclerosis.

OBJECTIVE: Stroke risk due to intracranial atherosclerosis increases with degree of arterial stenosis. We evaluated the previously unexplored role of collaterals in modifying stroke risk in intracranial atherosclerosis and impact on subsequent stroke characteristics. METHODS: Collateral flow was graded in blind fashion on 287 of 569 baseline angiograms (stenoses of 50-99% and adequate collateral views) in the Warfarin--Aspirin Symptomatic Intracranial Disease (WASID) trial. Statistical models predicted stroke in the symptomatic arterial territory based on collateral flow grade, percentage of stenosis, and previously demonstrated independent covariates. RESULTS: Across all stenoses, extent of collaterals was a predictor for subsequent stroke in the symptomatic arterial territory (hazard ratio [HR] none vs good, 1.14; 95% confidence interval [CI], 0.39-3.30; poor vs good, 4.36; 95% CI, 1.46-13.07; p < 0.0001). For 70 to 99% stenoses, more extensive collaterals diminished risk of subsequent territorial stroke (HR none vs good, 4.60; 95% CI, 1.03-20.56; poor vs good, 5.90; 95% CI, 1.25-27.81; p = 0.0427). At milder degrees of stenoses (50-69%), presence of collaterals was associated with greater likelihood of subsequent stroke (HR none vs good, 0.18; 95% CI, 0.04-0.82; poor vs good, 1.78; 95% CI, 0.37-8.57; p < 0.0001). In multivariate analyses, extent of collaterals was an independent predictor for subsequent stroke in the symptomatic arterial territory (HR none vs good, 1.62; 95% CI, 0.52-5.11; poor vs good, 4.78; 95% CI, 1.55-14.7; p = 0.0019). INTERPRETATION: Collateral circulation is a potent determinant of stroke risk in intracranial atherosclerosis, demonstrating a protective role with severe stenoses and identifying more unstable milder stenoses.

Collateral circulation in symptomatic intracranial atherosclerosis.

Collateral circulation in intracranial atherosclerosis has never been systematically characterized. We investigated collaterals in a multicenter trial of symptomatic intracranial atherosclerotic disease. Baseline angiography was reviewed for information on collaterals in stenoses of the internal carotid, middle cerebral, vertebral, and basilar arteries. A battery of angiographic scales was utilized to evaluate lesion site, arterial patency, antegrade flow, downstream territorial perfusion, and collateral circulation, blinded to all other data. Collateral circulation was adequately available for analysis in 287/569 (50%) subjects with proximal arterial stenoses ranging from 50% to 99%. Extent of collaterals was absent or none in 69%, slow or minimal in 10%, more rapid, yet incomplete perfusion of territory in 7%, complete but delayed perfusion in 11%, and rapid, complete collateral perfusion in 4%. Extent of collateral flow correlated with percentage of stenosis (P<0.0001), with more severe stenoses exhibiting greater compensation via collaterals. Overall, collateral grade increased with diminished antegrade flow across the lesion (thrombolysis in myocardial ischemia) and resultant downstream perfusion (thrombolysis in cerebral infarction) (both P<0.001). Our findings provide the initial detailed description of collaterals across a variety of stenoses, suggesting that collateral perfusion is a pivotal component in pathophysiology of intracranial atherosclerosis and implicating the need for further evaluation in ongoing studies.

Intratumoral heterogeneity of immunohistochemical marker expression in breast carcinoma: a tissue microarray-based study.

Core needle biopsies of breast carcinomas provide diagnostic, prognostic, and predictive information before neoadjuvant therapy. Possible intratumoral heterogeneity of biomarker expression questions the validity of core needle biopsy interpretation in small biopsy specimens. Using tissue microarray (TMA) technology, we studied intratumoral heterogeneity of 7 immunomarkers. Five TMAs were constructed from 44 breast carcinomas and 5 normal breast tissues, each represented by 1-mm cores in triplicate from each of 3 foci. TMAs were immunostained for monoclonal estrogen receptor (ER), monoclonal progesterone receptor (PR), polyclonal human epidermal growth factor receptor 2 (HER2), monoclonal E-cadherin (E-cad), monoclonal epidermal growth factor receptor (EGFR), monoclonal p53, and monoclonal MIB-1. Expression was quantified visually by light microscopy and by image cytometry as intensity, percentage of cells positive, and score. Using intraclass correlation coefficient, heterogeneity in the expression of the immunomarkers within subjects was compared with the overall variance. Intratumoral heterogeneity was seen with 5 immunomarkers: ER, PR, HER2, p53, and MIB-1. E-cad and EGFR failed to show intratumoral heterogeneity. Intratumoral heterogeneity in ER, PR, HER2, p53, and MIB-1 indicates their problematic interpretation in small biopsy specimens as indicative of the status of the entire tumor. A negative result does not exclude the expression of these markers in the remainder of the tumor. E-cad (positive in ductal carcinomas) and EGFR lacked heterogeneity.

An Internet-based migraine headache diary: issues in Internet-based research.

OBJECTIVE: The primary purpose of this study was to explore the feasibility and acceptability of using an Internet-based headache diary to obtain acceptable completion rates of daily diaries. BACKGROUND: Migraine sufferers often perceive that headaches are unpredictable, but 70% have prodromal warning symptoms that may be identified via daily headache diaries. Although diaries are widely used for tracking headaches, Internet-based diaries have not been used previously. METHODS: A conventional headache diary was formatted for the Internet to collect daily headache data over 4 months using a time-series design.Women between 18 and 55 years who were not pregnant or postmenopausal, and whose headaches met migraine criteria, were recruited primarily via the Internet, completed online consent forms, and were screened via telephone. They completed health history questionnaires and daily diary pages containing scales and open-ended questions,which were saved to a database. Diaries were reviewed and participants were contacted weekly. Completion dates were tracked electronically. Follow-up interviews addressed perceptions about study experiences, and participants received feedback about headache patterns. RESULTS: The majority of participants were recruited from discussion boards and free classified web sites. Of the 101 participants enrolled, 24 withdrew prior to completing 4 months of diary entries. Participants (n = 77) had a mean age of 37.5(7.5) years and were primarily white (82%) and well-educated (93%). They lived in 21 US states, and one in the UK. The majority (68%) completed at least 50% of their diary pages within 24 hours; 75% of all pages were completed within 2 days. At least 64 (83%) kept notes or printed pages when they lacked Internet access. In a follow-up survey (n = 67), 87% would have been willing to continue the diary for another 2 months; 69% had not previously participated in any research. Participants also reported that the study helped them better understand their headache patterns, that the study was a major commitment but worthwhile, and that they felt they had helped others by participating. CONCLUSION: The Internet-based headache diary is a feasible, acceptable data collection tool that can access geographically diverse populations who have not previously participated in research studies. Use of an Internet-based approach was found to be feasible for recruitment and retention of such diverse populations.

Effect of baseline plasma fatty acids on eicosapentaenoic acid levels in individuals supplemented with alpha-linolenic acid.

We previously reported a >50% increase in mean plasma eicosapentaenoic acid levels in a general medicine clinic population after supplementation with alpha-linolenic acid. In the current analysis, we evaluate the variability of changes in eicosapentaenoic acid levels among individuals supplemented with alpha-linolenic acid and evaluated the impact of baseline plasma fatty acids levels on changes in eicosapentaenoic acid levels in these individuals. Changes in eicosapentaenoic acid levels among individuals supplemented with alpha-linolenic acid ranged from a 55% decrease to a 967% increase. Baseline plasma fatty acids had no statistically significant effect on changes in eicosapentaenoic levels acid after alpha-linolenic acid supplementation. Changes in eicosapentaenoic acid levels varied considerably in a general internal medicine clinic population supplemented with alpha-linolenic acid. Factors that may impact changes in plasma eicosapentaenoic acid levels after alpha-linolenic acid supplementation warrant further study.

Insulin resistance is associated with decreased quadriceps muscle strength in nondiabetic adults aged >or=70 years.

OBJECTIVE: Lower-limb muscle strength is reduced in many people with diabetes. In this study, we examined whether quadriceps muscle strength is reduced in relation to insulin resistance in well-functioning ambulatory nondiabetic individuals. RESEARCH DESIGN AND METHODS: Participants (age >or=70 years) underwent dual-energy X-ray absorptiometry (DEXA) scanning to ascertain muscle and fat mass, tests of quadriceps strength, computed tomography scanning of the quadriceps to gauge muscle lipid content, and fasting insulin and glucose level measurements from which homeostasis model assessment of insulin resistance (HOMA-IR) was derived. RESULTS: In regression analysis, quadriceps strength per kilogram of muscle mass was negatively associated (P < 0.0001) with HOMA-IR independent of other factors negatively associated with strength such as increased age, female sex, low-physical activity, impaired fasting glucose, and increased total body fat. Muscle lipid content was not associated with strength. CONCLUSIONS: A small decrease in quadriceps muscle force is associated with increased HOMA-IR in well-functioning nondiabetic adults, suggesting that diminished quadriceps muscle strength begins before diabetes.