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1.  Development of functional imaging in the human brain (fMRI); the University of Minnesota experience 
NeuroImage  2012;62(2):613-619.
The human functional magnetic resonance imaging (fMRI) experiments performed in the Center for Magnetic Resonance Research (CMRR), University of Minnesota, were planned between two colleagues who had worked together previously in Bell Laboratories in the late nineteen seventies, namely myself and Seiji Ogawa. These experiments were motivated by the Blood Oxygenation Level Dependent (BOLD) contrast developed by Seiji. We discussed and planned human studies to explore imaging human brain activity using the BOLD mechanism on the 4 Tesla human system that I was expecting to receive for CMRR. We started these experiments as soon as this 4 Tesla instrument became marginally operational. These were the very first studies performed on the 4 Tesla scanner in CMRR; had the scanner became functional earlier, they would have been started earlier as well. We had positive results certainly by August 1991 annual meeting of the Society of Magnetic Resonance in Medicine (SMRM) and took some of the data with us to that meeting. I believe, however, that neither the MGH colleagues nor us, at the time, had enough data and/or conviction to publish these extraordinary observations; it took more or less another six months or so before the papers from these two groups were submitted for publication within five days of each other to the Proceedings of the National Academy of Sciences, USA, after rejections by Nature. Based on this record, it is fair to say that fMRI was achieved independently and at about the same time at MGH, in an effort credited largely to Ken Kwong, and in CMRR, University of Minnesota in an effort led by myself and Seiji Ogawa.
doi:10.1016/j.neuroimage.2012.01.135
PMCID: PMC3530260  PMID: 22342875
Neuroimaging; brain imaging; MRI; High field; Ultrahigh field; 4 Tesla; 4T; 7 Tesla; 7T; functional mapping; fMRI; functional mapping
2.  Endovascular Stent Graft Repair for Thoracic Aortic Aneurysms: The History and the Present in Japan 
Annals of Vascular Diseases  2013;6(2):129-136.
Stent-grafts for endovascular repair of thoracic aortic aneurysms have been commercially available for more than ten years in the West, whereas, in Japan, a manufactured stent-graft was not approved for the use until March 2008. Nevertheless, endovascular thoracic intervention began to be performed in Japan in the early 1990s, with homemade devices used in most cases. Many researchers have continued to develop their homemade devices. We have participated in joint design and assessment efforts with a stent-graft manufacturer, focusing primarily on fenestrated stent-grafts used in repairs at the distal arch, a site especially prone to aneurysm. In March 2008, TAG (W.L. Gore & Associates, Inc., Flagstaff, Arizona, USA) was approved as a stent graft for the thoracic area first in Japan, which was major turning point in treatment for thoracic aortic aneurysms. Subsequently, TALENT (Medtronic, Inc., Minneapolis, Minnesota, USA) was approved in May 2009, and TX2 (COOK MEDICAL Inc., Bloomington, Indiana, USA) in March 2011. Valiant as an improved version of TALENT was approved in November 2011, and TX2 Proform as an improved version of TX2 began to be supplied in October 2012. These stent grafts are excellent devices that showed good results in Western countries, and marked effectiveness can be expected by making the most of the characteristics of each device. A clinical trial in Japan on Najuta (tentative name) (Kawasumi Labo., Inc., Tokyo, Japan) as a line-up of fenestrated stent grafts that can be applied to distal arch aneurysms showing a high incidence, and allow maintenance of blood flow to the arch vessel was initiated. This trial was completed, and Najuta has just been approved in January of 2013 in Japan, and further development is expected. In the U.S., great efforts have recently been made to develop and manufacture excellent stent grafts for thoracic aneurysms, and rapid progress has been achieved. In particular, in the area of the aortic arch, in which we often experience aneurysmal change, but there are no commercially available devices which are urgently needed. Companies are competing keenly to develop devices. To our knowledge, more than 4 manufacturers are involved in the development of functionally new stent grafts in this area. The introduction of branched stent grafts may not be faraway.
doi:10.3400/avd.ra.12.00018
PMCID: PMC3692980  PMID: 23825491
stent; stent graft; aneurysm; thoracic aortic aneurysm; endovascular surgery
3.  Prehospital and Emergency Department Capacity for Acute Stroke Care in Minnesota 
Preventing Chronic Disease  2008;5(2):A55.
Introduction
Stroke is the third leading cause of death in Minnesota. One strategy to reduce the burden of stroke is to implement systems-level improvements in the prehospital and acute care settings. Two surveys conducted in 2006 obtained information about current practices and capacities of emergency medical services and emergency departments in Minnesota.
Methods
In 2006, the Minnesota Department of Health and the Minnesota Stroke Partnership (the statewide stroke collaborative group) conducted two surveys. The survey for emergency medical services organizations, mailed to every licensed ambulance service in Minnesota, asked about transportation policies and training needs. The survey for hospitals, mailed to every hospital in the state, asked about capacity to treat acute stroke. Results were calculated using simple frequency analyses.
Results
Of 257 surveys mailed to ambulance services, 199 (77%) were returned. Ambulance services generally considered stroke an emergency. Training on stroke was reported most effective in person annually or semiannually. Of 133 surveys mailed to hospitals, 120 (90%) were returned. Stroke capacity differed markedly between hospitals in rural areas and hospitals in the large Minneapolis–St. Paul metropolitan area. Many hospitals, particularly small hospitals, reported lacking stroke protocols. Training for stroke is needed overall but particularly in small hospitals.
Conclusion
Transport and treatment of people with acute stroke in Minnesota vary by hospital size and location. Standardization of transport and protocols for acute treatment may increase efficiency and overall care for stroke patients. In addition, the need to train ambulance personnel and emergency departments about stroke remains high.
PMCID: PMC2396958  PMID: 18341790
4.  Bringing Bike Share to a Low-Income Community: Lessons Learned Through Community Engagement, Minneapolis, Minnesota, 2011 
Background
High prevalence of physical inactivity contributes to adverse health outcomes. Active transportation (cycling or walking) is associated with better health outcomes, and bike-sharing programs can help communities increase use of active transportation.
Community Context
The Minneapolis Health Department funded the Nice Ride Minnesota bike share system to expand to the Near North community in Minneapolis, Minnesota. Near North is a diverse, low-income area of the city where residents experience health disparities, including disparities in physical activity levels.
Methods
The installation of new bike share kiosks in Near North resulted in an environmental change to support physical activity. Community engagement was conducted pre-intervention only and consisted of focus groups, community meetings, and interviews. Postintervention data on bike share trips and subscribers were collected to assess intervention effectiveness.
Outcome
Focus group participants offered insights on facilitators and barriers to bike share and suggested system improvements. Community engagement efforts showed that Near North residents were positive about Nice Ride and wanted to use the system; however, the numbers of trips and subscriptions in Near North were low.
Interpretation
Results show that the first season of the expansion was moderately successful in improving outreach efforts and adapting bike share to meet the needs of low-income populations. However, environmental change without adequate, ongoing community engagement may not be sufficient to result in behavior change.
doi:10.5888/pcd10.120274
PMCID: PMC3748276  PMID: 23948339
5.  ISMB/ECCB 2009 Stockholm 
Bioinformatics  2009;25(12):1570-1573.
The International Society for Computational Biology (ISCB; http://www.iscb.org) presents the Seventeenth Annual International Conference on Intelligent Systems for Molecular Biology (ISMB), organized jointly with the Eighth Annual European Conference on Computational Biology (ECCB; http://bioinf.mpi-inf.mpg.de/conferences/eccb/eccb.htm), in Stockholm, Sweden, 27 June to 2 July 2009. The organizers are putting the finishing touches on the year's premier computational biology conference, with an expected attendance of 1400 computer scientists, mathematicians, statisticians, biologists and scientists from other disciplines related to and reliant on this multi-disciplinary science. ISMB/ECCB 2009 (http://www.iscb.org/ismbeccb2009/) follows the framework introduced at the ISMB/ECCB 2007 (http://www.iscb.org/ismbeccb2007/) in Vienna, and further refined at the ISMB 2008 (http://www.iscb.org/ismb2008/) in Toronto; a framework developed to specifically encourage increased participation from often under-represented disciplines at conferences on computational biology. During the main ISMB conference dates of 29 June to 2 July, keynote talks from highly regarded scientists, including ISCB Award winners, are the featured presentations that bring all attendees together twice a day. The remainder of each day offers a carefully balanced selection of parallel sessions to choose from: proceedings papers, special sessions on emerging topics, highlights of the past year's published research, special interest group meetings, technology demonstrations, workshops and several unique sessions of value to the broad audience of students, faculty and industry researchers. Several hundred posters displayed for the duration of the conference has become a standard of the ISMB and ECCB conference series, and an extensive commercial exhibition showcases the latest bioinformatics publications, software, hardware and services available on the market today. The main conference is preceded by 2 days of Special Interest Group (SIG) and Satellite meetings running in parallel to the fifth Student Council Symposium on 27 June, and in parallel to Tutorials on 28 June. All scientific sessions take place at the Stockholmsmässan/Stockholm International Fairs conference and exposition facility.
Contact: bj@iscb.org
doi:10.1093/bioinformatics/btp280
PMCID: PMC2687994  PMID: 19447790
6.  The usefulness of monographic proceedings. 
Librarians have often questioned the usefulness of the proceedings of biomedical meetings. Because articles in proceedings are similar to journal articles, the usefulness of the two were compared. Thirty-two monographic cardiovascular proceedings were compared to thirty-five cardiovascular journals, all published in 1978. Citations to the articles in these samples were counted for the years 1978, 1979, and 1980, and an impact factor was calculated for each proceedings and journal. The mean impact factor of the journals (3.86) was significantly higher than the mean impact factor of the proceedings (0.98, p less than .001). A short delay in publication of a proceedings was not associated with a higher impact factor. There were no differences in impact factors between U.S. and non-U.S. meeting sites. Proceedings of "hot" topics were not associated with higher impact factors, and multiple-index coverage of proceedings was only weakly associated (tau = 0.27) with higher impact factors. While camera-ready proceedings had a significantly higher mean impact factor (2.37) than typeset proceedings (0.66, p less than .02), selection based on printing method is not recommended. It is concluded that most libraries can safely forego the purchase of monographic proceedings. If a library needs monographic proceedings, it should purchase only those recommended by subject specialists.
PMCID: PMC227229  PMID: 3370373
7.  Pseudoaneurysm Formation After Medtronic Freestyle Porcine Aortic Bioprosthesis Implantation: A Word of Caution 
The Annals of thoracic surgery  2014;98(6):2061-2067.
Background
A growing literature describes aneurysmal deterioration after implantation of the stentless porcine aortic Medtronic Freestyle bioprosthesis (MFB; Medtronic Inc, Minneapolis, MN), with some suggesting inadequate tissue fixation with immune response as a cause. However, disjointed reports make the significance of these findings difficult to interpret. We address this concern by aggregating available data.
Methods
We reviewed institutional data, the Food and Drug Administration’s Manufacturer and User Facility Device Experience registry, and the medical literature for mention of aneurysm or pseudoaneurysm after MFB. Case details were aggregated, and the rate of aneurysmal deterioration was estimated. Immunohistopathologic examination of institutional explanted specimens was performed to elucidate a cause.
Results
We found 42 cases of aneurysmal deterioration with adequate detail for analysis; all occurred with full root replacement and valve sizes ranging from 23 to 29 mm. The rate of aneurysmal deterioration considering all data sources was 1.1% (9 of 851; 95% confidence interval, 0.5% to 2.0%) vs 4.7% (4 of 86; 95% confidence interval, 1.3% to 11.5%) at our institution, where yearly surveillance imaging is performed. Rate of aneurysmal deterioration appeared constant until 5 years after the operation; however, events are reported out to 10 years. Consistent with previous reports, histopathology demonstrated an immune cell infiltrate in areas of MFB wall breakdown.
Conclusions
Aneurysmal deterioration is an increasingly described complication of MFB implantation as a full root, with an incidence as high as 4.7%. Given the observed immune reaction and lack of occurrence in smaller (19-mm and 21-mm) valve sizes, inadequate pressure fixation of larger valves is a potential etiology. Patients with MFB require annual surveillance imaging, and consideration of this complication should factor into preoperative decision making because treatment mandates redo root replacement, which may not be feasible in high-risk patients.
doi:10.1016/j.athoracsur.2014.06.062
PMCID: PMC4336162  PMID: 25301369
8.  Health sciences library building projects: 1995 survey. 
The Medical Library Association's fifth annual survey of recent health sciences library building projects identified twenty-five libraries planning, expanding, or constructing new library facilities. None of the fifteen new library projects are free standing structures; however, several occupy a major portion of the project space. Ten projects involve renovation of or addition to existing space. Information regarding size, cost of project, type of construction, completion date, and other factual data was provided for twelve projects. The remaining identified projects are in pre-design or early-design stages, or are awaiting funding approval. Library building projects for three hospital libraries, three academic medical libraries, and an association library are described. Each illustrates how considerations of economics and technology are changing the traditional library model from a centrally stored information depository housing a wide range of information under one roof where users come to the information, into an electronic model gradually shifting from investment in the physical presence of resources to investment in creating work space for creditible information specialists who help in-house and distanced users to obtain information electronically from any place and at any time. This new model includes a highly skilled library team to manage, filter, and package the information to users trained by these resident experts.
Images
PMCID: PMC226153  PMID: 8883981
9.  A prospective, non-randomized comparison of SAPIEN XT and CoreValve implantation in two sequential cohorts of patients with severe aortic stenosis 
Objectives: Few data is available comparing Edwards SAPIEN XT - SXT (Edwards Lifesciences, Irvine, California) with Medtronic CoreValve - CoV (Medtronic Inc., Minneapolis, Minnesota) in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). Methods: We selected consecutive patients undergoing transfemoral TAVR with SXT or CoV at our Institution. Main outcomes were Valve Academic Research Consortium (VARC)-combined safety endpoints. Results: A total of 100 patients (SXT, n=50 versus CoV, n=50) were analyzed. Both SXT and CoV showed good device success rates (98% versus 90%, p=0.20). SXT versus CoV reduced the occurrence of paravalvular regurgitation after TAVR (26% versus 90%, p<0.0001) though not affecting the rate of moderate/severe regurgitation (p=0.20). SXT versus CoV required less frequently a permanent pacemaker after TAVR (8% versus 38%, p<0.0001). In-hospital major vascular complications (8% versus 4%, p>0.99), life-threatening bleedings (2% versus 4%, p>0.99), stroke (4% versus 6%, p>0.99) and death (6% versus 2%, p>0.99) did not differ between SXT and CoV. However, safety endpoints favored SXT (17% versus 34.6%, p=0.01), due to a numerically higher incidence of ischemic stroke and Acute Kidney Injury Stage 3 after CoV. At multivariate analysis, TAVR with SXT (odds ratio=0.21, 95% confidence intervals [0.05-0.84], p=0.03) was predictive of fewer adverse events. Conclusions: Transcatheter valve implantation with Edwards SAPIEN XT was associated with lower VARC-combined safety endpoints as compared with Medtronic CoreValve. More extensive cohorts are needed to confirm these results.
PMCID: PMC4082233  PMID: 25006536
Aortic valve stenosis; TAVR; SAPIEN XT; CoreValve
10.  Estimated Kidney Function Based on Serum Cystatin C and Risk of Subsequent Coronary Artery Calcium in Young and Middle-aged Adults With Preserved Kidney Function: Results From the CARDIA Study 
American Journal of Epidemiology  2013;178(3):410-417.
Whether kidney dysfunction is associated with coronary artery calcium (CAC) in young and middle-aged adults who have a cystatin C–derived estimated glomerular filtration rate (eGFRcys) greater than 60 mL/min/1.73 m2 is unknown. In the Coronary Artery Risk Development in Young Adults (CARDIA) cohort (recruited in 1985 and 1986 in Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California), we examined 1) the association of eGFRcys at years 10 and 15 and detectable CAC over the subsequent 5 years and 2) the association of change in eGFRcys and subsequent CAC, comparing those with stable eGFRcys to those whose eGFRcys increased (>3% annually over 5 years), declined moderately (3%–5%), or declined rapidly (>5%). Generalized estimating equation Poisson models were used, with adjustment for age, sex, race, educational level, income, family history of coronary artery disease, diabetes, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and tobacco use. Among 3,070 participants (mean age 35.6 (standard deviation, 4.1) years and mean eGFRcys 106.7 (standard deviation, 18.5) mL/min/1.73 m2), 529 had detectable CAC. Baseline eGFRcys was not associated with CAC. Moderate eGFRcys decline was associated with a 33% greater relative risk of subsequent CAC (95% confidence interval: 5, 68; P = 0.02), whereas rapid decline was associated with a 51% higher relative risk (95% confidence interval: 10, 208; P = 0.01) in adjusted models. In conclusion, among young and middle-aged adults with eGFRcys greater than 60 mL/min/1.73 m2, annual decline in eGFRcys is an independent risk factor for subsequent CAC.
doi:10.1093/aje/kws581
PMCID: PMC3816347  PMID: 23813702
calcification; cardiovascular diseases; chronic kidney insufficiency; coronary arteries; coronary disease; cystatin C; glomerular filtration rate; kidney
11.  Relation of Length of Hospital Stay in Acute Myocardial Infarction to Post-Discharge Mortality 
The American journal of cardiology  2008;101(4):428-434.
Length of hospital stay (LOS) following acute myocardial infarction (AMI) has steadily decreased due both to improved treatments and cost considerations. Early discharge may adversely affect some patients who might benefit from extended monitoring. The Minnesota Heart Survey is a population-based study of AMI in acute-care hospitals in the Minneapolis-St. Paul metropolitan area. Medical records were abstracted on a random sample of patients hospitalized with AMI in 1985, 1990, 1995, and 2001. Case fatality rates, adjusted for age and gender, were identified using mortality data from the index hospitalization and Minnesota death certificates. 4940 patients with validated AMI were identified from the combined 1985 (n=1306), 1990 (n=1550), 1995 (n=1087), and 2001 (n=515) surveys. The median LOS were 9, 8, 6, and 4 days, respectively. Patients hospitalized ≤4 days formed an increasing proportion of the population increasing from 11% (1985) to 58%(2001). In-hospital case fatality declined from 1985 to 2001 (11.6% to 5.4%, p<0.0001 for trend). There was a significant decline in both 1 month (3.3% to 2.4%, p=0.002 for trend) and 6-month (8.9% to 5.4%, p<0.0001) post-discharge mortality from 1985 to 2001. In conclusion, the progressive and substantial reduction in hospital LOS following AMI in the past 2 decades has not been associated with increased post-discharge mortality. These reductions in LOS are associated with increasing use of effective therapies.
doi:10.1016/j.amjcard.2007.09.090
PMCID: PMC2730215  PMID: 18312752
acute myocardial infarction; length of stay; epidemiology
12.  Correlation of Specific Amyloid-β Oligomers With Tau in Cerebrospinal Fluid From Cognitively Normal Older Adults 
JAMA neurology  2013;70(5):594-599.
Objective
To investigate two specific amyloid-β (Aβ) oligomers, Aβ trimers and Aβ*56, in human cerebrospinal fluid (CSF), evaluate the effects of aging and Alzheimer's disease (AD), and obtain support for the hypothesis that they may be pathogenic by determining their relationships to CSF tau.
Design
A CSF sampling study.
Setting
The University of Minnesota Medical School in Minneapolis, Minnesota, and the Salhgrenska University Hospital, Sweden.
Participants
Older adults with mild cognitive impairment or Alzheimer's disease (Impaired), age-matched cognitively intact controls (Unimpaired), and younger, normal controls.
Main outcome measures
Measurements of CSF Aβ trimers, Aβ*56, Aβ1-42, total tau (T-tau), and phospho-tau (ptau-181).
Results
We observed that Aβ trimers and Aβ*56 levels increased with age, and within the Unimpaired group were elevated in subjects with T-tau/Aβ1-42 ratios above a cutoff that distinguished the Unimpaired group from AD subjects. In the Unimpaired group, T-tau and ptau-181 were found to correlate strongly with Aβ trimers and Aβ*56 (r > 0.63), but not with Aβ(1-42) (-0.10 < r < -0.01). The strong correlations were found to be attenuated in the Impaired group.
Conclusions
In cognitively intact older adults CSF Aβ trimers and Aβ*56 are elevated in individuals at risk for AD, and show stronger relationships with tau than does Aβ1-42, a surrogate for amyloid deposition. These data support the hypothesis that Aβ trimers or Aβ*56 are pathogenic in preclinical AD. However, the attenuation of these associations in symptomatic subjects suggests an uncoupling between the Aβ oligomers and tau in later stages of AD.
doi:10.1001/jamaneurol.2013.48
PMCID: PMC3725752  PMID: 23479202
13.  Staphylococcal Toxic Shock Syndrome 2000–2006: Epidemiology, Clinical Features, and Molecular Characteristics 
PLoS ONE  2011;6(8):e22997.
Introduction
Circulating strains of Staphylococcus aureus (SA) have changed in the last 30 years including the emergence of community-associated methicillin-resistant SA (MRSA). A report suggested staphylococcal toxic shock syndrome (TSS) was increasing over 2000–2003. The last population-based assessment of TSS was 1986.
Methods
Population-based active surveillance for TSS meeting the CDC definition using ICD-9 codes was conducted in the Minneapolis-St. Paul area (population 2,642,056) from 2000–2006. Medical records of potential cases were reviewed for case criteria, antimicrobial susceptibility, risk factors, and outcome. Superantigen PCR testing and PFGE were performed on available isolates from probable and confirmed cases.
Results
Of 7,491 hospitalizations that received one of the ICD-9 study codes, 61 TSS cases (33 menstrual, 28 non-menstrual) were identified. The average annual incidence per 100,000 of all, menstrual, and non-menstrual TSS was 0.52 (95% CI, 0.32–0.77), 0.69 (0.39–1.16), and 0.32 (0.12–0.67), respectively. Women 13–24 years had the highest incidence at 1.41 (0.63–2.61). No increase in incidence was observed from 2000–2006. MRSA was isolated in 1 menstrual and 3 non-menstrual cases (7% of TSS cases); 1 isolate was USA400. The superantigen gene tst-1 was identified in 20 (80%) of isolates and was more common in menstrual compared to non-menstrual isolates (89% vs. 50%, p = 0.07). Superantigen genes sea, seb and sec were found more frequently among non-menstrual compared to menstrual isolates [100% vs 25% (p = 0.4), 60% vs 0% (p<0.01), and 25% vs 13% (p = 0.5), respectively].
Discussion
TSS incidence remained stable across our surveillance period of 2000–2006 and compared to past population-based estimates in the 1980s. MRSA accounted for a small percentage of TSS cases. tst-1 continues to be the superantigen associated with the majority of menstrual cases. The CDC case definition identifies the most severe cases and has been consistently used but likely results in a substantial underestimation of the total TSS disease burden.
doi:10.1371/journal.pone.0022997
PMCID: PMC3157910  PMID: 21860665
14.  Incidence and Clinical Characteristics of Epiretinal Membranes in Children 
Archives of ophthalmology  2008;126(5):632-636.
Objective
To describe the incidence and clinical characteristics of epiretinal membranes in children.
Methods
The medical records of all pediatric (< 19 years of age) patients diagnosed with an epiretinal membrane from January 1, 1976, through December 31, 2005, at Olmsted Medical Group and Mayo Clinic were retrospectively reviewed. Incidence and clinical findings of childhood epiretinal membranes were obtained.
Results
Five of the 44 total patients were diagnosed as residents of Olmsted County, Minnesota, yielding an annual age- and gender-adjusted incidence of 0.54 per 100,000 patients, or 1 in 20,896 < 19 years of age. The mean age at diagnosis of the study patients was 12.4 years (range, 4 months to 18 years) with a preponderance of boys (70.5%). The presenting visual acuity in the affected eye was ≤ 20/60 in 22 (50%), while ten (22.2%) displayed strabismus. Common causes were trauma (38.6%), idiopathic (27.3%), and uveitis (20.5%). Eight (17.8%) of the 44 underwent pars plana vitrectomy with membrane peel, with at least 5 of the 8 experiencing an improvement in their postoperative visual acuity.
Conclusions
Epiretinal membranes are rare in children and are most frequently associated with a traumatic, idiopathic, or uveitic etiology. Those patients treated surgically generally have a favorable outcome.
doi:10.1001/archopht.126.5.632
PMCID: PMC2630717  PMID: 18474772
15.  The Incidence, Recurrence and Outcomes of Herpes Simplex Virus Eye Disease in Olmsted County, Minnesota, 1976 through 2007: The Impact of Oral Antiviral Prophylaxis 
Archives of ophthalmology  2010;128(9):1178-1183.
Objective
To provide an estimate of the incidence of herpes simplex virus (HSV) eye disease in a community-based cohort, and to investigate the impact of prophylactic oral antiviral therapy on HSV recurrences and outcomes.
Methods
All Olmsted County, Minnesota residents diagnosed with ocular HSV from 1976 through 2007 were retrospectively reviewed. The frequency of recurrences and adverse outcomes, such as vision loss or need for surgery, were compared between untreated patients and those treated prophylactically with oral antiviral medication.
Results
394 patients with ocular HSV were identified, yielding an annual incidence of new cases of 11.8 (95% C.I.: 10.6 to 13.0) per 100,000 population. No trends in incidence or adverse outcomes were identified over the 32 year period. Oral antiviral therapy was prescribed in 175 patients. Patients were 9.4 (95% C.I.: 5.0 to 17.9) times more likely to have a recurrence of epithelial keratitis, 8.4 (95% C.I.: 5.2 to 13.7) times more likely to have a recurrence of stromal keratitis, and 34.5 (95% C.I.: 10.8 to 111.1) times more likely to have a recurrence of blepharitis or conjunctivitis if not being treated prophylactically at the time of the recurrence. Twenty patients experienced adverse outcomes, and 17 (85%) were not being treated with oral antiviral medications immediately preceding the adverse event.
Conclusions
Oral antiviral prophylaxis was associated with a decreased risk of recurrence of epithelial keratitis, stromal keratitis, conjunctivitis and blepharitis due to HSV. Patients with adverse outcomes due to ocular HSV were usually not being treated with oral antiviral prophylaxis.
doi:10.1001/archophthalmol.2010.187
PMCID: PMC3103769  PMID: 20837803
16.  Evaluating various areas of process improvement in an effort to improve clinical research: Discussions from the 2012 Clinical Translational Science Award (CTSA) Clinical Research Management Workshop 
Emphasis has been placed on assessing the efficiency of clinical and translational research as part of the National Institutes of Health (NIH) goal to “improve human health”. Improvements identified and implemented by individual organizations cannot address the research infrastructure needs of all clinical and translational research conducted. NIH’s National Center for Advancing Translational Sciences (NCATS) has brought together 61 Clinical and Translational Science Award (CTSA) sites creating a virtual national laboratory that reflects the diversity and breadth of academic medical centers to collectively improve clinical and translational science. The annual Clinical Research Management workshop is organized by the CTSA consortium with participation from CTSA awardees, NIH, and others with an interest in clinical research management. The primary objective of the workshop is to disseminate information that improves clinical research management although the specific objectives of each workshop evolve within the consortium. The fifth annual workshop entitled “Learning by doing; applying evidence-based tools to re-engineer clinical research management” took place in June 2012. The primary objective of the 2012 workshop was to utilize data to evaluate, modify, and improve clinical research management. This report provides a brief summary of the workshop proceedings and the major themes discussed among the participants.
doi:10.1111/cts.12051
PMCID: PMC3740438  PMID: 23919369
17.  Risk of a Second Primary Cancer after Non-melanoma Skin Cancer in White Men and Women: A Prospective Cohort Study 
PLoS Medicine  2013;10(4):e1001433.
Studies have suggested a positive association between history of non-melanoma skin cancer (NMSC) and risk of subsequent cancer at other sites. This prospective study found a modestly increased risk of subsequent malignancies among individuals with a history of NMSC, specifically breast and lung cancer in women and melanoma in both men and women.
Background
Previous studies suggest a positive association between history of non-melanoma skin cancer (NMSC) and risk of subsequent cancer at other sites. The purpose of this study is to prospectively examine the risk of primary cancer according to personal history of NMSC.
Methods and Findings
In two large US cohorts, the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS), we prospectively investigated this association in self-identified white men and women. In the HPFS, we followed 46,237 men from June 1986 to June 2008 (833,496 person-years). In the NHS, we followed 107,339 women from June 1984 to June 2008 (2,116,178 person-years). We documented 29,447 incident cancer cases other than NMSC. Cox proportional hazard models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). A personal history of NMSC was significantly associated with a higher risk of other primary cancers excluding melanoma in men (RR = 1.11; 95% CI 1.05–1.18), and in women (RR = 1.20; 95% CI 1.15–1.25). Age-standardized absolute risk (AR) was 176 in men and 182 in women per 100,000 person-years. For individual cancer sites, after the Bonferroni correction for multiple comparisons (n = 28), in men, a personal history of NMSC was significantly associated with an increased risk of melanoma (RR = 1.99, AR = 116 per 100,000 person-years). In women, a personal history of NMSC was significantly associated with an increased risk of breast (RR = 1.19, AR = 87 per 100,000 person-years), lung (RR = 1.32, AR = 22 per 100,000 person-years), and melanoma (RR = 2.58, AR = 79 per 100,000 person-years).
Conclusion
This prospective study found a modestly increased risk of subsequent malignancies among individuals with a history of NMSC, specifically breast and lung cancer in women and melanoma in both men and women.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In the United Kingdom and the United States, about one in three people develop cancer during their lifetime and, worldwide, cancer is responsible for 13% of all deaths. Primary cancer, which can develop anywhere in the body, occurs when a cell begins to divide uncontrollably because of alterations (mutations) in its genes. Additional mutations allow the malignancy to spread around the body (metastasize) and form secondary cancers. The mutations that initiate cancer can be triggered by exposure to carcinogens such as cigarette smoke (lung cancer) or the ultraviolet (UV) radiation in sunlight (skin cancers). Other risk factors for the development of cancer include an unhealthy diet, physical inactivity, and alcohol use. In the United States, the most common cancer is non-melanoma skin cancer (NMSC). Although more than 2 million new cases of NMSC occur each year, fewer than 1,000 people die annually in the United States from the condition because the two types of NMSC—basal cell carcinoma and squamous cell carcinoma—rarely metastasize and can usually be treated by surgically removing the tumor.
Why Was This Study Done?
Some studies have suggested that people who have had NMSC have a higher risk of developing primary cancer at other sites than people who have not had NMSC. Such a situation could arise if exposure to certain carcinogens initiates both NMSC and other cancers or if NMSC shares a molecular mechanism with other cancers such as a deficiency in the DNA repair mechanisms that normally remove mutations. If people with a history of NMSC are at a greater risk of developing further cancers, a specific surveillance program for such people might help to catch subsequent cancers early when they can be successfully treated. In this prospective cohort study, the researchers examine the risk of primary cancer according to personal history of NMSC in two large US cohorts (groups)—the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS). The HPFS, which enrolled 51,529 male health professionals in 1986, and the NHS, which enrolled 121,700 female nurses in 1976, were both designed to investigate associations between nutritional factors and the incidence of serious illnesses. Study participants completed a baseline questionnaire about their lifestyle, diet and medical history. This information is updated biennially through follow-up questionnaires.
What Did the Researchers Do and Find?
The researchers identified 36,102 new cases of NMSC and 29,447 new cases of other primary cancers from 1984 in white NHS participants and from 1986 in white HPFS participants through 2008. They then used statistical models to investigate whether a personal history of NMSC was associated with a higher risk of subsequent primary cancers after accounting for other factors (confounders) that might affect cancer risk. A history of NMSC was significantly associated with an 11% higher risk of other primary cancers excluding melanoma (another type of skin cancer that, like NMSC, is linked to overexposure to UV light) in men and a 20% higher risk of other primary cancers excluding melanoma in women; a significant association is one that is unlikely to have happened by chance. The absolute risk of a primary cancer among men and women with a history of NMSC was 176 and 182 per 100,000 person-years, respectively. For individual cancer sites, after correction for multiple comparisons (when several conditions are compared in groups of people, statistically significant differences between the groups can occur by chance), a history of NMSC was significantly associated with an increased risk of breast and lung cancer in women and of melanoma in men and women.
What Do These Findings Mean?
These findings suggest that there is a modestly increased risk of subsequent malignancies among white individuals with a history of NMSC. Although the researchers adjusted for many confounding lifestyle factors, the observed association between NMSC and subsequent primary cancers may nevertheless be the result of residual confounding, so it is still difficult to be sure that there is a real biological association (due to, for example, a deficiency in DNA repair) between NMSC and subsequent primary cancers. Because of this and other study limitations, the findings reported here should be interpreted cautiously and do not suggest that individuals who have had NMSC should undergo increased cancer surveillance. These findings do, however, support the need for continued investigation of the apparent relationship between NMSC and subsequent cancers.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001433.
The US National Cancer Institute provides information on all aspects of cancer and has detailed information about non-melanoma skin cancer for patients and professionals (in English and Spanish)
The non-profit organization American Cancer Society provides information on cancer and how it develops and specific information on skin cancer (in several languages); its website includes personal stories about cancer
The UK National Health Service Choices website includes an introduction to cancer and a page on non-melanoma skin cancer
The non-profit organization Cancer Research UK provides basic information about cancer and detailed information on non-melanoma skin cancer
doi:10.1371/journal.pmed.1001433
PMCID: PMC3635863  PMID: 23630459
18.  Maintaining a High Physical Activity Level Over 20 Years and Weight Gain 
JAMA : the journal of the American Medical Association  2010;304(23):10.1001/jama.2010.1843.
Context
Data supporting physical activity guidelines to prevent long-term weight gain are sparse, particularly during the period when the highest risk of weight gain occurs.
Objective
To evaluate the relationship between habitual activity levels and changes in body mass index (BMI) and waist circumference over 20 years.
Design, Setting, and Participants
The Coronary Artery Risk Development in Young Adults (CARDIA) study is a prospective longitudinal study with 20 years of follow-up, 1985-86 to 2005-06. Habitual activity was defined as maintaining high, moderate, and low activity levels based on sex-specific tertiles of activity scores at baseline. Participants comprised a population-based multi-center cohort (Chicago, Illinois; Birmingham, Alabama; Minneapolis, Minnesota; and Oakland, California) of 3554 men and women aged 18 to 30 years at baseline.
Main Outcome Measures
Average annual changes in BMI and waist circumference
Results
Over 20 years, maintaining high levels of activity was associated with smaller gains in BMI and waist circumference compared with low activity levels after adjustment for race, baseline BMI, age, education, cigarette smoking status, alcohol use, and energy intake. Men maintaining high activity gained 2.6 fewer kilograms (+ 0.15 BMI units per year; 95 % confidence interval [CI] 0.11-0.18 vs +0.20 in the lower activity group; 95% CI, 0.17-0.23) and women maintaining higher activity gained 6.1 fewer kilograms (+0.17 BMI units per year; 95 % CI, 0.12-0.21 vs. +0.30 in the lower activity group; 95 % CI, 0.25-0.34). Men maintaining high activity gained 3.1 fewer centimeters in waist circumference (+0.52 cm per year; 95 % CI, 0.43-0.61 cm vs 0.67 cm in the lower activity group; 95 % CI, 0.60-0.75) and women maintaining higher activity gained 3.8 fewer centimeters (+0.49 cm per year; 95 % CI, 0.39-0.58 vs 0.67 cm in the lower activity group; 95 % CI, 0.60-0.75).
Conclusion
Maintaining high activity levels through young adulthood may lessen weight gain as young adults transition to middle age, particularly in women.
doi:10.1001/jama.2010.1843
PMCID: PMC3864556  PMID: 21156948
19.  Fractures of the Femur. End Results* 
Melvin Starkey Henderson was born in St. Paul, Minnesota and received his early schooling there and in Winnipeg, Manitoba [4]. He received his undergraduate and medical degrees from the University of Toronto. He then interned in the City and County Hospital in his home town of St. Paul, and in 1907 went to work as an assistant with the founders of the recently formed Mayo Clinic, William James and Charles Horace Mayo. To further his training and evidently at the suggestion of the Mayo brothers, in 1911 Dr. Henderson went abroad to work under Sir Robert Jones in Liverpool and then Sir Harold Stiles in Edinburgh. He returned to organize and direct the section of orthopaedic surgery at the Mayo Clinic and spent his entire professional career there.
Dr. Henderson was involved in many national and international organizations, and was a founder and first President of the American Board of Orthopaedic Surgeons when it was established at the Kahler Hotel in Rochester, Minnesota, on June 5, 1934, after several previous organizational meetings [5]. Wickstrom [5], describing the organization of the Board, commented, “After all, in the opinion of the East coast establishment, Dr. Henderson (who was born in St. Paul, was educated in Canada, and had his beginning with the Mayo brothers as a clinical assistant riding a bicycle around Rochester, making house calls on the Mayo brothers’ patients) was a mere upstart.” However, at the time Dr. Henderson was 50 years old and had been President of the American Orthopaedic Association and Clinical Orthopaedic Society, as well as prominent in the American Medical Association and other organizations. Dr. Henderson was one of three of the first 15 AAOS Presidents (the other two being Drs. Philip D. Wilson and John C. Wilson, Sr.) who had a son who succeeded him as President. He was greatly respected for his organizational abilities, particularly at the Board, whose objectives were uncertain in the beginning and required sage guidance [5].
We reproduce here an article in which Dr. Henderson reviewed 222 consecutive cases of femur fractures, 165 of which had been referred late because of complications of fractures treated elsewhere (clearly, by 1921, the Mayo Clinic was a referral source for others) [2]. Followup could not have been easy at a time when patients often came from a distance and travel was difficult, but it was described when available and in 40 of the 57 recent fractures, Henderson reported 87.5% were “cured.” Of the 165 old fractures, he was able to trace 143 (87%), a remarkable figure even today. He reported 90% of the femoral neck fractures were cured by various sorts of nonsurgical (6 patients) or surgical reconstructive (39 patients) means; 85% of the femoral shaft fractures were cured by either nonoperative (29 patients) or operative (69 patients) means. While he did not use the sort of outcomes we use today (the earliest orthopaedic outcome instruments were not introduced for four more decades: by Carroll B. Larson in 1963 [3] and William H. Harris in 1969 [1]), we can only presume Henderson meant union was achieved when patients were “cured” since nonunion or malunion would not have likely produced good results. That being the case, his rate of union was remarkable and would be enviable today in these sometimes difficult situations, attesting to his understanding of the individual situations and his skills. Melvin S. Henderson, MD is shown. Photograph is reproduced with permission and ©American Academy of Orthopaedic Surgeons. Fifty Years of Progress, 1983.
References
Harris WH. Traumatic arthritis of the hip after dislocation and acetabular fractures: treatment by mold arthroplasty: an end-result study using a new method of result evaluation. J Bone Joint Surg Am. 1969;51:737–755.Henderson MS. Fractures of the femur: end results. J Bone Joint Surg Am. 1921;3:520–528.Larson CB. Rating scale for hip disabilities. Clin Orthop Relat Res. 1963;31:85–93.Mostofi SB. Who's Who in Orthopedics. London, UK: Springer; 2005.Wickstrom JK. Fifty years of the American Board of Orthopaedic Surgery: 1934. Clin Orthop Relat Res. 1990;257:3–10.
doi:10.1007/s11999-007-0033-2
PMCID: PMC2505283  PMID: 18196372
20.  The Incidence of Central Retinal Artery Occlusion in Olmsted County, Minnesota 
American Journal of Ophthalmology  2011;152(5):820-3.e2.
Purpose
To determine the incidence of central retinal artery occlusion in Olmsted County, Minnesota.
Design
Retrospective chart review.
Methods
Medical records of all patients living in Olmsted County, MN between 1976 and 2005 diagnosed with central retinal artery occlusion cases were identified using the Rochester Epidemiology Project medical records linkage system.
Results
Forty-three cases were identified for an unadjusted annual incidence in females of 1.02 per 100,000 and in males 1.67 per 100,000 with a combined incidence of 1.33. Incidence rates were also age- and/or sex-adjusted to the 2000 census figures for the U.S. white population using direct standardization. Age adjusted annual incidence per 100,000 for females was 1.15 (95% confidence interval [CI], 0.60 – 1.71), for males was 2.78 (95% CI, 1.69 – 3.86), and combined was 1.87 (95% CI, 1.31 – 2.43). When adjusted for age and sex, the incidence was 1.90 per 100,000 (95% CI, 1.33 – 2.47).
Conclusion
Central retinal artery occlusion is a rare event. The incidence is 1.3 per 100,000 in Olmsted County, Minnesota, or 1.90 per 100,000 when age- and sex-adjusted for the United States white population.
doi:10.1016/j.ajo.2011.05.005
PMCID: PMC3326414  PMID: 21794842
21.  Trends in Cardiovascular Risk Factor Levels in the Minnesota Heart Survey (1980–2002) as Compared With the National Health and Nutrition Examination Survey (1976–2002): A Partial Explanation for Minnesota's Low Cardiovascular Disease Mortality? 
American Journal of Epidemiology  2011;173(5):526-538.
The authors compared trends in and levels of coronary heart disease (CHD) risk factors between the Minneapolis-St. Paul, Minnesota, metropolitan area (Twin Cities) and the entire US population to help explain the ongoing decline in US CHD mortality rates. The study populations for risk factors were adults aged 25–74 years enrolled in 2 population-based surveillance studies: the Minnesota Heart Survey (MHS) in 1980–1982, 1985–1987, 1990–1992, 1995–1997, and 2000–2002 and the National Health and Nutrition Examination Survey (NHANES) in 1976–1980, 1988–1994, 1999–2000, and 2001–2002. The authors found a continuous decline in CHD mortality rates in the Twin Cities and nationally between 1980 and 2000. Similar decreasing rates of change in risk factors across survey years, parallel to the CHD mortality rate decline, were observed in MHS and in NHANES. Adults in MHS had generally lower levels of CHD risk factors than NHANES adults, consistent with the CHD mortality rate difference. Approximately 47% of women and 44% of men in MHS had no elevated CHD risk factors, including smoking, hypertension, high cholesterol, and obesity, versus 36% of women and 34% of men in NHANES. The better CHD risk factor profile in the Twin Cities may partly explain the lower CHD death rate there.
doi:10.1093/aje/kwq367
PMCID: PMC3105433  PMID: 21273396
cardiovascular diseases; coronary disease; Minnesota; population surveillance; risk factors
22.  A report of the Sixth Annual Meeting of the International Society for the Prevention of Tobacco Induced Diseases (ISPTID) 
Tobacco Induced Diseases  2008;4(1):11.
The Sixth meeting of the International Society for the Prevention of Tobacco Induced Diseases (ISPTiD) was held in Little Rock, Arkansas on November 2–4, 2007 and has brought together 140 participants, scientists and experts in this specialized field from 30 countries across the World. The central theme of the conference was the "Translational Approaches to the Prevention of Tobacco Induced Diseases". Discussions held during the three days meeting's sessions (including poster session and platform discussion) promoted a better understanding of the connection between tobacco use and associated medical and health consequences. The Sixth Annual meeting of ISPTiD served as another successful step toward decrease in the huge sociological and economical burden that the entire World is facing with this addiction. The proceedings of the meeting were published in the conference booklet, the ISPTiD global web site and Cancer Database abstract web site. Funds generated from this meeting helped in part to establish the society's Journal "Tobacco Induced Diseases "into the major scientific journal index PubMed database and BioMed Central. The meeting set the tone for next the Annual meeting in Kyoto, Japan for the year 2008 with the theme "Tobacco free future".
doi:10.1186/1617-9625-4-11
PMCID: PMC2614959  PMID: 19091067
23.  Observations of cancer incidence surveillance in Duluth, Minnesota. 
In 1973, amphibole asbestos fibers were discovered in the municipal water supply of Duluth, Minnesota. The entire city population of approximately 100,000 was exposed from the late 1950s through 1976 at levels of 1-65 million fibers per liter of water. Because of previous epidemiologic studies that linked mesothelioma, lung and gastrointestinal cancers to occupational exposure to asbestos, surveillance of cancer incidence in residents of Duluth was initiated to determine the health effect from ingestion of asbestos. The methodology of the Third National Cancer Survey (TNCS) and SEER Program was used. Duluth 1969-1971 rates were compared with TNCS rates for the cities of Minneapolis and St. Paul during 1969-1971; Duluth rates during 1974-1976 are compared with Duluth 1969-1971; Duluth rates during 1979-1980 are compared with Duluth 1969-1971 and with Iowa SEER; and a table of the occurrence of malignant mesothelioma is presented. Statistically significant excesses are observed in several primary sites in Duluth residents. However, lung cancer in Duluth females is the only primary site considered also of biological significance. The mesothelioma incidence rate is no more than expected. This paper also describes the problems of long-term surveillance of exposed populations considered at risk of environment cancer, the need for improved study methodologies and the use of federal records for follow up of exposed individuals.
PMCID: PMC1569088  PMID: 6662096
24.  Management of single brain metastasis: a practice guideline 
Current Oncology  2007;14(4):131-143.
Questions
Should patients with confirmed single brain metastasis undergo surgical resection?
Should patients with single brain metastasis undergoing surgical resection receive adjuvant whole-brain radiation therapy (wbrt)?
What is the role of stereotactic radiosurgery (srs) in the management of patients with single brain metastasis?
Perspectives
Approximately 15%–30% of patients with cancer will develop cerebral metastases over the course of their disease. Patients identified as having single brain metastasis generally undergo more aggressive treatment than do those with multiple metastases; however, in the province of Ontario, management of patients with single brain metastasis varies. Given that conflicting evidence has been reported, the Neuro-oncology Disease Site Group (dsg) of the Cancer Care Ontario Program in Evidence-based Care felt that a systematic review of the evidence and a practice guideline were warranted.
Outcomes
Outcomes of interest were survival, local control of disease, quality of life, and adverse effects.
Methodology
The medline, cancerlit, embase, and Cochrane Library databases and abstracts published in the proceedings of the annual meetings of the American Society of Clinical Oncology (1997–2005) and American Society for Therapeutic Radiology and Oncology (1998–2004) were systematically searched for relevant evidence. The review included fully published reports or abstracts of randomized controlled trials (rcts), nonrandomized prospective studies, and retrospective studies.
The present systematic review and practice guideline has been reviewed and approved by the Neuro-oncology dsg, which comprises medical and radiation oncologists, surgeons, neurologists, a nurse, and a patient representative. External review by Ontario practitioners was obtained through an electronic survey. Final approval of the guideline report was obtained from the Report Approval Panel and the Neuro-oncology dsg.
Results
Quality of Evidence
The literature search found three rcts that compared surgical resection plus wbrt with wbrt alone. In addition, a Cochrane review, including a meta-analysis of published data from those three rcts, was obtained.
One rct compared surgical resection plus wbrt with surgical resection alone. One rct compared wbrt plus srs with wbrt alone. Evidence comparing srs with surgical resection or examining srs with or without wbrt was limited to prospective case series and retrospective studies.
Benefits
Two of three rcts reported a significant survival benefit for patients who underwent surgical resection as compared with those who received wbrt alone. Pooled results of the three rcts indicated no significant difference in survival or likelihood of dying from neurologic causes; however, significant heterogeneity was detected between the trials. The rct that compared surgical resection plus wbrt with surgical resection alone reported no significant difference in overall survival or length of functional independence; however, tumour recurrence at the site of the metastasis and anywhere in the brain was less frequent in patients who received wbrt as compared with patients in the observation group. In addition, patients who received wbrt were less likely to die from neurologic causes.
Results of the rct that compared wbrt plus srs with wbrt alone indicated a significant improvement in median survival in patients who received srs. No quality evidence compares the efficacy of srs with surgical resection or examines the question of whether patients who receive srs should also receive wbrt.
Harms
Pooled results of the three rcts that examined surgical resection indicated no significant difference in adverse effects between groups. Postoperative complications included respiratory problems, intracerebral hemorrhage, and infection. One rct reported no significant difference in adverse effects between patients who received wbrt plus srs and those who received wbrt alone.
Practice Guideline
Target Population
The recommendations that follow apply to adults with confirmed cancer and a single brain metastasis. This practice guideline does not apply to patients with metastatic lymphoma, small-cell lung cancer, germ-cell tumour, leukemia, or sarcoma.
Recommendations
Surgical excision should be considered for patients with good performance status, minimal or no evidence of extracranial disease, and a surgically accessible single brain metastasis amenable to complete excision. Because treatment in cases of single brain metastasis is considered palliative, invasive local treatments must be individualized. Patients with lesions requiring emergency decompression because of intracranial hypertension were excluded from the rcts, but should be considered candidates for surgery.
To reduce the risk of tumour recurrence for patients who have undergone resection of a single brain metastasis, postoperative wbrt should be considered. The optimal dose and fractionation schedule for wbrt is 3000 cGy in 10 fractions or 2000 cGy in 5 fractions.
As an alternative to surgical resection, wbrt followed by srs boost should be considered for patients with single brain metastasis. The evidence is insufficient to recommend srs alone as a single-modality therapy.
Qualifying Statements
No high-quality data are available regarding the choice of surgery versus radiosurgery for single brain metastasis. In general, the size and location of the metastasis determine the optimal approach.
The standard wbrt regimen for management of patients with single brain metastasis in the United States is 3000 cGy in 10 fractions, and this treatment is usually the standard arm in randomized studies of radiation in patients with brain metastases. Based solely on evidence, the understanding that no reason exists to choose 3000 cGy in 10 fractions over 2000 cGy in 5 fractions is correct; however, fraction size is believed to be important, and therefore 300 cGy daily (3000/10) is believed to be associated with fewer long-term neurocognitive effects than 400 cGy daily (2000/5) in the occasional long-term survivor. For that reason, many radiation oncologists in Ontario prefer 3000 cGy in 10 fractions. No data exist to either support or refute that preference; therefore, finding a resolution to this issue is not currently possible. The Neuro-oncology dsg will update the recommendations as new evidence becomes available.
PMCID: PMC1948870  PMID: 17710205
Brain metastasis; surgery; radiotherapy; radiosurgery; systematic review; practice guideline
25.  Arriving Safely and Avoiding a Puncture 
Texas Heart Institute Journal  2011;38(1):50-51.
The direct measurement of left ventricular pressure in the presence of a mechanical aortic valve is a technical challenge for the interventional cardiologist. Direct recording, which is rarely performed, becomes necessary when other imaging methods have failed to evaluate prosthetic valve stenosis or restrictive physiology. Left ventricular pressure has typically been measured after transseptal or direct left ventricular apical puncture.
In recent years, investigators have used the 0.014-in coronary Radi PressureWire™ (St. Jude Medical, Inc.; St. Paul, Minn) to cross the St. Jude bileaflet prosthetic aortic valve without the need for puncture. Although another bileaflet aortic valve, the ATS Open Pivot® (ATS Medical, Inc.; Minneapolis, Minn), has an overall design similar to that of the St. Jude valve, the ATS valve has an open-pivot hinge, which has the potential for wire entrapment.
Herein, we describe how we successfully measured left ventricular pressure by crossing an ATS Open Pivot prosthetic valve with a Radi PressureWire, in a 60-year-old man in whom pericardial constriction was suspected. The straightforward, uncomplicated procedure enabled confirmation of the diagnosis. We believe that further investigation of this technique is warranted.
PMCID: PMC3060743  PMID: 21423468
Angioplasty/instrumentation/methods; equipment design; heart catheterization/instrumentation/methods; heart valve prosthesis/adverse effects; heart ventricles/physiopathology; ventricular dysfunction, left/diagnosis; ventricular pressure

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