1030 Freeland Dr Suite 104
Salisbury NC 28144
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Reconsidering adjuvant versus salvage radiation therapy for prostate cancer in the genomics era. - Journal of comparative effectiveness research
We developed a decision analysis framework to simulate the clinical choice of early adjuvant versus delayed salvage radiation therapy after radical prostatectomy.We designed a Markov decision analysis model to represent two alternative treatment approaches for prostate cancer after prostatectomy over a 10-year time horizon. The model contained individualized inputs including genomic classifier score. Sensitivity analyses were performed to evaluate model results.Observation with delayed salvage radiation is preferred according to the base case, with greater average length and quality of life. However, adjuvant therapy is preferred over observation with salvage when genomics-based estimates of recurrence are high.Model results were sensitive to genomics-based estimates of cancer recurrence and to nonprostate cancer mortality.
Right Atrial Vacuum-Assisted Thrombectomy: Single-Center Experience. - The Journal of invasive cardiology
Right heart thrombus in the absence of structural heart disease, atrial fibrillation, or intracardiac catheter is rare. It typically represents a thrombus migrating from the venous system to the lung, known as thrombi-in-transit, and can lead to a life-threatening pulmonary embolism. The optimal therapy for thrombi-in-transit remains controversial. We report our experience using percutaneous removal of right heart thrombus using vacuum aspiration.Patients with right atrial mass who were hemodynamically stable and underwent vacuum thombectomy using the AngioVac system (AngioDynamics) at our institution were included in this analysis. Between December 2012 and August 2014, a total of 7 patients (2 men, 5 women) with a mean age of 51.5 years (range, 20-83 years) underwent right atrial thrombectomy. Data during the procedure and follow-up period were collected and analyzed.All patients were hemodynamically stable before the procedure. The procedure was considered successful in 6 patients. All patients survived through hospitalization. No periprocedural bleeding, stroke, or myocardial infarction occurred. One patient developed cardiogenic shock after the procedure that required extracorporeal membrane oxygenation support for <24 hours. There was no recurrent venous thromboembolism at a mean follow-up of 9 months.Vacuum-assisted thrombectomy can be a potential treatment option for hemodynamically stable patients with large right-sided intracardiac thrombus who are not surgical candidates.
Body Image & Quality of Life: Changes With Gastric Bypass and Body Contouring. - Annals of plastic surgery
Bariatric surgery has emerged as an effective method of combating the morbid obesity epidemic. However, the massive weight loss that follows may result in contour changes that can affect body image and quality of life. Our study examines the effects and consequences of bariatric surgery and subsequent body contouring on body image and quality of life.Patients were prospectively followed up through their experience with bariatric surgery and subsequent body contouring surgery. Using 2 validated survey instruments, the Multidimensional Body-Self Relations Questionnaire and the Short Form 36 (SF-36), patients completed questionnaires preoperatively and at 6, 12, and 24 months postoperatively. Mean scores were determined by repeated measures analyses of variance F tests.One hundred seventy-five patients were surveyed before bariatric surgery, with noted declines in survey completion at 6, 12, and 24 months. Appearance Evaluation scores improved significantly at all intervals (P = 0.0033), as did Body Area Satisfaction Scale and Appearance Orientation scores (P = 0.0079 and P = 0.044, respectively). While Overweight Preoccupation and Self-Classified Weight scores decreased over time, only the latter was significant (P < 0.0001). The composite SF-36 score for patients awaiting bariatric surgery (54.1%) with postoperative scores at 6 (67.6%,), 12 (at 74.0%), and 24 (76.7%) months being significantly higher (P < 0.0001).The body contouring group consisted of 41 patients who primarily had lower body procedures, with 31 patients surveyed at 6 months and 27 patients at 12 months. For this cohort, Appearance Evaluation and Body Area Satisfaction Scale scores both improved significantly (P = 0.0001 and P = 0.0005, respectively) whereas Appearance Orientation scores declined significantly (P = 0.0055). Both Overweight Preoccupation and Self-Classified Weight scores decreased with only the latter being statistically significant (P = 0.0286). Postoperative SF-36 scores at 6 (72.9%) and 12 (64.5%) months were no different than patients awaiting body contouring (71.3%).Using 2 validated survey instruments, we show that patients undergoing bariatric surgery have improvements in body image and quality of life. Subsequent postbariatric body contouring surgery results in further improvements in body image. Our findings provide measurable evidence for the value of body contouring after significant weight loss, which may favor greater insurance coverage for this patient population.
Morphometric and chronological behavior of 2.45Â GHz microwave ablation zones for colorectal cancer metastases and hepatocellular carcinoma in the liver: preliminary report. - Abdominal radiology (New York)
Percutaneous microwave ablation (MWA) is increasingly utilized in the treatment of primary and secondary hepatic malignancy. As an in-situ treatment appreciation of any signs of recurrence is critical for improving long-term oncological outcomes. Volumetry has been recognized as having advantages over orthogonal measurements in the response assessment of malignant lesions. Our study set out to look at the normal involution of an ablation zone (AZ) both volumetrically and morphologically to see if this information might aid the detection of local tumor progression.Cases were identified retrospectively from our database of liver MWA. We identified 34 AZs in total, 18 AZs in 16 hepatocellular carcinoma (HCC) patients with cirrhosis on imaging grounds and 13 AZs in patients with metastatic colorectal cancer. How these AZs developed over time was analyzed both morphologically and quantitatively using Siemens Syngo Via post-processing software. We used the software to produce volume measurements and short axis orthogonal measurements. A baseline measurement was taken on the first <30Â day post-ablation scan and the chronological changes were then plotted.We saw differences between the cirrhotic and non-cirrhotic patients both in terms of morphological and volumetric changes. 12/13 non-cirrhotic AZs had a volume of <50% of the baseline scan within the first year. The cirrhotic patients were less predictable, but 14/18 still shrunk to less than 50% of baseline volume in the first year. Orthogonal measurements were less useful in both groups. Qualitatively, there was initially a slightly less well-defined border to the AZ in the first 3Â months, which became better defined over time and certainly over the first year of AZ involution.Volumetric analysis is a useful adjunct to conventional measurements and qualitative analysis of AZs. This can be reassuring when orthogonal measurements are static or difficult to interpret. Our preliminary data suggest that the normal pattern in a non-cirrhotic liver is that the AZ volume should drop below 50% of baseline at 1Â year. Volumes in cirrhotic livers are less predictable, but the majority will still follow a similar pattern. Future studies could evaluate if failure to follow these patterns correlates with local tumor progression.
Refinement of the Hybrid Neuroendovascular Operating Suite: Current and Future Applications. - World neurosurgery
In early generation hybrid biplane endovascular operating rooms, switching from surgical to angiographic position is cumbersome. In this report, we highlight the unique design of a new hybrid neuroendovascular operating suite that allows surgical access to the head while keeping the biplane system over the lower body of the patient. Current and future hybrid neuroendovascular operating suite applications are discussed.We collaborated with engineers to implement the following modifications to the design of the angiographic system: translation of the bed towards the feet to allow biplane cerebral imaging in the head-side position and the biplane left-side position; translation of the base of the A-plane C-arm away from the feet to allow increased operator space at the head of the bed and to allow cerebral imaging in both the head-side and left-side positions; use of a specialized boom mount for the display panel to increase mobility; use of a radiolucent table top with attachments for the headrest or radiolucent head clamp system.The modified hybrid neuroendovascular operating suite allows for seamless transition between surgical and angiographic positions within seconds, improving workflow efficiency and decreasing procedure time as compared with early generation hybrid rooms.Combined endovascular and surgical applications are facilitated by co-locating their respective technologies and refining the ergonomics of the system to ease transition between both sets of technologies. In so doing, hybrid neuroendovascular operating suites can be anticipated to improve patient outcomes, generate novel treatment paradigms, and improve time and cost efficiency.Copyright Â© 2015 Elsevier Inc. All rights reserved.
Oligomerization of the microtubule-associated protein tau is mediated by its N-terminal sequences: implications for normal and pathological tau action. - Journal of neurochemistry
Despite extensive structure-function analyses, the molecular mechanisms of normal and pathological tau action remain poorly understood. How does the C-terminal microtubule-binding region regulate microtubule dynamics and bundling? In what biophysical form does tau transfer trans-synaptically from one neuron to another, promoting neurodegeneration and dementia? Previous biochemical/biophysical work led to the hypothesis that tau can dimerize via electrostatic interactions between two N-terminal 'projection domains' aligned in an anti-parallel fashion, generating a multivalent complex capable of interacting with multiple tubulin subunits. We sought to test this dimerization model directly. Native gel analyses of full-length tau and deletion constructs demonstrate that the N-terminal region leads to multiple bands, consistent with oligomerization. Ferguson analyses of native gels indicate that an N-terminal fragment (tau(45-230) ) assembles into heptamers/octamers. Ferguson analyses of denaturing gels demonstrates that tau(45-230) can dimerize even in sodium dodecyl sulfate. Atomic force microscopy reveals multiple levels of oligomerization by both full-length tau and tau(45-230) . Finally, ion mobility-mass spectrometric analyses of tau(106-144) , a small peptide containing the core of the hypothesized dimerization region, also demonstrate oligomerization. Thus, multiple independent strategies demonstrate that the N-terminal region of tau can mediate higher order oligomerization, which may have important implications for both normal and pathological tau action. The microtubule-associated protein tau is essential for neuronal development and maintenance, but is also central to Alzheimer's and related dementias. Unfortunately, the molecular mechanisms underlying normal and pathological tau action remain poorly understood. Here, we demonstrate that tau can homo-oligomerize, providing novel mechanistic models for normal tau action (promoting microtubule growth and bundling, suppressing microtubule shortening) and pathological tau action (poisoning of oligomeric complexes).Â© 2016 International Society for Neurochemistry.
Percutaneous image-guided cryoablation of small renal masses. - Abdominal radiology (New York)
Renal cell carcinoma is a common malignancy with increasing incidence due to the incidental detection of non-symptomatic small renal masses on imaging. Management of these small tumors has evolved toward minimally invasive nephron-sparing techniques which include partial nephrectomy and image-guided ablation. Cryoablation and radiofrequency ablation are the most utilized ablation modalities with the former more suited for larger and central renal masses due to intra-procedural visualization of the ablation zone and reduced pelvicalyceal injury. In this article, we review the epidemiology and natural history of renal cell carcinoma, the role of biopsy, and the management options available-surgery, image-guided ablation, and active surveillance-with a focus on cryoablation. The clinical outcomes of the longer term maturing cryoablation data are discussed with reference to partial nephrectomy and radiofrequency ablation. Image-guided ablation has often been the management choice in patients deemed unfit for surgery; however, growing evidence from published series demonstrates image-guided ablation as a sound alternative treatment with equivalent oncological outcomes and minimal patient impact.
South African surgical registrar perceptions of the research project component of training: Hope for the future? - South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde
The Health Professions Council of South Africa requires that a research project be submitted and passed before registration as a specialist.To describe surgical registrars' perceptions of the compulsory research project.Ethics clearance was received before commencing the study. A questionnaire was developed to collect feedback from surgical registrars throughout South Africa (SA). Completed questionnaires underwent descriptive analysis using MS Excel. Fisher's exact test and the Ï‡2 test were used to compare perceptions of the research-experienced and research-naive groups.All medical schools in SA were sampled, and 51.5% (124/241) of surgical registrars completed the questionnaire. Challenges facing registrars included insufficient time (109/124), inadequate training in the research process (40/124), inadequate supervision (31/124), inadequate financial resources (25/124) and lack of research continuity (11/124). Of the registrars sampled, 67.7% (84/124) believed research to be a valuable component of training. An overwhelming percentage (93.5%, 116/124) proposed a dedicated research block of time as a potential solution to overcoming the challenges encountered. Further proposals included attending a course in research methodology (79/124), supervision by a faculty member with an MMed or higher postgraduate degree (73/124), and greater research exposure as an undergraduate (56/124). No statistically significant differences were found between the perceptions of the research-experienced and research-naive groups.Challenges facing surgical registrars in their efforts to complete their research projects were identified and solutions to these problems proposed. It is heartening that respondents have suggested solutions to the problems they encounter, and view research as an important component of their careers.
Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood. - Proceedings of the National Academy of Sciences of the United States of America
The dynamics and molecular mechanisms underlying vaccine immunity in early childhood remain poorly understood. Here we applied systems approaches to investigate the innate and adaptive responses to trivalent inactivated influenza vaccine (TIV) and MF59-adjuvanted TIV (ATIV) in 90 14- to 24-mo-old healthy children. MF59 enhanced the magnitude and kinetics of serum antibody titers following vaccination, and induced a greater frequency of vaccine specific, multicytokine-producing CD4(+) T cells. Compared with transcriptional responses to TIV vaccination previously reported in adults, responses to TIV in infants were markedly attenuated, limited to genes regulating antiviral and antigen presentation pathways, and observed only in a subset of vaccinees. In contrast, transcriptional responses to ATIV boost were more homogenous and robust. Interestingly, a day 1 gene signature characteristic of the innate response (antiviral IFN genes, dendritic cell, and monocyte responses) correlated with hemagglutination at day 28. These findings demonstrate that MF59 enhances the magnitude, kinetics, and consistency of the innate and adaptive response to vaccination with the seasonal influenza vaccine during early childhood, and identify potential molecular correlates of antibody responses.
Formulation and development of ophthalmic in situ gel for the treatment ocular inflammation and infection using application of quality by design concept. - Drug development and industrial pharmacy
Context The conventional liquid ophthalmic delivery systems exhibit short pre-corneal residence time and the relative impermeability to the cornea which leads to poor ocular bioavailability. Objective The aim of this study was to apply quality by design (QbD) for development of dexamethasone sodium phosphate (DSP) and tobramycin sulfate (TS)-loaded thermoresponsive ophthalmic in situ gel containing Poloxamer 407 and hydroxyl propyl methyl cellulose (HPMC) K4M for prolonging the pre-corneal residence time, ocular bioavability and decreases the frequency of administration of dosage form. The material attributes and the critical quality attributes (CQA) of the in situ gel were identified. Central composite design (CCD) was adopted to optimize the formulation. Materials and methods The ophthalmic in situ forming gels were prepared by cold method. Materials attributes were the amount of Poloxamer 407 and HPMC and CQA identified were Gel strength, mucoadhesive index, gelation temperature and % of drug release of both drug. Results and discussion Optimized batch (F*) containing 16.75% poloxamer 407 and 0.54% HPMC K4M were exhibited all results in acceptable limits. Compared with the marketed formulation, optimized in situ gel showed delayed Tmax, improved Cmax and AUC in rabbit aqueous humor, suggesting the sustained drug release and better corneal penetration and absorption. Conclusion According to the study, it could be concluded that DSP and TS would be successfully formulated as in situ gelling mucoadhesive system for the treatment of steroid responsive eye infections with the properties of sustained drug release, prolonged ocular retention and improved corneal penetration.
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1030 Freeland Dr Suite 104 Salisbury, NC 28144
611 Mocksville Ave.
611 Mocksville Ave
1601 Brenner Ave Hefner Vamc Mh&Bs (11M-2)
1601 Brenner Ave 11M-2