Faculty Bibliography

PURPOSE/UNASSIGNED:The safety and effectiveness of water vapor for ablation of prostate tissue was assessed in men with intermediate-risk localized prostate cancer (PCa). MATERIALS AND METHODS/UNASSIGNED:A prospective, multi-center, single arm study (VAPOR 2) was conducted in 235 men at 26 centers across the US in men ≥50 years, with Gleason Grade Group 2 (GG2) PCa confined to a single PI-RADS 3 or 4 abnormality on multi-parametric magnetic resonance imaging (mpMRI) fusion biopsy, prostate-specific antigen (PSA) level ≤15 ng/ml, and clinical stage ≤T2c. Data presented is a pre-defined subset analysis of 110 men completing 12-month follow-up to assess only ablative efficacy and toxicity. Reported outcomes include biopsy 6-months post-treatment, PSA, prostate volume reduction, urinary/sexual function, quality-of-life questionnaires, and adverse events. The 3-year follow-up analysis will evaluate efficacy in PCa management, with 5-years total follow-up. RESULTS/UNASSIGNED:Median age was 65, with a median baseline PSA of 5.6 ng/mL and prostate volume of 40.7cc. On 6-month biopsy, targeted sampling of the treated region revealed benign tissue onlyin 75% and benign tissue or GG1 PCa in 91%. Regression analysis did not identify a significant baseline predictor of positive biopsy. PSA showed a median reduction of 58%, with a median 8cc reduction in prostate volume. Urinary and sexual function showed an initial decline followed by gradual recovery through 12 months. Perioperative adverse events were generally mild and resolved without sequelae, with no reports of rectal injury. CONCLUSIONS/UNASSIGNED:The VAPOR 2 study demonstrated effective ablation of prostate tissue in men with localized, intermediate risk PCa with low rates of procedural morbidity.

PURPOSE/OBJECTIVE:These studies were undertaken to determine if fexapotide triflutate 2.5 mg transrectal injectable (FT) has significant long-term (LT) safety and efficacy for the treatment of benign prostatic hyperplasia (BPH). METHODS:Two placebo controlled double-blind randomized parallel group trials with 995 BPH patients at 72 sites treated 3:2 FT:placebo, with open-label FT crossover (CO) re-injection in 2 trials n = 344 and long-term follow-up (LF) 2-6.75 years (mean 3.58 years, median 3.67 years; FT re-injection CO mean 4.27 years, median 4.42 years) were evaluated. 12 months post-treatment patients elected no further treatment, approved oral medications, FT, or interventional treatment. Primary endpoint variable was change in Symptom Score (IPSS) at 12 months and at LF. CO primary co-endpoints were 3-year incidence of (1) surgery for BPH in FT treated CO patients versus patients crossed over to oral BPH medications and (2) surgery or acute urinary retention in FT-treated CO placebo patients versus placebo patients crossed over to oral BPH medications. 28 CO secondary endpoints assessed surgical and symptomatic outcomes in FT reinjected patients versus conventional BPH medication CO and control subgroups at 2 and 3 years. RESULTS:FT injection had no significant safety differences from placebo. LF IPSS change from baseline was higher in FT treated patients compared to placebo (median FT group improvement - 5.2 versus placebo - 3.0, p < 0.0001). LF incidence of AUR (1.08% p = 0.0058) and prostate cancer (PCa) (1.1% p = 0.0116) were both reduced in FT treated patients. LF incidence of intervention for BPH was reduced in the FT group versus oral BPH medications (8.08% versus 27.85% at 3 years, p < 0.0001). LF incidence of intervention or AUR in placebo CO group with FT versus placebo CO group with oral medications was reduced (6.07% versus 33.3% at 3 years, p < 0.0001). 28/28 secondary efficacy endpoints were reached in LF CO re-injection studies. CONCLUSIONS:FT 2.5 mg is a safe and effective transrectal injectable for LT treatment of BPH. FT treated patients also had reduced need for BPH intervention, and reduced incidence of PCa and AUR.

Recently, we had the opportunity to review the progress that has been made in the field of cardiovascular disease over the past century in The FASEB Journal and, based on those thoughts, in this article we predict what may transpire inthis 'century of biology'. Although it is true that 'the best way to predict the future is to invent it', we gaze through the prism of modern biomolecular science for a vision of a possible future and see cardiology practice that is transformed. In the second half of the 20th century, we developed a more fundamental understanding of atherosclerotic vascular disorders and invented life-saving therapeutics. We saw a similar development of mechanism-based pharmacotherapy to address heart failure, primarily through agents that antagonize the excessive concentration of circulating neurohumoral agents. Now we are in the midst of the device era, from stents to cardiac resynchronization therapy to transcatheter valves.The next wave of treatments will build on an increasingly sophisticated understanding of the molecular determinants of cardiovascular disorders and engineering feats that are barely perceptible now. Genomic profiling, molecular prescriptions for prevention and personalized therapeutics, regenerative medicine and the new field of cardiovascular tissue bioengineering will transform cardiovascular medicine. If the human species can survive threats of our own doing, such as the related epidemics of obesity and diabetes, by the turn of the next century, treatment of cardiovascular disease will not resemble the present in almost any way. Touch Medical Media 2012

During the life span of The FASEB Journal, the decline in cardiovascular mortality was astonishing as the fundamental bases of the complex syndromes of cardiovascular disease were illuminated. In this Silver Anniversary Review, we highlight a few pivotal advances in the field and relate them to research in Pasteur's quadrant, the region of investigation driven by both a desire for fundamental understanding and the consideration of its use. In the second half of the 20th century, we advanced from little pathophysiologic understanding to a near-complete understanding and effective, evidence-based therapeutics for vascular disorders and a similar development of pharmacotherapy to address heart failure, primarily through agents that antagonize the excessive concentration of circulating neurohumoral agents. In the current era, we have witnessed 'the rise of the machines,' from stents to cardiac resynchronization therapy. The next wave of treatments will build on an increasingly sophisticated understanding of the molecular determinants of cardiovascular disorders. We briefly consider the promise of regenerative medicine and are intrigued by the possibility for the direct reprogramming of resident cardiac fibroblasts into cardiomyocytes. As for the future, genomic profiling should help physicians recommend individualized risk factor modification targeted to prevent specific manifestations of cardiovascular disease. Transcriptional and biomarker analyses will almost surely be used individually to tailor therapy for those at risk of or experiencing cardiovascular disease. Given the ongoing exponential expansion of scientific knowledge, all of human ingenuity will be needed to fully utilize the power of Pasteur's quadrant and to unleash another quarter century in cardiology as scientifically fruitful and effective on human health as the last.-Levin, R. I., Fishman, G. I. The power of Pasteur's quadrant: cardiovascular disease at the turn of the century

Contemporary medical education faces new challenges as the climate of the health care delivery system transforms. Diminished length-of-stay and continuity-of-care have radically altered the way medical students are exposed to and learn about illness. These educational challenges are particularly pronounced in the teaching of surgery. We developed a multimedia application, Surgical Interactive Multimedia Modules (SIMM), to utilize rich media objects and high-resolution video to overcome modern didactic challenges. The SIMM client was created using Macromedia Director MX and communicates using XML with an Oracle database containing the rich-media educational objects. The SIMMs integrate digital video, 3-D models, self-assessment tools, and current medical evidence to generate a dynamic learning environment encompassing core surgery topics. Students can access SIMM modules either via a high-speed network connection or by using a DVD. The interface was designed to focus on a narrative timeline that provided students with a familiar metaphor for interacting with the learning objects. Students on the surgery clerkship are currently using four SIMM modules and feedback indicates that they are regarded as compelling and useful educational tools for learning about complex surgical topics. Future areas of research will address student ability to annotate the learning objects and to maintain a personal repository of medical education resources