Transfusion Requirements After Cardiac Surgery The TRACS Randomized Controlled Trial

Context Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding optimal blood transfusion practice in patients undergoing cardiac surgery is lacking. Objective To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery. Design, Setting, and Patients The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n=502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat. Intervention Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit >= 30%) or to a restrictive strategy (hematocrit >= 24%). Main Outcome Measure Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at -8% (ie, 8% minimal clinically important increase in occurrence of the composite end point). Results Hemoglobin concentrations were maintained at a mean of 10.5 g/dL(95% confidence interval [CI], 10.4-10.6) in the liberal-strategy group and 9.1 g/dL (95% CI, 9.09.2) in the restrictive-strategy group (P<.001). A total of 198 of 253 patients (78%) in the liberal-strategy group and 118 of 249 (47%) in the restrictive-strategy group received a blood transfusion (P<.001). Occurrence of the primary end point was similar between groups (10% liberal vs 11% restrictive; between-group difference, 1% [95% CI, -6% to 4%]; P=.85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1.2 [95% CI, 1.1-1.4]; P=.002). Conclusion Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity. Trial Registration clinicaltrials.gov Identifier: NCT01021631 JAMA. 2010; 304(14):1559-1567 www.jama.com

Evaluation of Maxillary Alveolar Reconstruction Using a Resorbable Collagen Sponge with Recombinant Human Bone Morphogenetic Protein-2 in Cleft Lip and Palate Patients

Introduction: A resorbable collagen matrix with recombinant human bone morphogenetic protein (rhBMP-2) was compared with traditional iliac crest bone graft for the closure of alveolar defects during secondary dental eruption. Methods: Sixteen patients with unilateral cleft lip and palate, aged 8 to 12 years, were selected and randomly assigned to group 1 (rhBMP-2) or group 2 (iliac crest bone graft). Computed tomography was performed to assess both groups preoperatively and at months 6 and 12 postoperatively. Bone height and defect volume were calculated through Osirix Dicom Viewer (Pixmeo, Apple Inc.). Overall morbidity was recorded. Results: Preoperative and follow-up examinations revealed progressive alveolar bone union in all patients. For group 1, final completion of the defect with a 65.0% mean bone height was detected 12 months postoperatively. For group 2, final completion of the defect with an 83.8% mean bone height was detected 6 months postoperatively. Dental eruption routinely occurred in both groups. Clinical complications included significant swelling in three group 1 patients (37.5%) and significant donor-site pain in seven group 2 patients (87.5%). Conclusions: For this select group of patients with immature skeleton, rhBMP-2 therapy resulted in satisfactory bone healing and reduced morbidity compared with traditional iliac crest bone grafting.

Limb Salvage Using Bypass to the Perigeniculate Arteries

Objective: To describe bypass to perigeniculate vessels for limb salvage. Design: Retrospective cohort study. Material and methods: Between 1995 and 2009, 47 bypass procedures to perigeniculate collateral arteries were performed in 46 patients (15 women, 31 men; median age, 68 years). All patients presented with critical ischaemia (tissue loss in 87.5%, rest pain in 12.5%). Mean ankle brachial index was 0.27 +/- 0.17. The site of distal anastomosis was the descending genicular artery (DGA) in 23 bypasses (1 bilateral) and the medial sural artery (MSA) in 24. Proximal anastomosis was to the external iliac artery in 2 cases, common femoral artery in 23 cases, superficial femoral artery in 8 cases, deep femoral artery in 8 cases, above-knee poplitaeal artery in 2 cases, and previous graft in 4 cases. Results: There were four deaths during the immediate postoperative period. Mean follow-up duration was 27 months. Ten patients required major amputation. Mean ankle brachial index post-operatively was 0.60 +/- 0.21. At 3 years, primary patency was 74.7 +/- 7%, secondary patency was 83.4 +/- 8%, and the limb salvage and survival rates were 73.5 +/- 7% and 77.4 +/- 7%, respectively. Conclusion: Bypass to perigeniculate arteries is a viable treatment option for critical limb ischaemia in selected patients. (C) 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Effectiveness of Thalidomide and Tamoxifen in Preventing Neointimal Hyperplasia in Experimental Vascular Injury in Rats

Introduction. Chronic allograft vasculopathy is an important cause of graft loss. Considering the inflammatory response in the development of chronic vascular lesions, therapeutic approaches to target the inflammatory process may be useful. We sought to investigate the possible protective effects on balloon catheter-induced vascular injury of thalidomide and tamoxifen, 2 drugs with powerful anti-inflammatory, immunomodulatory, and antifibrotic effects, using an animal model that mimics the morphologic features of chronic allograft vasculopathy. Methods. Male Wistar rats subjected to balloon catheter carotid injury (INJ) were treated with thalidomide (100 mg/kg), or tamoxifen (10 mg/kg), or vehicle. Contralateral right carotid arteries were used as uninjured controls. Morphometric and immunohistochemical analyses were performed at 14 days postinjury. Results. Injured carotid arteries showed marked neointimal hyperplasia, which was significantly inhibited among animals treated with thalidomide or tamoxifen: neointimal/media ratios of 1.4 +/- 0.4 versus 0.2 +/- 0.1 versus 0.4 +/- 0.2, for INJ, INJ + Thalid, and INJ + Tamox; respectively (P < .001). The endothelial cell loss was significantly less pronounced among animals subjected to carotid balloon injury that were treated with thalidomide (24 +/- 14 vs 1 +/- 1 cells per section in INJ, respectively (P < .05). Therapy with either thalidomide or tamoxifen effectively maintained alpha-smooth muscle actin expression in the media, similar to uninjured arteries. In this setting, tamoxifen was additionally effective to prevent the migration of myofibroblasts in to the intima. Conclusion. Thalidomide and tamoxifen were effective to reduce neointimal hyperplasia secondary to vascular damage. The vasculoprotective effects of thalidomide were more pronounced to preserve endothelial cells, whereas tamoxifen inhibited smooth muscle cell migration and proliferation. A possible beneficial effect of combined therapy with thalidomide plus tamoxifen should be addressed in future studies.

The surgical repair of half-nose

Absence of half-nose is an extremely rare congenital malformation, which has a devastating impact on the patient and the family. A review of indexed English-language literature found 91 cases of half-nose, including 50 patients with proboscis lateralis. Pathogenesis is not clear, and the reported cases have sporadically occurred. Many aspects must be considered when reconstructing a congenital half-nose, such as timing of surgery, type of tissue to be used and the need to reconstruct nasal airway. The aim of this article is to present personal experience in seven cases of half-nose reconstruction, in order to review the literature regarding to this rare entity, highlighting aspects of incidence, pathogenesis and surgical treatment. Nasal reconstruction was performed at ages of 5-7 years to minimise psychological trauma. Forehead skin demonstrated to be an excellent donor site to re-surface the nose. For the inner lining, contralateral cutaneous nasal flap was our preference. Concerning the nasal framework reconstruction, alar contour was restored using a cartilage graft from the lower portion of ear tragus and concha. (C) 2008 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Muscle Transplants for Facial Reanimation Rationale and Results of Insertion Technique Using the Palmaris Longus Tendon

Thirty-one patients with unilateral long-standing facial palsy underwent I-stage reanimation with free gracilis muscle transplant innervated by the masseteric branch of the trigeminal nerve. They were divided into 2 nonrandomized groups according to insertion technique: group 1 (9 patients), interrupted suture between the free flap and the orbicularis oris of the upper and lower lip on the paralyzed side; group It (22 patients), palmaris longus tendon graft placed between the gracilis free flap and the orbicularis oris of the upper and lower lip on the nonparalyzed side. Qualitative evaluation of the smile demonstrated better results in patients from group II. Comparing the position Of the Cupid`s bow at rest, pre- and postoperatively in each patient, we observed significant improvement of facial symmetry in both groups. During smile, however, there was a significantly higher rate of centralization of the Cupid`s bow in patients submitted to reanimation with the use of the palmaris longus tendon (group II).

Comparative Analysis of the Influence of Perichondrium on Conjunctival Epithelialization on Conchal Cartilage Grafts in Eyelid Reconstruction: Experimental Study in Rabbits

Background: Although the role of cartilage grafts in reconstruction of the posterior eyelid lamella is well established, spontaneous conjunctival epithelialization on such grafts has yet to be fully proven. The aim of this study was to perform a comparative analysis of the influence of perichondrium on conjunctival epithelialization over conchal cartilage grafts used in eyelid reconstruction in rabbits. Methods: The posterior lamellae of 100 lower eyelids from 50 rabbits were reconstructed with autogenous grafts of conchal ear cartilage. In the right eyelids, cartilage was grafted with the perichondrium in direct contact with the eyeball, and the left eyelids were reconstructed in a similar manner but using cartilage grafts without perichondrium. The animals were killed after 1, 2, 3, 4, and 5 weeks, and their lower eyelids were analyzed macroscopically and histologically. Results: The percentage difference in conjunctival epithelialization on the cartilage with perichondrium and that without perichondrium was 11.41 percent in the first week of the experiment, 13.64 percent in the second week, 18.69 percent in the third week, 10.38 percent in the fourth week, and 6.17 percent in the fifth week. The average percentage conjunctival epithelialization in the eyelids reconstructed with a cartilage graft with perichondrium was significantly higher throughout the 5 weeks of the experiment than in the eyelids reconstructed with cartilage without perichondrium (p < 0.0002). Conclusion: It was found that the perichondrium had an important role in conjunctival epithelialization in eyelids reconstructed with a cartilage graft in the present study. (Plast. Reconstr. Surg. 123: 55, 2009.)

Multifocal Renal Allograft Biopsy: Impact on Therapeutic Decisions

Objective. There are no data to support the suggestion that samples removed from one segment of the transplanted kidney are representative of the whole graft. The aim of this study was to compare the histological differences between biopsies obtained from different portions of the renal allograft and their impact on treatment recommendations. Patients and Methods. Two hundred percutaneous biopsies were performed on kidney allografts and samples were collected from the upper and lower poles (100 kidneys). All samples were randomized and blindly reviewed. We obtained the discordance rates between the poles for the grading of acute rejection and for the diagnosis of nephrotoxicity due to immunosuppression. We also checked if the differences found were sufficient to call for different clinical recommendations. These values were compared with the intrapathologist variation rates. Results. In 70 kidneys adequate sampling was obtained from both poles. The diagnosis of acute rejection were made in 1.7. The discordance rate between the upper and lower poles was 82.3% (kappa = 0.34), higher than the intrapathologist variation (P =.002). Nephrotoxicity was found in 14 kidneys. The discordance rate between the upper and lower poles was 28.6% (kappa = 0.88), with no difference compared with the intrapathologist variation. In 14 of the 70 kidneys (25.7%), discordances between poles had impact on clinical recommendations, most of these cases due to different gradings of acute rejection (78%). This number was higher than the intrapathologist variation (P =.04). Conclusions. The histopathological changes in the kidney allograft are not always homogeneous. This heterogeneity may affect the therapeutic recommendations.

Preferential use of nonreversed vein grafts in above-knee femoropopliteal bypasses for critical ischemia: Midterm outcome

We evaluated nonreversed vein grafts in above-knee bypasses for chronic critical limb ischemia in a retrospective study with intention-to-treat analysis in patients who underwent above-knee bypass grafting. During a 4-year period, 51 patients (men, 32; women, 19; mean age 66 years) with 53 critically ischemic lower extremities underwent above-knee femoropopliteal bypass grafting. The follow-up evaluation consisted of clinical examination, assessment of the ankle- brachial systolic blood pressure index, and, whenever necessary, duplex scanning. Three ( 5.7%) deaths occurred within 30 days, two from myocardial infarction and one from an undetermined cause. The 2-year cumulative success rate was 82.5 +/- 9.6% for primary patency, 84.6 +/- 8.9% for secondary patency, 90.1 +/- 7.3% for tertiary patency, 86.9 +/- 7.6% for limb salvage, 77.7 +/- 8.4% for survival, 68.0 +/- 11.1% for composite patency, and 68.4 +/- 9.3% for amputation- free survival; the corresponding estimates for vein grafts alone were 86.6 +/- 9.2%, 88.9 +/- 8.6%, 89.0 +/- 8.5%, 88.1 +/- 8.1%, 81.1 +/- 9.1, 76.8 +/- 11.1%, and 72.6 +/- 10.2%. Three prosthetic grafts failed and were replaced with an arm vein graft. Nonreversed vein bypass grafts in above- knee revascularization of critically ischemic limbs are justified.

Usefulness of a quick decalcification of bone sections embedded in methyl metacrylate: an improved method for immunohistochemistry

Immunohistochemistry of undecalcified bone sections embedded in methyl methacrylate (MMA) is not commonly employed because of potential destruction of tissue antigenicity by highly exothermic polymerization. The aim of the present study was to describe a new technique in which a quick decalcification of bone sections embedded in MMA improves the results for immunohistochemistry. The quality of interleukin 1 alpha (IL-1 alpha) immunostaining according to the present method was better than the conventional one. Immunostaining for osteoprotegerin (OPG) and the receptor activator of NF-kappa B ligand (RANKL) in bone sections of chronic kidney disease patients with mineral bone disorders (CKD-MBD) was stronger than in controls (postmortem healthy subjects). The present study suggested that this method is easy, fast, and effective to perform both histomorphometry and immunohistochemistry in the same bone fragment, yielding new insights into pathophysiological aspects and therapeutic approaches in bone disease.

Induction of Indoleamine 2,3-Dioxygenase by Gene Delivery in Allogeneic Islets Prolongs Allograft Survival

Indoleamine 2,3-dioxygenase (IDO), an enzyme that plays a critical role in fetomaternal tolerance, exerts immunoregulatory functions suppressing T-cell responses. The aims of this study were to promote IDO expression in rat islets using a nonviral gene transfer approach, and to analyze the effect of the in vivo induction of IDO in a model of allogeneic islet transplantation. The IDO cDNA was isolated from rat placenta, subcloned into a plasmid and transfected into rat islets using Lipofectamine. The efficiency of transfection was confirmed by qRT-PCR and functional analysis. The in vivo effect of IDO expression was analyzed in streptozotocin-induced diabetic Lewis rats transplanted with allogeneic islets under the renal capsule. Transplantation of IDO-allogeneic islets reversed diabetes and maintained metabolic control, in contrast to transplantation of allogeneic nontransfected islets, which failed shortly after transplantation in all animals. Graft survival of allograft islets transfected with IDO transplanted without any immunosuppression was superior to that observed in diabetic rats receiving nontransfected islets. These data demonstrated that IDO expression induced in islets by lipofection improved metabolic control of streptozotocin-diabetic rats and prolonged allograft survival.

The effect of internal thoracic artery grafts on long-term clinical outcomes after coronary bypass surgery

Objectives: We sought to compare long-term outcomes after coronary bypass surgery with and without an internal thoracic artery graft. Methods: We analyzed clinical outcomes over a median follow-up of 6.7 years among 3,087 patients who received coronary bypass surgery as participants in one of 8 clinical trials comparing surgical intervention with angioplasty. We used 2 statistical methods (covariate adjustment and propensity score matching) to adjust for the nonrandomized selection of internal thoracic artery grafts. Results: Internal thoracic artery grafting was associated with lower mortality, with hazard ratios of 0.77 (confidence interval, 0.62-0.97; P = .02) for covariate adjustment and 0.77 (confidence interval, 0.57-1.05; P = .10) for propensity score matching. The composite end point of death or myocardial infarction was reduced to a similar extent, with hazard ratios of 0.83 (confidence interval, 0.69-1.00; P = .05) for covariate adjustment to 0.78 (confidence interval, 0.61-1.00; P = .05) for propensity score matching. There was a trend toward less angina at 1 year, with odds ratios of 0.81 (confidence interval, 0.61-1.09; P = .16) in the covariate-adjusted model and 0.81 (confidence interval, 0.55-1.19; P = .28) in the propensity score-adjusted model. Conclusions: Use of an internal thoracic artery graft during coronary bypass surgery seems to improve long-term clinical outcomes. (J Thorac Cardiovasc Surg 2011; 142: 829-35)

Impact of number of vessels disease on outcome of patients with stable coronary artery disease: 5-year follow-up of the medical, angioplasty, and bypass surgery study (MASS)

Objective: To evaluate whether the number of vessels disease has an impact on clinical outcomes as well as on therapeutic results accordingly to medical, percutaneous, or surgery treatment in chronic coronary artery disease. Methods: We evaluated 825 individuals enrolled in MASS study, a randomized study to compare treatment options for single or multivessel coronary artery disease with preserved left ventricular function, prospectively followed during 5 years. The incidence of overall mortality and the composite end-point of death, myocardial infarction, and refractory angina were compared in three groups: single vessel disease (SVD n = 214), two-vessel disease (2VD n = 253) and three-vessel disease (3VD n = 358). The relationship between baseline variables and the composite end-point was assessed using a Cox proportional hazards survival model. Results: Most baseline characteristics were similar among groups, except age (younger in SVD and older in 3VD, p < 0.001), lower incidence of hypertension in SVD (p < 0.0001), and lower levels of total and LDL-cholesterol in 3VD (p = 0.004 and p = 0.005, respectively). There were no statistical differences in composite end-point in 5 years among groups independent of the kind of treatment; however, there was a higher mortality rate in 3VD (p < 0.001). When we stratified our analysis for each treatment option, bypass surgery was associated with a tower number of composite end-point in all groups (SVD p < 0.001, 2VD p = 0.002, 3VD p < 0.001). In multivariate analysis, we found higher mortality risk in 3VD comparing to SVD (p = 0.005, HR 3.14, 95%Cl 1.4-7.0). Conclusion: Three-vessel disease was associated with worse prognosis compared to single-or two-vessel disease in patients with stable coronary disease and preserved ventricular function at 5-year follow-up. In addition, event-free survival rates were higher after bypass surgery, independent of the number of vessels diseased in these subsets of patients. (c) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Human leukocyte antigen-G expression after kidney transplantation is associated with a reduced incidence of rejection

HLA-G is a non-classic Human Leukocyte Antigen (HLA-G) Class I of low polymorphism and restricted tissue distribution that displays tolerogenic functions. In heart transplantation and in combined liver/renal allograft transplantation, the expression of HLA-G has been associated with a lower incidence of acute graft rejection episodes and absence of chronic dysfunction. Since the expression of HLA-G in renal biopsies has been investigated only in few patients who received a combined kidney and liver transplant, in this study we performed a cross-sectional study, systematically comparing the expression of HLA-G in post-transplanted renal grafts, stratifying patients according to the presence or absence of rejection. Patients and Methods: Seventy-three renal specimens (10 with acute rejection and 13 with chronic allograft nephropathy, and 50 with no signs of rejection) were immunohistochemically evaluated for HLA-G expression. Results: In the group as a whole, HLA-G molecules were detected in 40 cases (54.8%). Among specimens that presented HLA-G expression, 2 out of 40 (5%) exhibited acute rejection, 2 (5%) exhibited chronic allograft nephropathy, and the remaining 36 (90%) exhibited no signs of rejection. The comparison between patients with rejection and those without rejection showed that the expression of HLA-G was significantly increased in specimens exhibiting no signs of rejection (p<0.0001). Considering only patients with acute rejection, 8 out of 10 patients showed no HLA-G expression in their kidney biopsies when compared to patients exhibiting no signs of rejection and absence of HLA-G was observed in 14 out of 50 (p=0.0032). Similarly, considering only patients with chronic allograft nephropathy, absence of HLA-G expression was observed in I I out of 13 specimens, whereas in patients without rejection absence of HLA-G was observed in 14 out of 50 (p=0.003). Therapy with tacrolimus was significantly associated with the expression of HLA-G and a better graft prognosis. Conclusions: Our results suggest that HLA-G expression in the kidney allograft and the use of tacrolimus are associated with a lower frequency of acute renal rejection and chronic allograft nephropathy. (c) 2007 Elsevier B.V. All rights reserved.

Depression: a predictor of smoking relapse in a 6-month follow-up after hospitalization for acute coronary syndrome

Objective The objective of the study was to investigate whether depression is a predictor of postdischarge smoking relapse among patients hospitalized for myocardial infarction (MI) or unstable angina (ILIA), in a smoke-free hospital. Methods Current smokers with MI or UA were interviewed while hospitalized; patients classified with major depression (MD) or no humor disorder were reinterviewed 6 months post discharge to ascertain smoking status. Potential predictors of relapse (depression; stress; anxiety; heart disease risk perception; coffee and alcohol consumption; sociodemographic, clinical, and smoking habit characteristics) were compared between those with MD (n = 268) and no humor disorder (n = 135). Results Relapsers (40.4%) were more frequently and more severely depressed, had higher anxiety and lower self-efficacy scale scores, diagnosis of UA, shorter hospitalizations, started smoking younger, made fewer attempts to quit, had a consort less often, and were more frequently at the `precontemplation` stage of change. Multivariate analysis showed relapse-positive predictors to be MD [odds ratio (OR): 2.549; 95% confidence interval (CI): 1.519-4.275] (P<0.001); `precontemplation` stage of change (OR: 7.798; 95% CI: 2.442-24.898) (P<0.001); previous coronary bypass graft surgery (OR: 4.062; 95% CI: 1.356-12.169) (P=0.012); and previous anxiolytic use (OR: 2.365; 95% CI: 1.095-5.107) (P=0.028). Negative predictors were diagnosis of MI (OR: 0.575; 95% CI: 0.361-0.916) (P=0.019); duration of hospitalization (OR: 0.935; 95% CI: 0.898-0.973) (P=0.001); smoking onset age (OR: 0.952; 95% CI: 0.910-0.994) (P=0.028); number of attempts to quit smoking (OR: 0.808; 95% CI: 0.678-0.964) (P=0.018); and `action` stage of change (OR: 0.065; 95% CI: 0.008-0.532) (P= 0.010). Conclusion Depression, no motivation, shorter hospitalization, and severity of illness contributed to postdischarge resumption of smoking by patients with acute coronary syndrome, who underwent hospital-initiated smoking cessation.