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Framingham Center, MA, United States

Akabane H.,Metrowest Medical Center | Sullivan R.J.,Massachusetts General Hospital
American Journal of Clinical Dermatology

Melanoma is a malignancy of pigment-producing cells that is driven by a variety of genetic mutations and aberrations. In most cases, this leads to upregulation of the mitogen-activated protein kinase (MAPK) pathway through activating mutations of upstream mediators of the pathway including BRAF and NRAS. With the advent of effective MAPK pathway inhibitors, including the US FDA-approved BRAF inhibitors vemurafenib and dabrafenib and MEK inhibitor trametinib, molecular analysis has become an integral part of the care of patients with metastatic melanoma. In this article, the key molecular targets and strategies to inhibit these targets therapeutically are presented, and the techniques of identifying these targets, in both tissue and blood, are discussed. © 2015, Springer International Publishing Switzerland. Source

Mathew M.C.,Metrowest Medical Center
Cochrane database of systematic reviews (Online)

Age-related cataract is a major cause of visual impairment in the elderly. Oxidative stress has been implicated in its formation and progression. Antioxidant vitamin supplementation has been investigated in this context. To assess the effectiveness of antioxidant vitamin supplementation in preventing and slowing the progression of age-related cataract. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 2), MEDLINE (January 1950 to March 2012), EMBASE (January 1980 to March 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to March 2012), Open Grey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 2 March 2012. We also checked the reference lists of included studies and ongoing trials and contacted investigators to identify eligible randomized trials. We included only randomized controlled trials in which supplementation with one or more antioxidant vitamins (beta-carotene, vitamin C and vitamin E) in any form, dosage or combination for at least one year was compared to another antioxidant vitamin or to placebo. Two authors extracted data and assessed trial quality independently. We pooled results for the primary outcomes, i.e., incidence of cataract and incidence of cataract extraction. We did not pool results of the secondary outcomes - progression of cataract and loss of visual acuity, because of differences in definitions of outcomes and data presentation. We pooled results by type of cataract when data were available. We did not perform a sensitivity analysis. Nine trials involving 117,272 individuals of age 35 years or older are included in this review. The trials were conducted in Australia, Finland, India, Italy, the United Kingdom and the United States, with duration of follow-up ranging from 2.1 to 12 years. The doses of antioxidant vitamins were higher than the recommended daily allowance. There was no evidence of effect of antioxidant vitamin supplementation in reducing the risk of cataract, cataract extraction, progression of cataract or in slowing the loss of visual acuity. In the pooled analyses, there was no evidence of effect of beta-carotene supplementation in reducing the risk of cataract (two trials) (relative risk (RR) 0.99, 95% confidence interval (CI) 0.91 to 1.08; n = 57,703) or in reducing the risk of cataract extraction (three trials) (RR 1.00, 95% CI 0.91 to 1.10; n = 86,836) or of vitamin E supplementation in reducing the risk of cataract (three trials) (RR 0.97, 95% CI 0.91 to 1.04; n = 50,059) or of cataract extraction (five trials) (RR 0.98, 95% CI 0.91 to 1.05; n = 83,956). The proportion of participants developing hypercarotenodermia (yellowing of skin) while on beta-carotene ranged from 7.4% to 15.8%. There is no evidence from RCTs that supplementation with antioxidant vitamins (beta-carotene, vitamin C or vitamin E) prevents or slows the progression of age-related cataract. We do not recommend any further studies to examine the role of antioxidant vitamins beta-carotene, vitamin C and vitamin E in preventing or slowing the progression of age-related cataract. Costs and adverse effects should be weighed carefully with unproven benefits before recommending their intake above recommended daily allowances. Source

Grunwald I.Q.,Anglia Ruskin University | Kuhn A.L.,Metrowest Medical Center | Schmitt A.J.,University of Oxford | Schmitt A.J.,University College London | Balami J.S.,University of Oxford
Journal of Invasive Cardiology

The purpose of this article is to give an overview of the management of the most common complications encountered during subarachnoid hemorrhage and endovascular treatment of intracranial aneurysms. We reviewed the literature and identified the complications encountered during endovascular treatment of intracranial aneurysms. We report current management strategies of complications associated with subarachnoid hemorrhage and the interventional procedure. Aneurysmal subarachnoid hemorrhage remains a devastating condition, with high mortality and poor outcome among survivors. The successful treatment of intracranial aneurysms requires a multidisciplinary approach and the treating physicians need to be aware of predisposing factors for complications, their frequency, and also their management. Source

Cheungpasitporn W.,Mayo Medical School | Thongprayoon C.,Mayo Medical School | Chiasakul T.,Chulalongkorn University | Korpaisarn S.,Metrowest Medical Center | Erickson S.B.,Mayo Medical School

Background: The objective of this meta-analysis was to evaluate the risk of anemia in patients who received reninangiotensin system (RAS) inhibitors. Methods: A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through November, 2014. Studies that reported relative risks, odd ratios or hazard ratios comparing the anemia risk in patients who received angiotensin-converting-enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) vs. those who did not were included. We performed the prespecified sensitivity analysis including only only studies with confounder adjusted analysis. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated using a randomeffect, generic inverse variance method. Results: Seven studies (2 cohort and 5 cross-sectional studies) with 29 061 patients were included in the analysis to assess the risk of anemia and the RAS inhibitors use. The pooled RR of anemia in patients receiving ACEIs was 1.56 (95% CI, 1.40-1.73, I2 = 17%). When meta-analysis was limited only to studies with confounder adjusted analysis, the pooled RR of anemia in patients using ACEIs was 1.57 (95% CI, 1.43-1.73, I2 = 0%) The pooled RR of anemia in patients receiving ARBs was 1.60 (95% CI, 1.27-2.00, I2 = 39%). The meta-analysis of studies with confounder adjusted analysis demonstrated the pooled RR of anemia in patients using ARBs of 1.59 (95% CI, 1.38-1.83, I2 = 0%). Conclusions: Our meta-analysis demonstrates an association between anemia and the use of RAS inhibitors. Hematological parameters should be monitored in patients treated with RAS inhibitors. © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. Source

Baker J.R.,Weil Foot and Ankle Institute | Klein E.E.,Weil Foot and Ankle Institute | Weil Jr. L.,Weil Foot and Ankle Institute | Weil L.S.,Weil Foot and Ankle Institute | Knight J.M.,Metrowest Medical Center
Foot and Ankle Specialist

Subtalar joint arthroereisis is a surgical modality that has been shown to be an effective procedure for flexible flatfoot in both pediatric and adult populations. Despite advances in understanding its mechanics and function, complication and implant removal rates remain as high as 30% to 40%. Analysis was performed to determine the survivability of 2 subtalar joint arthroereisis implants, absorbable and nonabsorbable, used alone and in combination with other procedures in both the adult and pediatric populations. The 95 total arthroereisis procedures were analyzed in several major categories: absorbable implants versus nonabsorbable implants and adult versus pediatric patients. Each major group was then further subdivided to create further subgroups: absorbable isolated procedures, absorbable combined procedures, nonabsorbable isolated procedures, and nonabsorbable combined procedures. The overall survival rates were 83% for absorbable implants and 81% for nonabsorbable implants. A total of 11 (17%) absorbable implants and 6 (19%) nonabsorbable implants were removed, respectively, at an average of 9 months and 23 months postoperatively. When used alone and in combination with other procedures, 36% and 13% of absorbable implants and 18% and 19% of nonabsorbable implants, respectively, were removed. When comparing adult versus pediatric populations, the overall survival rates of the absorbable and nonabsorbable implants were 81% for absorbable implants and 79% for nonabsorbable implants in the adult population and 85% for absorbable implants and 100% for nonabsorbable implants in the pediatric population.Level of Evidence: Therapeutic, Level III; Retrospective comparative series © 2012 The Author(s). Source

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