A disease-causing mutation illuminates the protein membrane topology of the kidney-expressed prohibitin homology (PHB) domain protein podocin.

Mutations in the NPHS2 gene are a major cause of steroid-resistant nephrotic syndrome, a severe human kidney disorder. The NPHS2 gene product podocin is a key component of the slit diaphragm cell junction at the kidney filtration barrier and part of a multiprotein-lipid supercomplex. A similar complex with the podocin ortholog MEC-2 is required for touch sensation in Caenorhabditis elegans. Although podocin and MEC-2 are membrane-associated proteins with a predicted hairpin-like structure and amino and carboxyl termini facing the cytoplasm, this membrane topology has not been convincingly confirmed. One particular mutation that causes kidney disease in humans (podocin(P118L)) has also been identified in C. elegans in genetic screens for touch insensitivity (MEC-2(P134S)). Here we show that both mutant proteins, in contrast to the wild-type variants, are N-glycosylated because of the fact that the mutant C termini project extracellularly. Podocin(P118L) and MEC-2(P134S) did not fractionate in detergent-resistant membrane domains. Moreover, mutant podocin failed to activate the ion channel TRPC6, which is part of the multiprotein-lipid supercomplex, indicative of the fact that cholesterol recruitment to the ion channels, an intrinsic function of both proteins, requires C termini facing the cytoplasmic leaflet of the plasma membrane. Taken together, this study demonstrates that the carboxyl terminus of podocin/MEC-2 has to be placed at the inner leaflet of the plasma membrane to mediate cholesterol binding and contribute to ion channel activity, a prerequisite for mechanosensation and the integrity of the kidney filtration barrier.

Microtubule depolymerization in Caenorhabditis elegans touch receptor neurons reduces gene expression through a p38 MAPK pathway.

Microtubules are integral to neuronal development and function. They endow cells with polarity, shape, and structure, and their extensive surface area provides substrates for intracellular trafficking and scaffolds for signaling molecules. Consequently, microtubule polymerization dynamics affect not only structural features of the cell but also the subcellular localization of proteins that can trigger intracellular signaling events. In the nematode Caenorhabditis elegans, the processes of touch receptor neurons are filled with a bundle of specialized large-diameter microtubules. We find that conditions that disrupt these microtubules (loss of either the MEC-7 ß-tubulin or MEC-12 α-tubulin or growth in 1 mM colchicine) cause a general reduction in touch receptor neuron (TRN) protein levels. This reduction requires a p38 MAPK pathway (DLK-1, MKK-4, and PMK-3) and the transcription factor CEBP-1. Cells may use this feedback pathway that couples microtubule state and MAPK activation to regulate cellular functions.

Early postoperative outcomes and blood product utilization in adult cardiac surgery: the post-aprotinin era.

BACKGROUND: Aprotinin was a commonly used pharmacological agent for homeostasis in cardiac surgery but was discontinued, resulting in the extensive use of lysine analogues. This study tested the hypothesis that early postoperative adverse events and blood product utilization would affected in this post-aprotinin era. METHODS AND RESULTS: Adult patients (n=781) undergoing coronary artery bypass, valve replacement, or both from November 1, 2005, to October 31, 2008, at a single institution were included. Multiple logistic regression modeling and propensity scoring were performed on 29 preoperative and intraoperative variables in patients receiving aprotinin (n=325) or lysine analogues (n=456). The propensity-adjusted relative risk (RR) for the intraoperative use of packed red blood cells (RR, 0.75; 95% confidence interval [CI], 0.57 to 0.99), fresh frozen plasma (RR, 0.37; 95% CI, 0.21 to 0.64), and cryoprecipitate (RR:0.06; 95% CI, 0.02 to 0.22) were lower in the aprotinin versus lysine analog group (all P<0.05). The risk for mortality (RR, 0.53; 95% CI, 0.16 to 1.79) and neurological events (RR, 0.87; 95% CI, 0.35 to 2.18) remained similar between groups, whereas a trend for reduced risk for renal dysfunction was observed in the aprotinin group. CONCLUSIONS: In the post-aprotinin era, with the exclusive use of lysine analogues, the relative risk of early postoperative outcomes such as mortality and renal dysfunction have not improved, but the risk for the intraoperative use of blood products has increased. Thus, improvements in early postoperative outcomes have not been realized with the discontinued use of aprotinin, but rather increased blood product use has occurred with the attendant costs and risks inherent with this strategy.

Thirty-year experience with a bileaflet mechanical valve prosthesis.

BACKGROUND: The objective was to evaluate the long-term outcomes of the St Jude Medical (Saint Paul, Minn) mechanical valve prosthesis implantation. METHODS: Since 1979, every patient receiving this prosthesis has been followed annually. RESULTS: From January 1979 to December 2014, 1023 patients were accrued. Patients' ages ranged from 18 to 85 years. Aortic valve replacement was performed in 584 patients, and mitral valve replacement was performed in 439 patients. Follow-up was 95% complete. Operative mortality was 3% (17/584, aortic valve replacement) and 4% (18/439, mitral valve replacement). In patients undergoing aortic valve replacement, late actuarial survival was 62% ± 2%, 32% ± 2%, and 14% ± 3% at 10, 20, and 30 years, respectively. Thirty-year freedom from reoperation, thromboembolism, valve thrombosis, bleeding, and endocarditis was 92% ± 2%, 79% ± 3%, 96% ± 1%, 56% ± 5%, and 92% ± 2%, respectively. In patients undergoing mitral valve replacement, late actuarial survival was 64% ± 3%, 28% ± 3%, and 14% ± 3% at 10, 20, and 30 years, respectively. Thirty-year freedom from reoperation, thromboembolism, valve thrombosis, bleeding, and endocarditis was 85% ± 5%, 55% ± 6%, 99% ± 1%, 57% ± 6%, and 95% ± 2%, respectively. The incidence of bleeding was 2.5% and 2.0% per patient-year for aortic valve replacement and mitral valve replacement, respectively. The incidence of thromboembolism was 1.6% and 2.9% per patient-year for aortic valve replacement and mitral valve replacement, respectively. CONCLUSIONS: Annual follow-up of all of our patients receiving a St Jude Medical mechanical valves prosthesis has allowed better identification valve-related issues and events. After 3 decades of observation with close follow-up, the St Jude Medical mechanical valve continues to be a reliable prosthesis.

Outcomes of a cardiothoracic intensive care web-based online intravenous insulin infusion calculator study at a Medical University Hospital.

BACKGROUND: The purpose of this study was to examine whether a web-based, on-line intravenous insulin (IVI) infusion calculator (IVIIC) program for the delivery of IVI therapy in coronary artery bypass graft (CABG) patients was superior to a prior IVI protocol used in the cardiothoracic intensive care unit at our institution. METHODS: The study included 97 CABG patients studied from October 2004 to February 2005 pre-protocol (type 2 diabetes) and October 2005 to February 2006 post-protocol (with or without type 2 diabetes). The IVIIC was programmed to resemble an algorithm whereby any patient with type 2 diabetes or a blood glucose (BG) greater than 120 mg/dL was started on IVI with an insulin sensitivity factor, a multiplier of 0.03. The calculator used the following mathematical formula: rate of insulin infusion/hour = (current BG - 60 mg/dL) x 0.03. RESULTS: Pre- and post-protocol groups for patients with type 2 diabetes were similar in all demographics measured, including initial age, mean age, percentage female, and percentage African-American. Significant differences were observed between pre- and post-protocol groups in mean BG recorded over a 48-h period (P < 0.0001), percentage not at target within 48 h (P < 0.0001), mean hours to first BG between 80 to 120 mg/dL (P < 0.0001), mean hours to target (three consecutive BGs 80-120 mg/dL) (P < 0.0001), and hyperglycemic index (P < 0.0001). The incidence of hypoglycemia (percentage BG < 70 mg/dL) was not significantly increased in the post-protocol groups (P = 0.2581). CONCLUSIONS: We conclude that the IVIIC is a safe nurse-driven protocol with excellent BG outcomes.

Valve surgery in renal dialysis patients.

BACKGROUND AND AIM OF THE STUDY: Mechanical valves are used in dialysis patients due to the presumed rapid degeneration of tissue valves. The study aim was to compare the results of mechanical and tissue valves placed in renal dialysis patients. METHODS: Information obtained from a computer-based valve replacement database, telephone interviews and patient charts was reviewed for follow up data. RESULTS: Between 1991 and 2004, 50 dialysis patients underwent left-sided valve replacement. Of these patients, 17 received 21 St. Jude Medical mechanical valves (12 aortic, nine mitral), and 33 received 39 tissue valves (19 aortic, 20 mitral). The mean follow up for the mechanical and tissue valve groups was 19.4 +/- 21.3 and 21.4 +/- 18.7 months, respectively. Mortality at four years was 65% (11/17) for the mechanical valve group, and 42% (14/33) for the tissue valve group (p = 0.15). Freedom from reoperation was not significantly different. The tissue valve group had significantly higher Kaplan-Meier freedom from thromboembolism (100% versus 75 +/- 15%, p = 0.01), hemorrhage (97 +/- 3% versus 44 +/- 17%, p = 0.002), valve-related morbidity (74 +/- 9% versus 42 +/- 16%, p = 0.043), and valve-related morbidity and mortality (69 +/- 9% versus 37 +/- 14%, p = 0.037) at three years. Linearized rates of hemorrhage (21 versus 2%/pt-yr; p = 0.005), valve-related morbidity (36 versus 12%/pt-yr; p = 0.02) and valve-related morbidity and mortality (50 versus 17%/pt-yr; p = 0.008) were all significantly higher in the mechanical valve group. CONCLUSION: Dialysis patients had poor survival; prosthetic valve degeneration was negligible. Incidences of thromboembolism, bleeding and valve-related morbidity and mortality were higher with mechanical valves. Linearized, as opposed to actuarial, analysis further accentuated the unacceptably high rates of complications and death with mechanical valves.

Researcher perspectives on publication and peer review of data.

Data "publication" seeks to appropriate the prestige of authorship in the peer-reviewed literature to reward researchers who create useful and well-documented datasets. The scholarly communication community has embraced data publication as an incentive to document and share data. But, numerous new and ongoing experiments in implementation have not yet resolved what a data publication should be, when data should be peer-reviewed, or how data peer review should work. While researchers have been surveyed extensively regarding data management and sharing, their perceptions and expectations of data publication are largely unknown. To bring this important yet neglected perspective into the conversation, we surveyed ∼ 250 researchers across the sciences and social sciences- asking what expectations"data publication" raises and what features would be useful to evaluate the trustworthiness, evaluate the impact, and enhance the prestige of a data publication. We found that researcher expectations of data publication center on availability, generally through an open database or repository. Few respondents expected published data to be peer-reviewed, but peer-reviewed data enjoyed much greater trust and prestige. The importance of adequate metadata was acknowledged, in that almost all respondents expected data peer review to include evaluation of the data's documentation. Formal citation in the reference list was affirmed by most respondents as the proper way to credit dataset creators. Citation count was viewed as the most useful measure of impact, but download count was seen as nearly as valuable. These results offer practical guidance for data publishers seeking to meet researcher expectations and enhance the value of published data.

Achieving human and machine accessibility of cited data in scholarly publications.

Reproducibility and reusability of research results is an important concern in scientific communication and science policy. A foundational element of reproducibility and reusability is the open and persistently available presentation of research data. However, many common approaches for primary data publication in use today do not achieve sufficient long-term robustness, openness, accessibility or uniformity. Nor do they permit comprehensive exploitation by modern Web technologies. This has led to several authoritative studies recommending uniform direct citation of data archived in persistent repositories. Data are to be considered as first-class scholarly objects, and treated similarly in many ways to cited and archived scientific and scholarly literature. Here we briefly review the most current and widely agreed set of principle-based recommendations for scholarly data citation, the Joint Declaration of Data Citation Principles (JDDCP). We then present a framework for operationalizing the JDDCP; and a set of initial recommendations on identifier schemes, identifier resolution behavior, required metadata elements, and best practices for realizing programmatic machine actionability of cited data. The main target audience for the common implementation guidelines in this article consists of publishers, scholarly organizations, and persistent data repositories, including technical staff members in these organizations. But ordinary researchers can also benefit from these recommendations. The guidance provided here is intended to help achieve widespread, uniform human and machine accessibility of deposited data, in support of significantly improved verification, validation, reproducibility and re-use of scholarly/scientific data.

Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia.

Several molecular and histopathological prognostic markers have been proposed for the therapeutic stratification of medulloblastoma patients. Amplification of the c-myc oncogene, elevated levels of c-myc mRNA, or tumor anaplasia have been associated with worse clinical outcomes. In contrast, high TrkC mRNA expression generally presages longer survival. The goal of this study was to evaluate the prognostic value of c-myc, N-myc and TrkC expression in medulloblastomas and compare them to histopathological classification. We used in situ hybridization to measure expression of these molecular markers. c-myc mRNA was detected in 18 of 59 (31%) cases, and was significantly associated with shorter patient survival times on both univariate and multivariate analyses (p = 0.04). The presence of c-myc mRNA was also significantly associated with tumor anaplasia. While survival rates were higher for patients with low N-myc or high TrkC expression, these differences were not statistically significant. The group of patients with either moderate or severely anaplastic tumors showed only a trend towards shorter survival (p = 0.11). However, severe anaplasia alone was significantly prognostic (p = 0.002). Given the prognostic import of c-myc, we investigated 2 potential mechanisms by which its expression might be regulated: Wnt signaling and Mxi-1 mutation. Nuclear translocation of beta-catenin, a marker of Wnt pathway activation, was more common in medulloblastomas with high c-myc than in tumors overall, but the difference was not statistically significant. No Mxi-1 mutations were detected in the 22 cases examined. The association we describe between c-myc expression, tumor anaplasia, and worse clinical outcomes provides further evidence for the importance of this oncogene in medulloblastoma pathobiology.

Comparative genomic hybridization detects an increased number of chromosomal alterations in large cell/anaplastic medulloblastomas.

We correlate chromosomal changes in medulloblastomas with histologic subtype, reporting the analysis of 33 medulloblastoma specimens by comparative genomic hybridization, and a subset by fluorescence in situ hybridization. Of the 33 tumors, 5 were desmoplastic/nodular, 10 were histologically classic, and 18 were large cell/anaplastic. Chromosomal gains and losses were more common in anaplastic medulloblastomas than in non-anaplastic ones. We identified 4 medulloblastomas with c-myc amplification and 5 medulloblastomas with N-myc amplification; all 9 were of the large cell/anaplastic subtype. Additional regions with high level gains included 2q14-22, 3p23, 5p14-pter, 8q24, 9p22-23, 10p12-pter, 12q24, 12p11-12, 17p11-12, and Xp11. The majority of these high level gains occurred in anaplastic cases. We also found loss of chromosome 17p in 7 large cell/anaplastic cases but no nonanaplastic medulloblastomas. Finally, we detected a significantly increased overall number of chromosomal alterations in large cell/anaplastic medulloblastomas (6.8/case) compared to non-anaplastic ones (3.3/case). These findings support an association between myc oncogene amplification, 17p loss, and large cell/anaplastic histology.

Twenty-year experience with the St Jude Medical mechanical valve prosthesis.

BACKGROUND: We have prospectively followed all adult St Jude Medical mechanical valve recipients at the Medical University of South Carolina since the initial implant in January 1979 and now present our 20-year experience. METHODS: We prospectively followed 837 valve recipients (aortic valve replacement; n = 478; mitral valve replacement; n = 359) from January 1979 to December 2000 at 12-month intervals. RESULTS: Ages ranged from 19 to 84 years. Follow-up averaged (mean +/- standard deviation) 7 +/- 5 years (98% complete). Patients were in New York Heart Association class III or IV in 77% (aortic valve replacement) and 89% (mitral valve replacement) preoperatively. A 19-mm valve was implanted in 15.5% of aortic valve replacement patients. Coronary bypass was required in 31% of aortic valve replacements and 20% of mitral valve replacements. Operative mortality was 17/478 (3.6%) in aortic valve replacement and 19/359 (5.3%) in mitral valve replacement, and multivariable predictors were 19-mm valve size, 3 or more coronary bypass grafts, and New York Heart Association class IV for aortic valve replacement and New York Heart Association class IV and age for mitral valve replacement. Actuarial survivorship at 10 and 20 years was 57% +/- 3% and 26% +/- 5% for aortic valve replacement and 61% +/- 3% and 39% +/- 4% for mitral valve replacement. Multivariable predictors of late death were African-American ethnicity, New York Heart Association class III or IV, coronary bypass, and age for aortic valve replacement and New York Heart Association class III or IV, coronary bypass, and age for mitral valve replacement. For aortic valve replacement, effective orifice area was univariately (P =.002) but not multivariately (P =.378) predictive of late death. Structural valve deterioration was not observed. For aortic valve replacement, actuarial freedom (at 10 and 20 years) from reoperation was 93% +/- 1% and 90% +/- 2%; thromboembolism, 82% +/- 3% and 68% +/- 8%; bleeding events, 77% +/- 3% and 66% +/- 6%; prosthetic valve endocarditis, 94% +/- 1% and 94% +/- 1%; valve-related mortality, 94% +/- 2% and 86% +/- 4%; and valve-related mortality or morbidity, 58% +/- 3% and 32% +/- 8%. For mitral valve replacement, actuarial freedom (at 10 and 20 years) from reoperation was 96% +/- 1% and 90% +/- 3%; thromboembolism, 77% +/- 3% and 59% +/- 7%; bleeding events, 86% +/- 2% and 65% +/- 8%; prosthetic valve endocarditis, 98% +/- 1% and 96% +/- 2%; valve-related mortality, 89% +/- 0.2% and 74% +/- 8%; and valve-related mortality or morbidity, 63% +/- 3% and 29% +/- 7%. CONCLUSIONS: After 2 decades of observation with close follow-up, the St Jude Medical mechanical valve continues to be a reliable prosthesis.

Expression of stabilized beta-catenin in differentiated neurons of transgenic mice does not result in tumor formation.

BACKGROUND: Medulloblastomas, embryonal tumors arising in the cerebellum, commonly contain mutations that activate Wnt signaling. To determine whether increased Wnt signaling in the adult CNS is sufficient to induce tumor formation, we created transgenic mice expressing either wild-type or activated beta-catenin in the brain. METHODS: Wild-type and mutant human beta-catenin transgenes were expressed under the control of a murine PrP promoter fragment that drives high level postnatal expression in the CNS. Mutant beta-catenin was stabilized by a serine to phenylalanine alteration in codon 37. RESULTS: Expression of the mutant transgene resulted in an approximately two-fold increase in beta-catenin protein levels in the cortex and cerebellum of adult animals. Immunohistochemical analysis revealed nuclear beta-catenin in hippocampal, cortical and cerebellar neurons of transgenic animals but not in non-transgenic controls. Tail kinking was observed in some transgenic animals, but no CNS malformations or tumors were detected. CONCLUSIONS: No tumors or morphologic alterations were detected in the brains of transgenic mice expressing stabilized beta-catenin, suggesting that postnatal Wnt signaling in differentiated neurons may not be sufficient to induce CNS tumorigenesis.

Stereoselective analysis of carvedilol in human plasma using HPLC/MS/MS after chiral derivatization.

A relatively high-throughput high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method using a chiral derivatization reagent was developed for the quantitative determination of carvedilol enantiomers in human plasma. S-carvedilol and R-carvedilol are extracted from human plasma by protein precipitation using acetonitrile containing racemic [(2)H(5)]-carvedilol as an internal standard. Extracts are then derivatized with 2,3,4,6-tetra-O-acetyl-beta-glucopyranosyl isothiocyanate (GITC) and analysed using HPLC-MS/MS with a TurboIonspray (TIS) interface and selected reaction monitoring. Using 150microL of plasma, the method was validated over a concentration range of 0.2-200ng/mL. The maximum within-run precision observed in a three run quality control was 8.2% for S-carvedilol and 6.7% for R-carvedilol, respectively. The maximum percentage bias observed at all quality control sample concentrations was 9.4% for S-carvedilol and 11.6% for R-carvedilol, respectively. The HPLC-MS/MS method was also compared with a previously developed high-performance LC/fluorescence method by analysing 25 samples containing racemic carvedilol. Based on results obtained, these two methods were found to be equivalent. However, compared with LC/fluorescence method, HPLC-MS/MS method is more sensitive, uses less plasma, and also employs a less time-consuming sample preparation process.

Data publication consensus and controversies.

The movement to bring datasets into the scholarly record as first class research products (validated, preserved, cited, and credited) has been inching forward for some time, but now the pace is quickening. As data publication venues proliferate, significant debate continues over formats, processes, and terminology. Here, we present an overview of data publication initiatives underway and the current conversation, highlighting points of consensus and issues still in contention. Data publication implementations differ in a variety of factors, including the kind of documentation, the location of the documentation relative to the data, and how the data is validated. Publishers may present data as supplemental material to a journal article, with a descriptive "data paper," or independently. Complicating the situation, different initiatives and communities use the same terms to refer to distinct but overlapping concepts. For instance, the term published means that the data is publicly available and citable to virtually everyone, but it may or may not imply that the data has been peer-reviewed. In turn, what is meant by data peer review is far from defined; standards and processes encompass the full range employed in reviewing the literature, plus some novel variations. Basic data citation is a point of consensus, but the general agreement on the core elements of a dataset citation frays if the data is dynamic or part of a larger set. Even as data publication is being defined, some are looking past publication to other metaphors, notably "data as software," for solutions to the more stubborn problems.

Apicoaortic conduits: indications, complications, and imaging techniques.

Left ventricular apex to descending aorta conduits may be used as a last resort treatment of severe left ventricular outflow tract obstruction in cases in which alternative therapies are contraindicated. Although this technique is rarely used in current practice for congenital cases, its use in the elderly population is increasing, largely due to the expansion of this patient cohort and associated comorbidities precluding aortic valve replacement, the most common of which are a severely calcified "porcelain" aorta and/or previous coronary artery bypass grafts preventing aortic root manipulation. Diagnostic imaging is essential in the presurgical workup and subsequent follow-up of these patients, as complications of the procedure are potentially life threatening and are not rare. Several imaging modalities may be used, each with advantages and disadvantages. Both anatomic and functional assessments play a role in the comprehensive evaluation of both presurgical and postsurgical patients.

Combined carotid endarterectomy and coronary artery bypass grafting versus coronary artery bypass grafting alone: a retrospective review of outcomes at our institution.

BACKGROUND: It remains controversial whether patients with concomitant carotid and coronary disease should undergo operative repair separately or in combination. METHODS: Patients with documented cerebrovascular disease undergoing coronary artery bypass grafting (CABG) alone were matched by propensity scoring with patients undergoing combined carotid endarterectomy (CEA)/CABG procedures and compared for the occurrence of stroke, myocardial infarction (MI), and mortality. RESULTS: Of the 4943 patients undergoing CABG, 908 had known cerebrovascular disease. Among these, 134 underwent concomitant CEA, and these were propensity matched with 134 patients undergoing CABG only. No differences were observed in the perioperative risks of stroke (4% vs 3%, odds ratio [OR] 1.5, 95% confidence interval [CI] 0.4-5.5), MI (0.7% vs 0.7%, not significant [NS]), or combined cardiovascular events (6% vs 10%, OR 0.5, 95% CI [0.2-1.3]), although mortality (1% vs 8%, OR 0.2, 95% CI [0.04-0.8] was higher with CABG only. DISCUSSION: Addition of CEA to CABG did not significantly alter the risk of perioperative stroke relative to propensity-matched patients undergoing CABG alone.

Pacemaker and internal cardioverter defibrillator lead extraction: a safe and effective surgical approach.

BACKGROUND: Need for pacemaker or internal cardioverter defibrillator lead removal is increasing. Removal can be dangerous, difficult, or unsuccessful. METHODS: We retrospectively reviewed our results and the techniques we used in 365 patients from 1992 through 2009 for successful complete removal of leads and complications. Various techniques of extraction were analyzed for effectiveness and complications. The eras before (1992 to 1999) and after the availability of laser sheath extraction (2000 to 2009) are compared. RESULTS: Of 365 patients who underwent transvenous lead extraction, of which 235 were infected, and 130 had lead removal for noninfectious indication. Staphylococcus aureus was the infecting organism in 40%, and coagulase-negative Staphylococcus occurred in 33%. One-half of the organisms were methicillin resistant. Preimplant risk factors for infection included more than one device implant procedure in 105 (47%), preimplant Coumadin therapy (Bristol-Myers Squibb, Princeton, NJ) in 74 (31%), and hemodialysis in 9 (4%). Laser extraction became available in 2000. The era with the availability of laser extraction was associated with a better complete extraction rate (93% vs 89.55%) a lower bleeding rate (1.9% vs 3.1%), and complete extraction without the additional use of femoral workstation extraction tools. Mortality was 1.1%. No death was due to device removal. All deaths were the result of severe preoperative and continuing postextraction sepsis. CONCLUSIONS: A lead extraction protocol that included procedures done in an operating room environment allowing rapid, open intervention for bleeding, a varied choice of extraction tools, arterial line monitoring, transesophageal echocardiography, general anesthesia, and an experienced team yielded complete extraction in more than 90% of patients, with a low complication rate and no procedurally related deaths.

Twenty-five year experience with the St. Jude medical mechanical valve prosthesis.

BACKGROUND: We evaluated all adult St. Jude mechanical valve recipients at our institution since the initial implant in January 1979 and now present our 25-year experience. METHODS: Nine hundred forty-five valve recipients were followed prospectively at 12-month intervals from January 1979 to December 2007. RESULTS: Operative mortality was 3% in the aortic valve recipients and 5% in the mitral valve recipients. Follow-up was 95% complete. Among aortic valve recipients, late actuarial survival was 81% +/- 2%, 59% +/- 2%, 41% +/- 3%, 28% +/- 3%, and 17% +/- 4% at 5, 10, 15, 20, and 25 years, respectively. Twenty-five-year freedom from reoperation, thromboembolism, bleeding, and endocarditis was 90% +/- 2%, 69% +/- 5%, 67% +/- 3%, and 9% 3 +/- 2% respectively. Among mitral valve recipients late actuarial survival was 84% +/- 2%, 63% +/- 3%, 44% +/- 3%, 31% +/- 3%, and 23% +/- 4% at 5, 10, 15, 20, and 25 years, respectively. Twenty-five-year freedom from reoperation, thromboembolism, bleeding and endocarditis was 81% +/- 10%, 52% +/- 8%, 64% +/- 6%, and 97% +/- 1%. Freedom from valve-related mortality and morbidity at 25 years was 26% +/- 7% and 29% +/- 6% for aortic and mitral valve replacement, respectively. Freedom from valve-related mortality was 66% +/- 8% and 87% +/- 3% for aortic and mitral valve replacement, respectively. CONCLUSIONS: These results compare favorably with those for other mechanical prostheses. After two and a half decades of observation with close follow-up, the St. Jude mechanical valve continues to be a reliable prosthesis.