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In Germany, the African swine fever virus (ASFV) was first detected in a wild boar in September 2020 in the German federal state of Brandenburg near the border to Poland. It has since been spreading with currently more than 3,960 confirmed cases in wild boar and five outbreaks in domestic pigs (TSIS 2022). Feed has been mentioned as a possible source of ASFV transmission into domestic pig farms and stability of ASFV in feed and bedding has been defined as a knowledge gap on European and global level. A literature study was performed to examine the role different categories of feed materials could play for virus transmission to domestic pigs considering the impact of feed processing, transport and storage. The available information was used to estimate the risk of individual feed groups for domestic pigs with regard to their virus transmission probability. For processed by-products, e.g. grains, extraction meals and compound feed, it can be assumed that ASFV will become most likely inactivated during processing. Although recontamination with virus after the manufacturing process may occur, this scenario is assumed to be unlikely under general hygiene and HACCP principles. Due to the infectivity of ASFV and its resistance to environmental factors, virus transmission into domestic pig farms cannot be excluded for certain feed categories such as unprocessed, directly-fed feed materials. In contrast, processed feed probably does not play a role in ASFV transmission. According to literature, ASFV may be also retained in blood meal and spray-dried plasma after processing in the very unlikely case that blood or plasma from highly-infectious domestic pigs is used. Overall, the literature review pointed out that future research is needed to generate data on the main factors influencing the survival and transmission of ASFV in feed material for domestic pigs during processing and storage.

Hypoglycin A (HGA), methylenecyclopropylglycine (MCPrG), hypoglycin B (HGB), and γ-glutamyl-α-(methylenecyclopropyl) glycine (γ-glutamyl-MCPrG) are secondary plant metabolites occurring in sycamore maple ( Acer pseudoplatanus ) as well as several other Sapindaceae (e.g., Blighia sapida ). By interfering with energy metabolism, they may cause severe intoxication in humans and other species. However, to date, there is not enough data available concerning the intake, metabolism, or excretion of sycamore maple toxins in dairy cows. In May 2022, five cows were observed over four days, when they had first access to a pasture with two sycamore maples. Grazing of their seedlings that grew numerously in between the pasture plants was monitored by direct observation. Milk samples were drawn both from individual cows and from the bulk tank. Spontaneous urine samples were collected from all cows on day 3 after access to the pasture. Seedlings (100 g) were sampled on the pasture and analyzed, together with milk and urine samples, for sycamore toxins and their metabolites using liquid chromatography-tandem mass spectrometry and liquid chromatography-high-resolution mass spectrometry. Cows ingested sycamore seedlings while grazing. Values of HGA in milk were below the limit of quantification. However, metabolites of HGA and MCPrG were detected in individual milk samples already at the end of the first day of grazing. Urine samples of all five cows showed higher concentrations of conjugated HGA and MCPrG metabolites than in milk. Observations suggest that dairy cows may have a low susceptibility toward sycamore maple toxins. However, whether this could be attributed to foregut fermenting species in general requires further elucidation.

Lupin varieties with a low content of quinolizidine alkaloids (QAs) like blue sweet lupin (BSL) have long been used as a protein source for dairy cows. A health concern for humans may arise from the transfer of acute toxic QAs from feed into cow's milk. This study is the first to quantify the transfer of QAs from BSL into cow's milk with experimental and modeling methods. Four lactating dairy cows were subjected to two 7 day feeding periods with 1 and 2 kg/d BSL, respectively, each followed by a depuration period. BSL contained 1774 mg/kg dry matter total QAs. Individual milk samples were taken twice daily and QA contents in feed and milk determined with liquid chromatography-tandem mass spectrometry. Transfer of QAs into the milk was already seen with the administration of 1 kg/d BSL, with differences in transfer rates (TRs) between individual QAs. A toxicokinetic model was derived to quantify and predict QA feed-to-food transfer. For the four most prominent QAs, our model shows an α-half-life of around 0.27 d. TRs were obtained for six QAs and were between 0.13 (sparteine) and 3.74% (multiflorine). A toxicological assessment of milk containing QAs as measured in this study indicated a potential health concern.

Hypoglycin A (HGA) and methylenecyclpropylglycine (MCPrG) are formed by some maple trees ( Acer species) and have been associated with incidences of atypical myopathy among horses in pastures. In this work, a simple and sensitive ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method without derivatization was developed for the quantification of HGA and MCPrG in maple samples and validated according to EU guidelines. The LOQ presented here for HGA (16.4 µg/kg) is considerably lower than the lowest published LOQ (500 µg/kg). This method confirms that sycamore and box elder maple contain considerable amounts of HGA and MCPrG. In addition, the presence of the dipeptides hypoglycin B and γ-glutamyl-MCPrG in these two maple species is shown using high-resolution MS. This is the first report on the presence of these dipeptides in maple since 1973. The presence of HGB and γ-glutamyl-MCPrG could change the way we understand animal intoxication following the ingestion of maple.

Cancer stem cells (CSCs) are a major cause of tumor therapy failure. This is mainly attributed to increased DNA repair capacity and immune escape. Recent studies have shown that functional DNA repair via homologous recombination (HR) prevents radiation-induced accumulation of DNA in the cytoplasm, thereby inhibiting the intracellular immune response. However, it is unclear whether CSCs can suppress radiation-induced cytoplasmic dsDNA formation. Here, we show that the increased radioresistance of ALDH1-positive breast cancer stem cells (BCSCs) in S phase is mediated by both enhanced DNA double-strand break repair and improved replication fork protection due to HR. Both HR-mediated processes lead to suppression of radiation-induced replication stress and consequently reduction of cytoplasmic dsDNA. The amount of cytoplasmic dsDNA correlated significantly with BCSC content (p=0.0002). This clearly indicates that HR-dependent avoidance of radiation-induced replication stress mediates radioresistance and contributes to its immune evasion. Consistent with this, enhancement of replication stress by inhibition of ataxia telangiectasia and RAD3 related (ATR) resulted in significant radiosensitization (SER37 increase 1.7-2.8 Gy, p<0.0001). Therefore, disruption of HR-mediated processes, particularly in replication, opens a CSC-specific radiosensitization option by enhancing their intracellular immune response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Meyer, Engel, Krause, Wagner, Poole, Dubrovska, Peitzsch, Rothkamm, Petersen and Borgmann.)

Recombinant immunoglobulins (rIgGs) have become increasingly important as therapeutic agents and diagnostic tools in recent years. Genetic engineering allows the introduction of non-natural features such as the Sortase motif for site-directed labeling. In this study, the enzyme Sortase A (SrtA) was used for the proteolytic cleavage of rIgGs to produce their biotinylated Fab fragments by locating the cleavage site close to the hinge region. However, SrtA cleavage of engineered rabbit IgGs (rRb-IgGs) derived from human embryonic kidney (HEK) 293 cells showed significantly lower yields compared with their mouse counterparts. Nonrecombinant Rb-IgGs have N- and O-glycans, and the presence of O-glycans close to the hinge region of the rRb-IgGs might affect the susceptibility of these antibodies to SrtA cleavage. In addition, the glycosylation pattern of rIgGs differs depending on the host cell used for expression. Therefore, we analyzed the N- and O-glycans of various rRb-IgGs expressed in HEK293 cells, detecting and quantifying 13 different N-glycan and 3 different O-glycan structures. The distribution of the different detected glycoforms in our rRb-IgG N-glycan analysis is in agreement with previous studies on recombinant human IgG N-glycans, confirming the hypothesis that the host cell defines the glycosylation of the recombinant produced IgGs. O-glycosylation could be mapped onto the threonine residue within the hinge region sequence XPTCPPPX, as already described previously for nonrecombinant Rb-IgGs. Substitution of this threonine allowed an almost complete Fab fragment cleavage. Therefore, we could confirm the hypothesis that the O-glycans affect the SrtA activity, probably due to steric hindrance., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The United States Environmental Protection Agency (US EPA) is currently refining its approach for risk assessments conducted under the amended Toxic Substances Control Act (TSCA), largely based on recommendations from the National Academies of Sciences, Engineering, and Medicine (NASEM). We identified several issues with the current TSCA risk assessment approach that were not addressed by NASEM in its recommendations. Here, we demonstrate these issues with a case study of the 'Risk Evaluation for Asbestos, Part 1: Chrysotile Asbestos,' which US EPA released in December 2020. In this evaluation, US EPA found that occupational and some consumer uses of automotive brakes and clutches that contain asbestos result in unreasonable risks. These risks were calculated from estimated exposures during brake work and an inhalation unit risk (IUR) developed for chrysotile asbestos. We found that US EPA overestimated risk as a result of unrealistic inputs to both the exposure and toxicity components of the risk equation, and because the Agency did not fully consider relevant epidemiology and toxicity evidence in its systematic review. Our evaluation demonstrates areas in which the TSCA risk assessment approach could be improved to result in risk evaluations that are supported by the available scientific evidence.

Aim: Development and qualification of an easy-to-use ELISA for detection of IgM anti-drug antibodies (ADA) and its use in a clinical Phase I trial. Results & methodology: During the assay development two positive control (PC) approaches, the preparation of a chemically conjugated and a recombinant PC, were pursued. With both PCs, the assay was developed and successfully qualified considering the regulatory guidelines. For a case study, the IgM ADA isotyping assay with the recombinant PC was selected. Different courses and intensities of immune response regarding IgM signals were demonstrated. Conclusion: The easy-to-use ELISA allowed IgM-ADA detection in clinical samples. Conjugated and recombinant IgM PCs were comparable regarding assay sensitivity, precision and suitability.

Inflammasomes are a family of pro-inflammatory signaling complexes that orchestrate inflammatory responses in many tissues. The NLRP3 inflammasome has been implicated in several diseases associated with chronic inflammation. In this paper, we present an Adverse Outcome Pathway (AOP) for NLRP3-induced chronic inflammatory diseases that demonstrates how NLRP3 can cause a transition from acute to chronic inflammation, and ultimately the onset of disease. We present a simple graphical description of the main features of internal dose time courses that are important when pharmacodynamics are governed by an activation threshold. Similar considerations hold for other AOPs that are rate-limited by processes with activation thresholds. The risk analysis implications of AOPs with threshold or threshold-like pharmacodynamic responses include the need to consider how cumulative dose per unit time is distributed over time and the possibility that safe, or virtually safe, exposure concentrations can be defined for such processes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors had complete control over the design, conduct, interpretation, and composition of this manuscript. The contents of this manuscript are solely the responsibility of the authors and do not necessarily reflect the views or policies of their employers. J. Goodman and A. Engel received support from the George Washington University (GWU) for developing this manuscript. Dr. Goodman has served as an expert in multiple litigation matters involving asbestos-containing products. None of the underlying research or analysis for this paper was performed during the context of those engagements or was sponsored by any of the defendants. Dr. Cox's work on the risk modeling approach reported here was supported by his employer, Cox Associates LLC, which has received research funding in 2018–2020 from the following sources: (1) a research contract from the National Stone, Sand, and Gravel Association to develop and apply risk models and machine learning methods and causal analytics to risk assessment for mineral dusts and fibers; (2) a research project with the GWU Regulatory Studies Center to investigate and explain the role of the NLRP3 inflammasome in risk analysis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Esophageal cancers comprise about 1% of all cancers diagnosed in the US but are more prevalent in other regions of the world. Several regulatory agencies have classified asbestos as a known human carcinogen, and it is linked to multiple diseases and malignancies, including lung cancer and mesothelioma. In a 2006 review of the epidemiological literature, the Institute of Medicine (IOM) did not find sufficient evidence to demonstrate a causal relationship between asbestos exposure and esophageal cancer. To reevaluate this conclusion, we performed a critical review of the animal toxicological, epidemiological, and mechanism of action literature on esophageal cancer and asbestos, incorporating studies published since 2006. Although there is some evidence in the epidemiological literature for an increased risk of esophageal cancer in asbestos-exposed occupational cohorts, these studies generally did not control for critical esophageal cancer risk factors (e.g. smoking, alcohol consumption). Furthermore, data from animal toxicological studies do not indicate that asbestos exposure increases esophageal cancer risk. Based on our evaluation of the literature, and reaffirming the IOM's findings, we conclude that there is insufficient evidence to demonstrate a causal link between asbestos exposure and esophageal cancer.

Transient gene expression (TGE) in HEK293 cells was optimized by Vink et al. by co-expression of human cell cycle inhibitors p21 CIP /p27 KIP and Simian virus 40 large T antigen (SVLT). In this study, we investigated the effect of this enhancer protein complex on the TGE experiments in a cell-cycle arrested condition of HEK293F cells induced by valproic acid. Growth profiles, consumptions of nutrients, formations of waste products, and product titers of recombinant human antibodies (huAb) were monitored during the 7-day cultivation time. Our results showed that the use of enhancer proteins increased the product yields in a growth arrest condition as well. During the growth phase, no differences were detected regarding viable cell densities (VCDs), viabilities, growth rates, and cell diameters between the TGE experiments with and without enhancer proteins. However, during the declining phase VCD and viability showed slightly higher values at day 6 and 7 in the presence of enhancers. Furthermore, we could not detect any differences in glucose and glutamine metabolism during batch cultivations with co-expression of enhancer proteins. Taken together, the special complex of enhancer proteins did not contribute to further enhancement of growth arrest and shift in the main cell metabolisms, but resulted in higher cell viability during the decline phase. Our observations suggest that the human cell cycle inhibitors p21 CIP /p27 KIP together with very low amount of SVLT antigen may induce alternative functional activities than growth arrest to further improve the yield of recombinant proteins., (© 2019 American Institute of Chemical Engineers.)

In 2009, the government of the province of Ontario, Canada passed new legislation to promote the development of renewable energy facilities, including wind energy facilities in the province. Throughout the legislative process, concerns were raised with respect to the effect of wind energy facilities on human health. Ultimately, the government established setbacks and sound level limits for wind energy facilities and provided Ontario residents with the right to appeal the approval of a wind energy facility on the ground that engaging in the facility in accordance with its approval will cause serious harm to human health. The first approval of a wind facility under the new legislation was issued in 2010 and since then, Ontario's Environmental Review Tribunal as well as Ontario's courts has been considering evidence proffered by appellants seeking revocation of approvals on the basis of serious harm to human health. To date, the evidence has been insufficient to support the revocation of a wind facility approval. This article reviews the legal basis for the dismissal of human-health based appeals.

Investigation of protein-protein interactions (PPIs) and protein phosphorylation in clinical tissue samples can offer valuable information about the activation status and function of proteins involved in disease progression. However, existing antibody-based methods for phosphorylation detection have been found to lack specificity, and methods developed for examining PPIs in vitro cannot be easily adapted for tissues samples. In this study, we eliminated some of these limitations by developing a specific immunohistochemical staining method that uses "dual binders" (DBs), which are bispecific detection agents consisting of two Fab fragment molecules joined by a flexible linker, to detect PPIs and protein phosphorylation. We engineered DBs by selecting Fab fragments with fast off-rate kinetics, which allowed us to demonstrate that stable target binding was achieved only upon simultaneous, cooperative binding to both epitopes. We show that DBs specifically detect the activated HER2/HER3 complex in formalin-fixed, paraffin-embedded cancer cells and exhibit superior detection specificity for phospho-HER3 compared to the corresponding monoclonal antibody. Overall, the performance of DBs makes them attractive tools for future development for clinical applications., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Human β-galactoside α-2,6-sialyltransferase I (ST6Gal-I) establishes the final glycosylation pattern of many glycoproteins by transferring a sialyl moiety to a terminal galactose. Complete sialylation of therapeutic immunoglobulins is essential for their anti-inflammatory activity and protein stability, but is difficult to achieve in vitro owing to the limited activity of ST6Gal-I towards some galactose acceptors. No structural information on ST6Gal-I that could help to improve the enzymatic properties of ST6Gal-I for biotechnological purposes is currently available. Here, the crystal structures of human ST6Gal-I in complex with the product cytidine 5'-monophosphate and in complex with cytidine and phosphate are described. These complexes allow the rationalization of the inhibitory activity of cytosine-based nucleotides. ST6Gal-I adopts a variant of the canonical glycosyltransferase A fold and differs from related sialyltransferases by several large insertions and deletions that determine its regiospecificity and substrate specificity. A large glycan from a symmetry mate localizes to the active site of ST6Gal-I in an orientation compatible with catalysis. The glycan binding mode can be generalized to any glycoprotein that is a substrate of ST6Gal-I. Comparison with a bacterial sialyltransferase in complex with a modified sialyl donor lends insight into the Michaelis complex. The results support an SN2 mechanism with inversion of configuration at the sialyl residue and suggest substrate-assisted catalysis with a charge-relay mechanism that bears a conceptual similarity to serine proteases.

Angiogenesis, the formation of new blood vessels from existing vessels is required for many physiological processes and for growth of solid tumors. Initiated by hypoxia, angiogenesis involves binding of angiogenic factors to endothelial cell (EC) receptors and activation of cellular signaling, differentiation, migration, proliferation, interconnection and canalization of ECs, remodeling of the extracellular matrix and stabilization of newly formed vessels. Experimentally, these processes can be studied by several in vitro and in vivo assays focusing on different steps in the process. In vitro, ECs form networks of capillary-like tubes when propagated for three days in coculture with fibroblasts. The tube formation is dependent on vascular endothelial growth factor (VEGF) and omission of VEGF from the culture medium results in the formation of clusters of undifferentiated ECs. Addition of angiogenesis inhibitors to the coculture system disrupts endothelial network formation and influences EC morphology in two distinct ways. Treatment with antibodies to VEGF, soluble VEGF receptor, the VEGF receptor tyrosine kinase inhibitor SU5614, protein tyrosine phosphatase inhibitor (PTPI) IV or levamisole results in the formation of EC clusters of variable size. This cluster morphology is a result of inhibited EC differentiation and levamisole can be inferred to influence and block VEGF signaling. Treatment with platelet factor 4, thrombospondin, rapamycin, suramin, TNP-470, salubrinal, PTPI I, PTPI II, clodronate, NSC87877 or non-steriodal anti-inflammatory drugs (NSAIDs) results in the formation of short cords of ECs, which suggests that these inhibitors have an influence on later steps in the angiogenic process, such as EC proliferation and migration. A humanized antibody to VEGF is one of a few angiogenesis inhibitors used clinically for treatment of cancer. Levamisole is approved for clinical treatment of cancer and is interesting with respect to anti-angiogenic activity in vivo since it inhibits ECs in vitro with a morphology resembling that obtained with antibodies to VEGF.

Background: Advances in optics and instrumentation with the da Vinci S Surgical System have facilitated minimally invasive and robotic cardiac procedures including mitral valve repair and atrial myxoma excision. We report our retrospective data comparing robotically assisted myxoma excision with standard median sternotomy excision., Methods: Data were collected for cardiac myxoma resection performed between January 2000 and December 2009. The resulting cohort included a total of 57 patients. These patients were grouped into two categories: robotic-assisted (n = 17) surgical procedures and traditional (nonrobotic; n = 40) surgical procedures. Presurgical and surgical risk factors were examined., Results: Univariate analysis comparing the surgical procedure groups and surgical risk factors found a significant difference in 3 of the 14 variables. Cannulation in all patients undergoing robotic-assisted cardiac myxoma excision was performed through cannulating the common femoral artery and vein while cannulation for the traditional procedures was performed using the aorta and atrium except for two patients. For aortic occlusion, 14 of the robotic-assisted cardiac myxoma patients had balloon occlusion and 34 of the traditional cardiac myxoma patients had aortic cross-clamp occlusion. Operating time was significantly shorter for robotic cases (2.7 hours) compared with traditional cases (3.5 hours)., Conclusion: Robotic excision of atrial myxomas is safe and may be an alternative to traditional open surgery in selected patients., (© 2012 Wiley Periodicals, Inc.)

Background: The purpose of this study was to describe the incidence and clinical/pathologic characteristics of papillary thyroid microcarcinoma (PMC) in a community hospital setting and to evaluate the frequency and characteristics of these lesions when unsuspected preoperatively., Methods: A total of 723 patients underwent a partial or total thyroidectomy. A retrospective review was performed., Results: A total of 194 of the 723 patients had a final diagnosis of papillary carcinoma. Ninety-six (49%) of these tumors were PMCs defined as being 1.0 cm or less in diameter. One third (32 of 96) of these lesions were multifocal and 16.7% (16 of 96) were found to have regional lymph node metastases. The majority (58%) of PMCs were found on final pathology and were clinically unsuspected (occult). Multifocality was found in 32.1% (18 of 56) of patients with clinically unsuspected PMC, with nodal metastases in 3.6% (2 of 56). The other 40 patients with PMC had surgeries performed for a clinical reason related to that pathologic lesion. This clinically suspected group was comparably multifocal (35%), but more likely to have cervical lymph node metastasis (35%). Sixty-six percent (37 of 56) diagnosed with a clinically unsuspected PMC underwent a partial thyroidectomy at the initial surgery., Conclusions: The prevalence of clinically unsuspected PMC in our population undergoing thyroidectomy was 7.7% (56 of 723). In our institution, this is more than half of all PMCs. The incidence of cervical lymph node metastasis in clinically unsuspected PMC was only 3.6% compared with 35% in clinically suspected disease, suggesting that the biological behavior (and possibly treatment) may be different. Long-term follow-up evaluation is needed to better evaluate the significance of these differences., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to evaluate patient satisfaction in an outpatient community-based surgical clinic to seek opportunities for improvement., Methods: A paper survey was distributed to patients at the Faculty Medical Center Clinic over a 12-week period. The survey allowed patients to rate their experience on a 5-point scale from "very dissatisfied" to "very satisfied." The survey addressed referral to the clinic, appointment scheduling, visit experience, wait times, laboratory testing, and satisfaction with surgery. Separate from the surveys, data were collected regarding wait time in clinic prior to being placed in an examining room, time spent waiting for the physician, time spent with the physician, overall time spent in clinic, and appointment time to surgery., Results: During the 12-week time period, 87 surveys were returned from patients in the surgery clinic for a 69% response rate. Most patients were referred to the surgery clinic from the emergency department or their primary care physicians at 44% and 43%, respectively. Just over half of the patients responded that they were "very satisfied" with their overall experience. Of those surveyed, 40% of patients were "very satisfied" with their wait time for the first visit to the clinic, 52% with time in waiting room, 43% with time in examining room, and 47% with time spent with physician. Only 16.4% of patients were "very dissatisfied" or "mostly dissatisfied" with time waiting for appointment, 17.9% with time available for appointment, 14.3% with time in waiting room, 18.2% in time waiting in examination room for the physician, and 20.9% of time wait to schedule surgery. Data were also collected on 203 surgical clinic patients during this time. Of the 203 patients, 55% were new patients, 31% were postoperative patients, and 14% were in the clinic for another type of visit., Conclusions: Overall patient satisfaction was good for the clinic, yet there were areas to improve. Efficiency of scheduling patients, improving wait time for waiting room, examining room, and time prior to scheduling surgery are areas that need improvement. Modification of the current practice at the surgery clinic could result in improvement of patient satisfaction in future evaluation., (Copyright © 2011 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

This study investigated and compared the risk factors and outcomes of patients undergoing coronary artery bypass graft surgery with and without the occurrence of prolonged mechanical ventilation. Data in a cardiac surgery database were examined retrospectively. Data selected included any isolated coronary artery bypass graft surgery performed by the surgical group from August 2005 to June 2009. The resulting cohort included a total of 2933 patients which was comprised of 116 patients with a ventilation time of greater than 72 hours (prolonged ventilation) and 2817 patients with a ventilation time of 72 hours or less (no prolonged ventilation). Patients with a prolonged ventilation time were matched (1:3 ratio) to patients not requiring a prolonged ventilation time by year of surgery resulting in our study cohort of 464 patients. To generate the unadjusted risks of each factor, χ(2) and t test analysis were performed. Logistic regression analysis was then used to investigate the adjusted risk between cases and controls and each of the significant variables. χ(2) and t tests were conducted comparing cases and controls with the outcome variables. Patients undergoing coronary artery bypass graft that experienced a prolonged ventilation time (cases) were more likely female, had a New York Hospital Association functional class of III or IV, and had a longer perfusion time. There was no significant difference between cases and controls with diabetes, chronic obstructive pulmonary disease, left ventricular ejection fraction, or body mass index while controlling for all significant risk factors. Careful patient selection and preparation during preoperative evaluation may help identify patients at risk for prolonged mechanical ventilation and thus help prevent the added morbidity and mortality associated with it.

Objective: The accreditation Council for Graduate Medical Education (ACGME) restricts residents from working more than 80 hours per week averaged over a 4-week period. No such restriction exists, however, for attending surgeons. Little exploration has been done of the public's perception of the number of hours that surgeons work and how residents work with the staff surgeons at a teaching institution., Methods: A survey was designed to study the public's belief on surgeon work hours and habits. The survey also asked their opinion on resident involvement. All patients and accompanying persons arriving through the Surgicare Center for elective procedures older than age 18 were surveyed. The overall survey responses were calculated, and the results then were stratified by sex, age, race, and education., Results: Of the 1516 surveys distributed, 370 were completed and returned (24.4%). Of those responding, 91% believed that a work hour limit should be in place for surgeons, and 77% believed the limit should be 12 consecutive hours or less. Eighty-four percent of the population believed that limit should be in place on the hours/week that a surgeon works, and 68% believe that it should be 60 hours or less. Although 82% would reschedule if they knew their surgeon had less than 4 hours of sleep the night before their procedure, 79% trust their surgeon's judgment to cancel if he/she were too tired. Only 28% of those surveyed were aware whether a resident was involved in their care, and 14% were against resident involvement. Respondents also were asked if the attending surgeon deemed a resident capable, then what percent of the procedure should the resident be able to perform? Ninety-one percent of those surveyed believed that the attending should be present for the entire case, and 78% believed that they should not be able to schedule more than 1 procedure at any given time., Conclusions: These findings illustrate a difference between the public's beliefs in regard to the hours a surgeon should be permitted to work and the reality of a surgeon's work life. Although the public may not be aware of the surgeon's schedule at a given time, they do trust the surgeon would cancel if too fatigued. The majority surveyed were not aware of resident involvement, but they trusted the attending surgeon's judgment with deciding how much of the actual procedure he/she could perform. With work-hour restrictions and resident involvement continuing to evolve, keeping the public informed should be a priority., (Copyright © 2011 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit tumor growth and angiogenesis. Covalent linkage of naproxen to human serum albumin (HSA) has been shown to target it efficiently to the liver and this may potentially be exploited for liver-selective inhibition of angiogenesis. With the aim of investigating the anti-angiogenic efficiency of NSAID-HSA conjugates in vitro, three NSAIDs, aspirin, ibuprofen, and naproxen were conjugated to HSA using different concentrations of their N-hydroxysuccinimide esters. Conjugation ratios from 10 to 50 were achieved and the conjugates retained a growth inhibitory effect on endothelial cells at or above the level of the non-conjugated NSAIDs in an in vitro angiogenesis assay.

Background: Patient quality outcomes are a major focus of the health care industry. It is unknown what effect involvement in graduate medical education (GME) has on patient outcomes. The purpose of this study is to begin to examine whether GME involvement in postoperative care impacts patient quality outcomes., Methods: The retrospective cohort included all patients who underwent a nonemergent colectomy from January 1, 2007 to January 1, 2008 at a 2-hospital system. Data collected included patient demographics, patient quality outcomes, complications, and GME involvement. Patient quality outcomes were based on compliance with the Surgical Care Improvement Project (SCIP) guidelines., Results: A total of 159 nonemergent colectomies were analyzed. The GME group accounted for 116 (73%) patients. A significant difference was found in several SCIP process-based measures of quality when comparing the GME group with the non-GME group. Postoperative antibiotics were more likely to be stopped within 24 hours (p = 0.010), and preoperative heparin and postoperative deep vein thrombosis (DVT) prophylaxis were more likely to be administered (p < 0.001). Additionally, patients in the GME group showed improved quality outcomes as there were significantly fewer postoperative complications (p < 0.001) and a shorter duration of stay (p = 0.008). The use of gastrointestinal prophylaxis was more common in the non-GME group (p = 0.002). No significant differences were observed between the 2 groups in respect to age, sex, diabetes, preoperative antibiotics, antibiotics, 1 hour before surgery, postoperative antibiotics, and continuation of home beta blockade., Conclusions: GME at teaching institutions has a positive impact on patient quality outcomes. At our institution, many of the SCIP measurable outcomes had improved compliance if an attending physician participated in the GME program., (Copyright 2010 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: More than one third of adults in the United States are obese. Coronary artery bypass graft surgery (CABG) has become necessary for many obese persons. We evaluated the effect of this procedure on in-hospital mortality and morbidity of patients based on their body mass index (BMI)., Methods: Data in a cardiac surgery database were examined retrospectively. Data selected from the database included CABG surgery from January 2003 to December 2007. The resulting cohort included a total of 10,590 patients. The BMI was grouped into four categories: underweight (BMI < or = 19), normal weight (BMI 20 to 29), obese (BMI 30 to 39), and morbidly obese (BMI > or = 40). Regression analysis was conducted to determine whether BMI was an independent predictor of morbidity and mortality after CABG., Results: Our results indicate that patients with an obese BMI are not at greater risk for morbidity or mortality after CABG. Logistic regression analysis found that CABG patients in the underweight body mass index group had the greatest risk of mortality, prolonged ventilation, reoperation for bleeding, and renal failure. Linear regression indicated length of hospital stay and intensive care unit stay after surgery were the longest for patients with an underweight BMI., Conclusions: Despite the comorbidities that are often present with obesity, an obese BMI was not found to be an independent predictor of morbidity or mortality after CABG. On the contrary, the underweight patients are at greater risk for mortality and complications after CABG surgery.

The aim of this study was to describe the epidemiology of chronic wounds in a large cohort of patients from a tertiary hospital out-patient clinic, and examine the significance of serum mannan-binding lectin for the occurrence and clinical presentation of such wounds. The study comprised 489 consecutive patients with chronic foot and leg ulcers. A clinical classification of wound- aetiology was performed, and mannan-binding lectin was measured in the sera of patients and healthy controls. The patients presented with 639 wounds altogether; diabetic foot ulcers (309), venous leg ulcers (188), arterial ulcers (109), and vasculitis (33). The mannan-binding lectin levels of patients with venous leg ulcer, alone or in combination with other types of wounds, differed significantly from the control group, and the frequency of values < 100 ng/ml was significantly higher. In diabetic and arterial ulcer patients the frequency of values >or= 3000 ng/ml was significantly higher than that of the control group. This suggests a role for the innate immunity in the pathology of venous leg ulcers, and indicates different roles for mannan-binding lectin in the development of ulcers with different aetiologies; it further suggests that mannan-binding lectin substitution should be tested in a controlled clinical trial.

Objective: The objective of this study was to assess outcome differences in aortic valve replacement based on gender., Methods: A study from a ten-year hospitalization cohort with prospective data collection was conducted. Included in the study were patients undergoing aortic valve replacement surgery between March 1997 and July 2003 (N=406). There were 223 males and 183 females included in the study. The study examined 41 potential confounding risk factors and 16 outcome variables., Results: Univariate analysis on potential confounding risk factors revealed a significant difference between males and females on 12 factors. Co-morbid disease, hypertension, current vascular disease, aortic insufficiency, body surface area, blood added on pump, and annulus size significantly correlated with age. The correlation resulted in five confounding risk factors: age, tobacco history, obesity, left ventricular hypertrophy, and creatinine level. Logistic regression analysis found that after controlling for age, tobacco history, obesity, left ventricular hypertrophy, and creatinine level, there is no difference between males and females on outcomes following aortic valve replacement. Additionally, choice of vascular prosthesis had no impact on post-operative outcomes., Conclusion: After controlling for confounding variables, similar outcomes were observed for males and females undergoing aortic valve replacement.

Objective: Although rare, aortic dissection is one of the most devastating, but least studied, intraoperative complications. The objective of this study was to assess risk factors of aortic dissection and assess outcomes in patients with aortic dissection experience., Methods: A study from a 10-year hospitalization cohort (N = 12,907) with prospective data collection was conducted. Patients without aortic dissection were matched to 33 aortic dissection patients 3:1 on the type of procedure. The study examined 24 potential confounding risk factors and 12 outcome variables., Results: Univariate analysis on potential confounding risk factors revealed two significant risk factors. There was a significant difference between aortic dissection and nonaortic dissection patients with New York Heart Association (NYHA) functional class (p = 0.03). Patients with aortic dissection were more likely to be in Class I or II. Patients with aortic dissection had significantly longer perfusion time (p = 0.008). There was a significant difference between patients with and without aortic dissection on four outcome variables. Patients with an aortic dissection were more likely to need prolonged ventilation (p = 0.046), have renal failure (p = 0.005), require intraaortic balloon pump (IABP) (0.043), and have a higher mortality rate (p < 0.001)., Conclusion: Aortic dissection occurs infrequently during coronary artery bypass grafting, but is a devastating complication and greatly increases morbidity. Although few patients dissect intraoperatively, this study attempted to identify predictors that may label a patient as high risk for possible aortic dissection. Although two factors in this study were statistically significant, they are not reliable preoperative predictors of high-risk patients that can be used to screen patients and help prevent aortic dissection and its sequela.

The study objective was to determine predictors, and adverse outcomes of postoperative type II neurologic complications. An 11-year cohort (N=12,706) study with 595 coronary artery bypass graft (CABG) patients with a neurologic complication, and 7793 patients without any neurologic complications was conducted. This study examined 26 potential risk factors and 13 outcome variables. Logistic regression analysis found that patients were more likely to experience a neurologic complication after CABG if they were older than 70 years of age [odds ratio (OR), 3.8; 95% confidence interval (CI), 3.1-4.5; P < 0.001], had a previous intervention within 10 days before surgery (OR, 3.4; 95% CI, 1.4-8.3; P = 0.008), or had a higher creatinine level (OR, 0.9; 95% CI, 0.95-0.99; P = 0.013). Additionally, there was a significant difference between CABG patients with and without neurologic complications on 12 outcome variables. Type II neurologic complications after CABG are common and associated with an increased risk of postoperative morbidity and mortality.

The envelope glycoproteins of Rubella virus, E1 and E2, mediate cell tropism, and E1 in particular plays a pivotal role in the fusion of the virus with the endosomal membrane. Both are the prime targets of the humoral immune response. Recombinant variants of the E1 ectodomain as well as E1 antigen preparations from virus lysates are commonly used to detect anti-Rubella immunoglobulins in human sera. Hitherto, recombinant E1 for diagnostic applications has been produced chiefly in eukaryotic expression systems. Here, we report the high-yield overproduction of an engineered E1 ectodomain in the Escherichia coli cytosol and its simple and convenient renaturation into a highly soluble and immunoreactive conformation. C-Terminal fusion to one or two units of the E. coli chaperone SlyD enhances expression, facilitates in vitro refolding, and improves the overall solubility of Rubella E1. As part of this fusion protein, the E1 ectodomain fragment of residues 201-432 adopts an immunoreactive fold, providing a promising tool for the sensitive and specific detection of anti-E1 IgG in Rubella serology. Two disulfide bonds in the membrane-adjacent part of the E1 ectodomain are sufficient to generate conformations with a high and specific antigenicity. The covalently attached chaperone modules do not impair antibody recognition and binding of Rubella E1 when assessed in a heterogeneous immunoassay. SlyD and related folding helpers are apparently generic tools for the expression and refolding of otherwise unavailable proteins of diagnostic or medical importance.

Background: With the institution of the 80-hour work week, residency programs have worked to institute programs that decrease the time that residents spend in the hospital while maintaining patient safety. This study was intended to assess the amount of time saved using computerized patient information in the form of a personal data assistant (PDA)., Methods: A community hospital surgical residency program with 22 residents initially collected data daily for 4 weeks without PDA use. Data included preround time, check-out time, total number of patients, number of medical/surgical patients, and number of intensive care unit patients. The definition of prerounding time was started when residents first began collecting information on their patients in the morning until 6:00 am. Check-out time started at 5:00 pm and lasted until the discussion of patient care with the night team had finished. Residents were then given PDAs allowing immediate up-to-date access to patient information, which most importantly included current vital signs, laboratory data, radiological dictations, medication lists, and fluid intake and output. After a 4-week acquaintance period with the PDA had passed, data were again collected from the residents daily for 4 weeks. Daily averages for each week and an overall total average were calculated. Daily averages were also calculated for each PGY level. Paired t-tests compared the pre-PDA and post-PDA total averages., Results: No significant difference was found between the total number of patients pre-PDA and post-PDA (7.6 and 7.6, respectively, p = 0.98), the average number of medical/surgical patients (4.7 and 7.1, respectively, p = 0.16), or the average number of intensive care unit patients (2.6 and 0.4, respectively, p = 0.06). Also, no significant difference was found between pre-PDA and post-PDA with average check-out time (24.5 minutes and 21.9 minutes, respectively, p = 0.06). However, a significant decrease in rounding time occurred with pre-PDA round time at 50.5 minutes and post-PDA round time at 40.7 minutes (p = 0.02)., Conclusion: Results of this study support the hypothesis that the prerounding time dramatically decreases with the PDA compared to without. Not only does this decrease in time help to keep residents under the 80-hour work week rule, but also it helps to eliminate much of the confusion that can cause patient safety issues.

Objective: The objective was to examine the influence of gender in diabetic patients following coronary artery bypass graft (CABG) surgery., Methods: A study from an 11-year hospitalization cohort with prospective data collection was conducted. Included in the study were diabetic patients undergoing CABG surgery between October 1993 and May 2004 (n = 2781). Patients who underwent any surgery other than CABG or had a previous cardiac surgery were excluded. The study examined 25 risk factors and 14 outcome variables., Results: Twelve risk factors were found to be significantly different between male and female diabetic patients undergoing CABG. Correlation coefficients were computed among the 12 significant risk factors. Three main risk factors emerged: age 70 years or greater, abnormal LVH, and number of grafts. For outcome variables, females experienced more renal complications, intraoperative complications, longer hospital stay, and mortality. Logistic regression analysis showed that after controlling for age, LVH, and number of grafts, female diabetic patients undergoing CABG were more likely to experience intraoperative complications (OR 1.8, 95% CI 1.1-3.0, p = 0.025) and longer hospital stay (OR 0.99, 95% CI 0.97-0.99, p = 0.039). However, there was no significant difference between male and female diabetic patients after CABG surgery with renal complications (OR 1.39, 95% CI 0.95-2.1, p = 0.132) or mortality (OR 1.6, 95% CI 0.85-2.8, p = 0.153)., Conclusion: Female diabetic patients, when compared to male diabetic patients undergoing CABG, have significantly more intraoperative complications and longer hospital stays following surgery.

Purpose: Our aim was to assess the feasibility of totally endoscopic robotic mitral valve surgery using a novel atrial retractor manipulated by a fourth arm da Vinci surgical system (Intuitive Surgical Inc, Sunnyvale, CA)., Description: Eighteen patients with mitral valve disease underwent totally endoscopic mitral valve surgery using the retractor. It was inserted in the second or third intercostal space just lateral to the sternum, and it was manipulated at the robotic console for dynamic exposure of the valve structures., Evaluation: Mitral valve repair procedures were feasible in all patients with the robotic-controlled atrial retractor providing superior exposure of the mitral valve anatomy. The time until satisfactory exposure of the mitral valve was noticeably decreased with the robotic retractor. All patients were discharged home in sinus rhythm and transesophageal echocardiography revealed competent mitral valves., Conclusions: The EndoWrist atrial retractor (Intuitive Surgical Inc) facilitated complex totally endoscopic mitral valve surgery, including concomitant procedures, regardless of pathology with excellent clinical outcomes.

The addition of GB virus C (GBV-C) E2 protein to cells inhibits HIV replication in vitro, presumably triggered by interactions with a specific cellular receptor. Indirect evidence suggests that CD81 is the GBV-C E2 cellular receptor. We found that E2 binding to cells was not dependent upon human CD81, and that soluble CD81 did not compete with GBV-C E2 for cell binding. GBV-C E2 protein thus does not appear to interact with CD81.

Epidemiological studies have revealed an association between GB virus C (GBV-C) long-term viraemia and ameliorated HIV disease progression. We have provided evidence that a single protein of GBV-C, the glycoprotein E2, interferes with early HIV replication steps of both X4- and R5-tropic HIV strains. Preincubation with anti-E2 antibody specifically abrogates the inhibitory effect. Results were confirmed by the in-vitro expression of GBV-C E1/E2 encoding RNA.

Objective: : The purpose of this study was to demonstrate the feasibility of simple to complex endoscopic robotic mitral valve repair, using a lateral approach., Methods: : Data were retrospectively collected on 201 patients undergoing a lateral "ports only" endoscopic robotic mitral valve repair at three institutions. Techniques of aortic occlusion included the endoaortic balloon or a transthoracic clamp. The efficacy of the repair was measured intraoperatively by transesophageal echocardiogram., Results: : Two hundred one patients with a mean age of 55.2 ± 14.2 were intended to undergo elective robotic mitral valve surgery. One hundred eighty-six (92.5%) were scheduled for a repair procedure and 15 (7.5%) were scheduled for replacement. The repair was accomplished in 179 of 186 (96.2%) of patients. Eight patients (4.3%) required a conversion to sternotomy incision. Seven converted patients received a mitral valve repair and one received a replacement mitral valve. Mitral valve pathology included 10% isolated anterior leaflet involvement, 43% isolated posterior leaflet involvement, and 6% bileaflet pathology, and the remaining patients had dilated annulus, chordal rupture, or elongation. One hundred seventy-nine patients (96.2%) had regurgitation grade of 0 to 1 after repair. Two patients (1%) died. Other adverse events included reoperation for valve-related complications, 2 of 201 (1%); reoperation for cardiac-related complications, 3 of 201 (1.5%); and new onset of atrial fibrillation, 35 of 201 (17.4%)., Conclusions: : A lateral endoscopic robotic approach to mitral valve repair is safe, feasible, and can be performed consistently with acceptable postoperative results. Further follow-up is required to determine the long-term efficacy of this approach to robotic mitral valve repair.

A cohort study with prospective data collection was conducted to determine which risk factors and outcome variables are statistically significant clinical predictors of mortality from infective endocarditis. A study was performed from an eleven-year, hospitalization cohort (N=11,230) in which the data were collected prospectively. The study examined 21 potential risk factors and 14 outcome variables. The risk factors were categorized into these various groups: patient factors, cardiac factors, co-morbidities, operative factors, infectious factors, and complications. The outcome variables were categorized into operative factors, infectious factors, and complications. Inclusion criteria included patients with endocarditis (N=87). Longer operative time, operative complications, and postoperative complications. Overall mortality was 11.5 percent (N=10). Endocarditis patients who died were significantly older (p=0.023) and had a longer pump time (p=0.017) than those who survived. Endocarditis patients who died were more likely to experience an unstable hemodynamic status (p=0.012). There was a significant difference between survival and non-survival of patients with endocarditis on nine outcome variables. They were more likely to require a re-operation for bleeding (p=0.034). Renal complications (p=0.016), neurological complications (p=0.004), pulmonary complications (p=0.001), intra-operative complications (p=0.035), and IAPB (p<0.001) were all more likely to occur in endocarditis patients who died. There are risk factors that serve as predictors of mortality from infectious endocarditis. These include age greater than 65 years, longer pump time, and unstable hemodynamic status. Outcome variables that reflected significant mortality included operative complications and post-operative complications. These factors may identify those patients with infective endocarditis eligible for more aggressive treatment.

GB virus type C (GBV-C) is a human flavivirus that may cause persistent infection, although most infected individuals clear viremia and develop antibodies to the envelope glycoprotein E2. To study GBV-C E2 antigenicity and cell binding, murine anti-E2 monoclonal antibodies (MAbs) were evaluated to topologically map immunogenic sites on GBV-C E2 and for the ability to detect or block recombinant E2 binding to various cell lines. Five competition groups of MAbs were identified. Groups I and II did not compete with each other. Group III competed with both groups I and II. Group IV did not compete with group I, II, or III. One MAb competed with all of the other MAbs, suggesting that the epitopes bound by these MAbs are intimately related. Individually, none of the MAbs competed extensively with polyclonal human convalescent antibody (PcAb); however, combinations of all five MAb groups completely blocked PcAb binding to E2, suggesting that the epitopes bound by these MAbs form a single, immunodominant antigenic site. Only group I and III MAbs detected purified recombinant E2 bound to cells in binding assays. In contrast, group II MAbs neutralized the binding of E2 to cells. Both PcAb and MAbs were conformation dependent, with the exception of one group II MAb (M6). M6 bound to a five-amino-acid sequence on E2 if the peptide included four C-terminal or eight N-terminal residues, suggesting that the GBV-C E2 protein contains a single immunodominant antigenic site which includes a complex epitope that is involved in specific cellular binding.

Hypothesis: There is an increased operative risk in patients with a history of peripheral vascular disease (PVD) who undergo coronary artery bypass grafting (CABG). There are also outcome differences associated with these patients., Design: A study from a 10-year hospitalization cohort with prospective data collection., Setting: Multiple hospitals in the Greater Cincinnati area with 1 surgical group of cardiac surgeons., Participants: Cases were CABG patients with PVD, which was defined as having a history of type 1 neurologic injury, prior vascular surgery, or current vascular disease (n = 1561). Controls were CABG patients without PVD (n = 6328)., Interventions: The study examined 42 potential confounding risk factors and 16 outcome variables., Results: Twenty-nine potential risk factors were found to be significantly different between CABG patients with and without PVD. Twenty-six confounding risk factors were correlated with 3 factors. Logistic regression analysis showed that even after controlling for sex, significant associative disorders, and other procedures, CABG patients with PVD still experienced more arrhythmias requiring treatment (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.03-1.33; P = .01), neurological complications (OR, 1.7; 95% CI, 1.43-2.07; P<.001), pulmonary complications (OR, 1.4; 95% CI, 1.23-1.62; P<.001), low output (OR, 1.3; 95% CI, 1.09-1.45; P = .001), and intraoperative complications (OR, 1.39; 95% CI, 1.06-1.83; P = .02)., Conclusions: Patients with a PVD history undergoing CABG had more coexistent risk factors. These patients also exhibited higher rates of cardiac, systemic, renal, neurologic, and pulmonary complications.

The purpose of this study was to identify and validate novel serological protein biomarkers of human colorectal cancer (CRC). Proteins from matched CRC and adjacent normal tissue samples were resolved by two-dimensional gel electrophoresis. From each gel all spots were excised, and enveloped proteins were identified by MS. By comparison of the resulting protein profiles, dysregulated proteins can be identified. A list of all identified proteins and validation of five exemplarily selected proteins, elevated in CRC was reported previously (Roessler, M., Rollinger, W., Palme, S., Hagmann, M. L., Berndt, P., Engel, A. M., Schneidinger, B., Pfeffer, M., Andres, H., Karl, J., Bodenmuller, H., Ruschoff, J., Henkel, T., Rohr, G., Rossol, S., Rosch, W., Langen, H., Zolg, W., and Tacke, M. (2005) Identification of nicotinamide N-methyltransferase as a novel serum tumor marker for colorectal cancer. Clin. Cancer Res. 11, 6550-6557). Here we describe identification and initial validation of another potential marker protein for CRC. Comparison of tissue protein profiles revealed strong elevation of proteasome activator complex subunit 3 (PSME3) expression in CRC tissue. This dysregulation was not detectable based on the spot pattern. The PSME3-containing spot on tumor gels showed no visible difference to the corresponding spot on matched control gels. MS analysis revealed the presence of two proteins, PSME3 and annexin 4 (ANXA4) in one and the same spot on tumor gels, whereas the matched spot contained only one protein, ANXA4, on control gels. Therefore, dysregulation of PSME3 was masked by ANXA4 and could only be recognized by MS-based analysis but not by image analysis. To validate this finding, antibody to PSME3 was developed, and up-regulation in CRC was confirmed by Western blot analysis and immunohistochemistry. Finally by developing a highly sensitive immunoassay, PSME3 could be detected in human sera and was significantly elevated in CRC patients compared with healthy donors and patients with benign bowel disease. We propose that PSME3 be considered a novel serum tumor marker for CRC that may have significance in the detection and in the management of patients with this disease. Further studies are needed to fully assess the potential clinical value of this marker candidate.

With the goals of creating a better match between medical students and general surgery programs and providing a program that is desirable to medical students who are interested in pursuing careers in surgery, a survey was designed to categorize student interests and to determine what factors are used in choosing a general surgery program. The survey focused on the reasons that surgical resident candidates select a program. Each statement was rated for importance on a 5-point scale, and then the top 10 statements were ranked in order of importance. The survey was distributed to 19 community hospitals, 23 university programs, and medical students interviewing for surgical residency. A total of 286 surveys were returned from 18 programs and medical students. The statements with the three highest ratings were "amount of operative exposure," "diversity of operative cases," and "perceived relationships among faculty and residents." "Amount of operative exposure," "diversity of operative cases," and "ability to pursue fellowship training after residency" received the top rankings. There was a significant difference between men and women in the ratings of three statements. However, there was no difference with the ranking of the statements. There was also a significant difference between residents early and late in their training on ratings of five statements and on the ranking of two statements. The ratings of six statements were significantly different between community and university programs. A significant difference between types of program was also found with the rankings of four statements. There was a difference between small and large programs on two ratings of statements and one ranking. This data provides a useful resource for programs and candidates in preparing for candidate/residency selection.

Background: Beating heart totally endoscopic coronary artery bypass grafting (TECAB) utilizing a computer-enhanced telemanipulation system is a technically challenging procedure. The objective of our study was to compare two different anastomotic techniques., Methods: Ten canine beating heart TECAB procedures were performed using Intuitive's daVinci surgical system. Left internal mammary artery (LIMA) to left anterior descending coronary artery (LAD) anastomosis was performed on all subjects. Anastomosis varied between a conventional running suture (8-0 Gore-tex) (group I) and an interrupted nitinol u-clip anastomosis (group II). On-table angiography was then performed to assess graft patency., Results: While internal mammary artery (IMA) mobilization time decreased over the course of the study (p = 0.017), there was no significant difference in ischaemia time, anastomosis time or angiographic assessment between anastomotic techniques. Although operative time in group II was significantly shorter than in group I, this was likely due to the small sample size. There were no differences in anastomotic time or coronary occlusion time. There were also no significant differences in canine weight, IMA mobilization time, lipectomy/pericardiotomy, LAD identification, subxiphoid port placement, stabilizer position, or LAD dissection time between the cases performed with the conventional running suture and the cases performed with u-clips., Conclusion: Interrupted nitinol clip anastomosis or conventional running suture anastomoses are equally favourable in the short term when performing a TECAB procedure., (Copyright 2006 John Wiley & Sons, Ltd.)

We sought to assess predictors and outcomes of sternal wound complications in patients after coronary artery bypass grafting (CABG). A nested, case-control study from a 10-year hospitalization cohort with prospective data collection was conducted. Included in the cohort were patients age 18 and above undergoing CABG surgery between March 1997 and July 2003 (n = 7889). Patients who underwent any surgery other CABG were excluded. Cases were matched to controls 1:3 on year of surgery. Cases were CABG patients with sternal wound complications, which was defined as requiring antibiotics and/or topical treatment, requiring extra nursing care, dehiscence, or requiring surgical intervention (n = 89). Controls were CABG patients without sternal wound complications (n = 267). The study examined 29 risk factors and 10 outcome variables. Univariate analysis on the risk factors revealed 10 significant risk factors. Logistic regression analysis was conducted and the risk factors that significantly predicted sternal wound complications after CABG surgery included older age (odds ratio [OR] = 0.85, 95% confidence interval [CI] 0.808-0.892), previous CABG surgery (OR = 3.9, 95% CI 1.03-15.37), and in class three or four of the New York Heart Association functional class (OR = 2.8, 95% CI 1.27-6.12). There was a significant difference between CABG patients with and without sternal wound complications on nine outcome variables. Of the 29 predictors of post-CABG sternal wound infections being examined, 10 proved to be significant. Further analysis demonstrated only three variables that significantly predicted sternal wound complications. Older age, previous CABG surgery, and class three or four of the New York Heart Association functional class predispose CABG patients to sternal wound infections.

Our objective was to assess surgical outcomes between male and female patients undergoing off-pump coronary artery bypass grafting (CABG). The study was conducted from a 10-year hospitalization cohort (n = 11,230) in which the data were collected prospectively. Inclusion criteria included an off-pump CABG-only procedure. There were 526 men and 250 women included in the study. Fourteen potential confounding risk factors and 14 outcome variables were examined. Six potential risk factors were found to be significantly different between men and women. Men were younger (P = 0.014), had a larger body surface area (P < 0.001), a higher creatinine level (P < 0.001), required more grafts (P < 0.001), and were more likely to have a cerebrovascular history (P = 0.020) and a history of tobacco use (P < or = 0.001). Logistic regression analysis showed that even after controlling for age, body surface area, creatinine level, number of grafts, and tobacco history, women had longer length of hospitalization (odds ratio, 1.97; 95% confidence interval, 1.28-3.04, P = 0.002) and more sternal wound complications than men (odds ratio, 1.07; 95% confidence interval, 1.01-2.11, P = 0.028) after off-pump CABG. Although not statistically different, women had lower operative mortality than men after off-pump CABG (0.8% [2 of 10] compared with 1.5% [8 of 10], respectively). Despite women requiring a longer hospitalization and having a greater incidence of sternal wound infections than men, there was no significant difference in mortality.

Human umbilical vein endothelial cells (HUVEC) propagated in co-culture with fibroblasts form capillary-like networks of tubes. Here we characterize the morphology and ultrastructure of HUVEC in such co-cultures and investigate the influence of different angiogenesis inhibitors on endothelial cell morphology. Addition of angiogenesis inhibitors to the co-culture disrupted endothelial network formation and influenced endothelial cell morphology in two distinct ways. Instead of characteristic capillary-like networks, the endothelial cell morphology appeared as either short cords or compact cell clusters of variable size. Electron microscopy (EM) showed that in co-culture untreated HUVEC formed capillary-like tubes with lumina and retained important ultrastructural and physiological properties of endothelial cells in functional vessels as they contained both Weibel-Palade bodies and transport vesicles. Immuno-EM showed that the endothelial cell marker CD 31 stained endothelial membranes at cell-cell contacts, and at the luminal and abluminal side of the capillary-like tubes, although most abundantly at the luminal membranes. No ultrastructural signs of apoptosis were seen in HUVEC in inhibitor-treated co-cultures. Our results demonstrate that treatment with levamisole or anti-VEGF inhibits endothelial cell differentiation into tubes or instead induces formation of compact endothelial cell clusters. Treatment with platelet factor 4, suramin and TNP-470 results in formation of short endothelial cell cords. We discuss the implications of these findings.

Objective: To assess risk predictors of increased intensive care unit (ICU) length of stay in patients undergoing isolated coronary artery bypass surgery (CABG) and assess outcomes associated with increased ICU length of stay., Methods: We conducted a nested case-control study from a 9-year hospitalization cohort with prospective data collection (N = 9869). Cases were CABG patients with ICU greater than or equal to 168 hours (N = 236) and controls were CABG patients with an ICU stay of less than 168 hours (N = 708). We examined 15 risk factors and 11 outcomes., Results: Nine risk factors proved significant in predicting an increased ICU length of stay. Cases were more likely to be older, with an increased pump time, and a lower body surface area. Cases tended to be female, with COPD, hypertension, and undergoing an urgent surgical procedure. Controls tended to have hypercholesterolemia and abnormal left ventricular hypertrophy. There was no significant difference between the cases and controls for the remaining six risk factors. Five of the nine significant predictors correlated with four predictors: age, urgent surgical procedure, pump time, and chronic obstructive pulmonary disorder (COPD). Using logistic regression analysis, we found that patients undergoing CABG had an increased ICU length of stay if they were older than 70 years (OR 2.59, 95% CI 1.86 to 3.62), with longer pump time (OR 2.45, 95% CI 1.75 to 3.44), had COPD (OR 2.04, 95% CI 1.36 to 3.05), and had an urgent surgical procedure (OR 1.59, 95% CI 1.12 to 2.26). Patients with an extended ICU length of stay were also found to experience 11 additional negative outcomes., Conclusion: In patients undergoing CABG surgery an increased age, increased pump time, COPD, and urgent surgical procedure significantly increased the risk of an increased ICU length of stay. Patients with an increased ICU length of stay also experienced more negative outcomes.