Ten-year experience of infrainguinal bypass with endoscopic vein harvest.

OBJECTIVES: There is conflicting data comparing minimally invasive vein harvest (MIVH) using endoscopic technique and open vein harvest (OVH) in terms of bypass patency, wound infection incidence, and patient morbidity. Our institution has performed MIVH since 2003 for peripheral bypass procedures with a consistent team of specialized endoscopic vein harvesters. This study reviewed the major outcomes of MIVH infrainguinal bypass at our institution given a predominant cohort of critical limb ischemia. METHODS: We performed a 10-year, retrospective, single-institution review from January 2005 to December 2014, identifying all patients undergoing MIVH for obstructive infrainguinal disease. Primary outcomes were primary patency, operative time, intraoperative complications, surgical site infection (SSI), and freedom from amputation. RESULTS: A total of 289 patients (70% male) underwent MIVH infrainguinal bypass at an average age of 68 ± 12 years old, an obesity prevalence of 28%, and with critical limb ischemia in 81% of the patient cohort (20% rest pain, 61% tissue loss/gangrene). Ninety-four percent of patients had no intraoperative complications, 2.5% had adverse cardiac or technical complications, and 4.2% of patients required transfusion. Average operative time was 4.2 h. Femoral-popliteal TASC classification C and D constituted 80% of our patient cohort. At the last follow-up, toe pressures had increased from 30 ± 30 to 62 ± 40 mmHg (p < 0.0001). Primary bypass patency in the first 30 days was 95%. SSI incidence requiring surgical treatment was only 6%. Our median length of stay was 4.0 days, with median intravenous narcotic use of 1 day. In addition, 77% of patients returned to their baseline mobility at first follow-up (median 19 days), and 83% of patients had freedom from amputation at last follow-up (median 820 days). CONCLUSIONS: In a center with experience in MIVH and a consistent group of experienced endoscopic vein harvesters, MIVH bypass has excellent patency, low surgical site infection, short length of stay, and prompt return to baseline mobility.

Extracellular Hsp90 mediates an NF-κB dependent inflammatory stromal program: implications for the prostate tumor microenvironment.

BACKGROUND: The tumor microenvironment (TME) plays an essential role in supporting and promoting tumor growth and progression. An inflammatory stroma is a widespread hallmark of the prostate TME, and prostate tumors are known to co-evolve with their reactive stroma. Cancer-associated fibroblasts (CAFs) within the reactive stroma play a salient role in secreting cytokines that contribute to this inflammatory TME. Although a number of inflammatory mediators have been identified, a clear understanding of key factors initiating the formation of reactive stroma is lacking. METHODS: We explored whether tumor secreted extracellular Hsp90 alpha (eHsp90α) may initiate a reactive stroma. Prostate stromal fibroblasts (PrSFs) were exposed to exogenous Hsp90α protein, or to conditioned medium (CM) from eHsp90α-expressing prostate cancer cells, and evaluated for signaling, motility, and expression of prototypic reactive markers. In tandem, ELISA assays were utilized to characterize Hsp90α-mediated secreted factors. RESULTS: We report that exposure of PrSFs to eHsp90 upregulates the transcription and protein secretion of IL-6 and IL-8, key inflammatory cytokines known to play a causative role in prostate cancer progression. Cytokine secretion was regulated in part via a MEK/ERK and NF-κB dependent pathway. Secreted eHsp90α also promoted the rapid and durable activation of the oncogenic inflammatory mediator signal transducer and activator of transcription (STAT3). Finally, eHsp90 induced the expression of MMP-3, a well-known mediator of fibrosis and the myofibroblast phenotype. CONCLUSIONS: Our results provide compelling support for eHsp90α as a transducer of signaling events culminating in an inflammatory and reactive stroma, thereby conferring properties associated with prostate cancer progression.

Improved measurement of the positive-muon lifetime and determination of the Fermi constant.

The mean life of the positive muon has been measured to a precision of 11 ppm using a low-energy, pulsed muon beam stopped in a ferromagnetic target, which was surrounded by a scintillator detector array. The result, tau(micro)=2.197 013(24) micros, is in excellent agreement with the previous world average. The new world average tau(micro)=2.197 019(21) micros determines the Fermi constant G(F)=1.166 371(6)x10(-5) GeV-2 (5 ppm). Additionally, the precision measurement of the positive-muon lifetime is needed to determine the nucleon pseudoscalar coupling g(P).

PATRIC: the VBI PathoSystems Resource Integration Center.

The PathoSystems Resource Integration Center (PATRIC) is one of eight Bioinformatics Resource Centers (BRCs) funded by the National Institute of Allergy and Infection Diseases (NIAID) to create a data and analysis resource for selected NIAID priority pathogens, specifically proteobacteria of the genera Brucella, Rickettsia and Coxiella, and corona-, calici- and lyssaviruses and viruses associated with hepatitis A and E. The goal of the project is to provide a comprehensive bioinformatics resource for these pathogens, including consistently annotated genome, proteome and metabolic pathway data to facilitate research into counter-measures, including drugs, vaccines and diagnostics. The project's curation strategy has three prongs: 'breadth first' beginning with whole-genome and proteome curation using standardized protocols, a 'targeted' approach addressing the specific needs of researchers and an integrative strategy to leverage high-throughput experimental data (e.g. microarrays, proteomics) and literature. The PATRIC infrastructure consists of a relational database, analytical pipelines and a website which supports browsing, querying, data visualization and the ability to download raw and curated data in standard formats. At present, the site warehouses complete sequences for 17 bacterial and 332 viral genomes. The PATRIC website (https://patric.vbi.vt.edu) will continually grow with the addition of data, analysis and functionality over the course of the project.

The aortic homograft: evolution of indications, techniques, and results in 107 patients.

BACKGROUND: Homograft aortic valve replacement has been performed in 107 patients during the past 7 years. Two primary methods of implantation were used (intraaortic and root replacement). Results of both methods are presented. METHODS: Intraaortic implantation (subcoronary or cylinder technique) was performed in 36 patients (mean age, 54 years) for aortic stenosis or regurgitation (31 patients) and endocarditis (5 patients). Aortic root replacement was performed in 71 patients (mean age, 62 years). The majority (58 patients) had complex root pathologies such as ascending aneurysm, dissection, or prosthetic endocarditis with annular destruction. Early results were assessed with intraoperative or predischarge echocardiography; annual echocardiograms provided long-term follow-up. Left ventricular mass was calculated in patients with long-standing pathology for whom preoperative and postoperative data were available. RESULTS: Early valvular insufficiency was documented in 16 of the 36 intraaortic implants (44%); 9 of these have had progression of the insufficiency. Of the 20 patients who had trivial or no early insufficiency, significant insufficiency has developed in 7 and mild insufficiency has developed in 5. Calculation of left ventricular mass revealed a mean reduction of 11% at 1 year. There has been no mortality, endocarditis, or homograft-related reoperation in the intraaortic group with a mean follow-up of 50 months. The root replacement group had a hospital mortality of 17%. The cardiac pathology was limited to the aortic valve in 12 patients; mortality in this subset was zero. There has been no significant early or late postoperative valvular insufficiency in the 59 surviving patients. More rapid left ventricular mass reduction was seen in this group with a 26% mean reduction within 1 year. A mean follow-up of 32 months in the root replacement group has seen no homograft-related reoperations. CONCLUSIONS: Although the lack of early mortality in the intraaortic group makes this technique appealing, the high incidence of early insufficiency with the realistic expectation of progression has led to our abandonment of the intraaortic technique. Homograft aortic root replacement confers a higher mortality based on the severity of aortic pathology, but offers excellent long-term hemodynamics in any patient. We have expanded our indication for homograft root replacement to include patients with isolated valvular disease rather than reserving it for those patients with extensive root pathology.

Depression in patients with coronary heart disease. A 12-month follow-up.

Little is known about the course and outcome of depression in patients with coronary heart disease, despite its prevalence and effect on medical prognosis. A series of 200 patients undergoing diagnostic cardiac catheterization and coronary angiography were administered a psychiatric diagnostic interview. Seventeen percent were diagnosed with a current major depressive episode, and another 17% with a current minor depressive episode. Ninety percent of those patients who consented to follow-up completed the study. Half of the patients with major depression either remained depressed or relapsed within 12 months. Nearly half of the patients with minor depression remitted, but 42% subsequently developed major depression. These results suggest that major depression, if left untreated, is persistent in patients with coronary heart disease. Furthermore, minor depression is nearly as likely to progress to major depression as to remit over the course of the 12 months following diagnostic angiography.