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).

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.

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.

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.

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.

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.

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.

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.

Testing reminder and motivational telephone calls to increase screening mammography: a randomized study.

BACKGROUND: Prospective randomized trials have demonstrated that motivational telephone calls increase adherence to screening mammography. To better understand the effects of motivational calls and to maximize adherence, we conducted a randomized trial among women aged 50-79 years. METHODS: We created a stratified random sample of 5062 women due for mammograms within the Group Health Cooperative of Puget Sound, including 4099 women with prior mammography and 963 without it. We recruited and surveyed 3743 (74%) of the women before mailing a recommendation. After 2 months, 1765 (47%) of the 3743 women had not scheduled a mammogram and were randomly assigned to one of three intervention groups: a reminder post-card group (n = 590), a reminder telephone call group (n = 585), and a motivational telephone call addressing barriers group (n = 590). The telephone callers could schedule mammography. We used Cox proportional hazards models to estimate the hazard ratio (HR) and 95% confidence interval (CI) for documented mammography use by 1 year. RESULTS: Women who received reminder calls were more likely to get mammograms (HR = 1.9; 95% CI = 1.6-2.4) than women who were mailed postcards. The motivational and reminder calls (average length, 8.5 and 3.1 minutes, respectively) had equivalent effects (HR = 0.97; 95% CI = 0.8-1.2). After we controlled for the intervention effect, women with prior mammography (n = 1277) were much more likely to get a mammogram (HR = 3.4; 95% CI = 2.7-4.3) than women without prior use (n = 488). Higher income, but not race or more education, was associated with higher adherence. CONCLUSIONS: Reminding women to schedule an appointment was as efficacious as addressing barriers. Simple intervention groups should be included as comparison groups in randomized trials so that we better understand more complex intervention effects.

A peptidomimetic antagonist of the integrin alpha(v)beta3 inhibits Leydig cell tumor growth and the development of hypercalcemia of malignancy.

The integrin alpha(v)beta3 interacts with the arginine-glycine-aspartic acid (RGD) tripeptide recognition sequence of a variety of extracellular matrix proteins. Recent studies show that alpha(v)beta3 plays an important role in tumor-induced angiogenesis and tumor growth and that antagonists of alpha(v)beta3 inhibit angiogenic processes that include endothelial cell adhesion and migration. Consequently, we reasoned that an RGD-based peptidomimetic antagonist of alpha(v)beta3 might inhibit tumor angiogenesis and tumor growth in vivo. An RGD-peptidomimetic library was screened to identify antagonists of vitronectin binding to alpha(v)beta3, and the compounds chosen were modified to produce selective and potent inhibitors of alpha(v)beta3. One of these compounds, beta-[[2-2-[[[3-[(aminoiminomethyl)amino]-phenyl]carbonyl]amino]ac etyl]amino]-3,5-dichlorobenzenepropanoic acid (SC-68448), inhibited vitronectin binding to both alpha(v)beta3 and the closely related platelet receptor, alpha(IIb)beta3, in a dose-responsive manner. SC-68448 inhibited vitronectin binding to alpha(v)beta3 (IC50, 1 nM) and fibrinogen binding to the platelet receptor alpha(IIb)beta3 (IC50, >100 nM), demonstrating that SC-68448 was 100-fold more potent as an inhibitor of alpha(v)beta3 versus alpha(IIb)beta3. In cell-based studies, SC-68448 inhibited alpha(v)beta3-mediated endothelial cell proliferation in a dose-dependent manner but did not inhibit tumor cell proliferation, suggesting that effects on endothelial cell proliferation were not due to SC-68448-induced cytotoxicity. In accord with these results, SC-68448 inhibited angiogenesis in vivo in a basic fibroblast growth factor-induced rat corneal neovascularization model. A xenogeneic severe combined immune deficiency mouse/rat Leydig cell tumor model was developed for testing SC-68448 as an inhibitor of tumor growth in vivo. Rat Leydig cell tumors grew rapidly in severe combined immune deficiency mice and produced humoral hypercalcemia of malignancy. SC-68448 inhibited the growth of the tumors in mice by up to 80% and completely blocked the development of hypercalcemia. Together, these results demonstrate the feasibility of antitumor therapies based upon the development of nontoxic small molecule pharmacological antagonists of integrin alpha(v)beta3.

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.

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.

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.

Isolation and characterization of 1-O-alpha-2-acetamido-2-deoxy-D-galactopyranosyl-myo-inositol from pregnancy urine.

A new neutral glycoside of myo-inositol was isolated from the pregnancy urine of a single donor. Its structure was investigated by 1H-NMR spectroscopy and mass spectroscopy. It was identified as 1-O-alpha-2-acetamido-2-deoxy-D-galactopyranosyl-myo-inositol. No such structure or sequence has previously been reported in either myo-inositol or glucose glycosides.

Peptidomimetic antagonists of alphavbeta3 inhibit bone resorption by inhibiting osteoclast bone resorptive activity, not osteoclast adhesion to bone.

Osteoclasts are actively motile on bone surfaces and undergo alternating cycles of migration and resorption. Osteoclast interaction with the extracellular matrix plays a key role in the osteoclast resorptive process and a substantial body of evidence suggests that integrin receptors are important in osteoclast function. These integrin receptors bind to the Arg-Gly-Asp (RGD) sequence found in a variety of extracellular matrix proteins and it is well established that the interaction of osteoclast alpha v beta 3 integrin with the RGD motif within bone matrix proteins is important in osteoclast-mediated bone resorption. In this study, we characterized the effects of two synthetic peptidomimetic antagonists of alpha v beta 3, SC-56631 and SC-65811, on rabbit osteoclast adhesion to purified matrix proteins and bone, and on bone resorption in vitro. SC-56631 and SC-65811 are potent inhibitors of vitronectin binding to purified alpha v beta 3. Both SC-56631 and SC-65811 inhibited osteoclast adhesion to osteopontin- and vitronectin-coated surfaces and time-lapse video microscopy showed that osteoclasts rapidly retract from osteopontin-coated surfaces when exposed to SC-56631 and SC-65811. SC-56631 and SC-65811 blocked osteoclast-mediated bone resorption in a dose-responsive manner. Further analysis showed that SC-65811 and SC-56631 reduced the number of resorption pits produced per osteoclast and the average pit size. SC-65811 was a more potent inhibitor of bone resorption and the combination of reduced pit number and size led to a 90% inhibition of bone resorption. Surprisingly, however, osteoclasts treated with SC-65811, SC-56631 or the disintegrin echistatin, at concentrations that inhibit bone resorption did not inhibit osteoclast adhesion to bone. These results suggest that alphavbeta3 antagonists inhibited bone resorption by decreasing osteoclast bone resorptive activity or efficiency but not by inhibiting osteoclast adhesion to bone per se.

Results of extracorporeal membrane oxygenation in neonates with sepsis. The Extracorporeal Life Support Organization experience.

Use of extracorporeal membrane oxygenation for treatment of respiratory failure caused by sepsis is controversial because of concerns over survival benefit and hemorrhage-related complications. To evaluate the impact of the primary diagnosis of sepsis on outcome, we reviewed data from 6853 neonates in the Extracorporeal Life Support Organization Registry and defined two groups: group 1 (n = 1060), all patients undergoing extracorporeal membrane oxygenation with a primary diagnosis of sepsis; group 2 (n = 5793), those with any other primary diagnosis. A multivariate logistic regression analysis that considered 15 variables present before extracorporeal membrane oxygenation (including age, sex, birth weight, prior cardiopulmonary arrest, arterial blood gas results, and ventilator settings) was used to compare outcomes between groups. Survival was not different between the two groups (77%, group 1; 82%, group 2; p = 0.2480), although lung recovery was less frequent in the patients with sepsis (p = 0.0185). Group 1 had a higher incidence of complications including seizures (odds ratio 1.446, p = 0.0346), cerebral infarct or hemorrhage (2.310, p = 0.0001), need for dialysis (1.478, p = 0.0131), hypernatremia (2.089, p = 0.0019), hyperbilirubinemia (2.423, p = 0.0001), and dobutamine use (1.918, p = 0.0001). Neonates with sepsis are more likely to have neurologic, renal, and metabolic complications from extracorporeal membrane oxygenation but may still achieve a survival benefit equivalent to those without sepsis. From these data, extracorporeal membrane oxygenation should not be withheld from neonates solely on the basis of sepsis. Rather, management strategies should focus on limiting the incidence or severity of the common complications.

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.

Does human leukocyte antigen matching influence the outcome of lung transplantation? An analysis of 3,549 lung transplantations.

BACKGROUND AND OBJECTIVE: Human leukocyte antigen (HLA) compatibility has been shown to improve the outcome of renal and cardiac transplantation. However, its impact on outcome following lung transplantation is not clear, with several single-center studies reporting inconsistent results. We studied the influence of HLA matching on survival and the development of rejection and obliterative bronchiolitis after lung transplantation, using data from the United Network for Organ Sharing/International Society for Heart and Lung Transplantation registry. METHODS: The study population included adult patients who received cadaveric lung transplants between October 1987 and June 1997 for whom HLA data were available. Two cohorts were examined, depending on the era of transplantation: (1) October 1987 to June 1997 (n = 3,549): Differences in actuarial survival as stratified by either the total number of HLA mismatches or the number of mismatches at each HLA locus were determined using a log-rank test. Multivariate logistic regression models were developed to determine independent predictors of survival at 1, 3, and 5 years following lung transplantation. (2) April 1994 to June 1997 (n = 1,796): The association of HLA mismatching with acute rejection and obliterative bronchiolitis was determined using a chi-squared analysis. RESULTS: Only 164 patients (4.6%) received lung grafts with 2 or fewer HLA mismatches. Univariate analyses demonstrated a significant difference in post-transplant survival by mismatch level, with the total number of HLA mismatches (p = 0.0008) and mismatching at the HLA-A locus (p = 0.002) associated with worse survival. Multivariate logistic regression demonstrated that the number of mismatches at the HLA-A and HLA-DR loci predicted 1-year mortality (incremental odds ratios 1.18, p = 0.01, and 1.15, p = 0. 03, respectively). The total number of HLA mismatches predicted 3- and 5-year mortality (incremental odds ratios 1.13 at 3 years, p = 0. 0004, and 1.14 at 5 years, p = 0.0002). However, other covariates such as repeat transplantation, transplantation for congenital heart disease, advanced recipient age, and an early era of transplantation were stronger predictors of mortality. We found no significant association between HLA mismatching and the development of obliterative bronchiolitis, although there was an association between mismatching at the HLA-A locus and acute rejection episodes requiring hospital admission (p = 0.008). We also found no association between mismatching at the HLA-B locus and rejection episodes requiring either hospitalization or the alteration of anti-rejection medications (p = 0.034). CONCLUSION: Although the number of HLA mismatches at the HLA-A and HLA-DR loci predicted 1-year mortality and the total number of mismatches predicted 3- and 5-year mortality following lung transplantation, the effect of each covariate was small in this multicenter study of 3,549 patients. Further close follow-up of registry patients is necessary to determine the effect of HLA matching on long-term survival and freedom from obliterative bronchiolitis and rejection following lung transplantation. A prospective study of HLA matching for lung transplantation should not yet be considered in view of the small number of grafts with 2 or fewer mismatches and the modest effect of HLA matching on outcome.