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Objectives Approximately 0.2% to 2.7% of children with congenital heart disease require a tracheostomy after cardiac surgery with the majority having single ventricle (SV) type heart lesions. Tracheostomy in SV patients is reported to be associated with high mortality. We hypothesized that short- and long-term survival of patients with SV heart disease would vary according to tracheostomy indication. Methods This is a single center, 20-year, retrospective review of all patients with SV heart disease who underwent tracheostomy. Demographic, cardiac anatomy, surgical, intensive care unit, and hospital course data were collected. The primary outcome was survival following tracheostomy. Secondary outcome was the completion of staged palliation to Fontan. Results In total, 25 patients with SV heart disease who underwent tracheostomy were included. Indications for tracheostomy included one or more of the following: tracheobronchomalacia (n = 8), vocal cord paralysis (n = 7), tracheal/subglottic stenosis (n = 6), primary respiratory insufficiency (n = 4), diaphragm paralysis (n = 3), suboptimal hemodynamics (n = 2), and other upper airway issues (n = 1). Survival at six months, one year, five years, and ten years was 76%, 68%, 63%, and 49%, respectively. Most patients completed Fontan palliation (64%). Patients who underwent tracheostomy for suboptimal hemodynamics and/or respiratory insufficiency had a higher mortality risk compared to those with indications of upper airway obstruction or diaphragm paralysis (hazard ratio 4.1, 95% confidence interval 1.2-13.7; P = .02). Conclusions Mortality risk varies according to tracheostomy indication in patients with SV heart disease. Tracheostomy may allow staged surgical palliation to proceed with acceptable risk if it was indicated for anatomic or functional airway dysfunction.

Background Animal data demonstrate that intracardiac patches of decellularized porcine small intestine submucosa (CorMatrix; CorMatrix Cardiovascular, Atlanta, GA) become repopulated with native cells, suggesting the possibility of a substrate for regenerative tissue in humans. Although human studies have not demonstrated this regenerative property with intracardiac patches, it is possible that other environments may better promote native cell repopulation. We report a prospective series of explanted CorMatrix extracardiac patches placed in infants with congenital heart disease. Methods CorMatrix Tyke patches were used in pulmonary artery patch closure during the Norwood procedure. The patch material was explanted as part of the hemi-Fontan procedure. Specimens were analyzed with the use of hematoxylin and eosin, Movat pentachrome, and trichrome stains. Results Of the 11 implantations, 9 specimens were explanted. One patient did not survive to hemi-Fontan procedure. One patient’s patch was removed, but not analyzed. Acellular material, chronic inflammation, fibrosis, and foreign body giant cell reaction was seen in all explanted patches. No explanted CorMatrix Tyke material demonstrated evidence of ingrowth of native endothelial tissue at a median of 4.9 months in vivo. Conclusions CorMatrix Tyke patch material, placed as a pulmonary artery patch in an extracardiac position, remained pliable and mostly free of calcification. However, these patches did not show evidence of native endothelial tissue at a median of 4.9 months in vivo.

Tracheobronchomalacia is a condition of dynamic collapse of the trachea and mainstem bronchi. The clinical significance of tracheobronchomalacia depends on its severity. Mild cases may be medically managed with limited symptomology, while severe cases require advanced therapies, lengthy hospital stays, and carry significant morbidity and mortality. Current therapies for severe tracheobronchomalacia include tracheostomy with prolonged mechanical ventilation, aortopexy, tracheobronchopexy, and intraluminal metallic, silicone, or bioresorbable stents. Three-dimensional (3D)-printed, patient-specific, bioresorbable airway splinting is a novel treatment option that is undergoing investigation in a cohort of critically ill children with severe tracheobronchomalacia. At the time of our last review of our data, 29 splints had been implanted in 15 children with intrathoracic tracheobronchomalacia. The median follow-up was 8.5 months. There were 12 long-term survivors, and all but one lived at home. This article discusses the details of our institution's development and use of 3D-printed, patient-specific, bioresorbable splints for treatment of severe tracheobronchomalacia in the pediatric population.

Background The influence of ventricular morphology on Fontan outcomes is controversial. Objectives This study hypothesized that dysfunction of the single right ventricle (RV) and right atrioventricular valve regurgitation (AVVR) increases over time and adversely impacts late outcomes following a Fontan operation. A single-center retrospective study was performed. Methods From 1985 through 2018, 1,162 patients underwent the Fontan procedure at our center and were included in this study. Transplant and takedown free survival, ventricular, and atrioventricular valve dysfunction after Fontan were analyzed. Death or heart transplantation information was obtained from the National Death Index and the Scientific Registry of Transplant Recipients. Results The follow-up rate was 99%. Morphologic RV was present in 58% of patients. Transplant and takedown free survival were 91%, 75%, and 71% at 10 years, 20 years, and 25 years, respectively. Morphologic RV was an independent risk factor for transplant, takedown free survival (hazard ratio: 2.4; p = 0.008). The AVVR, which preceded ventricular dysfunction in most cases, was associated with the development of ventricular dysfunction after Fontan (odds ratio: 4.3; 95% confidence interval: 2.7 to 6.7; p Conclusions Morphologic RV is negatively associated with the long-term survival following the Fontan, possibly due to a tendency toward progressive AVVR and deterioration of the single ventricle function. Additional volume overload caused by AVVR may be one of the main factors accelerating the dysfunction of the single RV, implying that early valve intervention may be warranted.

We report an intricate aortic root replacement in a young male patient suffering from native valve infective endocarditis due to Serratia marcescens. Further complicating the total root replacement, there was an unknown infected aortic thrombus and a concomitant anomalous right coronary artery with an intramural course. As a result of our more aggressive approach, we believe that we lowered the risk of recurrent infection of the bioprosthesis of the aortic root.

Purpose Timely and high-quality feedback is important in cardiothoracic (CT) surgery education. Feedback on operative proficiency is an area for improvement in CT surgery programs. Traditional evaluations significantly lag behind operative interactions. We hypothesized that use of the System for Improving and Measuring Procedural Learning (SIMPL) app would improve operative feedback for trainees. Methods Use of SIMPL was evaluated from December 2018 to January, 2021 within an academic CT surgery training program. Ratings include level of supervision, complexity of the operation, and trainee performance. Completion was limited to 72 h after the operation. Descriptive statistics of the users and ratings are presented. Results Over 28 months, 816 evaluations were completed, and of these, 495 had a rating from both the faculty and trainee. There were 19 trainees representing post-graduate years 1-8 and 19 faculty members who received or submitted at least one evaluation over the study period. The number of evaluations for each trainee ranged from 1 to 166 and from 1 to 81 for each of the faculty. The response rate for faculty ranged from 0% to 100%. "Active help" was the most common type of supervision (50.7% by the faculty, 60.4% from the trainees). Conclusions Use of SIMPL within a CT surgery training program was feasible and engagement was observed from both trainees and faculty. SIMPL provided trainees with timely, concise feedback on operative performance. Further work will focus on correlating SIMPL ratings with pre-existing assessments of performance.

Background Stroke is a feared complication of cardiac surgery. Modern clot-retrieval techniques provide effective treatment for large vessel occlusion (LVO) strokes. The purpose of this study was to 1) report the incidence of LVO stroke after cardiac surgery at a large academic center, and 2) describe outcomes of postoperative LVO strokes. Methods All patients experiencing stroke within 30 days after undergoing cardiac surgery at a single center in 2014-2018 were reviewed. LVOs were identified through review of imaging and medical records, and their characteristics and clinical courses were examined. Results Over the study period, 7,112 cardiac surgeries, including endovascular procedures, were performed. Acute ischemic stroke within 30 days after surgery was noted in 163 patients (2.3%). Among those with a stroke, 51/163 (31.3%) had a CTA or MRA, and 15/163 (9.2%) presented with LVO stroke. For all stroke patients, the median time from surgery to stroke was 2 days (interquartile range, IQR, 0–6 days), and for patients with LVO, the median time from surgery to stroke was 4 days (IQR 0–6 days). The overall rate of postoperative LVO was 0.2% (95% CI 0.1–0.4%), though only 6/15 received thrombectomy. LVO patients receiving thrombectomy were significantly more likely to return to independent living compared to those managed medically (n = 4/6, 66.6% for mechanical thrombectomy vs. n = 0/9, 0% for medical management, P = .01). Of the 9 patients who did not get thrombectomy, 6 may currently be candidates for thrombectomy given new expanded treatment windows. Conclusions The rate of LVO after cardiac surgery is low, though substantially elevated above the general population, and the majority do not receive thrombectomy currently. Patients receiving thrombectomy had improved neurologic outcomes compared to patients managed medically. Optimized postoperative care may increase the rate of LVO recognition, and cardiac surgery patients and their caregivers should be aware of this effective therapy.

Objective Although over half of medical students are females, women comprise only 21% of cardiothoracic (CT) surgery residency applicants and 5% of the CT workforce. We sought to gain insight into female medical students’ perceptions of CT surgery and identify targets to increase interest. Design A 33-question survey queried career selection factors, perceptions of CT surgery, and ways to increase interest in the field. Responses were stratified by sex and preclinical versus clinical years. Setting Women at 13 US medical schools were compared to men at a Midwest medical school. Participants Surveys were distributed to approximately 4400 women and were completed by 372 (8.5%) women. Comparison surveys were distributed to approximately 170 preclinical men and were completed by 98 (57.6%) men. Results Preclinical woman had broad interests, whereas clinical women were more interested in primary care (p = 0.0124). Intellectual interest and lifestyle were important in specialty selection for men and women (91% versus 90%; 78% versus 86%). Although preclinical men valued perceived prestige and salary significantly more than preclinical women (39% versus 20%, p = 0.0014; 64% versus 48%, p = 0.0173), preclinical women valued caring for specific ethnicities and addressing health disparities significantly more than preclinical men (26% versus 15%, p = 0.0173; 53% versus 33%, p = 0.0019). Making family plans was cited by 83% of women as difficult if they choose to become a CT surgeon. Women thought that attaining their career interests and life goals (76%) or access to female CT surgery mentors (63%) would make the field more appealing. Over 70% of preclinical women were interested in shadowing a CT surgeon. Of these women, 12% attempted to shadow. Conclusions Although baseline interest in CT surgery is low among women, there are many targets for increasing interest especially during preclinical years. Residency programs have the opportunity to entice women to the field by addressing their priorities of lifestyle, family planning, and addressing health disparities.

Background Analyses of the HeartMate II left ventricular assist device are routinely performed after explant if returned to the manufacturer. Findings from manufacturer-reported pump analyses have not been correlated with pre-explant serum lactate dehydrogenase (LDH) values. Methods Between May 2004 and December 2014, 502 patients underwent primary HeartMate II implantation. Seventy pumps were explanted in 58 patients and returned to the manufacturer for pump analysis: 51 (73%) for suspected pump thrombosis, 12 (17%) for device-related infection, and 7 (13%) for percutaneous lead fracture. Median time from implant to explant was 12.4 months (range, 1 to 57 months). Results Pump thrombus was confirmed in 53 of 70 pumps (76%). Stratified by major clinical indications for explant of suspected pump thrombus or infection and lead fracture, the presence of pump thrombus was identified in 47 of 51 (92%) and 6 of 19 (32%), respectively. The median of 1) all LDH values, 2) maximum LDH values, and 3) interval change in LDH between 6 and 2 months before device explant were 1,061, 1,940, and −27 IU/L with thrombus present and 533, 504, and 13 IU/L in the absence of thrombus. Density estimation of LDH concentrations identified that a LDH value of 1,155 IU/L in the 6 months preceding pump thrombus had a 78% sensitivity and 90% specificity for findings of pump thrombus at the time of pump analysis. Conclusions Pre-explant LDH concentrations significantly correlated with findings on manufacture-performed pump analysis. These data validate LDH surveillance as an important clinical tool for identification of pump thrombus.

The influence of ventricular morphology on Fontan outcomes is controversial. Based on our observations, we hypothesized that dysfunction of the single right ventricle (RV) and right atrioventricular valve increases over time and adversely impacts the clinical outcomes of the Fontan. To investigate

Objective— Deep vein thrombosis (VT) can result in vein wall injury, which clinically manifests as post-thrombotic syndrome. Postinjury fibrosis may be modulated in part through cellular cysteine-cysteine receptor 7 (CCR7)–mediated events. We tested the hypothesis that late vein wall fibrotic remodeling is dependent on CCR7. Approach and Results— CCR7 −/− and C57BL/6 wild-type mice had inferior vena cava VT induced by nonstasis or stasis mechanisms. In both models, VT size was largest at day 1 and trended down by day 21, and CCR7 + cells peaked at day 8 in wild-type mice. No significant differences in VT resolution were found in CCR7 −/− as compared with wild type in either model. In the nonstasis VT model, vein wall changes consistent with fibrotic injury were evidenced by significant increases in collagen I, III, matrix metalloproteinase 2, and transforming growth factor-β gene expression, increases in α-smooth muscle actin and fibroblast specific protein-1 antigen, and total collagen at 8 days. Correspondingly, SM22α and fibroblast specific protein-1, but not DDR2 + cells, were increased at 8 days. Early wild-type thrombus exposure inhibited profibrotic gene expression in CCR7 −/− in ex vivo vein wall culture. Bone marrow chimera experiments further showed that circulating CCR7 + leukocytes partially rescued midterm profibrotic changes in CCR7 −/− mice. In human histological sections of chronic thrombosed femoral veins, CCR7 + cells were present in the fibrotic areas. Conclusions— Post-thrombotic vein wall remodeling is impaired in CCR7 −/− mice, with a profibrotic phenotype, is dependent on the thrombotic mechanism, and is mediated by circulating CCR7 + cells. Unlike other postinjury fibrotic responses, CCR7 + signaling may be important for positive vein wall remodeling after VT.

Post thrombotic syndrome therapy is primarily palliative, and the associated vein wall inflammatory mechanisms are unclear. Vein wall fibrotic injury following deep venous thrombosis (VT) is associated with elevated matrix metalloproteinases (MMPs). Whether and by what mechanism MMP9 directly contributes to vein wall remodeling after VT is unknown.WT and MMP9 -/- mice underwent stasis VT by ligation of the inferior vena cava (IVC) and tissue was harvested at 2, 8, and 21days. Assessment of thrombus size, and gene, protein and structural vein wall determinations were done.VT resolution was increased in MMP9-/- mice as compared with controls at 21d only. The primary phenotypic fibrotic vein wall differences occurred at 8d post VT, with significantly less vein wall collagen content as assessed by Picosirius red staining in MMP9 -/- mice as compared with WT. Increased monocytic vein wall influx with less IL-1b and TGFb was found in MMP9 -/- vein walls as compared with WT. Corresponding levels of PAI-1 were increased in MMP9 -/- compared with WT, and no difference in FSP-1+cells as compared with controls.In stasis VT, MMP9 modulates midterm vein wall collagen content, with an altered local inflammatory and profibrotic environment, likely directed by monocytes. Thus, MMP9 plays a role in both vein wall responses as well as late thrombus resolution.

ObjectiveDeep vein thrombosis (DVT) resolution instigates an inflammatory response, resulting in vessel wall damage and scarring. Urokinase-plasminogen activator (uPA) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), are integral components of the fibrinolytic system, essential for venous thrombosis (VT) resolution. This study determined the vein wall response when exposed to increased and decreased plasmin activity.MethodsA mouse inferior vena cava (IVC) ligation model in uPA −/− or PAI-1 −/− and their genetic wild types (B6/SvEv and C57/BL6, respectively) was used to create stasis thrombi, with tissue harvest at either 8 or 21 days. Tissue analysis included gene expression of vascular smooth muscle cells (alpha smooth muscle actin [αSMA], SM22) and endothelial marker (CD31), by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, matrix metalloproteinase (MMP)-2 and -9 activity by zymography, and vein wall collagen by picro-Sirius red histologic analysis. A P < .05 was considered significant.ResultsThrombi were significantly larger in both 8-day and 21-day uPA −/− as compared with wild type (WT) and were significantly smaller in both 8-day and 21-day PAI-1 −/− as compared with WT. Correspondingly, 8-day plasmin levels were reduced in half in uPA −/− and increased three-fold in PAI-1 −/− when compared with respective WT thrombi (P < .05; n = 5-6). The endothelial marker CD31 was elevated two-fold in PAI-1 −/− mice at 8 days, but reduced 2.5-fold at 21 days in uPA −/− as compared with WT (P = .02; n = 5-6), suggesting less endothelial preservation. Vein wall vascular smooth muscle cell (VSMC) gene expression showed that 8-day and 21-day PAI-1 −/− mice had 2.3- and 3.8-fold more SM22 and 1.8- and 2.3-fold more αSMA expression than respective WT (P < .05; n = 5-7), as well as 1.8-fold increased αSMA (+) cells (P ≤ .05; n = 3-5). No significant difference in MMP-2 or -9 activity was found in the PAI-1 −/− mice compared with WT, while 5.4-fold more MMP-9 was present in 21-day WT than 21-day uPA −/− (P = .03; n = 5). Lastly, collagen was ∼two-fold greater at 8 days in PAI-1 −/− IVC as compared with WT (P = .03; n = 6) with no differences observed in uPA −/− mice.ConclusionsIn stasis DVT, plasmin activity is critical for thrombus resolution. Divergent vein wall responses occur with gain or loss of plasmin activity, and despite smaller VT, greater vein wall fibrosis was associated with lack of PAI-1.Clinical RelevanceDVT resolution is dependent on many factors. Clinical studies suggest that slowly resolving extensive DVTs are associated with greater likelihood of post-thrombotic syndrome, and this is experimentally modeled by vein wall fibrosis and inflammation. The current study suggests a more complex relationship in that the plasmin-mediated events are central to thrombus resolution as well as to how the vessel wall responds. Surprisingly, a larger thrombus from a stasis model is not associated with greater vein wall damage. Thus, novel modalities such as PAI-1 inhibition may require supplemental anticoagulants for full efficacy.

Background The optimal surgical procedure for repair of supravalvar aortic stenosis (SVAS) remains uncertain. Proponents of multisinus repair techniques suggest improved outcomes compared with the single-patch technique. We evaluated the outcomes after an extended single-patch technique for relief of SVAS. Methods A cross-sectional retrospective analysis was performed of all SVAS patients who underwent repair from 1996 to 2009. Patient, procedural, and hospital course data were obtained through a review of the medical records. At follow-up, patients were evaluated for residual SVAS gradient, valvar aortic stenosis, aortic insufficiency, and need for reintervention. Results Twenty-two patients (mean age, 2.4 ± 2.4 years) underwent repair of SVAS (discrete form, 59%). Mean preoperative peak gradient was 77 ± 27 mm Hg (range, 20 to 139 mm Hg). There were no hospital deaths. Median postoperative length of stay was 5 days (range, 3 to 68 days). Mean follow-up was 4.1 ± 3.5 years (range, 0.7 to 13 years). Follow-up Doppler echocardiography revealed a peak left ventricular outflow tract gradient of 10 ± 12 mm Hg (range, 0 to 41 mm Hg). No patient had significant valvar aortic stenosis or insufficiency. Two patients (9%) required catheter-based reintervention that was unrelated to the SVAS repair. Conclusions This study demonstrates that a simple, extended single-patch technique for repair of SVAS provides excellent medium-term results. A durable reduction in gradient with low complication and recurrence rates can be achieved without the need for more complicated multisinus patch repairs.

Recently, both living and deceased organ donation rates have hit a plateau, despite increases in need for viable organs. One approach to improve donation rate is public education and policy; thus, it is necessary to understand the information the public is receiving regarding organ donation. We hypothesized that primetime medical dramas portray organ donation and transplantation in a negative manner. We compiled data on all primetime medical drama episodes with transplant themes from November 2008 through June 2010 and assessed depictions of organ donors and transplant candidates. Positive and negative thematic elements surrounding the process and individuals involved were also identified. One hundred and fifty-five million and 145 million households watched episodes containing any negative message and any positive message, respectively. Episodes containing only negative messages had over twice the household viewership per episode compared to episodes containing only positive messages (8.4 million vs. 4.1 million, p = 0.01). Widespread exposure to these representations may reinforce public misconceptions of transplantation. The transplant community should consider the popularity of medical dramas as an opportunity to impact the perception of organ donation and transplantation for millions of Americans.

Objective— Toll-like receptors (TLR) bridge innate immunity and host responses, including inflammation. Sterile inflammation such as a venous thrombus (V t ) may involve TLR signaling, including TLR9. Methods and Results— TLR9 signaling on thrombus resolution was investigated using a mouse model of stasis V t . V t were significantly larger in TLR9−/− mice compared with wild-type (WT) at 2 and 8 days, despite a 2-fold increase in thrombus polymorphonucleic neutrophils at 2 days and monocytes at 8 days, whereas thrombus collagen and neovascularization was 55% and 37% less, respectively, at 8 days. Coincidently, decreased fibrinogen and increased thrombin-antithrombin complex were observed in TLR9−/− mouse thrombi. Vein wall interferon-α, interleukin-1α, and interleukin-2 were significantly reduced in TLR9−/− mice compared with WT. Thrombus cell death pathway markers were not significantly altered at 2 days, but caspase-1 was reduced in TLR9−/− thrombi at 8 days. MyD88 confers TLR9 intracellular signaling, but MyD88−/− mice had V t resolution similar to that of WT. However, inhibition of the NOTCH ligand δ-like 4 was associated with larger V t . Finally, stimulation with a TLR9 agonist was associated with smaller V t . Conclusion— TLR9 signaling is integral for early and mid-V t resolution through modulation of sterile inflammation, maintaining a TH1 milieu, and effects on the thrombosis pathway.

Venous thrombus resolution sets up an early intense inflammatory reaction, from which vein wall damage results. Tissue response to injury includes matrix metalloproteinase (MMP) activation and extracellular matrix protein turnover. This study sought to determine the effect of exogenous MMP inhibition and its potential attenuation of early vein wall injury.Rats received treatment beginning 24 hr after a stasis venous thrombosis by near occlusive ligation and until harvest at day 7. Three groups were evaluated: (1) vehicle saline controls (NaCl), (2) low molecular weight heparin (LMWH; Lovenox, 3 mg/kg daily SQ), and (3) doxycycline (DOXY, 30 mg/kg daily PO). Thrombus size (mg/mm), levels of tumor necrosis factor alpha (TNF alpha) and D-dimer by colorimetric assay, and monocytes counts by immunohistochemistry were assessed. Vein wall assessment included stiffness by tensiometry, interleukin 1beta (IL-1 beta protein levels by enzyme-linked immunosorbent assay, MMP2 and -9 by zymography, and histological analysis of intimal thickness (IT). Comparisons were by t-test to control. p0.05 was considered significant.Thrombus sizes were similar at days 2 and 7 for all three groups, while thrombus TNFalpha was increased in 2-day LMWH- and DOXY-treated groups (NaCl = 1.0 +/- 0.8, LWMH = 9 +/- 3, DOXY = 27 +/- 5 pg/mg protein, n = 6-8, p0.05) and at 7 days in the DOXY group (NaCl = 3.0 +/- 2.5, DOXY = 23 +/- 4.2 pg/mg protein, n = 5, p0.05). Vein wall stiffness at 7 days was less with LMWH treatment, but not with DOXY, compared to controls (NaCl = 0.33 +/- 0.05, LMWH = 0.17 +/- 0.03, DOXY = 0.43 +/- 0.09 N/mm, n = 5-7, p0.05). Vessel-wall IL-1 beta was reduced only in the DOXY group at 7 days (NaCl = 26 +/- 3, LMWH = 38 +/- 17, DOXY = 6 +/- 3 pg/mg protein, n = 4-6, p0.05), as was the IT score versus controls (NaCl = 2.2 +/- 0.6, LMWH =1.7 +/- 0.3, DOXY = 0.8 +/- 0.20, n = 4-6, p0.05). Zymographic MMP9 activity was significantly reduced at 2 days in the LMWH and DOXY groups (NaCl = 85 +/- 24, LMWH = 23 +/- 7( *), DOXY = 13 +/- 5 U/mg protein, n = 6-8, p0.05). MMP2 zymographic activity, thrombus monocyte cell counts, and D-dimer activity were not significantly different across groups.Treatment with LMWH or DOXY did not alter the size of deep vein thrombosis, mildly altered thrombus composition, and differentially affected vein wall injury, despite similar reductions in early MMP9 activity. Whether exogenous MMP inhibition affects long-term vein wall fibrosis will require further study.

La resolution du thrombus veineux est a la source d’une reaction inflammatoire intense precoce, provoquant les lesions de la paroi veineuse. La reponse des tissus aux lesions inclut l’activation de metalloproteinases de la matrice (MMP) et la regeneration des proteines de la matrice extracellulaire. Cette etude a cherche a determiner l’effet de l’inhibition exogene des MMP et de son attenuation potentielle des lesions parietales veineuses precoces. Methodes Des rats ont recu le traitement commencant 24 heures apres une thrombose veineuse par stase due a une ligature pre-occlusive et jusqu’a prelevement au 7 ieme jour. Trois groupes ont ete evalues : (1) groupe controle avec solution salee (NaCl), (2) heparine de bas poids moleculaire (HBPM ; Lovenox, 3 mg/kg par jour sous cutanee), et (3) doxycycline (DOXY, 30 mg/kg par jour per os). La taille des thrombus (mg/mm), les niveaux du facteur α de necrose tumorale (TNF α) et des D-dimere par analyse colorimetrique, ainsi que la numeration de monocytes par immunohistochimie ont ete evalues. L’evaluation de la paroi veineuse comprenait la rigidite evaluee par tensiometrie, l’interleukine 1β (IL-1 β), le niveau de proteines par analyse ELISA, MMP2 et -9 par zymographie, et l’analyse histologique de l’epaisseur intimale (EI). Les comparaisons etaient realisees par rapport au controle par le test t. p Resultats Les tailles de thrombus etaient semblables aux 2 ieme et au 7 ieme jours pour chacun des trois groupes, alors que le taux de TNFα du thrombus etait augmente dans les groupes traites par HBPM et DOXY a deux jours (NaCl = 1.0 ± 0.8, HBPM = 9 ± 3, DOXY = 27 ± 5 pg/mg de proteine, N = 6-8, p N = 5, p N = 5-7, p N = 4-6, p N = 4-6, p N = 6-8, p Conclusion Le traitement par HBPM ou DOXY n’a pas modifie la taille de la thrombose veineuse profonde, a moderement change la composition du thrombus, et a differemment modifie les lesions de la paroi veineuse, en depit d’une reduction semblable de l’activite precoce en MMP9. D’autres etudes seront necessaires pour determiner si l’inhibition exogene de MMP affecte la fibrose a long terme de la paroi veineuse.

ObjectiveVein wall endothelial turnover after stasis deep vein thrombosis (DVT) has not been well characterized. The purpose of this study was to quantify re-endothelialization after DVT and determine if low-molecular-weight heparin (LMWH) therapy affects this process.MethodsStasis DVT was generated in the rat by inferior vena cava ligation, with harvest at 1, 4, and 14 days. Immunohistologic quantification of vascular smooth muscle cells and luminal endothelialization was estimated by positive staining for α-smooth muscle actin and von Willebrand factor, respectively. In separate experiments, rats were treated either before or after DVT with subcutaneous LMWH (3 mg/kg daily) until harvesting at 4 and 14 days. The inferior vena cava was processed for histologic analysis or was processed for organ culture after the thrombus was gently removed. The vein wall was stimulated in vitro with interleukin-1β (1 ng/mL), and the supernatant was processed at 48 hours for nitric oxide. Cells were processed by real-time polymerase chain reaction for endothelial nitric oxide synthase, inducible nitric oxide synthase, cyclooxygenase-1 and -2, and thrombomodulin at 4 and 14 days, and collagen I and III at 14 days. Comparisons were done with analysis of variance or t test. A P < .05 was significant.ResultsThrombus size peaked at 4 days, whereas luminal re-endothelialization increased over time (1 day, 11% ± 2%; 4 days, 23% ± 4%; 14 days, 64% ± 7% (+) von Willebrand factor staining; P < .01, n = 3 to 4, compared with non-DVT control). Similarly, vascular smooth muscle cell staining was lowest at day 1 and gradually returned to baseline by 14 days. Both before and after DVT, LMWH significantly increased luminal re-endothelialization, without a difference in thrombus size at 4 days, but no significant difference was noted at 14 days despite smaller thrombi with LMWH treatment. Pretreatment with LMWH was associated with increased vascular smooth muscle cell area and recovery of certain inducible endothelial specific genes. No significant difference in nitric oxide levels in the supernatant was found at 4 days. At 14 days, type III collagen was significantly elevated with LMWH treatment.ConclusionsVenous re-endothelialization occurs progressively as the DVT resolves and can be accelerated with LMWH treatment, although this effect appears limited to the early time frame. These findings may have clinical relevance for LMWH timing and treatment compared with mechanical forms of therapy.Clinical RelevanceHow the vein wall endothelium responds after deep vein thrombosis (DVT) has not been well documented owing to limited human specimens. This report shows that low-molecular-weight heparin accelerates or protects the endothelium and preserves medial smooth muscle cell integrity after DVT, but that this effect is limited to a relatively early time period. Although most DVT prophylaxis is pharmacologic (a heparin agent), use of nonpharmacologic measures is also common. The use of heparin prophylaxis, compared with after DVT treatment, and the acceleration of post-DVT re-endothelialization require clinical correlation.

ObjectiveRepair of isolated aortic arch aneurysms (nontraumatic) by either open (OAR) or endovascular (TEVAR) methods is associated with need for hypothermic circulatory arrest, complex debranching procedures, or use of marginal proximal landing zones. This study evaluates outcomes for treatment of this cohort.MethodsOf 2153 patients undergoing arch repair (1993-2013), 137 (mean age, 60 years) were treated with isolated arch resection for nontraumatic aneurysms. Treatment was by open (n = 93), hybrid (n = 11), or TEVAR (n = 33) methods, with the last two approaches reserved for poor OAR candidates. Treatment was predominantly for saccular (n = 53) or fusiform (n = 30) aneurysms or dissection (n = 15). Rupture was present in 15%. Prior aortic repair was performed in the ascending (n = 30), arch (n = 40), descending (n = 24), or abdominal (n = 9) aorta. Propensity score adjustment was performed for multivariable analysis to account for baseline differences in patient groups as well as treatment selection bias.ResultsEarly mortality was seen in nine patients (7%). Morbidity included stroke (n = 9), paraplegia (n = 1), and need for dialysis (n = 5) or tracheostomy (n = 10). A composite outcome of death and stroke was independently predicted by advancing age (P = .055) and performance of a hybrid procedure (P = .012). The 15-year survival was 59%, with late mortality predicted by increasing age, presence of peripheral vascular disease, and perioperative stroke (all P < .05). The 10-year freedom from aortic rupture or reintervention was 75% and was higher after OAR (2-year OAR, 94% vs TEVAR or hybrid, 78%; P = .018). After propensity-adjusted Cox regression analysis, both prior abdominal aortic aneurysmectomy (P = .017) and an endovascular or hybrid procedure (P = .001) independently predicted late aortic rupture or need for reintervention.ConclusionsIsolated arch repair remains a high-risk procedure occurring frequently in the reoperative setting. Despite being performed in a higher risk group, endovascular strategies yielded similar outcomes but with an increased risk for aorta-related complications. These data support ongoing efforts to develop branched endografts specifically tailored for arch disease to potentially reduce morbidity related to currently available approaches.

Penetrating aortic ulcers (PAU) often occur in a debilitated elderly population. Although early results of repair for PAU are well described, late outcomes remain poorly characterized and are the focus in this report.Ninety-five patients (mean age 70.7 years) underwent distal arch/descending aortic repair for PAU (1993 to 2011). Indications for intervention included rupture, saccular aneurysm, or symptoms. Associated intramural hematoma (IMH) was present in 41. Treatment was by open descending aortic repair (DTAR, n=37) or thoracic endovascular aortic repair (TEVAR, n=58). The DTAR group was younger (68 years versus TEVAR 72.5 years, p=0.02), and less frequently presented with rupture (24% versus TEVAR 43%, p=0.09).Early morbidity included death (9 patients; 9.5%), stroke (8), permanent paraplegia (2), and dialysis (5). Early adverse events were independently predicted by rupture, total descending repair, and DTAR (all p0.01). Ten-year survival was 47.9%. Predictors of late mortality included advancing age (p=0.016) and urgent presentation (p=0.002), but not repair type. Ten-year freedom from aortic reintervention/rupture was 71.4%. Associated IMH increased the risk for reintervention/rupture (5-year freedom PAU 97.1% versus PAU/IMH 72.1%, p=0.01), primarily because of decreased efficacy after TEVAR for PAU/IMH (5-year freedom 57.7% versus DTAR 100%, p=0.05).Despite the presence of an older, more complex TEVAR group, late outcomes after repair for PAU were affected more by age and type of presentation than by treatment strategy. Recognizing the perils of intervention in this high-risk population, TEVAR emerges as the therapy of choice to reduce early morbidity and provide similar late survival.

Recently, both living and deceased organ donation rates have hit a plateau, despite increases in need for viable organs. One approach to improve donation rate is public education and policy; thus, it is necessary to understand the information the public is receiving regarding organ donation. We hypothesized that primetime medical dramas portray organ donation and transplantation in a negative manner. We compiled data on all primetime medical drama episodes with transplant themes from November 2008 through June 2010 and assessed depictions of organ donors and transplant candidates. Positive and negative thematic elements surrounding the process and individuals involved were also identified. One hundred and fifty-five million and 145 million households watched episodes containing any negative message and any positive message, respectively. Episodes containing only negative messages had over twice the household viewership per episode compared to episodes containing only positive messages (8.4 million vs. 4.1 million, p = 0.01). Widespread exposure to these representations may reinforce public misconceptions of transplantation. The transplant community should consider the popularity of medical dramas as an opportunity to impact the perception of organ donation and transplantation for millions of Americans.

SummaryDeep-vein thrombosis (DVT) resolution is thought to be primarily a urokinase plasminogen activator (uPA) -dependent mechanism, although observations suggest other non-fibrinolytic mechanisms may exist. We explored the role of matrix metalloproteinase (MMP) -2 and –9 in early DVT resolution in uPA-deficient mice. Male B6/SVEV (WT) and genetically matched uPA -/- mice underwent inferior vena cava (IVC) ligation to create stasis venous thrombi, with IVC and thrombus harvest. Thrombus size was similar between WT and uPA -/- mice at day 4, suggesting early non uPA-dependent resolution. Intrathrombus neutrophils and monocytes were reduced 3- and 3.5-fold in uPA -/- mice as compared with WT. By ELISA, tumour necrosis factor α and interleukin 1β were not altered, while interferon (IFN)γ was significantly elevated in uPA -/- mice. A compensatory increase in thrombus tPA was not observed, plasmin activity was reduced and PAI-1 was elevated 2.5-fold in uPA -/- mice. Active MMP2, but not MMP9, was elevated 3-fold in uPA-/- mice as compared with WT as well as MMP-14, an MMP2 activator. Collagen type IV and fibrinogen were reduced in uPA -/- mice thrombi as compared with WT. IFNγ induces MMP2, and blockade of IFNγ was associated with larger venous thrombi and reduced active MMP2, as compared with WT. Consistently, MMP2 -/- mice had larger VT as compared with WT controls, despite normal thrombus plasmin levels. Taken together, early experimental venous thrombus resolution is independent of uPA, and, in part, inflammatory cell influx. MMP2-dependent thrombolysis is an important compensatory mechanism of venous thrombus resolution, possibly by collagen type IV metabolism, and may represent an exploitable therapeutic avenue.

Introduction. Deep venous thrombosis (DVT) resolution involves the plasmin and the matrix metalloproteinase (MMP) system. This study tested the hypothesis that pharmacological inhibition of the plasmin system would impair DVT resolution and worsen vein wall damage. Methods. A rat model of stasis DVT by inferior vena cava (IVC) ligation was performed with intravenous control saline or aprotinin (AP; 2.8 mg/kg at operation), and harvest of thrombosed IVC at 7 days. After laser Doppler imaging, DVT were separated and weighed, and vein wall stiffness was assessed by tensiometry. Thrombus and vein wall tissue analysis included total collagen by colorimetric assay, cytokines, chemokines, and D-dimer by ELISA, urokinase-plasminogen activator (uPA), and plasminogen activator inhibitor-1 (PAI-1) by immune-blotting, MMP-2 and -9 by zymography, and neutrophil (PMN) and monocyte (ED-1) leukocytes by immunohistochemistry. Results. DVT weights were 2-fold greater in the AP-treated rats (P < 0.05), but no significant differences in thrombus perfusion, collagen, or D-dimer levels were found. Vein wall stiffness was reduced 50% (P < 0.05), suggesting less biomechanical injury. The total vein wall MMP-9 was increased (P < 0.05) 5-fold in the AP group compared with controls, while MMP-2 was elevated but did not reach significance. No difference was found in vein wall tumor necrosis factor-alpha, tissue growth factor-beta, vein wall or thrombus monocytes, PMN, or uPA/PAI-1 ratio between groups. Discussion. AP inhibition of the plasmin system was associated with larger thrombi but less vein wall injury, but no difference in other measures of resolution, possibly because of increased vein wall MMP-9 activity. These data suggest an important redundant mechanism for DVT resolution.

BackgroundVein wall fibrotic injury following deep venous thrombosis (VT) is associated with elevated matrix metalloproteinases (MMPs). Whether and by what mechanism MMP2 contributes to vein wall remodeling after VT is unknown.MethodsStasis VT was produced by ligation of the inferior vena cava and tissue was harvested at 2, 8, and 21 days in MMP2 -/- and genetic wild type (WT) mice. Tissue analysis by immunohistochemistry, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and zymography was performed.ResultsThrombus resolution was less at 8 days in MMP2 -/- compared with WT, evidenced by a 51% increase in VT size (P < .01), and threefold fewer von Willebrand's factor positive channels (P < .05). In MMP2 -/- mice, the main phenotypic fibrotic differences occurred at 8 days post-VT, with significantly less vein wall collagen content (P = .013), fourfold lower procollagen III gene expression (P < .01), but no difference in procollagen I compared with WT. Decreased inflammation in MMP2 -/- vein walls was suggested by ∼ threefold reduced TNFα and IL-1β at 2 days and 8 days post-VT (P < .05). A fourfold increase in vein wall monocytes (P = .03) with threefold decreased apoptosis (P

Objective The optimal timing for neonatal cardiac surgery is unknown. We aimed to determine the relationship between age at surgery and perioperative outcomes, hypothesizing that earlier intervention would be associated with lower morbidity and mortality. Methods A retrospective review was performed of neonates who had undergone an arterial switch operation, stage 1 palliation for functional single ventricle, or systemic-to-pulmonary shunt for obstructed pulmonary blood flow from January 1, 2005, to December 31, 2010. The subjects with clinical indications for delayed surgery or prematurity were excluded. Age at surgery was evaluated as both a continuous and a categorical variable. The primary outcome was a composite endpoint of mortality or prolonged intensive care stay. Results Of 344 subjects, 286 (77 arterial switch operation, 124 stage 1 palliation, 85 systemic-to-pulmonary shunt) met the inclusion criteria. In each group, age at surgery was not associated with the primary composite endpoint. The patients who died after systemic-to-pulmonary shunt had a median age at surgery of 3 days versus 6 days for the survivors ( P = .04). A similar, but nonsignificant, pattern was seen for patients undergoing arterial switch operations (4.5 vs 7 days; P = .09). Earlier surgery was not associated with a reduced duration of vasoactive support, mechanical ventilation, or intensive care unit length of stay in any group. Stage 1 palliation subjects in the upper age quartile (≥8 days) at surgery were less likely to require prolonged mechanical ventilation ( P = .03). Conclusions Younger age at intervention in the neonatal period was not associated with reduced morbidity or mortality in any procedural subgroup studied. In our cohort, earlier systemic-to-pulmonary shunt for obstructed pulmonary blood flow was associated with a greater likelihood of a poor outcome.