Viz.ai Implementation of Stroke Augmented Intelligence and Communications Platform to Improve Indicators and Outcomes for a Comprehensive Stroke Center and Network.

BACKGROUND AND PURPOSE: Comprehensive stroke centers continually strive to narrow neurointerventional time metrics. Although process improvements have been put in place to streamline workflows, complex pathways, disparate imaging locations, and fragmented communications all highlight the need for continued improvement. MATERIALS AND METHODS: This Quality Improvement Initiative (VISIION) was implemented to assess our transition to the Viz.ai platform for immediate image review and centralized communication and their effect on key performance indicators in our comprehensive stroke center. We compared periods before and following deployment. Sequential patients having undergone stroke thrombectomy were included. Both direct arriving large-vessel occlusion and Brain Emergency Management Initiative telemedicine transfer large-vessel occlusion cases were assessed as were subgroups of OnHours and OffHours. Text messaging thread counts were compared between time periods to assess communications. Mann-Whitney U and Student t tests were used. RESULTS: Eighty-two neurointerventional cases were analyzed pre vs. post time periods: (DALVO-OnHours 7 versus 7, DALVO-OffHours 10 versus 5, BEMI-OnHours 13 versus 6, BEMI-OffHours 17 versus 17). DALVO-OffHours had a 39% door-to-groin reduction (157 versus 95 minutes, P = .009). DALVO-All showed a 32% reduction (127 versus 86 minutes, P = .006). BEMI-All improved 33% (42 versus 28 minutes, P = .036). Text messaging thread counts improved 30% (39 versus 27, P = .04). CONCLUSIONS: There was an immediate improvement following Viz.ai implementation for both direct arriving and telemedicine transfer thrombectomy cases. In the greatest opportunity subset (direct arriving large-vessel occlusion-OffHours: direct arriving cases requiring team mobilization off-hours), we noted a 39% improvement. With Viz.ai, we noted that immediate access to images and streamlined communications improved door-to-groin time metrics for thrombectomy. These results have implications for future care processes and can be a model for centers striving to optimize workflow and improve thrombectomy timeliness.

Maternal insulin resistance, triglycerides and cord blood insulin are not determinants of offspring growth and adiposity up to 5 years: a follow-up study.

AIMS: Metabolic dysregulation in utero may influence fetal metabolism and early growth. We previously investigated relationships between maternal indices of glucose homeostasis and triglycerides as well as cord blood insulin with offspring anthropometry up to 2 years. The aim of this analysis was to follow these relationships up to the age of 5 years. METHODS: Associations between maternal metabolic variables of glucose and lipid metabolism measured at 32 weeks' gestation and cord blood insulin with growth and body composition of 162 offspring aged 3-5 years were explored. Both indirect (i.e. body weight, BMI percentiles, sum of four skinfold thicknesses) and direct (i.e. ultrasonography, magnetic resonance imaging in a subgroup) measurement techniques were employed. RESULTS: Maternal metabolic indices were largely unrelated to child body composition. Cord blood insulin was negatively associated with fat mass and lean body mass at 3 years in unadjusted analyses, and the sum of four skinfold thicknesses and body fat percentage in adjusted analyses, whereas the association with lean body mass was no longer observed. An inverse relationship between cord blood insulin and weight gain up to 5 years was observed in girls only with small effect sizes. CONCLUSIONS: Results from this follow-up do not provide convincing evidence that these markers are independently related to offspring growth and adiposity in early childhood. Although cord blood insulin was weakly inversely related to weight gain in girls at 5 years, we cannot conclude that the observed changes in outcomes are clinically meaningful. (Clinical Trials Registry No: NCT00362089).

Non-enhanced CT Maximum Intensity Projections for the Detection of Large Vessel Occlusions.

BACKGROUND: Identification of large vessel occlusions (LVO) is important with recent guidelines supporting endovascular therapy in selected acute ischemic stroke patients. Many stroke centers perform CT angiography (CTA) in patients with suspected LVO, however this requires additional time and contrast administration. Non-enhanced CT maximum intensity projection (NECT-MIPs) may offer a rapid alternative to CTA. METHODS: We retrospectively reviewed acute stroke patients with LVO in the UCSD Stroke Registry, presenting between 6/2014-7/2016. NECT-MIPs were evaluated for presence of LVO. Gold standard comparison was to CTA. Results were stratified by level of training (Faculty, Fellow and Acute Care Practitioners [ACPs]). Inter-rater agreement was assessed using Fleiss' Kappa Coefficient. RESULTS: We reviewed 24 patients using NECT-MIPs for the detection of LVO. Faculty had a sensitivity and specificity of 95% & 92% for ICA/M1, 42% & 100% for M2, and 67% & 96% for basilar occlusions. Fellows and ACPs had a sensitivity and specificity of 61% & 94% for ICA/M1, 19% & 83% for M2, and 75% & 95% for basilar occlusions. Inter-rater agreement among Faculty readers was k=0.75 for ICA/M1, k=0.79 for M2 and k=0.14 for basilar occlusions. Among Fellows and ACPs, k=0.57 for ICA/M1, k=0.40 for M2, and k=0.27 for basilar occlusions. CONCLUSIONS: NECT-MIPs have high sensitivity and specificity for the detection of LVO when compared to CTA. Inter-rater agreement is fair and higher amongst more experienced reviewers. These results suggest that NECT-MIPs may be helpful to streamline the identification of LVO and reduce door to needle and door to intervention times.

The relationship between breast milk leptin and adiponectin with child body composition from 3 to 5 years: a follow-up study.

BACKGROUND: Research indicates that breast milk contains bioactive components that influence metabolism in infancy and may play a role in the prevention of obesity in early childhood. In our initial study, 147 breastfeeding mother/child pairs were followed from birth to 2 years of age to examine the relationship between breast milk leptin and total adiponectin (collected at 6 weeks and 4 months postpartum) and infant body composition. Higher breast milk total adiponectin was related to greater fat mass and weight gain in children at 1 and 2 years of age, whereas leptin showed no association. OBJECTIVES/METHODS: In this follow-up, we examined the relationship between both adipokines and children's body weight, body mass index percentiles, sum of four skin-folds, percentage of body fat, fat mass and lean body mass at 3, 4 and 5 years of age. RESULTS: Breast milk adipokines were largely unrelated to child anthropometric measures. CONCLUSION: Our results do not provide significant evidence that breast milk adipokines can predict adiposity in preschool children.

Total 'shrink' losses, and where they occur, in commercially sized silage piles constructed from immature and mature cereal crops.

Silage 'shrink' (i.e., fresh chop crop lost between ensiling and feedout) represents losses of potential animal nutrients which degrade air quality as volatile carbon compounds. Regulatory efforts have, in some cases, resulted in semi-mandatory mitigations (i.e., dairy farmers select a minimum number of mitigations from a list) to reduce silage shrink, mitigations often based on limited data of questionable relevance to large commercial silage piles where silage shrink may or may not be a problem of a magnitude equal to that assumed. Silage 'shrink' is generally ill defined, but can be expressed as losses of wet weight (WW), oven dry matter (oDM), and oDM corrected for volatiles lost during oven drying (vcoDM). As no research has documented shrink in large cereal silage piles, 6 piles ranging from 1456 to 6297tonnes (as built) were used. Three used cereal cut at an immature stage and three at a mature stage. Physiologically immature silages had generally higher (P<0.01) levels of total volatile fatty acids (especially acetic acid; P=0.01) and total alcohols (P<0.01) than did physiologically mature crops, suggesting higher carbon compound volatilization potential from immature silages. However expressed as WW, oDM and vcoDM, total shrink (as well as from where in the piles it occurred) was little impacted by crop maturity, and whole pile vcoDM shrink was only ~35g/kg. Overall, real shrink losses (vcoDM) of large well managed cereal silage piles were relatively low, and a lower potential contributor to aerosol emissions of volatile carbon compounds than has often been assumed. Losses from the silage mass and the exposed silage face were approximately equal contributors to vcoDM shrink. Mitigations to reduce these relatively low emission levels of volatile organic compounds from cereal silage piles should focus on the ensiled mass and the exposed silage face.

'Shrink' losses in commercially sized corn silage piles: Quantifying total losses and where they occur.

Silage 'shrink' (i.e., loss of fresh chopped crop between ensiling and feedout) represents a nutrient loss which can degrade air quality as volatile carbon compounds, degrade surface waterways due to seepage, or degrade aquifers due to seepage. Virtually no research has documented shrink in large silage piles. The term 'shrink' is often ill defined, but can be expressed as losses of wet weight (WW), oven dry matter (oDM), and oDM corrected for volatiles lost in the drying oven (vcoDM). Corn silage piles (4 wedge, 2 rollover/wedge, 1 bunker) from 950 to 12,204 tonnes as built, on concrete (4), soil (2) and a combination (1) in California's San Joaquin Valley, using a bacterial inoculant, covered within 24 h with an oxygen barrier inner film and black/white outer plastic, fed out using large front end loaders through an electronic feed tracking system, and from the 2013 crop year, were used. Shrink as WW, oDM and vcoDM were 90±17, 68±18 and 28±21 g/kg, suggesting that much WW shrink is water and much oDM shrink is volatiles lost during analytical oven drying. Most shrink occurred in the silage mass with losses from exposed silage faces, as well as between exposed face silage removal and the total mixed ration mixer, being low. Silage bulk density, exposed silage face management and face use rate did not have obvious impacts on any shrink measure, but age of the silage pile during silage feedout impacted shrink losses ('older' silage piles being higher), but most strongly for WW shrink. Real shrink losses (i.e., vcoDM) of large well managed corn silage piles are low, the exposed silage face is a small portion of losses, and many proposed shrink mitigations appeared ineffective, possibly because shrink was low overall and they are largely directed at the exposed silage face.

The future direction of the adult heart allocation system in the United States.

Ensuring equitable and fair organ allocation is a central charge of the United Network for Organ Sharing (UNOS) as the Organ Procurement and Transplantation Network (OPTN) through its contract with the Department of Health and Human Services (DHHS). The OPTN/UNOS Board initiated a reassessment of the current allocation system. This paper describes the efforts of the OPTN/UNOS Heart Subcommittee, acting on behalf of the OPTN/UNOS Thoracic Organ Transplantation Committee, to modify the current allocation system. The Subcommittee assessed the limitations of the current three-tiered system, outcomes of patients with status exceptions, emerging ventricular assist device (VAD) population, options for improved geographic sharing and status of potentially disenfranchised groups. They analyzed waiting list and posttransplant mortality rates of a contemporary cohort of patient groups at risk, in collaboration with the Scientific Registry of Transplant Recipients to develop a proposed multi-tiered allocation scheme. This proposal provides a framework for simulation modeling to project whether candidates would have better waitlist survival in the revised allocation system, and whether posttransplant survival would remain stable. The tiers are subject to change, based on further analysis by the Heart Subcommittee and will lead to the development of a more effective and equitable heart allocation system.

Salivary diagnostics and its impact in dentistry, research, education, and the professional community.

Oral fluid-based (salivary) tests have the potential to create practical, point-of-care clinical instruments that are convenient, practical, and comfortable to use in dentistry and medicine. Currently, there are no simple, accurate, and inexpensive sampling, screening, or detection methods to support definitive diagnostic platforms across dental and medical disciplines. Though the benefits from advancing screening and detection technologies seem eminent, analytical, chemical, molecular, genetic, and protein markers are still under development. Clinical applications in patient care must be validated independently to ensure that they are clinically accurate, reliable, precise, and uniformly consistent for screening and detecting specific diseases or conditions. As technology designed to improve patient care through risk assessment, prevention, and disease management is transferred into clinical practice, dentistry may need to reassess its role in general health care.

Effect of pyruvate and HEPES on rat lung allograft acidosis and cell death after long-term hypothermic storage.

BACKGROUND: We have previously demonstrated that adding pyruvate to Perfadex increased graft metabolism during 24-hour storage and improved reperfusion lung function. This increased metabolism was associated with progressively lower pH of the storage solution during the preservation interval. OBJECTIVE: To determine whether more effective pH regulation would result in further improvements in lung survival after hypothermic storage. MATERIALS AND METHODS: Rat lungs were stored for 24 hours in Perfadex, Perfadex with HEPES (N-2-hydroxyethylpiperazine-propanesulfonic acid) buffer, pyruvate-modified Perfadex, and pyruvate-modified Perfadex with HEPES. Change in pH in the storage solution was measured. Structural lung injury was evaluated using hematoxylin-eosin stained tissue sections. Cell death was quantified by measuring necrotic cells using trypan blue exclusion and apoptotic cells via the TUNEL (terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling) assay. RESULTS: Lungs stored in Perfadex demonstrated the greatest degree of cell death. Lungs in the Pyruvate group exhibited decreased cell death despite greater acidosis. The addition of HEPES reduced cell death and preservation solution acidosis in both Perfadex and pyruvate-modified Perfadex (P < .05). Almost all cell death resulted from necrosis. Adding pyruvate to the preservation solution increases acid formation during storage, but decreases cell death. HEPES ameliorates this acidosis and decreases allograft cell destruction. CONCLUSION: Increasing the preservation solution buffering capacity may be a simple strategy for improving lung preservation for transplantation.

Intra-articular injection of tumor necrosis factor-alpha in the rat: an acute and reversible in vivo model of cartilage proteoglycan degradation.

OBJECTIVE: To develop an in vivo model for rapid assessment of cartilage aggrecan degradation and its pharmacological modulation. DESIGN: Tumor necrosis factor-alpha (TNFalpha) was injected intra-articularly (IA) in rat knees and aggrecan degradation was monitored at various times following challenge. Articular cartilage was assessed for aggrecan content by Safranin O staining and by immunohistochemistry for the NITEGE epitope. Synovial fluids (SFs) were analyzed for sulfated glycosaminoglycans (GAGs) using the dimethylmethylene blue dye assay and for aggrecan fragments generated by specific cleavage at aggrecanase-sensitive sites by Western blot analysis with neoepitope antibodies. Indomethacin, dexamethasone, and an aggrecanase inhibitor were evaluated for their ability to modulate TNFalpha-induced proteoglycan degradation in vivo. RESULTS: (1) IA injection of TNFalpha in the knee joint of rats resulted in transient aggrecan degradation and release of aggrecanase-generated aggrecan fragments from the articular cartilage into the SF; (2) a correlation was observed between histologically assessed depletion of aggrecan from the articular cartilage and the appearance of specific neoepitopes in the SF; (3) aggrecan degradation was inhibited by an aggrecanase inhibitor as well as by dexamethasone, but not by the non-steroidal anti-inflammatory drug (NSAID), indomethacin. CONCLUSION: TNFalpha injection in the knee joints of rats results in rapid transient cartilage proteoglycan degradation, mediated by cleavage at the aggrecanase sites. Biomarker read-out of specific neoepitopes in the SF enables the use of this mechanism-based model for rapid evaluation of aggrecanase-mediated aggrecan degradation in vivo.

The effectiveness of sealants in managing caries lesions.

A barrier to providing sealants is concern about inadvertently sealing over caries. This meta-analysis examined the effectiveness of sealants in preventing caries progression. We searched electronic databases for comparative studies examining caries progression in sealed permanent teeth. We used a random-effects model to estimate percentage reduction in the probability of caries progression in sealed vs. unsealed carious teeth. Six studies, including 4 randomized-controlled trials (RCT) judged to be of fair quality, were included in the analysis (384 persons, 840 teeth, and 1090 surfaces). The median annual percentage of non-cavitated lesions progressing was 2.6% for sealed and 12.6% for unsealed carious teeth. The summary prevented fraction for RCT was 71.3% (95%CI: 52.8%-82.5, no heterogeneity) up to 5 years after placement. Despite variation among studies in design and conduct, sensitivity analysis found the effect to be consistent in size and direction. Sealing non-cavitated caries in permanent teeth is effective in reducing caries progression.

Transcriptional profiling and pathway analysis of monosodium iodoacetate-induced experimental osteoarthritis in rats: relevance to human disease.

OBJECTIVE: The objective of this study was to characterize the rat monosodium iodoacetate (MIA)-induced model for osteoarthritis (OA) and determine the translatability of this model to human disease. This was accomplished through pathway, network and system level comparisons of transcriptional profiles generated from animal and human disease cartilage. METHODS: An OA phenotype was induced in rat femorotibial joints following a single injection of 200mug MIA per knee joint for a period of 2 or 4 weeks. Lesion formation in the rat joints was confirmed by histology. Gene expression changes were measured using the Agilent rat whole genome microarrays. Cartilage was harvested from human knees and gene expression changes were measured using the Agilent human arrays. RESULTS: One thousand nine hundred and forty-three oligos were differentially expressed in the MIA model, of these, approximately two-thirds were up-regulated. In contrast, of the 2130 differentially expressed oligos in human disease tissue, approximately two-thirds were down-regulated. This dramatic difference was observed throughout each level of the comparison. The total overlap of genes modulated in the same direction between rat and human was less than 4%. Matrix degradation and inflammatory genes were differentially regulated to a much greater extent in MIA than human disease tissue. CONCLUSION: This study demonstrated, through multiple levels of analysis, that little transcriptional similarity exists between rat MIA and human OA derived cartilage. As disease modulatory activities for potential therapeutic agents often do not translate from animal models to human disease, this and like studies may provide a basis for understanding the discrepancies.

FDI report on adverse reactions to resin-based materials.

Resin-based restorative materials are considered safe for the vast majority of dental patients. Although constituent chemicals such as monomers, accelerators and initiators can potentially leach out of cured resin-based materials after placement, adverse reactions to these chemicals are rare and reaction symptoms commonly subside after removal of the materials. Dentists should be aware of the rare possibility that patients could have adverse reactions to constituents of resin-based materials and be vigilant in observing any adverse reactions after restoration placement. Dentists should also be cognisant of patient complaints about adverse reactions that may result from components of resin-based materials. To minimise monomer leaching and any potential risk of dermatological reactions, resin-based materials should be adequately cured. Dental health care workers should avoid direct skin contact with uncured resin-based materials. Latex and vinyl gloves do not provide adequate barrier protection to the monomers in resin-based materials.

Single vs bilateral, sequential lung transplantation for end-stage emphysema: influence of recipient age on survival and secondary end-points.

BACKGROUND: The appropriate age to perform bilateral, sequential lung transplants (BSLT) in patients with chronic obstructive pulmonary disease (COPD) remains controversial. Although single lung transplant (SLT) offers an advantage in terms of organ availability, the long-term survival may not warrant this strategy in all age groups. METHODS: We analyzed 2,260 lung transplant recipients (1835 SLT, 425 BSLT) with COPD recorded in the International Society for Heart and Lung Transplantation/United Network for Organ Sharing thoracic registry between January 1991 and December 1997. To assess mortality, we performed univariate (Kaplan-Meier method and the chi-square statistic) and multivariate analyses (proportional hazards method). Because of incomplete morbidity data in the international registry, only data from U.S. centers (n = 1778, 1467 SLT, 311 BSLT) were used in the morbidity analysis. RESULTS: Survival rates (%) computed using the Kaplan-Meier method at 30 days, 1 year, and 5 years for the patients aged < 50 years were 93.6, 80.2, and 43.6, respectively, for the SLT patients, and 94.9, 84.7, and 68.2, respectively, for the BSLT patients. For patients aged 50 to 60 years, survival rates (%) were 93.5, 79.4, and 39.8 for the SLT patients compared with 93.0, 79.7, and 60.5 for the BSLT patients. For those aged > 60 years, SLT survival (%) was 93.0, 72.9, and 36.4, compared with 77.8 and 66.0 for the BSLT group (a 5-year rate could not be completed in this group). The multivariate model showed a higher risk ratio for mortality in patients aged 40 to 57 years who received SLT vs BSLT. Recipient age and procedure type did not appear to affect the development of rejection, bronchiolitis obliterans, bronchial stricture, or lung infection. CONCLUSIONS: Single lung transplant may offer acceptable early survival for patients with end-stage respiratory failure. However, long-term survival data favors BSLT in recipients until approximately age 60 years. These data suggest that a BSLT approach offers a significant survival advantage to recipients younger than 60 years of age.

Indications for using video-assisted thoracoscopic surgery to diagnose diaphragmatic injuries after penetrating chest trauma.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has been shown to be an accurate method for identifying diaphragmatic injuries (DIs). The purpose of this investigation was to establish specific indications for the use of VATS after penetrating chest trauma. METHODS: A retrospective review of all patients undergoing VATS after penetrating chest trauma at a level 1 trauma center over an 8-year period was performed. Logistic regression was used in an attempt to identify independent predictors of DI. RESULTS: One hundred seventy-one patients underwent VATS assessment of a hemidiaphragm, and 60 patients (35%) were found to have a DI. Five independent risk factors for DI were identified from analyzing the patient records: abnormal chest radiograph, associated intraabdominal injuries, high-velocity mechanism of injury, entrance wound inferior to the nipple line or scapula, and right-sided entrance wound. CONCLUSIONS: In the largest published series of patients undergoing VATS to exclude a DI, this review identifies five independent predictors of DI after penetrating chest trauma. A diagnostic algorithm incorporating these five factors was designed with the goal of reducing the number of unrecognized DIs after penetrating chest trauma by using VATS for patients at greatest risk for such injuries.

Load versus humoral activation in the genesis of early hypertensive heart disease.

BACKGROUND: The role of load versus angiotensin II (Ang II) and endothelin-1 (ET) in the pathogenesis of hypertensive heart disease is controversial. We sought to determine whether alterations in cardiac structure and function due to hypertension (HTN) were dependent on Ang II or ET activation. Methods and Results-- Bilateral renal wrapping to produce HTN (n=12) or sham surgery (n=6) was performed in adult dogs. Weekly blood pressure, plasma renin activity, Ang II, ET, and catecholamines were measured. Systolic (end-systolic elastance, Ees) and diastolic (tau) function were assessed in sham and HTN dogs at 5 (HTN-5wk) or 12 (HTN-12wk) weeks. Ang II and ET were assayed in the left ventricle (LV) and kidney. Mean arterial pressure was higher in renal wrap dogs at week 1 (*P<0.05 versus controls: 139+/-4* versus 123+/-4 mm Hg), week 5 (174+/-7* versus 124+/-4 mm Hg), and week 12 (181+/-12* versus 124+/-4 mm Hg). LV mass index was increased in HTN-5wk (22%*) and HTN-12wk (39%*). LV fibrosis was increased in HTN-12wk. Ees was preserved in HTN-5wk and HTN-12wk. tau was increased in HTN-5wk (50+/-3* ms) and HTN-12wk (62+/-10* ms) dogs compared with sham (41+/-2 ms). Plasma Ang II, ET, catecholamines, and plasma renin activity were unchanged during the progressive HTN. Ang II and ET in LV and kidney were not different from controls. CONCLUSIONS: Systemic HTN induces LV hypertrophy, myocardial fibrosis, and isolated diastolic dysfunction in the absence of local or systemic activation of Ang II or ET. These findings suggest that load is the prevailing stimulus for the structural and functional changes associated with early hypertensive heart disease.

Differential effects of natriuretic peptides and NO on LV function in heart failure and normal dogs.

beta-Adrenergic hyporesponsiveness in congestive heart failure (CHF) is mediated, in part, by nitric oxide (NO). NO and brain natriuretic peptide (BNP) share cGMP as a second messenger. Left ventricular (LV) function and inotropic response to intravenous dobutamine (Dob) were assessed during sequential intracoronary infusion of saline, HS-142-1 (a BNP receptor antagonist), and HS-142-1 + N(G)-monomethyl-L-arginine (L-NMMA) in anesthetized dogs with CHF due to rapid pacing and in normal dogs during intracoronary infusion of saline, exogenous BNP, and sodium nitroprusside (SNP). In CHF dogs, intracoronary HS-142-1 did not alter the inotropic response to Dob [percent change in first derivative of LV pressure (% Delta dP/dt) 47 +/- 4% saline vs. 54 +/- 7% HS-142-1, P = not significant]. Addition of intracoronary L-NMMA to HS-142-1 enhanced the response to Dob (% Delta dP/dt 73 +/- 8% L-NMMA + HS-142-1, P < 0.05 vs. H142-1). In normal dogs, intracoronary SNP blunted the inotropic response to Dob (% Delta dP/dt 93 +/- 6% saline vs. 71 +/- 5% SNP, P < 0.05), whereas intracoronary BNP had no effect. In CHF dogs, the time constant of LV pressure decay during isovolumic relaxation increased with intracoronary HS-142-1 (48 +/- 4 ms saline vs. 58 +/- 5 ms HS-142-1, P < 0.05) and further increased with intracoronary L-NMMA (56 +/- 6 ms HS-142-1 vs. 66 +/- 7 ms L-NMMA + HS-142-1, P < 0.05). Endogenous BNP and NO preserve diastolic function in CHF, whereas NO but not BNP inhibits beta-adrenergic responsiveness.

Effect of donor age and ischemic time on intermediate survival and morbidity after lung transplantation.

BACKGROUND: Pressure to expand the donor pool has required the use of lungs from older donors or from more-distant procurement areas. The long-term consequences of this policy have not yet been fully addressed. The effect of donor age and donor ischemic time on intermediate survival and important secondary end points after lung transplantation was therefore examined. METHODS: A cohort of 1,800 lung transplant recipients with complete 2-year follow-up, operated on in the United States between April 1, 1993, and March 31, 1996, was studied to assess survival. For analysis of secondary end points, the cohort was limited to 1,450 patients. RESULTS: Donor age when analyzed independently did not significantly affect intermediate survival (p = 0.4). Secondary end points were also not affected by age, with the exception of the incidence of hospitalization for rejection in the univariate analysis (p = 0.02) and in the multivariate analysis (p = 0.04). Moreover, there was not a significant impact of donor age or ischemic time independently on survival in the multivariate analysis. Similarly, when the interaction between ischemic time and donor age was examined in all of the multivariate models, none of the secondary end points were found to be significantly influenced. However, the combined interaction between donor age and ischemia time demonstrated a significantly worse survival at 2 years (p = 0.02) with donor age of > 50 years and donor ischemic time > 7 h. CONCLUSIONS: Donor age and donor ischemic time did not independently influence survival or important secondary end points after lung transplantation. However, intermediate-term survival was affected by the use of older donors when combined with a prolonged ischemic time. The impact of this combination should be considered when attempting to expand the donor pool.

Mechanically strained cells of the osteoblast lineage organize their extracellular matrix through unique sites of alphavbeta3-integrin expression.

Bone cells transduce mechanical signals into anabolic biochemical responses. However, the mechanisms of mechanotransduction are unknown. To address this issue, we performed studies in primary cells of the human osteoblast lineage grown on collagen/vitronectin-coated supports. We discovered that mechanical strain stimulated a redistribution of the alphavbeta3-integrin to irregular plaque-like areas at the cell-extracellular matrix surface. Proteins involved in integrin-matrix interactions in focal adhesions, vinculin and talin, did not localize to the plaque-like areas of alphavbeta3-expression, but signaling molecules such as focal adhesion kinase (FAK) did. Mechanical strain increased the number and size of the plaques defined by surface expression of alphavbeta3-integrin. Osteopontin was secreted as a cross-linked macromolecular complex, likely through the action of tissue transglutaminase that also was found in the plaques of alphavbeta3-integrin cell-matrix interaction. Mechanical strain increased mineralization of the extracellular matrix that developed in these plaques in alphavbeta3-integrin-dependent manner. Because the plaque-like areas of cell-matrix interaction exhibit macromolecular assembly and mineralization, we conclude that they may represent subcellular domains of bone formation and that alphavbeta3-integrin activation represents one mechanism by which mechanical strain stimulates bone formation.

Histologic evidence of the safety of endoscopic saphenous vein graft preparation.

BACKGROUND: Endoscopic methods of saphenous vein procurement have recently been introduced. These techniques have been successful in limiting pain and wound complications, but less information on assessing potential trauma to the harvested vein segment is available. METHODS: Fourteen male patients undergoing coronary artery bypass grafting were included in the study. Nine patients underwent endoscopic procurement of saphenous vein whereas 5 patients underwent procurement using standard open techniques. Histologic appearance and immunohistochemical studies (factor VIII:vWF [von Willebrand factor protein] and CD34) of the vein segments were reviewed in a blinded fashion. RESULTS: On histologic analysis, no differences in the intima, media, or adventitia were found between endoscopically and conventionally obtained vein segments. Immunohistochemical staining for factor VIII:vWF and CD34 showed no differences between veins harvested by the two techniques. CONCLUSIONS: Endoscopic saphenous vein harvesting does not appear to traumatize the vessel wall any more than open techniques. Longitudinal assessment is necessary to evaluate long-term patency in vein grafts procured using this method.