Distinguishing Intrathyroid Parathyroid Adenoma from Colloid Nodules and Papillary Thyroid Carcinomas Using Multiphasic Multidetector Computed Tomography.

OBJECTIVE: The aim of the study is to determine whether multiphase multidetector computed tomography (4D-MDCT) can differentiate between intrathyroid parathyroid adenomas (ITPAs), colloid nodules, and papillary thyroid carcinoma (PTC). METHODS: We studied 22 ITPAs, 22 colloid nodules, and 11 PTCs in 55 patients. Hounsfield unit (HU) values of the nodules were measured on 4D-MDCT in the precontrast, arterial, venous, and delayed phases. Raw HU values, phase with peak enhancement, and washout percentages between the phases were evaluated. RESULTS: Regardless of size, all ITPAs (22/22) showed peak enhancement in the arterial phase, which was significantly greater than both colloid nodules (15/22) and PTC (6/11, P = 0.002); thus, nodules with peak enhancement in the venous or delayed phase were not ITPAs (specificity = 1). For nodules with peak enhancement in the arterial phase, the percentage washout in the arterial-to-venous phases separated ITPAs from PTC and colloid nodules (P < 0.001) with greater than or equal to 23.95% loss of HU value implying IPTA (area under curve, 0.79). This left a subset of colloid nodules or PTC that either peaked in the venous or delayed phase or had an arterial-to-venous phase washout of less than 23.95%. From this subset, PTC measuring 1 cm or greater could be separated from colloid based on HU values in the arterial phase with a cutoff HU value less than 81.4 for PTC (area under curve, 0.72) and an HU value greater than 164.5 suggested colloid. CONCLUSIONS: Intrathyroid parathyroid adenomas can be distinguished from colloid nodules and PTC by peak enhancement in the arterial phase and rapid washout. A subset of colloid and PTC measuring 1 cm or greater can be separated using arterial phase HU values.

Pulmonary Valve-Sparing Techniques for Tetralogy of Fallot: A Systematic Approach for Maximizing Success and Minimizing Risk.

Valve-sparing techniques for the treatment of Tetralogy of Fallot with pulmonary stenosis have evolved over the past few decades. This article will discuss the rationale for a more aggressive approach to sparing the pulmonary valve, the various techniques available (including commissurotomy, leaflet thinning and debridement, balloon dilation, and finally modified monocusp repair), as well as a systematic approach for employing these techniques based on individual patient anatomy in a manner that takes full advantages of the benefits of the valve-sparing approach while mitigating the risks involved.

TCP4-dependent induction of CONSTANS transcription requires GIGANTEA in photoperiodic flowering in Arabidopsis.

Photoperiod is one of the most reliable environmental cues for plants to regulate flowering timing. In Arabidopsis thaliana, CONSTANS (CO) transcription factor plays a central role in regulating photoperiodic flowering. In contrast to posttranslational regulation of CO protein, still little was known about CO transcriptional regulation. Here we show that the CINCINNATA (CIN) clade of class II TEOSINTE BRANCHED 1/ CYCLOIDEA/ PROLIFERATING CELL NUCLEAR ANTIGEN FACTOR (TCP) proteins act as CO activators. Our yeast one-hybrid analysis revealed that class II CIN-TCPs, including TCP4, bind to the CO promoter. TCP4 induces CO expression around dusk by directly associating with the CO promoter in vivo. In addition, TCP4 binds to another flowering regulator, GIGANTEA (GI), in the nucleus, and induces CO expression in a GI-dependent manner. The physical association of TCP4 with the CO promoter was reduced in the gi mutant, suggesting that GI may enhance the DNA-binding ability of TCP4. Our tandem affinity purification coupled with mass spectrometry (TAP-MS) analysis identified all class II CIN-TCPs as the components of the in vivo TCP4 complex, and the gi mutant did not alter the composition of the TCP4 complex. Taken together, our results demonstrate a novel function of CIN-TCPs as photoperiodic flowering regulators, which may contribute to coordinating plant development with flowering regulation.

Primary synovial chondromatosis of the subtalar joint: case report and review of the literature.

Primary synovial chondromatosis is a rare benign condition of uncertain etiology manifested by synovial proliferation. In the radiology literature, there is only 1 prior case report of primary synovial chondromatosis involving the subtalar joint with only partial description of the imaging appearance. We present a 28-year-old female with primary synovial chondromatosis of the subtalar joint and conduct a literature review of the imaging features of primary synovial chondromatosis presenting in the feet.

Sonographic Evaluation of Intrathyroid Metastases.

OBJECTIVES: Intrathyroid metastases from extrathyroid primary tumors are rare. Clinical findings may be subtle, but detection of intrathyroid metastases has improved with sonography. The objective of this study was to evaluate the sonographic appearance of intrathyroid metastases. METHODS: Patients with thyroid masses with cytopathologic features matching those of an extrathyroid primary tumor were retrospectively identified. The appearances of intrathyroid metastases on sonography were reviewed for the following features: size, margin regularity, echogenicity, echotexture, vascularity on power or color Doppler ultrasonography, and the presence or absence of any associated cervical adenopathy. RESULTS: The study included 52 patients. The most frequent primary tumor sites were lung, head and neck, and breast. Intrathyroid metastases presented as a discrete nodule in 34 patients and as diffuse infiltration of the gland in 18 patients. The discrete nodules ranged in size from 1.1 to 5.6 cm (mean ± SD, 2.5 ± 1.2 cm). Thirty-three lesions (63%) had irregular margins, and 19 (37%) had well-defined margins. Most of the lesions were heterogeneously hypoechoic (n = 50, 96%). Vascularity was present in 32 of 50 measured lesions (64%) that were evaluated with Doppler sonography. Cervical adenopathy was present in 37 patients (71%). CONCLUSIONS: Intrathyroid metastases have sonographic characteristics similar to those described for both benign and malignant thyroid diseases. In patients with a previous or current extrathyroid malignancy, thyroid nodules or diffuse infiltration of the thyroid gland on sonography should be viewed as a potential intrathyroid metastasis and evaluated via ultrasound-guided fine-needle aspiration regardless of the site of the primary tumor.

Operative treatment of type II supracondylar humerus fractures: does time to surgery affect complications?

BACKGROUND: Because of the changing referral patterns, operative pediatric supracondylar humerus fractures are increasingly being treated at tertiary referral centers. To expedite patient flow, type II fractures are sometimes pinned in a delayed manner. We sought to determine if delay in surgical treatment of modified Gartland type II supracondylar humerus fractures would affect the rate of complications following closed reduction and percutaneous pinning. METHODS: We performed a retrospective review of a consecutive series of 399 modified Gartland type II supracondylar fractures treated operatively at a tertiary referral center over 4 years. Mean patient age in the type II group was 5 years (range, 1 to 15 y). A total of 48% were pinned within 24 hours, 52% pinned >24 hours after the injury. RESULTS: No difference was in detected in rates of major complications between the early and delayed treatment group. Four percent of patients sustained a complication (16 patients). There were no compartment syndromes, vascular injuries, or permanent nerve injuries. Complications included nerve injury (3), physical therapy referral for stiffness (3), pin site infection (2 treated with oral antibiotics, 4 treated with debridement), refracture (2), and loss of fixation or broken hardware (2). Of the 3 patients who sustained nerve injuries, all underwent surgery within 24 hours of injury. One patient developed an ulnar motor and sensory nerve palsy after fixation with crossed K-wires. This resolved by 7 weeks postoperatively. Two patients presented with an anterior interosseous nerve palsy-1 resolved 1 week after surgery, the other by 8 weeks postoperatively. CONCLUSIONS: Delay in surgery did not result in an increased rate of major complications following closed reduction and percutaneous pinning of type II supracondylar humerus fractures in children. Further prospective work is necessary to determine if there are subtle treatment benefits from emergent treatment of type II supracondylar humerus fractures. LEVEL OF EVIDENCE: Level III-retrospective comparative series.

Clinical characteristics of severe supracondylar humerus fractures in children.

BACKGROUND: The safety of delayed surgical treatment of severe supracondylar elbow fractures in children remains debated. No large studies have evaluated complications of injury and surgery evaluating only type 3 fractures. Our aim was to review the results of our experience treating children with severe supracondylar elbow fractures at various time points after injury. METHODS: All children treated operatively for supracondylar humerus fractures from 2004 to 2007 at a single pediatric trauma center were identified. A total of 1296 children had operative treatment, of which 872 had type 3 fractures. Clinical records were reviewed to identify time to surgery from presentation at our institution. Patients were grouped into 4 cohorts [<6 h (n=325), 6 to 12 h (n=224), 12 to 24 h (n=295), and >24 h (n=28)]. Emergency, operative, inpatient, and outpatient records were reviewed to determine morbidity at presentation as well as operative and postoperative complications. RESULTS: There was no difference in sex, age, or energy mechanism between children in the various time groups. An absent pulse was found in 54 children (6%) at presentation, of which only 5 ultimately required a vascular intervention. Nerve injury occurred in 105 patients (12%). Use of a medial entry pin was not associated with ulnar nerve injury. Increased time from presentation to surgery was not associated with increased morbidity from the injury or treatment complications. In contrast, there was a trend to steady decrease in morbidity and complication rates with increased time to surgery. CONCLUSIONS: This is the largest single-center study of severe supracondylar humerus fractures and describes rates of vascular compromise, nerve injury, infection, and other complications of these injuries. Most children with type 3 supracondylar humerus fractures can be treated safely in a delayed manner. Appropriate clinical judgment is imperative to optimize outcomes. LEVEL OF EVIDENCE: Level III--retrospective comparative study.

True external diameter better predicts hemodynamic performance of bioprosthetic aortic valves than the manufacturers' stated size.

BACKGROUND AND AIM OF THE STUDY: Currently, there is no universal standard for sizing bioprosthetic aortic valves. Hence, a standardized comparison was performed to clarify this issue. METHODS: Every size of four commercially available bioprosthetic aortic valves marketed in the United States (Biocor Supra; Mosaic Ultra; Magna Ease; Mitroflow) was obtained. Subsequently, custom sizers were created that were accurate to 0.0025 mm to represent aortic roots 18 mm through 32 mm, and these were used to measure the external diameter of each valve. Using the effective orifice area (EOA) and transvalvular pressure gradient (TPG) data submitted to the FDA, a comparison was made between the hemodynamic properties of valves with equivalent manufacturer stated sizes and valves with equivalent measured external diameters. RESULTS: Based on manufacturer size alone, the valves at first seemed to be hemodynamically different from each other, with Mitroflow valves appearing to be hemodynamically superior, having a large EOA and equivalent or superior TPG (p < 0.05). However, Mitroflow valves had a larger measured external diameter than the other valves of a given numerical manufacturer size. Valves with equivalent external diameters were then compared, regardless of the stated manufacturer sizes. For truly equivalently sized valves (i.e., by measured external diameter) there was no clear hemodynamic difference. There was no statistical difference in the EOAs between the Biocor Supra, Mosaic Ultra, and Mitroflow valves, and the Magna Ease valve had a statistically smaller EOA (p < 0.05). On comparing the mean TPG, the Biocor Supra and Mitroflow valves had statistically equivalent gradients to each other, as did the Mosaic Ultra and Magna Ease valves. CONCLUSION: When comparing valves of the same numerical manufacturer size, there appears to be a difference in hemodynamic performance across different manufacturers' valves according to FDA data. However, comparing equivalently measured valves eliminates the differences between valves produced by different manufacturers.

Surgical Valve Choices for Pulmonary Valve Replacement.

The range of valve choices available to the cardiac surgeon for placement in the pulmonary position continues to expand. This article will provide a brief compendium of the most clinically relevant among these choices and review the contemporary literature regarding their relative durability as well as risk factors for structural valve deterioration and reintervention. The unique advantages and disadvantages of each of these valve choices will be discussed as they pertain to unique patient-specific factors, including patient size and the anatomy of the right ventricular outflow tract, that inform the choice of one prosthesis over another. Finally, general principles regarding the approach to valve choice, and future directions will be discussed.

Codelivery of synergistic antimicrobials with polyelectrolyte nanocomplexes to treat bacterial biofilms and lung infections.

Bacterial biofilm infections, particularly those of Pseudomonas aeruginosa (PA), have high rates of antimicrobial tolerance and are commonly found in chronic wound and cystic fibrosis lung infections. Combination therapeutics that act synergistically can overcome antimicrobial tolerance; however, the delivery of multiple therapeutics at relevant dosages remains a challenge. We therefore developed a nanoscale drug carrier for antimicrobial codelivery by combining approaches from polyelectrolyte nanocomplex (NC) formation and layer-by-layer electrostatic self-assembly. This strategy led to NC drug carriers loaded with tobramycin antibiotics and antimicrobial silver nanoparticles (AgTob-NCs). AgTob-NCs displayed synergistic enhancements in antimicrobial activity against both planktonic and biofilm PA cultures, with positively charged NCs outperforming negatively charged formulations. NCs were evaluated in mouse models of lung infection, leading to reduced bacterial burden and improved survival outcomes. This approach therefore shows promise for nanoscale therapeutic codelivery to treat recalcitrant bacterial infections.

Increased severity of type III supracondylar humerus fractures in the preteen population.

BACKGROUND: Supracondylar humerus fractures are the most common operative fractures in children; however, no studies describe the older child with this injury. The purpose of this study was to compare Gartland type III supracondylar humerus fractures in children older than 8 years of age with those in younger children than age 8. We hypothesized that there would be more complications in older children, reflecting a higher-energy injury mechanism. METHODS: A retrospective chart review of supracondylar humerus fractures managed at a single level I pediatric trauma institution from 2004 to 2007 was performed. Patients with type III fractures were divided into groups based on age at presentation greater or less than 8. Baseline demographics, fracture characteristics, mechanism of injury, operative technique, and complications were analyzed. RESULTS: A consecutive series of 1297 pediatric patients with surgically treated supracondylar humerus fractures was retrospectively reviewed including 873 (67.3%) type III fractures. Of those, 160 (18.3%) patients were older than age 8 at time of injury. Older children were more likely to have fractures from high-energy mechanisms (45.1% vs. 28.7%, P<0.001) and more open fracture (3.8% vs. 1.3%, P=0.0097). There was no difference in preoperative or iatrogenic neuropraxias between groups. There was a shorter delay between presentation and surgery in older children (mean, 217 vs. 451 min, P<0.0001). Three or more pins were used more often in older patients (61.8% in older children vs. 43.6% in younger children, P<0.0001). Major complications including reoperation, loss of fixation, or compartment syndrome were rare in both groups (1.1% in younger group vs. 0.6% in older group, P=1.000). There was a trend toward more pin site infections in older children (3.75% vs. 1.56%, P=0.071). Physical therapy was required nearly 4 times more frequently in older children for management of residual stiffness (20.0% vs. 5.7%, P<0.0001). CONCLUSIONS: Children older than 8 years of age have a higher rate of open supracondylar humerus fractures, although nerve injury rates are similar. Surgeons placed more pins for fixation of fractures in older patients and elbow stiffness requiring physical therapy occurred more commonly after surgical intervention. EVIDENCE: III Retrospective cohort.

Complete atrioventricular septal defect with absent or diminutive primum component: Incidence, anatomic characteristics, and outcomes.

BACKGROUND: Repair of complete atrioventricular septal defect with absent or diminutive primum defect is challenging because of atrial septal malposition and abnormal anatomy of the left atrioventricular valve. We sought to define the incidence, anatomy, and surgical outcomes of this entity. METHODS: We identified all patients in our institutional database presenting for complete atrioventricular septal defect repair from 2006 to 2018. Operative reports and echocardiograms were reviewed to determine the presence and size of the primum defect, atrioventricular valve anatomy, degree of atrioventricular valve regurgitation, repair method, and complications, including reoperation for atrioventricular valve regurgitation. Functionally univentricular patients and those receiving repair at an outside institution were excluded. RESULTS: Of 183 patients with complete atrioventricular septal defect, absent/diminutive primum defect occurred in 16 patients (8.7%; 10 absent, 6 diminutive). Six patients (38%) had leftward malposition of the atrium septum on the common atrioventricular valve. The rate of reoperation for left atrioventricular valve regurgitation was 31% (3 early, 2 late), for which preoperative predictors included leftward malposition of the atrial septum onto the common atrioventricular valve (4/6 patients with malposition required reoperation, P = .036, Fisher exact test). One patient exhibiting this risk factor died. The overall rate of moderate or greater left atrioventricular valve regurgitation on the most recent postoperative echocardiogram was 13% (2/16 patients; median follow-up, 141 days; range, 3-2236 days). CONCLUSIONS: Complete atrioventricular septal defect with absent or diminutive primum defect is a unique variant of complete atrioventricular septal defect for which the risk of reoperation for left atrioventricular valve regurgitation after complete repair is high and risk factors include leftward malposition of the atrial septum on the common atrioventricular valve.

Neonatal venoarterial extracorporeal membrane oxygenation cannulation technique.

Peripheral cannulation for initiation of neonatal venoarterial extracorporeal membrane oxygenation is an essential technical skill in the armamentarium of every congenital cardiac surgeon and is necessary for the care of newborns with congenital heart disease and other conditions presenting with cardiopulmonary failure. With certain exceptions, it is usually performed via a right neck cut-down to expose the right internal jugular vein and common carotid artery.   A strong understanding of the fundamental techniques, as well as strategies for avoiding common pitfalls, is critical to the success of cardiopulmonary rescue afforded by cannulation, especially considering the emergent conditions under which cannulation must usually be performed. We review here the operative approach and technique for neck cannulation for peripheral neonatal venoarterial extracorporeal membrane oxygenation.

Ascending Aortoplasty in Pediatric Patients Undergoing Aortic Valve Procedures.

BACKGROUND: The risks of ascending aortic dilation and indications for intervention in pediatric patients are unclear. Given the concern for aortic size mismatch with growth, larger ascending aortic diameters have been accepted in pediatric patients. The purpose of this study was to evaluate the effectiveness of ascending aortic reduction at the time of aortic valve surgery and its effect on recurrent aortic regurgitation. METHODS: A retrospective 8-year observational review (2010-2018) was conducted in pediatric patients with dilated ascending aorta undergoing aortic valve surgery at a single institution. RESULTS: Forty-seven patients underwent ascending aortoplasty during aortic valve surgery, of which 39 patients with complete data points had preoperative mean ascending aortic Z-scores of 5.35 ± 1.52 reduced to 1.22 ± 1.63 (P < .001) postoperatively. Ascending aortic Z-scores remained similar at 1.37 ± 1.72 at latest follow-up (P = .306). In contrast our matched control group (n = 39) without ascending aortoplasty had preoperative mean ascending aortic Z-scores of 4.15 ± 1.65 reduced to 3.26 ± 2.0 at the midterm follow-up. This reduction was significantly larger in the aortoplasty group, with an average difference in these changes of 3.12 (95% confidence interval, 2.43-3.8; P < .001). Multivariable logistic regression (controlling for aortic valve intervention type and body surface area) showed a 6.84 odds of moderate to severe aortic regurgitation at follow-up in the control group compared with the aortoplasty group (95% confidence interval, 1.43-32.8; P = .016). There were no complications associated with ascending aortoplasty. CONCLUSIONS: Ascending aortoplasty is effective in reducing ascending aortic dimensions and recurrent aortic regurgitation in pediatric patients. Longer-term follow-up is necessary to determine continued rate of growth.

Screening for HPV-related oropharyngeal, anal, and penile cancers in middle-aged men: Initial report from the HOUSTON clinical trial.

BACKGROUND: The Human papillomavirus (HPV)-related Oropharyngeal and Uncommon Cancers Screening Trial of Men (HOUSTON) was designed to determine the prevalence of IgG antibodies to HPV type 16 E proteins (HPV16EAbs), to screen for persistence of HPV and/or detect HPV-related premalignancies and cancers, and to assess acceptance of screening among middle-aged men. METHODS: HOUSTON consists of a cross-sectional study and a longitudinal cohort study of men aged 50-64 years. Serologic HPV16EAb status and oral rinse HPV16 status were determined. All HPV16EAb-positive (HPV16EAb+) men and a matched cohort of HPV16EAb-negative (HPV16EAb-) men as well as all oral rinse HPV16-positive (HPV16+) men were included in the longitudinal study (blinded to their results) and underwent oropharyngeal screening every 6 months as well as one-time anal and penile screening. RESULTS: Of 553 men enrolled in the cross-sectional study, six (1.1%) were HPV16EAb+ (two were also oral rinse HPV16+), and 41 (7.4%) were HPV16EAb- but oral rinse HPV16+. These 47 men, along with five matched controls, were invited to participate in the longitudinal study, and 42 (81%) agreed and completed baseline in-person screening, with 93% and 90% completeing 6-month and 12-month follow-up visits. One HPV16EAb+ (also oral rinse HPV16+) man, who declined participation in the longitudinal study, presented 4 months after enrollment with an early-stage HPV16-related pharyngeal cancer. Additionally, one HPV16EAb+ (oral rinse HPV16-) man and two oral rinse HPV16+ (HPV16EAb-) men were diagnosed with oncogenic HPV-associated anal dysplasia. CONCLUSIONS: This biomarker panel deserves further prospective study to explore potential utility for HPV-related cancer screening among men.

Early Distal Migration of a Self-Expanding Aortic Valve Prosthesis Causing Myocardial Infarction.

Early distal migration after transcatheter aortic valve replacement is a rare but potentially catastrophic complication that presents unique technical challenges for subsequent surgical management. This report describes a case of early distal migration of a Medtronic CoreValve Evolut R bioprosthesis (Minneapolis, MN) causing myocardial infarction from coronary ostial obstruction and provides a practical technique for open surgical device explantation and aortic valve re-replacement. Snaring the stent of the device using standard instruments is a simple but effective method for transcatheter aortic valve replacement explant that allows for optimal positioning of a single aortotomy at the standard anatomic site to facilitate subsequent surgical aortic valve replacement.

Oblique Lateral Closing-Wedge Osteotomy for Cubitus Varus in Skeletally Immature Patients.

BACKGROUND: We perform an oblique lateral closing-wedge osteotomy of the distal end of the humerus to correct cubitus varus deformity in children. This deformity is often the consequence of undertreatment, malreduction, or malunion of supracondylar humeral fractures1. Although standard arcs of motion may be altered, cosmesis was traditionally considered a primary surgical indication. However, uncorrected cubitus varus leads to posterolateral rotatory instability of the elbow (PLRI)2, lateral condylar fractures3, snapping medial triceps, and ulnar nerve instability4. A contemporary understanding of these delayed sequelae has expanded our current indications. Detailed parameters predictive of late sequelae are needed to further specify surgical indications. DESCRIPTION: We remove an oblique lateral closing wedge from the distal end of the humerus via a standard lateral approach. The osteotomy is angled away from the varus joint line such that lateral cortices after reduction lack prominence. Kirschner wires provide adequate fixation in young patients. In older children, extension is simultaneously corrected, and fragments are stabilized via plate osteosynthesis. ALTERNATIVES: Patients who decline surgery are counseled regarding risks of delaying treatment until symptoms are present. PLRI manifests as lateral elbow pain or instability while rising from a chair. Once symptomatic, the lateral ulnar collateral ligament (LUCL) is irreversibly attenuated and morphologic changes in the ulnohumeral joint necessitate more extensive surgery to include distal humeral osteotomy, LUCL reconstruction, and possibly ulnar nerve transposition5. Alternative osteotomy techniques are described and categorized as simple lateral closing wedge, step-cut6-9, dome, 3-dimensional10, or distraction osteogenesis. Simple closing-wedge osteotomies include a distal cut parallel to the joint line and retain a problematic lateral prominence (if the medial cortex is intact or the distal end of the humerus is not translated medially)11,12. Step-cut osteotomies theoretically minimize this lateral prominence while enhancing inherent stability. However, these additional cuts mandate wide surgical exposure despite similar outcomes13. Three-dimensional planning employs computed tomography to create expensive anatomic cutting guides that address varus, extension, and internal rotation. However, residual internal rotation is generally well tolerated, derotation is associated with loss of fixation, and the extension deformity will successfully remodel in patients who are <10 years old14. We employ 3-dimensional planning in skeletally mature patients with complex deformity and no remodeling potential. RATIONALE: The oblique lateral closing wedge is ideal for skeletally immature patients because it is simple, reproducible, and efficient. It avoids the lateral prominence without increasing complexity or complications.

Warm ischemia provokes inflammation and regional hypercoagulability within the heart during off-pump coronary artery bypass: a possible target for serine protease inhibition.

OBJECTIVE: Accumulating evidence suggests that a hypercoagulable state influences early graft failure after off-pump coronary artery bypass (OPCAB). We hypothesized that regional myocardial ischemia caused by obligatory periods of coronary occlusion during OPCAB is an important trigger for this prothrombotic state. METHODS: Using a series of biomarkers, 60 consecutive patients undergoing OPCAB were monitored for myocardial injury (myoglobin), inflammation (TNF-alpha, IL-8) and thrombosis (thrombin generation-F1.2, contact activation pathway-FXII-a, platelet derived microparticles-via flow cytometry). The transcardiac gradients of these markers were determined by assaying both arterial and coronary sinus blood just after protamine administration. Intramyocardial pH was monitored continuously during coronary occlusion in a subset (N=30 grafts, 11 patients). The influence of management strategies affecting hemostasis (e.g. antiplatelet therapy, anti-fibrinolytics, peak activated clotting time (ACT) during heparinization) was analyzed. RESULTS: Ischemic injury, depicted by the transcardiac myoglobin gradient, significantly correlated with intramyocardial acidosis during coronary occlusion (R=0.96, p<0.0001) and predicted the transcardiac gradients of TNF-alpha (R=0.83, p<0.001) and F1.2 (R=0.72, p<0.0001). Transcardiac F1.2 strongly correlated with TNF-alpha (R=0.73, p=0.01) and IL-8 (R=0.51, p=0.02). Patients receiving aprotinin (N=20) showed significantly lower transcardiac gradients for myoglobin (4.1+/-7.5% vs 72.9+/-108.8% change, p=0.002), F1.2 (31+/-37% vs 89+/-149%, p=0.03), FXII-a (2.6+/-4.1% vs 19.2+/-34%, p=0.04) and microparticles (7+/-3.9% vs 12.9+/-8%, p=0.01). CONCLUSIONS: Strong correlations between myocardial ischemia and the transcardiac gradients of markers for inflammation and thrombosis suggest that even brief episodes of coronary occlusion in the beating heart may have pathophysiologic consequences. Aprotinin, but not other factors that influence the coagulation system, appears to mitigate this process during OPCAB.