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Mayo Clinic

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Hip and spine strength effects of adding versus switching to teriparatide in postmenopausal women with osteoporosis treated with prior alendronate or raloxifene
Keaveny, Tony M. , Kopperdahl, David L. , Wermers, Robert A. , Wan, Xiaohai, Krohn, Kelly, Krege, John H. , Cosman, Felicia

Journal of Bone and Mineral Research | December 22, 2012 | Volume: 28 | Issue: 6 | Pages: 1328-1336

10.1002/jbmr.1853 | PMID 23281041 Get It

ABSTRACT Many postmenopausal women treated with teriparatide for osteoporosis have previously received antiresorptive therapy. In women treated with alendronate (ALN) or raloxifene (RLX), adding versus switching to teriparatide produced different responses in areal bone mineral density (aBMD) and biochemistry; the effects of these approaches on volumetric BMD (vBMD) and bone strength are unknown. In this study, postmenopausal women with osteoporosis receiving ALN 70 mg/week (n = 91) or RLX 60 mg/day (n = 77) for ≥18 months were randomly assigned to add or switch to teriparatide 20 µg/day. Quantitative computed tomography scans were performed at baseline, 6 months, and 18 months to assess changes in vBMD; strength was estimated by nonlinear finite element analysis. A statistical plan specifying analyses was approved before assessments were completed. At the spine, median vBMD and strength increased from baseline in all groups (13.2% to 17.5%, p < 0.01); there were no significant differences between the Add and Switch groups. In the RLX stratum, hip vBMD and strength increased at 6 and 18 months in the Add group but only at 18 months in the Switch group (Strength, Month 18: 2.7% Add group, p < 0.01 and 3.4% Switch group, p < 0.05). In the ALN stratum, hip vBMD increased in the Add but not in the Switch group (0.9% versus –0.5% at 6 months and 2.2% versus 0.0% at 18 months, both p ≤ 0.004 group difference). At 18 months, hip strength increased in the Add group (2.7%, p < 0.01) but not in the Switch group (0%); however, the difference between groups was not significant (p = 0.076). Adding or switching to teriparatide conferred similar benefits on spine strength in postmenopausal women with osteoporosis pretreated with ALN or RLX. Increases in hip strength were more variable. In RLX-treated women, strength increased more quickly in the Add group; in ALN-treated women, a significant increase in strength compared with baseline was seen only in the Add group.
Intrinsic microvasculature of the sciatic nerve in the rat
Zamir, M. , Twynstra, Jasna , Vercnocke, Andrew J. , Welch, Ian, Jorgensen, Steve M., Ritman, Erik L., Holdsworth, David W. , Shoemaker, J. Kevin , Jorgensen, Steven M., Shoemaker, J Kevin

Journal of the Peripheral Nervous System | December 22, 2012 | Volume: 17 | Issue: 4 | Pages: 377-384

10.1111/j.1529-8027.2012.00435.x | PMID 23279338 Get It

AbstractMicrovasculature associated with the sciatic nerve was examined using high‐resolution micro‐CT scanning in one group of rats and surgical exploration in another. The results indicate that blood supply to the sciatic nerve is an “open‐ended” system in which the vessels run longitudinally within the epineurium and connect with external vasculature primarily at junction points. Although the range of vasculature found extended down to 4–5 μ, only a few isolated vessels of this size were found, with no capillary “mesh” as such, possibly because of the close proximity of the intrinsic vessel to nerve fibers within the epineurium. While the study did not include direct measurements of flow or nerve function, the “open‐ended” pattern of vasculature found has important implications regarding the relationship between the two. Specifically, the nerve is less vulnerable to a severe or complete disruption in blood supply than it would be under a close‐ended system such as that of the heart or brain, where a severe disruption can occur with the obstruction of only a single vessel. Indeed, the pattern of vasculature found, subject to further study of vasculature at the capillary level, suggests that flow within the intrinsic vessels may be in either direction, depending on circumstances, somewhat like flow within the circle of Willis in the cerebral circulation.
Standard and saturation transrectal prostate biopsy techniques are equally accurate among prostate cancer active surveillance candidates
Linder, Brian J. , Frank, Igor, Umbreit, Eric , Shimko, Mark, Rangel, Laureano J. , Karnes, R. Jeffrey , Fernández, Nicolás , Linder, Brian J

International Journal of Urology | December 22, 2012 | Volume: 20 | Issue: 9 | Pages: 860-864

10.1111/iju.12061 | PMID 23278942 Get It

ObjectivesTo examine the ability of standard and saturation transrectal prostate biopsy techniques to predict appropriate candidates for active surveillance.MethodsBetween 2005 and 2007, 500 consecutive patients underwent transrectal ultrasound‐guided biopsy by a standard template (12 cores) or saturation template (≥18 cores, median 27 cores), with subsequent radical prostatectomy. Using the criteria of Gleason score ≤6, clinical stage T1 or T2a, prostate‐specific antigen <10 and ≤33% of cores involved, 218 patients were potential candidates for active surveillance. Pathology results from the prostatectomy specimens were used to determine the accuracy of each biopsy technique. Biochemical failure after prostatectomy was evaluated using logistic and Cox proportional hazards regression.ResultsA standard biopsy was carried out for 124 patients and saturation biopsy for 94 patients. There was no statistically significant difference between the groups in terms of median age (P = 0.14), preoperative prostate‐specific antigen (P = 0.52) and clinical stage (P = 0.23). Similar rates of Gleason score ≥7 at the time of radical prostatectomy were found, with 14% for standard biopsy and 15% for saturation biopsy (P = 0.70). Upstaging was shown in two standard biopsy patients (1.6%) and no saturation biopsy patients (P = 0.62). A multivariate analysis adjusting for prior prostate biopsy, preoperative prostate‐specific antigen and clinical stage showed no difference in the rate of upgrading based on biopsy technique (P = 0.26). During follow up, 5‐year biochemical failure‐free survival estimates were not significantly different (P = 0.11).ConclusionsIn men with prostate cancer, standard and saturation transrectal prostate biopsies techniques are equally predictive of candidates for active surveillance.
Interaction of adjuvant androgen deprivation therapy with patient comorbidity status on overall survival after radical prostatectomy for high‐risk prostate cancer
Linder, Brian J. , Boorjian, Stephen A. , Umbreit, Eric , Carlson, Rachel E. , Rangel, Laureano J. , Bergstralh, Eric J., Karnes, R. Jeffrey , Linder, Brian J

International Journal of Urology | December 22, 2012 | Volume: 20 | Issue: 8 | Pages: 798-805

10.1111/iju.12047 | PMID 23278850 Get It

BackgroundTo evaluate the impact of adjuvant hormonal therapy after radical prostatectomy on overall survival in high‐risk prostate cancer patients, stratified by comorbidity status.MethodsWe identified 1247 patients who underwent radical prostatectomy from 1988 to 2004 for high‐risk prostate cancer, as defined by National Comprehensive Cancer Network classification. Comorbidity status was stratified by Charlson Comorbidity Index as 0, 1 or >2, as well as by the presence or absence of cardiovascular disease. Overall survival was estimated by the Kaplan–Meier method, and compared within each comorbidity category/adjuvant hormonal therapy strata with the log–rank test.ResultsMedian patient age was 65 years, and the median postoperative follow up was 11.2 years. In total, 419 patients (34%) received adjuvant hormonal therapy. The distribution of Charlson Comorbidity Index was 0, 1 and ≥2 in 861 (69%), 244 (20%) and 142 (11%) patients, respectively. The 10‐year overall survival for patients who received adjuvant hormonal therapy versus those who did not was 75% versus 82% (P = 0.54) for patients with Charlson Comorbidity Index = 0, 72% versus 76% (P = 0.83) with Charlson Comorbidity Index = 1, and 70% versus 68% (P = 0.33) with Charlson Comorbidity Index ≥2. Meanwhile, 155 (12%) patients had cardiovascular disease, and the 10‐year overall survival for patients with cardiovascular disease who received adjuvant hormonal therapy was 72%, compared with 76% without adjuvant hormonal therapy (P = 0.97). On multivariate analysis, receipt of adjuvant hormonal therapy was not associated with non‐prostate cancer mortality (P = 0.24).ConclusionsAdjuvant hormonal therapy after radical prostatectomy for high‐risk prostate cancer does not increase non‐prostate cancer mortality, even among patients with multiple comorbidities. Additional studies are warranted to determine optimal multimodal treatment approach for high‐risk patients.
Evaluation of Fracture Resistance in Aqueous Environment of Four Restorative Systems for Posterior Applications. Part 1
Dhima, Matilda, Assad, Daniel, Volz, John E., An, Kai‐Nan, Berglund, Lawrence J., Carr, Alan B. , Salinas, Thomas

Journal of Prosthodontics | December 22, 2012 | Volume: 22 | Issue: 4 | Pages: 256-260

10.1111/j.1532-849x.2012.00948.x | PMID 23279080 Get It

AbstractPurposeThe goals of this study were to: (1) establish a range of the performance of four restorative systems for posterior single‐tooth crowns under single load to fracture submerged in an aqueous environment, (2) identify restorative system(s) of interest to be examined in the second study phase under sliding contact step‐stress fatigue as full‐contour anatomically appropriate single posterior tooth restoration(s), (3) establish a range for loading/testing for phase 2.Materials and MethodsForty specimens (n = 10/group) of 2 mm uniform thickness were tested. Group 1: monolithic lithium disilicate IPS e.max Press; group 2: IPS e.max ZirPress, 0.8 mm zirconia core with 1.2 mm pressed veneering porcelain; group 3: IPS e.max ZirPress, 0.4 mm zirconia core with 1.6 mm pressed veneering porcelain; group 4: IPS InLine PoM. Specimens were bonded to a block of polycast acrylic resin on a 30° sloped surface with resin cement. Specimens were axially single loaded to failure while submerged under water.ResultsThere was a statistically significant difference (p < 0.001) in failure load among the four restorative systems. Lithium disilicate showed a mean failure load similar to mean maximum posterior bite forces (743.1 ± 114.3 N). IPS e.max Zirpress with a 0.4 mm zirconia core exhibited the lowest mean failure load (371.4 ± 123.0 N).ConclusionFracture resistance of monolithic lithium disilicate in an aqueous environment is promising and requires second phase testing to evaluate the potential of various thicknesses appropriate for posterior single tooth applications. Doubling the IPS e.max Zirpress zirconia core from 0.4 mm to 0.8 mm increased the fracture resistance of this restorative system threefold.
Incidence and Time Trends of Herpes Zoster in Rheumatoid Arthritis: A Population‐Based Cohort Study
Veetil, Bharath Manu Akkara, Myasoedova, Elena , Matteson, Eric L. , Gabriel, Sherine E., Green, Abigail B., Crowson, Cynthia S. , Myasoedova, Elena

Arthritis Care & Research | December 22, 2012 | Volume: 65 | Issue: 6 | Pages: 854-861

10.1002/acr.21928 | PMID 23281295 Get It

ObjectiveTo determine the incidence, time trends, risk factors, and severity of herpes zoster in a population‐based cohort of patients with newly diagnosed rheumatoid arthritis (RA) compared to a group of individuals without RA from the same population.MethodsAll residents of Olmsted County, Minnesota fulfilling for the first time the 1987 American College of Rheumatology criteria for RA between January 1, 1980 and December 31, 2007 and a cohort of similar residents without RA were assembled and followed by retrospective chart review until death, migration, or December 31, 2008.ResultsThere was no difference in the presence of herpes zoster prior to the RA incidence/index date between the cohorts (P = 0.85). During followup, 84 patients with RA (rate 12.1 cases per 1,000 person‐years) and 44 subjects without RA (rate 5.4 cases per 1,000 person‐years) developed herpes zoster. Patients with RA were more likely to develop herpes zoster than those without RA (hazard ratio [HR] 2.4 [95% confidence interval (95% CI) 1.7–3.5]). Herpes zoster occurred more frequently in patients diagnosed with RA more recently (HR 1.06 per year [95% CI 1.02–1.10]). Erosive disease, previous joint surgery, and use of hydroxychloroquine and corticosteroids were significantly associated with the development of herpes zoster in RA. There was no apparent association of herpes zoster with the use of methotrexate or biologic agents. Complications of herpes zoster occurred at a similar rate in both cohorts.ConclusionThe incidence of herpes zoster is increased in RA and has risen in recent years. There also has been an increasing incidence of herpes zoster in more recent years in the general population. RA disease severity is associated with the development of herpes zoster.
Human Studies in the Pathophysiology of Migraine: Genetics and Functional Neuroimaging
Cutrer, F. Michael , Smith, Jonathan

Headache: The Journal of Head and Face Pain | December 21, 2012 | Volume: 53 | Issue: 2 | Pages: 401-412

10.1111/head.12024 | PMID 23278104 Get It

The expansion of technologies available for the study of migraine pathophysiology has evolved greatly over the last 15 years. Two areas of rapid progress are investigations focusing on the genetics of migraine and others utilizing novel functional neuroimaging techniques. Genetic studies are increasingly focusing on sporadic migraine and the utilization of unbiased searches of the human genome to identify novel variants associated with disease susceptibility. At the same time, neuroimaging studies have provided novel insights into the altered neuronal and network dynamics of the migrainous brain. These 2 parallel approaches provide complementary insights into the complexity and heterogeneity of migraine.
Natural orifice transluminal endoscopic surgery ( NOTES ): where are we going? A bibliometric assessment
Yakoubi, Rachid, White, Wesley M. , Gettman, Matthew T., Sio, Marco De , Quattrone, Carmelo, Palma, Carmine Di, Izzo, Alessandro , Correia‐Pinto, Jorge , Kaouk, Jihad , Lima, Estêvão , Autorino, Riccardo

BJU International | December 21, 2012 | Volume: 111 | Issue: 1 | Pages: 11-16

10.1111/j.1464-410x.2012.11494.x | PMID 23323699 Get It

What's known on the subject? and What does the study add? The safe and successful development of NOTES has the potential to create a paradigm shift in minimally invasive surgery. However, anecdotal diagnostic and therapeutic NOTES procedures, many of which were strictly performed in an investigative fashion, have taught us that continued, focused translational research is imperative to address myriad, and as yet unaddressed, technical issue. This study analyses the NOTES ‐related research in the medical literature over the last 5 years in an attempt to identify trends and/or progress towards its meaningful use. It shows that NOTES is still in a developmental stage and much work is still needed to refine techniques, verify safety and document efficacy. Since the first description of the concept of NOTES , >2000 clinical cases, irrespective of specialty, have been reported. NOTES remains a field of intense clinical and experimental research in various surgical specialties. The aim of this study was to analyse natural orifice transluminal endoscopic surgery ( NOTES )‐related publications over the last 5 years. A systematic literature search was done to retrieve publications related to NOTES from 2006 to 2011. The following variables were recorded: year of publication; article type; study design; setting; Journal Citation Reports® journal category; authors area of surgical speciality; geographic area of origin; surgical procedure; NOTES technique; NOTES access route; number of clinical cases. A time‐trend analysis was performed by comparing early (2006–2008) and late (2009–2011) study periods. Overall, 644 publications were included in the analysis and most papers were found in general surgery journals (50.9%). Studies were most frequently clinical series (43.9%) and animal experimental (48%), with the articles focusing primarily on cholecystectomy, access creation and closure, and peritoneoscopy. Pure NOTES techniques were performed in most of the published reports (85%) with the remaining cases being hybrid NOTES (7.4%) and NOTES ‐assisted procedures (6.1%). The access routes included transgastric (52.5%), transcolonic (12.3%), transvesical (12.5%), transvaginal (10.5%), and combined (12.3%). From the early to the late period, there was a significant increase in the number of randomised controlled trials (5.6% vs 7.2%) or non‐randomised but comparative studies (5.6% vs 22.9%) ( P < 0.001) and there was also a significant increase in the number of colorectal procedures and nephrectomies ( P = 0.002). Pure NOTES remained the most studied approach over the years but with increased investigation in the field of NOTES ‐assisted techniques ( P = 0.001). There was also a significant increase in the adoption of transvesical access (7% vs 15.6%) ( P = 0.007). NOTES is in a developmental stage and much work is still needed to refine techniques, verify safety and document efficacy. Since the first description of the concept of NOTES , >2000 clinical cases, irrespective of specialty, have been reported. NOTES remains a field of intense clinical and experimental research in various surgical specialities.
Automated liver stiffness measurements with magnetic resonance elastography
Dzyubak, Bogdan , Glaser, Kevin J. , Yin, Meng , Talwalkar, Jayant A., Chen, Jun , Manduca, Armando , Ehman, Richard L. , Dzyubak, Bogdan , Yin, Meng

Journal of Magnetic Resonance Imaging | December 21, 2012 | Volume: 38 | Issue: 2 | Pages: 371-379

10.1002/jmri.23980 | PMID 23281171 Get It

PurposeTo provide a fully automated algorithm for obtaining stiffness measurements from hepatic magnetic resonance elastography (MRE) images that are consistent with measurements performed by expert readers.Materials and MethodsAn initial liver contour was found using an adaptive threshold and expanded using an active contour to select a homogeneous area of the liver. The confidence map generated during the stiffness calculation was used to select a region of reliable wave propagation. The average stiffness within the automatically generated region of interest (ROI) was compared to measurements by two trained readers in a set of 88 clinical test cases ranging from healthy to severely fibrotic.ResultsThe stiffness measurements reported by the readers differed by −6.76% ± 22.8% (95% confidence) and had an intraclass correlation coefficient (ICC) of 0.972 (P < 0.05). The algorithm and the more experienced reader differed by 4.32% ± 14.9 with an ICC of 0.987.ConclusionThe automated algorithm performed reliably, even though MRE acquisitions often have motion artifacts present. The correlation between the automated measurements and those from the trained readers was superior to the correlation between the readers. J. Magn. Reson. Imaging 2013;38:371–379. © 2013 Wiley Periodicals, Inc.
Faculty Opinions recommendation of Akt-mediated regulation of autophagy and tumorigenesis through Beclin 1 phosphorylation.
Kaufmann, Scott H. , Kaufmann, Scott H

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature | December 21, 2012 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.3410/f.717961620.793467527 Get It