Hydroxychloroquine Therapy in Sarcoidosis-Associated Uveitis.

BACKGROUND/PURPOSE: To assess the efficacy and tolerance of hydroxychloroquine in sarcoidosis-associated uveitis. METHODS: Retrospective study on all patients with sarcoidosis-associated uveitis who were treated with hydroxychloroquine between 2003 and 2019 in a French university hospital. RESULTS: Twenty-seven patients with sarcoidosis-associated uveitis received hydroxychloroquine. The mean duration of treatment was 20.0 ± 10.9 months. At the end of the follow-up, hydroxychloroquine success was achieved in 15 (55.6%) patients. Four of them were also on oral corticosteroids, with a prednisone dose ≤5 mg/day. Under treatment, the median prednisone dose decreased from 20.0 (interquartile range (IQR), 7-25) to 5.0 (IQR, 3-6.5) mg/day (p = .02). The incidence rate of flare decreased from 204.6 to 63.8 per 100 person-years (p = .02). Hydroxychloroquine was discontinued in 12 (44.4%) patients during follow-up, including 8 (29.6%) for ineffectiveness, and three who experienced side effects. CONCLUSION: Hydroxychloroquine appears as an interesting option in sarcoidosis-associated uveitis.Abbreviations: AZA: Azathioprine; BAL: Bronchoalveolar Lavage; BCVA: Best-Corrected Visual Acuity; ENT: Ears, Nose and Throat; HCQ: Hydroxychloroquine; IOP: Intra-Ocular Pressure; IQR: interquartile range; MHC: Major Histocompatibility Complex; MMF: Mycophenolate Mofetil; MTX: Methotrexate; PMSI: Programme de Médicalisation du Système d'Information; SAU: Sarcoidosis-Associated Uveitis; SD: Standard Deviation; SUN: Standard Uveitis Nomenclature.

Etiological Diagnosis of Uveitis: Contribution of the of the Extra-Ophthalmological Clinical Examination.

PURPOSE: Determining uveitis etiology is a challenge. It is based primarily on demographic data and the characteristics of eye examination. It is not clear to what extent extraocular physical signs contribute to elucidating the etiology. This study aimed to establish the contribution of the clinical extra-ophthalmological features for the assessment of the underlying etiology of uveitis. METHODS: We retrospectively reviewed 1307 patients with uveitis referred to our tertiary center between 2003 and 2021. Uveitis was classified according to the Standardization of Uveitis Nomenclature. Clinical features were collected at diagnosis by internists before the etiological diagnosis was made. The main outcome description was the contribution of clinical features. RESULTS: Clinical extra-ophthalmological features contributed to the assessment of the underlying etiology of uveitis in 363 (27.8%) patients. The joint and the skin examinations were the most useful for etiological investigations, respectively in 12.3% and 11.8% of patients. Five etiologies of uveitis accounted for 80% of the cases: sarcoidosis, HLA-B27-related uveitis, Behçet's disease, multiple sclerosis, and Vogt-Koyanagi-Harada disease. Clinical extra-ophthalmological features were particularly important in the etiological diagnosis of acute bilateral anterior uveitis and panuveitis. CONCLUSION: This study suggests that clinical extra-ophthalmological features are essential for the etiological diagnosis of uveitis in more than a quarter of patients. It demonstrates once again the value of collaboration between ophthalmologists and other specialists experienced in performing extra-ophthalmological clinical examinations, particularly in patients with acute bilateral anterior uveitis and panuveitis.

Long-Term Outcomes of Birdshot Chorioretinopathy Treated with Corticosteroids: A Case Reports.

PURPOSE: To report the progression of patients diagnosed with birdshot chorioretinopathy (BSCR) initially treated with corticosteroids. METHODS: We included 39 BSCR patients that were followed for ≥1 year. We analyzed their progression under treatment after 1, 3, 6 months, 1 year, and at the end of follow-up. In order to determine the efficiency of initial loading doses, patients were classified into two groups according to their initial treatment: methylprednisolone followed by prednisone (n = 28) and prednisone alone (n = 11). RESULTS: At the end of follow-up, 31/39 (79.5%) patients had reached inflammation control. Thirteen out of 28 (46.4%) and 6/11 (54.5%) patients were treated exclusively with corticosteroids, and 18/19 (94.7%) of them had reached inflammation control at the end of follow-up; their mean (range) corticosteroid dose was 3.5 (0-10) mg/day. CONCLUSIONS: We found that the prolonged corticosteroid therapy treatment strategy resulted in inflammation control in half of BSCR patients. This control was maintained with low doses of cortisone, usually <5 mg/day.

Sarcoidosis-Related Uveitis: A Review.

Sarcoidosis is an inflammatory disease that involves the eyes in 10-55% of cases, sometimes without systemic involvement. All eye structures can be affected, but uveitis is the most common ocular manifestation and causes vision loss. The typical ophthalmological appearance of these uveitis is granulomatous (in cases with anterior involvement), which are usually bilateral and with synechiae. Posterior involvement includes vitritis, vasculitis and choroidal lesions. Tuberculosis is a classic differential diagnosis to be wary of, especially in people who have spent time in endemic areas. The diagnosis is based on histology with the presence of non-caseating epithelioid granulomas. However, due to the technical difficulty and yield of biopsies, the diagnosis of ocular sarcoidosis is often based on clinico-radiological features. The international criteria for the diagnosis of ocular sarcoidosis have recently been revised. Corticosteroids remain the first-line treatment for sarcoidosis, but up to 30% of patients require high doses, justifying the use of corticosteroid-sparing treatments. In these cases, immunosuppressive treatments such as methotrexate may be introduced. More recent biotherapies such as anti-TNF are also very effective (as they are in other non-infectious uveitis etiologies).

Challenging Mimickers in the Diagnosis of Sarcoidosis: A Case Study.

Sarcoidosis is a systemic granulomatous disease of unknown cause characterized by a wide variety of presentations. Its diagnosis is based on three major criteria: a clinical presentation compatible with sarcoidosis, the presence of non-necrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. Many conditions may mimic a sarcoid-like granulomatous reaction. These conditions include infections, neoplasms, immunodeficiencies, and drug-induced diseases. Moreover, patients with sarcoidosis are at risk of developing opportunistic infections or lymphoma. Reliably confirming the diagnosis of sarcoidosis and better identifying new events are major clinical problems in daily practice. To address such issues, we present seven emblematic cases, seen in our department, over a ten-year period along with a literature review about case reports of conditions misdiagnosed as sarcoidosis.

Performance of allogeneic bioengineered replacement pulmonary valves in rapidly growing young lambs.

BACKGROUND: Cardiac allometric organ growth after pediatric valve replacement can lead to patient-prosthesis size mismatch and valve re-replacement, which could be mitigated with allogeneic decellularized pulmonary valves treated with collagen conditioning solutions to enhance biological and mechanical performance, termed "bioengineered valves." In this study, we evaluated functional, dimensional, and biological responses of these bioengineered valves compared with traditional cryopreserved valves implanted in lambs during rapid somatic growth. METHODS: From a consanguineous flock of 13 lambs, the pulmonary valves of 10 lambs (mean weight, 19.6 ± 1.4 kg) were replaced with 7 bioengineered valves or 3 classically cryopreserved valves. After 6 months, the 10 lambs with implanted valves and 3 untreated flock mates were compared by echocardiography, cardiac catheterization, and explant pathology. RESULTS: Increases in body mass, valve geometric dimensions, and effective orifice areas were similar in the 2 groups of lambs. The bioengineered valves had higher median cusp-to-cusp coaptation areas (34.6%; interquartile range, 21.00%-35.13%) and were more similar to native valves (43.4%; interquartile range, 42.59%-44.01%) compared with cryopreserved valves (13.2%; interquartile range, 7.07%-13.91%) (P = .043). Cryopreserved valves cusps, but not bioengineered valve cusps, were thicker than native valve cusps (P = .01). Histologically, cryopreserved valves demonstrated less than native cellularity, whereas bioengineered valves that were acellular at the time of surgery gained surface endothelium and subsurface myofibroblast interstitial cells in pulmonary artery, sinus wall, and cusp base regions. CONCLUSIONS: Biological valve conduits can enlarge via passive dilatation without matrix synthesis, but this would result in decreased cusp coaptational areas. Bioengineered valves demonstrated similar annulus enlargement as cryopreserved valves but usually retained larger areas of cuspal coaptation. Heat-shock protein 47-positive (collagen-synthesizing) cells were present in previously acellular bioengineered sinus walls and cusp bases, but rarely in more distal cusp matrices.

Point-of-Care Hemoglobin/Hematocrit Testing: Comparison of Methodology and Technology.

OBJECTIVE: Point-of-care (POC) testing allows rapid assessment of hemoglobin (Hgb) and hematocrit (Hct) values. This study compared 3 POC testing devices--the Radical-7 pulse oximeter (Radical-7, Neuchȃtel, Switzerland), the i-STAT (Abbott Point of Care, Princeton, NJ), and the GEM 4000 (Instrumentation Laboratory, Bedford, MA)--to the hospital reference device, the UniCel DxH 800 (Beckman Coulter, Brea, CA) in cardiac surgery patients. DESIGN: Prospective study. SETTING: Tertiary care cardiovascular center. PARTICIPANTS: Twenty-four consecutive elective adult cardiac surgery patients. INTERVENTIONS: Hgb and Hct values were measured using 3 POC devices (the Radical-7, i-STAT, and GEM 4000) and a reference laboratory device (UniCel DxH 800). Data were collected simultaneously before surgery, after heparin administration, after heparin reversal with protamine, and after sternal closure. Data were analyzed using bias analyses. POC testing data were compared with that of the reference laboratory device. MEASUREMENTS AND MAIN RESULTS: Hgb levels ranged from 6.8 to 15.1 g/dL, and Hct levels ranged from 20.1% to 43.8%. The overall mean bias was lowest with the i-STAT (Hct, 0.22%; Hgb 0.05 g/dL) compared with the GEM 4000 (Hct, 2.15%; Hgb, 0.63 g/dL) and the Radical-7 (Hgb 1.16 g/dL). The range of data for the i-STAT and Radical-7 was larger than that with the GEM 4000, and the pattern or slopes changed significantly with the i-STAT and Radical-7, whereas that of the GEM 4000 remained relatively stable. The GEM 4000 demonstrated a consistent overestimation of laboratory data, which tended to improve after bypass and at lower Hct/Hgb levels. The i-STAT bias changed from overestimation to underestimation, the latter in the post-cardiopulmonary bypass period and at lower Hct/Hgb levels. By contrast, the Radical-7 biases increased during the surgical procedure and in the lower ranges of Hgb. CONCLUSION: Important clinical differences and limitations were found among the 3 POC testing devices that should caution clinicians from relying on these data as sole determinants of when or when not to perform transfusion in patients. Even though a low bias might support the use of POC data, further analysis of the bias plots demonstrates pattern changes during the surgical procedure and across the range of Hct/Hgb data.

Long-term survival after use of internal thoracic artery in octogenarians is gender related.

OBJECTIVE: The goal of this study is to assess the benefits of a left internal thoracic artery as a bypass conduit in octogenarians undergoing elective coronary artery bypass grafting. We hypothesize that there is no survival advantage and that outcome may be gender related. METHODS: In a retrospective analysis of 1141 octogenarians (aged >80 years) undergoing isolated coronary artery bypass grafting from 1996 to 2012, patients were divided into 2 groups: Group I (coronary artery bypass grafting-left internal thoracic artery) included 870 patients (339 female/531 male), and group II (coronary artery bypass grafting-saphenous vein graft) included 271 patients (131 female/140 male). RESULTS: The overall 30-day mortality was 5.7%: 4.3% in group I and 7.0% in group II (P = .1). Group II had a lower trend of any postoperative complication (P = .05) and pneumonia (P = .05). When analyzed by gender, there were no discernable differences in long-term survival for male patients in group I (65% at 5 years and 29% at 10 years) versus male patients in group II (65% at 5 years and 31% at 10 years) (P = .2). However, survival was significantly greater for female patients in group I (70% at 5 years and 35% at 10 years) versus female patients in group II (63% at 5 years and 21% at 19 years) (P = .01). Multiple logistic and Cox regression analysis showed that left internal thoracic artery use is associated with improved survival in female patients (hazard ratio [HR], 0.72; confidence interval [CI], 0.56-0.93) but not in male patients (HR, 1.14; CI, 0.9-1.4). Advanced age was associated with an increased risk of mortality (HR, 1.08 per year; CI, 1.05-1.1). Both patient age (P = .01) and Society of Thoracic Surgeons-predicted 30-day mortality (P = .03) remain in the final model for 30-day mortality. The benefit of the left internal thoracic artery after coronary artery bypass grafting in octogenarians may be gender related. CONCLUSIONS: This study shows that the benefit of the left internal thoracic artery in the octogenarian population undergoing coronary artery bypass grafting may be gender related. For elderly female patients, the use of the left internal thoracic artery as a bypass conduit was associated with better long-term survival, whereas no significant difference was found among the male population. The use of the left internal thoracic artery was associated with a greater postoperative pulmonary morbidity for the study population as a whole. The present study does not refute the benefit of the left internal thoracic artery-left anterior descending graft, but instead distinguishes a subset who might benefit more.

The influence of seasons and lunar cycle on hospital outcomes following ascending aortic dissection repair.

OBJECTIVES: The effect of the lunar cycle and seasonal variation on ascending aortic dissection surgery outcomes is unknown. We investigated these temporal effects on risk-adjusted hospital mortality and then on the length of stay (LOS) following surgery for survivors. METHODS: We examined prospectively collected data from cardiac operations at two major centres within a single state between January 1996 and December 2011. We first examined the relationship between the lunar cycle and seasonal variation, along with demographic and risk profile covariates, with mortality using univariate analyses, followed by multiple logistic regression modelling that controlled for demographic and patient risk variables including age, gender, risk profile (diabetes, hypertension, dyslipidaemia and renal failure), and two surgical groups: Group A, consisting of patients having repair of ascending aorta dissection repair only, and Group B, with those having ascending aorta repair plus aortic valve surgery or coronary bypass surgery or both. We further examined the relationship with LOS using both univariate and multiple regression analyses. RESULTS: There were 210 patients who had repair of dissection in the study period, with 109 patients in Group A and 101 in Group B. The average age of this sample was 59.5 (standard deviation = 16.0), 65.7% were male and 18.1% died prior to discharge following repair. The greatest percentage of deaths occurred in winter (31.6%, n = 12), while the least were in summer (21.1%, n = 8) and fall (21.1%, n = 8). An overall χ(2) test found there was no difference in mortality for season (P = 0.55). Univariate analyses also found the age of patients who died vs lived was significantly higher (65.9 vs 58.1 years; P = 0.001), and a significantly greater (P = 0.029) percentage of patients with diabetes vs without diabetes died (41.7 vs 16.7%). Univariate analyses found all other covariates were not significantly related to mortality. In the multiple logistic regression model, there was no significant effect for season, while the odds of dying increased with age (odds ratio [OR] = 1.04, 95% confidence interval [95% CI] = 1.01-1.07, P = 0.012), and the odds of dying in the full-moon cycle vs the new moon cycle was significantly reduced (OR = 0.21, 95% CI = 0.05-0.81, P = 0.024). No other covariate significantly increased or decreased the odds of death, including diabetes risk, which had been significantly related to death in the univariate analysis. Within a linear regression model that examined the relationship with LOS, Group B (P = 0.020), male sex (P = 0.036) and the full-moon lunar phase (P = 0.001) were significantly related to shorter LOS. CONCLUSIONS: Season had no effect on mortality or LOS following aortic dissection repair, while patient age significantly increased the odds of death. The full-moon cycle appeared to reduce the odds of death, and the full-moon cycle, along with being male and requiring a concomitant cardiac procedure, was associated with shorter LOS.

Bioengineered human and allogeneic pulmonary valve conduits chronically implanted orthotopically in baboons: hemodynamic performance and immunologic consequences.

OBJECTIVE: This study assesses in a baboon model the hemodynamics and human leukocyte antigen immunogenicity of chronically implanted bioengineered (decellularized with collagen conditioning treatments) human and baboon heart valve scaffolds. METHODS: Fourteen baboons underwent pulmonary valve replacement, 8 with decellularized and conditioned (bioengineered) pulmonary valves derived from allogeneic (N = 3) or xenogeneic (human) (N = 5) hearts; for comparison, 6 baboons received clinically relevant reference cryopreserved or porcine valved conduits. Panel-reactive serum antibodies (human leukocyte antigen class I and II), complement fixing antibodies (C1q binding), and C-reactive protein titers were measured serially until elective sacrifice at 10 or 26 weeks. Serial transesophageal echocardiograms measured valve function and geometry. Differences were analyzed with Kruskal-Wallis and Wilcoxon rank-sum tests. RESULTS: All animals survived and thrived, exhibiting excellent immediate implanted valve function by transesophageal echocardiograms. Over time, reference valves developed a smaller effective orifice area index (median, 0.84 cm(2)/m(2); range, 1.22 cm(2)/m(2)), whereas all bioengineered valves remained normal (effective orifice area index median, 2.45 cm(2)/m(2); range, 1.35 cm(2)/m(2); P = .005). None of the bioengineered valves developed elevated peak transvalvular gradients: 5.5 (6.0) mm Hg versus 12.5 (23.0) mm Hg (P = .003). Cryopreserved valves provoked the most intense antibody responses. Two of 5 human bioengineered and 2 of 3 baboon bioengineered valves did not provoke any class I antibodies. Bioengineered human (but not baboon) scaffolds provoked class II antibodies. C1q(+) antibodies developed in 4 recipients. CONCLUSIONS: Valve dysfunction correlated with markers for more intense inflammatory provocation. The tested bioengineering methods reduced antigenicity of both human and baboon valves. Bioengineered replacement valves from both species were hemodynamically equivalent to native valves.

Transesophageal Echocardiography in Healthy Young Adult Male Baboons (Papio hamadryas anubis): Normal Cardiac Anatomy and Function in Subhuman Primates Compared to Humans.

Implantable, viable tissue engineered cardiovascular constructs are rapidly approaching clinical translation. Species typically utilized as preclinical large animal models are food stock ungulates for which cross species biological and genomic differences with humans are great. Multiple authorities have recommended developing subhuman primate models for testing regenerative surgical strategies to mitigate xenotransplant inflammation. However, there is a lack of specific quantitative cardiac imaging comparisons between humans and the genomically similar baboons (Papio hamadryas anubis). This study was undertaken to translate to baboons transesophageal echocardiographic functional and dimensional criteria defined as necessary for defining cardiac anatomy and function in the perioperative setting. Seventeen young, healthy baboons (approximately 30 kg, similar to 5 year old children) were studied to determine whether the requisite 11 views and 52 measurement parameters could be reliably acquired by transesophageal echocardiography (TEE). The obtained measurements were compared to human adult normative literature values and to a large relational database of pediatric "normal heart" echo measurements. Comparisons to humans, when normalized to BSA, revealed a trend in baboons toward larger mitral and aortic valve effective orifice areas and much larger left ventricular muscle mass and wall thickness, but similar pulmonary and tricuspid valves. By modifying probe positioning relative to human techniques, all recommended TEE views except transgastric could be replicated. To supplement, two transthoracic apical views were discovered that in baboons could reliably replace the transgastric TEE view. Thus, all requisite echo views could be obtained for a complete cardiac evaluation in Papio hamadryas anubis to noninvasively quantify cardiac structural anatomy, physiology, and dimensions. Despite similarities between the species, there are subtle and important physiologic and anatomic differences when compared to human.

Performance and morphology of decellularized pulmonary valves implanted in juvenile sheep.

BACKGROUND: Because of cryopreserved heart valve-mediated immune responses, decellularized allograft valves are an attractive option in children and young adults. The objective of this study was to investigate the performance and morphologic features of decellularized pulmonary valves implanted in the right ventricular outflow tract of juvenile sheep. METHODS: Right ventricular outflow tract reconstructions in juvenile sheep (160±9 days) using cryopreserved pulmonary allografts (n=6), porcine aortic root bioprostheses (n=4), or detergent/enzyme-decellularized pulmonary allografts (n=8) were performed. Valve performance (echocardiography) and morphologic features (gross, radiographic, and histologic examination) were evaluated 20 weeks after implantation. RESULTS: Decellularization reduced DNA in valve cusps by 99.3%. Bioprosthetic valves had the largest peak and mean gradients versus decellularized valves (p=0.03; p<0.001) and cryopreserved valves (p=0.01; p=0.001), which were similar (p=0.45; p=0.40). Regurgitation was minimal and similar for all groups (p=0.16). No cusp calcification was observed in any valve type. Arterial wall calcification was present in cryopreserved and bioprosthetic grafts but not in decellularized valves. No autologous recellularization or inflammation occurred in bioprostheses, whereas cellularity progressively decreased in cryopreserved grafts. Autologous recellularization was present in decellularized arterial walls and variably extending into the cusps. CONCLUSIONS: Cryopreserved and decellularized graft hemodynamic performance was comparable. Autologous recellularization of the decellularized pulmonary arterial wall was consistently observed, with variable cusp recellularization. As demonstrated in this study, decellularized allograft valves have the potential for autologous recellularization.

Pediatric cardiopulmonary bypass adaptations for long-term survival of baboons undergoing pulmonary artery replacement.

Cardiopulmonary bypass (CPB) protocols of the baboon (Papio cynocephalus anubis) are limited to obtaining experimental data without concern for long-term survival. In the evaluation of pulmonary artery tissue engineered heart valves (TEHVs), pediatric CPB methods are adapted to accommodate the animals' unique physiology enabling survival up to 6 months until elective sacrifice. Aortic access was by a 14F arterial cannula and atrial access by a single 24F venous cannula.The CPB circuit includes a 3.3 L/min flow rated oxygenator, 1/4" x %" arterial-venous loop, 3/8" raceway, and bubble trap. The prime contains 700 mL Plasma-Lyte, 700 units heparin, 5 mL of 50% dextrose, and 20 mg amiodarone. Heparinization (200 u/kg) targets an activated clotting time of 350 seconds. Normothermic CPB was initiated at a 2.5 L/m2/min cardiac index with a mean arterial pressure of 55-80 mmHg. Weaning was monitored with transesophageal echocardiogram. Post-CPB circuit blood was re-infused. Chest tubes were removed with cessation of bleeding. Extubation was performed upon spontaneous breathing. The animals were conscious and upright 3 hours post-CPB. Bioprosthetic valves or TEHVs were implanted as pulmonary replacements in 20 baboons: weight = 27.5 +/- 5.6 kg, height = 73 +/- 7 cm, body surface area = 0.77 m2 +/- 0.08, mean blood flow = 1.973 +/- .254 L/min, core temperature = 37.1 +/- .1 degree C, and CPB time = 60 +/- 40 minutes. No acidosis accompanied CPB. Sixteen animals survived, four expired. Three died of right ventricular failure and one of an anaphylactoid reaction. Surviving animals had normally functioning replacement valves and ventricles. Baboon CPB requires modifications to include high systemic blood pressure for adequate perfusion into small coronary arteries, careful CPB weaning to prevent ventricular distention, and drug and fluid interventions to abate variable venous return related to a muscularized spleno-splanchnic venous capacity.

Decellularization reduces calcification while improving both durability and 1-year functional results of pulmonary homograft valves in juvenile sheep.

OBJECTIVE: The juvenile sheep functional valve chronic implant calcification model was used to compare long-term calcification rates, functional performance, and durability for 3 types of right ventricular outflow tract implants: classically cryopreserved homografts and 2 decellularized pulmonary valved conduits. METHODS: Fifteen juvenile sheep were randomly assigned to one of 3 study arms and underwent pulmonary valve replacement. The arms included the following: (1) cryopreserved ovine pulmonary valves; (2) cryopreserved, decellularized, saline (1 degrees C-10 degrees C)-stored ovine pulmonary valves; and (3) cryopreserved, decellularized, glycerolized (-80 degrees C) stored ovine pulmonary valves. Animal growth, serial echocardiographic results (with valve performance assessment), dimensions, and tissue-specific calcification measurements were compared with pre-explant angiographic analysis and right ventricular outflow tract pressure measurements, cardiac magnetic resonance imaging, specimen radiographic analysis, gross explant pathology, and histopathology. Parametric and nonparametric statistical analysis were performed. RESULTS: All but 2 study animals receiving implants thrived postoperatively, with similar growth rates, explant valve dimensions, ventricular functions, cardiac output, and indices during the study. As determined by means of echocardiographic analysis, 3 animals in arm 1 (and one in arm 2) had leaflet dysfunction. Valve regurgitation was recognized in 1 survivor each from both arms 1 and 2. Although 1 arm 1 animal died with calcified subacute bacterial endocarditis, and the other 4 had leaflet and conduit wall calcification by the time of death, no arm 2 or arm 3 animals demonstrated leaflet calcium, and no arm 3 and only 1 arm 2 animals had calcium in the conduit wall over the entire year, as determined with any measurement method. All cryopreserved conduit walls had calcium by 20 weeks, whereas only 1 of 10 decellularized conduits (arms 2 plus 3) had wall calcium. CONCLUSION: Cryopreserved-decellularized-glycerolized valves retained normal valve function, with absent leaflet and minimal wall calcifications 1 year postoperatively, as opposed to classically cryopreserved allografts. These results might be predictive of the prolonged durability and functionality of a cryopreserved-decellularized-glycerolized allograft valve.

Perioperative renal outcome in cardiac surgical patients with preoperative renal dysfunction: aprotinin versus epsilon aminocaproic acid.

OBJECTIVE: The administration of aprotinin to patients with pre-existing renal dysfunction who are undergoing cardiac surgery is controversial. Therefore, the authors present their experience with the use of aprotinin for patients with preoperative renal dysfunction who underwent elective cardiac surgery requiring cardiopulmonary bypass (CPB). DESIGN: Retrospective analysis. SETTING: University hospital. PARTICIPANTS: Consecutive cardiac surgical patients with preoperative serum creatinine (SCr) > or =1.8 mg/dL undergoing nonemergent cardiac surgery requiring CPB. INTERVENTIONS: None. METHODS: One hundred twenty-three patients either received epsilon aminocaproic acid (EACA, n = 82) or aprotinin (n = 41) as decided by the attending anesthesiologist and surgeon. Data were collected from the Society of Thoracic Surgeons database and from automated intraoperative anesthesia records. Renal function was assessed from measured serum creatinine (SCr) and calculated creatinine clearances (CrCls). Acute perioperative renal dysfunction was defined as a worsening of perioperative renal function by > or =25% and/or the need for hemodialysis (HD). ANALYSIS: Data were recorded as mean and standard deviation or percentage of population depending on whether the data were continuous or not. Data were compared by using an analysis of variance, chi-square analysis, Student paired and unpaired t tests, Fisher exact test, Wilcoxon rank sum test, and Mann-Whitney U test. A p value <0.05 was considered significant. RESULTS: Overall, 32% and 41% of patients had acute perioperative renal dysfunction measured by CrCl and SCr, respectively. Seven patients required HD (5.7%). Six of these 7 had complicated postoperative courses. Of all the variables measured, only the duration of the aortic crossclamp (AoXCl) and CPB were significantly associated with acute perioperative renal dysfunction. Acute perioperative renal dysfunction was associated with increased intensive care unit and hospital stays, postoperative blood transfusion, dialysis, and major infection. Aprotinin patients were significantly older (75.2 v 70.2 years, p < 0.05), had lower left ventricular ejection fraction (44.4% v 49.2%, p < 0.05), a greater preoperative history of congestive heart failure (63 v 44%, p < 0.05), a greater renal risk score (5.8 v 4.9, p < 0.05), and underwent more nonisolated coronary artery bypass graft surgeries (77% v 29%, p < 0.0001). CPB time (126.0 v 96.5 minutes, p < 0.001) and AoXCl duration (100.9 v 78.0 minutes, p < 0.005) were longer in the aprotinin group. Diabetes (60.5% v 41.5%, p < 0.05) and hypertension (90.1% v 73.2%, p < 0.05) were more prevalent in the EACA group. Baseline renal function and renal outcomes were not significantly different between the aprotinin and EACA groups. Six of the 7 patients who required HD received EACA (p = 0.1). The earliest SCr recorded > or =3 months after surgery was significantly lower in the aprotinin group compared with the EACA group (1.8 v 2.2 mg/dL, p < 0.05). CONCLUSION: Acute perioperative renal dysfunction was associated with worse patient outcome and longer CPB and AoXCl times. Demographic and surgical variables indicated that the sicker patients undergoing more complex surgeries were more likely to be treated with aprotinin. Although aprotinin patients had a higher renal risk score, the administration of aprotinin did not negatively impact renal outcome.

The effects of vasoactive agents on flow through saphenous vein grafts during lower-extremity peripheral vascular surgery.

PURPOSE: The purpose of this study was to assess the effects of hemodynamic alterations on vein graft flow during peripheral vascular surgery. It was hypothesized that vasopressors can be administered without compromising flow through the vein grafts. SETTING: Tertiary care center, university medical center. STUDY DESIGN: Randomized placebo-controlled double-blinded study. METHODS: The effects of phenylephrine, epinephrine, milrinone, intravenous fluid, and placebo on newly constructed peripheral vein grafts were assessed in 60 patients (12 patients in each of 5 groups). Systemic and central hemodynamics were measured by using intra-arterial and pulmonary artery catheters. Vein graft flow was measured by using a transultrasonic flow probe (Transultrasonic Inc, Ithaca, NY). RESULTS: Phenylephrine increased systemic mean blood pressure (mBP) (68.2-94.0 mmHg, p < 0.01), systemic vascular resistance (SVR) (1,091-1,696 dynes x sec x cm(-5), p < 0.001), and vein graft flow (39.5-58.9 mL/min, p < 0.01), whereas cardiac output remained unchanged. Epinephrine resulted in increased cardiac output (4.4-6.9 L/min, p < 0.01) and mBP (72.7-89.1 mmHg, p < 0.01), whereas vein graft flow was reduced in 6 of 12 patients. Intravenous fluid administration resulted in a relatively smaller increase in graft flow (37.6-46.0 mL/min, p < 0.05), an increase in cardiac output, and an insignificant decrease in SVR. Other treatments had either little or no effect on vein graft flow. CONCLUSION: The study hypothesis was partly supported. Although both phenylephrine and epinephrine increased blood pressure, only the former increased vein graft flow in all patients. In conjunction with increases in graft flow after fluid administration, these data suggest that factors affecting vein graft flow are not just simply related to systemic hemodynamics.

The influence of cognitive reserve on neuropsychological functioning following coronary artery bypass grafting (CABG).

Neuropsychological impairment is common, yet variable, after coronary artery bypass grafting (CABG). Similar variability has been observed in other CNS-related diseases. Empirical findings in Alzheimer's disease and HIV, among other areas, suggest cognitive reserve (CR) may mediate the cognitive impact of these diseases. The present study examined whether CR mediates neuropsychological outcome after CABG. Participants were 42 (N=42) individuals who underwent elective, normothermic CABG. Each was placed in high (n=22) or low (n=20) CR groups based on estimated premorbid intelligence and occupational attainment. All were administered neuropsychological tests preoperatively and at discharge. The total incidence of neuropsychological decline (66.7%) was not significantly different between CR groups. However, on working memory and executive function tests, specifically, the high CR group demonstrated greater post-operative decline compared to the low CR group. These data are considered in the context of a threshold model of CR theory.