Long-Term Outcomes of Bovine versus Porcine Mitral Valve Replacement: A Multicenter Analysis.

Introduction: Recent national guidelines recommending mitral valve replacement (MVR) for severe secondary mitral regurgitation have resulted in an increased utilization of mitral bioprosthesis. There is a paucity of data on how longitudinal clinical outcomes vary by prosthesis type. We examined long-term survival and risk of reoperation between patients having bovine vs. porcine MVR. Study Design. A retrospective analysis of MVR or MVR + coronary artery bypass graft (CABG) from 2001 to 2017 among seven hospitals reporting to a prospectively maintained clinical registry was conducted. The analytic cohort included 1,284 patients undergoing MVR (801 bovine and 483 porcine). Baseline comorbidities were balanced using 1 : 1 propensity score matching with 432 patients in each group. The primary end point was all-cause mortality. Secondary end points included in-hospital morbidity, 30-day mortality, length of stay, and risk of reoperation. Results: In the overall cohort, patients receiving porcine valves were more likely to have diabetes (19% bovine vs. 29% porcine; p < 0.001), COPD (20% bovine vs. 27% porcine; p=0.008), dialysis or creatinine >2 mg/dL (4% bovine vs. 7% porcine; p=0.03), and coronary artery disease (65% bovine vs. 77% porcine; p < 0.001). There was no difference in stroke, acute kidney injury, mediastinitis, pneumonia, length of stay, in-hospital morbidity, or 30-day mortality. In the overall cohort, there was a difference in long-term survival (porcine HR 1.17 (95% CI: 1.00-1.37; p=050)). However, there was no difference in reoperation (porcine HR 0.56 (95% CI: 0.23-1.32; p=0.185)). In the propensity-matched cohort, patients were matched on all baseline characteristics. There was no difference in postoperative complications or in-hospital morbidity and 30-day mortality. After 1 : 1 propensity score matching, there was no difference in long-term survival (porcine HR 0.97 (95% CI: 0.81-1.17; p=0.756)) or risk of reoperation (porcine HR 0.54 (95% CI: 0.20-1.47; p=0.225)). Conclusions: In this multicenter analysis of patients undergoing bioprosthetic MVR, there was no difference in perioperative complications and risk of reoperation of long-term survival after matching.

Constitutively elevated levels of SOCS1 suppress innate responses in DF-1 immortalised chicken fibroblast cells.

The spontaneously immortalised DF-1 cell line is rapidly replacing its progenitor primary chicken embryo fibroblasts (CEFs) for studies on avian viruses such as avian influenza but no comprehensive study has as yet been reported comparing their innate immunity phenotypes. We conducted microarray analyses of DF-1 and CEFs, under both normal and stimulated conditions using chicken interferon-α (chIFN-α) and the attenuated infectious bursal disease virus vaccine strain PBG98. We found that DF-1 have an attenuated innate response compared to CEFs. Basal expression levels of Suppressor of Cytokine Signalling 1 (chSOCS1), a negative regulator of cytokine signalling in mammals, are 16-fold higher in DF-1 than in CEFs. The chSOCS1 "SOCS box" domain (which in mammals, interacts with an E3 ubiquitin ligase complex) is not essential for the inhibition of cytokine-induced JAK/STAT signalling activation in DF-1. Overexpression of SOCS1 in chIFN-α-stimulated DF-1 led to a relative decrease in expression of interferon-stimulated genes (ISGs; MX1 and IFIT5) and increased viral yield in response to PBG98 infection. Conversely, knockdown of SOCS1 enhanced induction of ISGs and reduced viral yield in chIFN-α-stimulated DF-1. Consequently, SOCS1 reduces induction of the IFN signalling pathway in chicken cells and can potentiate virus replication.

Atmospheric deposition of nitrogen, sulfur and base cations in jack pine stands in the Athabasca Oil Sands Region, Alberta, Canada.

Atmospheric deposition in the Athabasca Oil Sands Region decreased exponentially with distance from the industrial center. Throughfall deposition (kg ha(-1) yr(-1)) of NH(4)-N (.8-14.7) was double that of NO(3)-N (.3-6.7), while SO(4)-S ranged from 2.5 to 23.7. Gaseous pollutants (NO(2), HNO(3), NH(3), SO(2)) are important drivers of atmospheric deposition but weak correlations between gaseous pollutants and deposition suggest that particulate deposition is also important. The deposition (eq ha(-1)) of base cations (Ca + Mg + Na) across the sampling network was highly similar to N + S deposition, suggesting that acidic deposition is neutralized by base cation deposition and that eutrophication impacts from excess N may be of greater concern than acidification. Emissions from a large forest fire in summer 2011 were most prominently reflected in increased concentrations of HNO(3) and throughfall deposition of SO4-S at some sites. Deposition of NO(3)-N also increased as did NH(4)-N deposition to a lesser degree.

Deep sequencing analysis of defective genomes of parainfluenza virus 5 and their role in interferon induction.

Preparations of parainfluenza virus 5 (PIV5) that are potent activators of the interferon (IFN) induction cascade were generated by high-multiplicity passage in order to accumulate defective interfering virus genomes (DIs). Nucleocapsid RNA from these virus preparations was extracted and subjected to deep sequencing. Sequencing data were analyzed using methods designed to detect internal deletion and "copyback" DIs in order to identify and characterize the different DIs present and to approximately quantify the ratio of defective to nondefective genomes. Trailer copybacks dominated the DI populations in IFN-inducing preparations of both the PIV5 wild type (wt) and PIV5-VΔC (a recombinant virus that does not encode a functional V protein). Although the PIV5 V protein is an efficient inhibitor of the IFN induction cascade, we show that nondefective PIV5 wt is unable to prevent activation of the IFN response by coinfecting copyback DIs due to the interfering effects of copyback DIs on nondefective virus protein expression. As a result, copyback DIs are able to very rapidly activate the IFN induction cascade prior to the expression of detectable levels of V protein by coinfecting nondefective virus.

Failure to activate the IFN-ß promoter by a paramyxovirus lacking an interferon antagonist.

It is generally thought that pathogen-associated molecular patterns (PAMPs) responsible for triggering interferon (IFN) induction are produced during virus replication and, to limit the activation of the IFN response by these PAMPs, viruses encode antagonists of IFN induction. Here we have studied the induction of IFN by parainfluenza virus type 5 (PIV5) at the single-cell level, using a cell line expressing GFP under the control of the IFN-ß promoter. We demonstrate that a recombinant PIV5 (termed PIV5-VΔC) that lacks a functional V protein (the viral IFN antagonist) does not activate the IFN-ß promoter in the majority of infected cells. We conclude that viral PAMPs capable of activating the IFN induction cascade are not produced or exposed during the normal replication cycle of PIV5, and suggest instead that defective viruses are primarily responsible for inducing IFN during PIV5 infection in this system.

A model for cardiopulmonary bypass redesign.

INTRODUCTION: A portion of patients undergoing cardiac surgery may develop focal and/or subtle brain injuries secondary to cardiac surgery. There is evidence that, in some cases, these injuries may be related to cardiopulmonary bypass (CPB). Embolism and hypoperfusion are the dominant mechanisms for focal neurologic injuries among coronary artery bypass graft (CABG) surgery patients. Recent studies suggest that these mechanisms may also produce the more prevalent subtle neurological deficits. The aim of our current work is to obtain a thorough understanding of the processes of care associated with the production of embolic activity, cerebral hypoperfusion, and hemodynamic aberrations that often occur during CPB. METHODS: We developed a system for simultaneous recording of physiologic parameters, embolic activity in the CPB circuit and in the cerebral arteries, and near infrared regional cerebral oxyhemoglobin saturation (NIRS) during cardiac surgery. All data were synchronized with a video recording of the surgical procedure. Periods of embolic activity and NIRS were subsequently related to surgical and CPB processes of care through a systematic review of the patient's surgical case video. RESULTS: To date, we have enrolled 47 patients undergoing coronary and/or valvular procedures. We have observed wide variation across patients in detected cerebral embolic counts, NIRS and physiologic parameters. We have identified increased embolic counts in the CPB circuit related to specific processes and events such as the method of venous drainage, the entrainment of air in the venous line, the injection of medications into the CPB circuit and blood sampling from the CPB circuit. A portion of detected changes in NIRS were related to periods of hypotension and positioning of the heart during the construction of distal coronary artery grafts on the posterior coronary artery vessels. SUMMARY: Use of this model provides the surgical team with detailed information regarding the contribution of CPB to the creation of precursors of neurological injury. This system provides meaningful data to guide the surgical team in the redesign of the CPB system and associated techniques.

Lowest hematocrit on bypass and adverse outcomes associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: Cardiac surgery patients' hematocrits frequently fall to low levels during cardiopulmonary bypass. METHODS: We investigated the association between nadir hematocrit and in-hospital mortality and other adverse outcomes in a consecutive series of 6,980 patients undergoing isolated coronary artery bypass graft surgery. The lowest hematocrit during cardiopulmonary bypass was recorded for each patient. Patients were divided into categories based on their lowest hematocrit. Women had a lower hematocrit during bypass than men but both sexes are represented in each category. RESULTS: After adjustment for preoperative differences in patient and disease characteristics, the lowest hematocrit during cardiopulmonary bypass was significantly associated with increased risk of in-hospital mortality, intra- or postoperative placement of an intraaortic balloon pump and return to cardiopulmonary bypass after attempted separation. Smaller patients and those with a lower preoperative hematocrit are at higher risk of having a low hematocrit during cardiopulmonary bypass. CONCLUSIONS: Female patients and patients with smaller body surface area may be more hemodiluted than larger patients. Minimizing intraoperative anemia may result in improved outcomes for this subgroup of patients.

Mediastinitis and long-term survival after coronary artery bypass graft surgery.

BACKGROUND: Mediastinitis is a dreaded complication of coronary artery bypass surgery (CABG). The long-term effect of mediastinitis on mortality after CABG has not been well studied. METHODS: We examined the survival of 15,406 consecutive patients undergoing isolated CABG surgery from 1992 through 1996. Patient records were linked to the National Death Index. Mediastinitis was defined as occurring during the index admission and requiring reoperation. RESULTS: Mediastinitis occurred in 193 patients (1.25%). Patients with mediastinitis were older and more likely to have had emergency surgery, diabetes, peripheral vascular disease, chronic obstructive pulmonary disease, and preoperative dialysis-dependent renal failure. Patients with mediastinitis were also more likely to be severely obese and had somewhat lower preoperative ejection fraction. After multivariate adjustment for these factors, the first year post-CABG survival rate was 78% with mediastinitis and 95% without, and the hazard ratio for mortality during the entire follow-up period was 3.09 (CI 95% 2.28, 4.19; p < 0.0001). CONCLUSIONS: Mediastinitis is associated with a marked increase in mortality during the first year post-CABG and a threefold increase during a 4-year follow-up period.

MediCaring: development and test marketing of a supportive care benefit for older people.

OBJECTIVES: To develop an alternative healthcare benefit (called MediCaring) and to assess the preferences of older Medicare beneficiaries concerning this benefit, which emphasizes more home-based and supportive health care and discourages use of hospitalization and aggressive treatment. To evaluate the beneficiaries' ability to understand and make a choice regarding health insurance benefits; to measure their likelihood to change from traditional Medicare to the new MediCaring benefit; and to determine the short-term stability of that choice. DESIGN: Focus groups of persons aged 65+ and family members shaped the potential MediCaring benefit. A panel of 50 national experts critiqued three iterations of the benefit. The final version was test marketed by discussing it with 382 older people (men > or = 75 years and women > or = 80 years) in their homes. Telephone surveys a few days later, and again 1 month after the home interview, assessed the potential beneficiaries' understanding and preferences concerning MediCaring and the stability of their responses. SETTINGS: Focus groups were held in community settings in New Hampshire, Washington, DC, Cleveland, OH, and Columbia, SC. Test marketing occurred in New Hampshire, Cleveland, OH; Columbia, SC, and Los Angeles, CA. PARTICIPANTS: Focus group participants were persons more than 65 years old (11 focus groups), healthcare providers (9 focus groups), and family decision-makers (3 focus groups). Participants in the in-home informing (test marketing group) were persons older than 75 years who were identified through contact with a variety of services. MEASUREMENTS: Demographics, health characteristics, understanding, and preferences. RESULTS: Focus group beneficiaries between the ages of 65 and 74 generally wanted access to all possible medical treatment and saw MediCaring as a need of persons older than themselves. Those older than age 80 were mostly in favor of it. Test marketing participants understood the key points of the new benefit: 74% generally liked it, and 34% said they would take it now. Preferences were generally stable at 1 month. In multivariate regression, those preferring MediCaring were wealthier, more often white, more often living in senior housing, and using more homecare services. However, they were not more often in poor health or needing ADL assistance. CONCLUSIONS: Older persons aged more than 80 years can understand a health benefit choice; most liked the aims of a new supportive care benefit, and 34% would change immediately from Medicare to a supportive care benefit such as MediCaring,. These findings encourage further development of special programs of care, such as MediCaring, that prioritize comfort and support for the old old.

Transperineal 125iodine implantation for treatment of clinically localized prostate cancer: 5-year tumor control and morbidity.

PURPOSE: To evaluate the efficacy and toxicity of transperineal 125I implants for clinically localized prostate cancer in elderly men in a community cancer setting. METHODS AND MATERIALS: From 1988 to 1993, 206 patients, median age 77 years, with localized (Stage T1 and T2), low-grade (Gleason score < or = 7) prostate cancer were treated using pre-planned 125I transperineal implants. Patients were followed for biochemical freedom from disease, overall survival, and treatment-associated morbidity. RESULTS: The 5-year actuarial biochemical freedom from failure rate for all patients available for follow-up was 63%. Specifically, biochemical freedom from failure was 76% in patients with pretreatment PSA < or = 10 ng/ml, compared to 51% of patients with values > 10 ng/ml (median observation time 35 months). Actuarial freedom from failure for patients with PSA < or = 4 ng/ml was 84%. Stage and Gleason score did not predict outcome. PSA nadir was the strongest predictor of long-term biochemical disease-free survival (p < 0.001) with only 2 failures in 62 patients who achieved a posttreatment PSA nadir < or = 0.5 ng/ml. CONCLUSION: Transperineal 125I implants for early prostate cancer are efficacious and feasible for certain populations of elderly patients with favorable prognostic indicators in the community cancer setting. Patients with poor prognostic indicators at diagnosis do not appear to be candidates for treatment with implant alone. ( 1999 El.vit r 'Cio;noo lnc

Construction and characterization of a glycoprotein E gene-deleted bovine herpesvirus type 1 recombinant.

OBJECTIVE: To construct and characterize a recombinant glycoprotein (g)E gene-deleted bovine herpesvirus (BHV) type 1 (BHV-1). PROCEDURE: The BHV-1 gEgene-coding region and the flanking upstream and downstream sequences were cloned. The aforementioned cloned DNA was digested with suitable enzymes to release the amino terminal two thirds of that region, and was ligated to the beta-galactosidase (beta-gal) gene. The resulting plasmid DNA was cotransfected with DNA from full-length, wild-type (WT), BHV-1 Cooper strain of the virus. Recombinant viruses expressing beta-gal (blue plaques) were plaque purified and assayed further by blot hybridization for genetic characterization and by immunoblotting for reactivity against BHV-1 gE peptide-specific rabbit polyclonal antibody. One recombinant virus, gEdelta3.1IBR, was characterized in vitro and in vivo. The ability of the recombinant virus to induce BHV-1 neutralizing antibodies in infected calves was investigated by plaque-reduction tests. RESULTS AND CONCLUSIONS: The gEdelta3.1IBR virus contained a deletion in the viral gE gene-coding sequences where a stable chimeric reporter (beta-gal) gene was inserted. One-step growth kinetics and virus yield of the recombinant and parent viruses were similar, but early after infection, the recombinant virus yield was comparatively less. After intranasal inoculation, the recombinant gEdelta3.1IBR virus replicated in the upper respiratory tract of calves, but the amount of progeny viruses produced was hundredsfold reduced, and duration of virus shedding was shorter. Results of in vivo calf experiments and serum neutralization tests indicated that deleting the gE gene has little effect on inducing neutralizing antibodies against BHV-1, but is sufficient to reduce BHV-1 virulence in calves.

Developing staff nurse experts in nursing diagnosis-based care planning.

In this article, the authors describe the Program to Increase Nursing Knowledge and Facilitate the Utilization of Nursing Diagnosis (PINK FUND) undertaken at the Medical College of Virginia Hospitals. The program prepared unit-based nurses to be facilitators for nursing diagnosis-based care planning. Major curriculum threads included theory of nursing diagnosis, planned change, and adult learning. Instructors modeled innovative instructional methodologies for participants. Program planners vigorously marketed the program to nurses within the institution. The program succeeded in preparing nurses to use the nursing process to deliver planned care. The program description will serve as a potential model for staff development educators seeking to increase staff competence in nursing care planning and documentation.

Radon and man-made vitreous fibers.

Epidemiologic studies of miners have established a causal association between radon exposure and development of lung cancer. During the past decade the focus of attention has turned to the potential risks from exposure to radon in indoor air. Governmental involvement thus far has primarily been aimed at gathering further data and issuing voluntary guidelines for radon control in the indoor environment. The federal government's most recent risk assessment for exposure to indoor radon published in 1992 concluded that exposure to indoor radon results in 13,600 radon-induced lung cancer deaths in the United States each year. As public awareness of such environmental issues continues to grow, physicians will be faced with the need to respond to inquiries regarding potential health effects. Man-made vitreous fibers are silicate glass that have a noncrystalline structure. They have been in production for more than 100 years and are used in numerous applications in residential and commercial settings. The health risks from man-made vitreous fibers that are used in residential and commercial settings are limited to skin and occasional respiratory tract irritation under circumstances of improper installation or maintenance. When glass fiber contaminates an indoor environment, proper repair measures and thorough cleaning of the indoor environment will lead to resolution of any resultant irritant symptoms.

Indoor air quality medicolegal issues.

The regulatory and legal communities have begun only recently to address the medicolegal issues surrounding indoor air quality. No single governmental agency is responsible for indoor air quality issues. The focus of the federal government's indoor air quality programs is on the gathering and dissemination of information rather than on the regulation of indoor air pollution. State and local regulatory controls vary but may include antismoking ordinances, building codes, and contractor certification programs. Numerous lawsuits involving various parties and legal theories have been filed on the basis of illness allegedly related to indoor air quality. Further regulatory and legal review of indoor air problems will likely occur in the near future, particularly as a result of the characterization of environmental tobacco smoke as a class A carcinogen.

The influence of FK-506 on the thymus: an immunophenotypic and structural analysis.

The influence of the powerful new immunosuppressant FK-506 on the thymus was investigated in Sprague-Dawley rats that were immunized with sheep erythrocytes and treated with FK-506 (1 mg/kg/day i.m.) for 7 days. Suppression of humoral immunity in drug-treated animals was accompanied by reductions in circulating lymphocytes bearing activation markers (interleukin-2 receptor beta-chain and OX40, activated CD4+ cells) and by striking thymic medullary atrophy. There were, however, no significant differences in thymic weights or in thymocyte numbers between experimental and control groups during the period of FK-506 administration. Reduction of the medullary compartment was visualized immunohistochemically, by decreases in major histocompatibility complex (MHC) class I- and MHC class II-positive cells and in CD37+ (mature medullary) thymocytes. Flow cytometric analysis of thymocytes showed that FK-506 induced increases in bright, Thy-1.1+ cells and in numbers of CD4+ and CD8+ thymocytes, whilst CD37+ cells were less numerous than in controls. Percentages of MHC class I- and MHC class II-positive cells varied little throughout the course of FK-506 administration. Evidence of selective damage to medullary epithelial cells, attributable to FK-506, was found at both the light and electron microscopic levels, whilst thymic macrophages in drug-treated rats displayed features of enhanced phagocytic activity, including ingestion of damaged epithelial cells. These FK-506-induced abnormalities were reversed within 14 days of drug withdrawal. These findings suggest that, like cyclosporin A, FK-506 reversibly disrupts the thymic microenvironment and may interfere with the function/maturation of T lymphocytes.