5,188 research outputs found
Salvage Fractionated Stereotactic Re-irradiation (FSRT) for Patients with Recurrent High Grade Gliomas Progressed after Bevacizumab Treatment
Purpose/Objectives: Bevacizumab failure is a major clinical problem in the manage- ment of high grade gliomas (HGG), with a median overall survival of less than 4 months (m). This study evaluated the efficacy of fractionated stereotactic re-irradiation (FSRT) for patients with HGG after progression on Bevacizumab.
Materials/Methods: Retrospective review was conducted of patients treated with FSRT after progression on bevacizumab. A total of 36 patients were identified. FSRT was most commonly delivered in 3.5 Gy fractions to a total dose of 35 Gy. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were utilized as study endpoints. Univariate and multivariate analysis was performed.
Results: Among the 36 patients, 31 patients had recurrent glioblastoma, and 5 patients had recurrent anaplastic astrocytoma. The median time from initial bevacizumab treatment to FSRT was 8.5 m (range 2.3 – 32.0 m). The median plan target volume for FSRT was 27.5 cc (range 1.95 – 165 cc). With a median follow up of 20.4 m, the overall survival of the patients since initial diagnosis was also 24.9 m. The median overall survival after initiation of bevacizumab was 13.4 months. The median overall survival from FSRT was 4.8 m. FSRT treatment was well tolerated with no Grade \u3e3 toxicity.
Conclusions: Favorable outcomes were observed in patients with recurrent HGG who received salvage FSRT after bevacizumab failure. The treatment was well tolerated. Prospective study is warranted to further evaluate the efficacy of salvage FSRT for selected patients with recurrent HGG amenable to FSRT, who had failed bevacizumab treatment
Smartphone Mobile Application to Enhance Diagnosis of Skin Cancer: A Guide for the Rural Practitioner
Primary care physicians occupy a vital position to impact many devastating conditions, especially those dependent upon early diagnosis, such as skin cancer. Skin cancer is the most common cancer in the United States and despite improvements in skin cancer therapy, patients with a delay in diagnosis and advanced disease continue to have a grave prognosis. Due to a variety of barriers, advanced stages of skin cancer are more prominent in rural populations. In order to improve early diagnosis four things are paramount: increased patient participation in prevention methods, establishment of screening guidelines, increased diagnostic accuracy of malignant lesions, and easier access to dermatologists. Recent expansion in smartphone mobile application technology offers simple ways for rural practitioners to address these problems. More than 100,000 health related applications are currently available, with over 200 covering dermatology. This review will evaluate the newest and most useful of those applications offered to enhance the prevention and early diagnosis of skin cancer, particularly in the rural population
Spectrum of Renal Biopsy Findings in TRIDENT Cohort
Introduction: Diabetic kidney disease is the most common cause of chronic end stage renal failure in the USA. Kidney biopsy is the gold standard diagnostic criteria; however, it is an invasive procedure; not everyone undergoes diagnostic biopsy. The relationship between histological and clinical parameters and prognosis in DKD is incompletely understood. TRIDENT, (Transformative research in diabetic nephropathy) plans to enroll 400 diabetic subjects undergoing clinically indicated renal biopsies and performs multi-omics characterization of subjects to identify pathways associated with kidney function decline. Genetic studies indicated that podocytes influence albuminuria and diabetic kidney disease development. We seek to understand whether podocyte and basement membrane changes correlate with kidney function, degree of albuminuria, and histopathologic features of diabetic nephropathy using electron microscopy and digital light microscopy.
Methods: I performed quantitative characterization of podocyte foot process morphology using TRIDENT subject biopsies. Podocyte foot process width (FPW) was measured using electron micrographs in ImageJ and calculated: FPW = (π/4) × (ΣGBM length/Σfoot process).
Results: In our cohort, the average FPW was 1.624μm, and the glomerular basement membrane (GBM) average thickness was 773.27μm. The average FPW and GBM thickness ranged from 519μm-4.806μm and 200μm-3230μm per patient, respectively. Using a Pearson’s correlation coefficient: GBM thickness positively correlates with RPS Class (.424240229), %interstitial fibrosis (.203720183), arteriolar hyalinosis (0.307801899), proteinuria (.639114291).
Discussion: Podocyte features such as FPW and GBM thickness showed stronger correlation with proteinuria than other parameters. Some samples were collected in patients with advanced DKD; collecting samples earlier in the disease process may represent more accurate correlations between EM findings and disease severity. Overall podocyte structural changes strongly correlate with proteinuria, indicating the key role of podocytes in proteinuria
Phase I Study of Ipilimumab Combined with Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients with Brain Metastases
Purpose: We performed a phase I study to determine the maximum tolerable dose (MTD) and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT) in patients with brain metastases (BM) from melanoma.
Methods: Based on intracranial (IC) disease burden, patients were treated with WBRT (Arm A) or SRS (Arm B). Ipilimumab starting dose was 3 mg/kg (every 3 weeks, starting on day 3 of WBRT or 2 days after SRS). Ipilimumab was escalated to 10 mg/kg using a two-stage, 3+3 design. The primary endpoint was to determine the MTD of ipilimumab combined with radiotherapy. Secondary endpoints were overall survival (OS), IC and extracranial (EC) control, progression free survival (PFS), and toxicity. This trial is regis- tered with ClinicalTrials.gov, number NCT01703507.
Results: Characteristics of the 16 patients enrolled between 2011 and 2014 were: mean age, 60; median BM, 2 (1 to \u3e10); number with EC disease, 13 (81%). Treatment included WBRT (n=5), SRS (n=11), ipilimumab 3mg/kg (n=7), 10 mg/kg (n=9). Median follow-up was 8 months (Arm A) and 10.5 months (Arm B). There were 21 grade 1-2 neuro- toxic effects with no dose-limiting toxicities (DLTs). One patient experienced grade 3 neurotoxicity prior to ipilimumab administration. Ten additional grade 3 toxicities were reported with gastrointestinal (n=5, 31%) as the most common. There were no grade 4/5 toxicities. Median PFS and OS, respectively, in Arm A were 2.5 months and 8 months, and in Arm B were 2.1 months and not reached.
Conclusion: Concurrent ipilimumab 10 mg/kg with SRS is safe. The WBRT arm was closed early due to slow accrual, but demonstrated safety with ipilimumab 3 mg/kg. No patient experienced DLT. Larger studies with ipilimumab 10 mg/kg and SRS are warranted
Countering Home-Grown Terrorists in Australia: An Overview of Legislation, Policy and Actors Since 2001
This article explores the impact of counter-terrorism legislation and policy in Australia. In particular it explores how legislation facilitated prosecution and conviction of persons involved in home-grown terrorism, including analysis of investigation and prosecution policy surrounding the ul-Haque and Haneef cases. Particular attention is given to the terrorism trials involving Benbrika & Ors and Elomar & Ors. What makes these trials intriguing is the fact that most of those convicted could be more easily described as more vulnerable than menacing. Sentencing of those convicted was cognate with no policies for rehabilitation. The small number of convictions under the legislation when considered against the increased funding of counter-terrorism, loss of traditional rights and privileges and Australia’s involvement in Afghanistan and Iraq raises issues about adequate policy setting in this area
Cytoreductive surgery for patients with recurrent epithelial ovarian carcinoma.
OBJECTIVE: This study aims to identify favorable preoperative characteristics and examine the impact of secondary cytoreductive surgery on survival for patients with recurrent epithelial ovarian carcinoma.
METHODS: Patients who underwent cytoreductive surgery for recurrent epithelial ovarian cancer were identified in our surgical database for the period 1988-2004. Patient charts were reviewed and data collected regarding patient demographics, surgical management, preoperative evaluation, perioperative complications, and oncologic outcome.
RESULTS: Eighty-five patients met eligibility criteria. Preoperative factors that correlated with improved survival were disease-free interval of greater than 12 months (por=1 cm (p
CONCLUSION: When selecting patients for secondary cytoreduction, the most significant preoperative factors are disease-free interval and success of a prior cytoreductive effort. Once secondary cytoreductive surgery is attempted, the most important factor for improved survival is optimal cytoreduction. Of equal importance is counseling regarding the significant risk for bowel surgery, colostomy, and complications
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Low-Flow (7-Day, 10-Year) Classical Statistical and Improved Machine Learning Estimation Methodologies
Water resource managers require accurate estimates of the 7-day, 10-year low flow (7Q10) of streams for many reasons, including protecting aquatic species, designing wastewater treatment plants, and calculating municipal water availability. StreamStats, a publicly available web application developed by the United States Geologic Survey that is commonly used by resource managers for estimating the 7Q10 in states where it is available, utilizes state-by-state, locally calibrated regression equations for estimation. This paper expands StreamStats’ methodology and improves 7Q10 estimation by developing a more regionally applicable and generalized methodology for 7Q10 estimation. In addition to classical methodologies, namely multiple linear regression (MLR) and multiple linear regression in log space (LTLR), three promising machine learning algorithms, random forest (RF) decision trees, neural networks (NN), and generalized additive models (GAM), are tested to determine if more advanced statistical methods offer improved estimation. For illustrative purposes, this methodology is applied to and verified for the full range of unimpaired, gaged basins in both the northeast and mid-Atlantic hydrologic regions of the United States (with basin sizes ranging from 2–1419 mi2) using leave-one-out cross-validation (LOOCV). Pearson’s correlation coefficient (R2), root mean square error (RMSE), Kling–Gupta Efficiency (KGE), and Nash–Sutcliffe Efficiency (NSE) are used to evaluate the performance of each method. Results suggest that each method provides varying results based on basin size, with RF displaying the smallest average RMSE (5.85) across all ranges of basin sizes
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