Mini-extracorporeal circulation minimizes coagulation abnormalities and ameliorates pulmonary outcome in coronary artery bypass grafting surgery

Hemostasis is impaired during CABG and coagulation abnormalities often result in clinically relevant organ dysfunctions, eventually increasing morbidity and mortality rates. Fifteen consecutive patients with coronary artery disease submitted to conventional extracorporeal circulation (cECC) have been compared with 15 matched patients, using mini-ECC (MECC). Postoperative lung function was evaluated according to gas exchange, intubation time and lung injury score. In the MECC group, thrombin-antithrombin complex levels (TaTc), prothrombin fragments (PF1+2) formation and thromboelastography (TEG) clotting times were lower compared to the cECC group (p=0.002 and p<0.001, respectively) whereas postoperative blood loss was higher in the cECC group (p=0.030) and more patients required blood transfusion (p=0.020). In the MECC group, postoperative gas exchange values were better, intubation time shorter and lung injury score lower (p<0.001 for all comparisons). Our study suggests that MECC induces less coagulation disorders, leading to lower postoperative blood loss and better postoperative lung function. This approach may be advantageous in high-risk patients. © The Author(s) 2013

The effect of bilateral internal thoracic artery harvesting on superficial and deep sternal infection: The role of skeletonization

Objective: To determine the relative risk of sternal dehiscence in patients undergoing bilateral internal thoracic artery harvesting and to assess whether and to what extent the technique of artery skeletonization might reduce this risk. Methods: Prospectively collected data on patients undergoing coronary artery bypass operations with at least a single internal thoracic artery were reviewed. The last 450 patients receiving bilateral internal thoracic artery grafts were compared with 450 patients who received a single internal thoracic artery during the same period. The left internal thoracic artery was always harvested in a pedicled fashion. Among patients receiving a bilateral internal thoracic artery, both arteries were harvested in a pedicled fashion in 300 cases, whereas both internal thoracic arteries were skeletonized in the remaining 150 cases. Results: Compared with a single internal thoracic artery, harvesting both internal thoracic arteries either in a skeletonized or in a pedicled fashion increased the chance of deep (1.1% vs 3.3% vs 4.7%; P =. 01) or superficial (4.8% vs 7.8% vs 12%; P =. 002) sternal infection. However, the technique of artery harvesting (odds ratio, 4.1; 95% confidence interval, 1.4-12.1); the presence of peripheral arteriopathy (odds ratio, 3.1; 95% confidence interval, 1.2-8.5), and resternotomy for bleeding (odds ratio, 8.2; 95% confidence interval, 2.0-33.6) were the only independent predictors for deep sternal infection, whereas the technique of artery harvesting (odds ratio, 3.0; 95% confidence interval, 1.6-5.4), female sex (odds ratio, 2.2; 95% confidence interval, 1.2-4.2), and diabetes (odds ratio, 1.7; 95% confidence interval, 1.0-2.9) were the only independent predictors of superficial sternal infection. In diabetic patients, there was no difference in the incidence of deep sternal infection among patients receiving a single internal thoracic artery or double skeletonized internal thoracic arteries (P =. 4). Conclusions: Bilateral internal thoracic artery harvesting carries a higher risk of sternal infection than harvesting a single internal thoracic artery. Skeletonization of both internal thoracic arteries significantly decreases this risk. A strategy of bilateral thoracic artery grafting can also be offered to patients at high risk for wound infection. Copyright © 2005 by The American Association for Thoracic Surgery

Study of the susceptibility to benznidazole in a Trypanosoma cruzi isolated from a patient of Mendoza

La enfermedad de Chagas es una patología endémica en 21 países de América, transportada a través de migraciones a países no endémicos como Estados Uni-dos y algunos países de Europa, Oceanía y Asia. En Argen-tina, la enfermedad de Chagas afecta de 6 a 8 millones de personas y provoca, en promedio, 12.000 muertes al año. Mendoza es una de las 6 provincias que aún figura con alto riesgo de trasmisión vectorial. Hasta el momento, Benznida-zol (BNZ) y Nifurtimox son las únicas drogas aprobadas para el tratamiento del Chagas. Si bien son muy eficaces para el tratamiento de la infección aguda, existen pocos anteceden-tes del efecto de las mismas en la etapa crónica. Objetivos: estudiar la susceptibilidad de un aislado de T. cruzi de Mendoza (TcM) frente a la droga BNZ comparando con la susceptibilidad de la cepa TcY mantenida en labora-torio, la cual es considerada me-dianamente resistente a la droga BNZ. Nos propusimos estudiar nuevas alternativas para mejorar el trata-miento de la enfermedad mediante el uso combinado de BNZ y otra droga utilizada para el trata-miento del parásito T. brucei, agente etiológico de la tripano-somiasis africana conocida como Eflornitina (DFMO)

Dietary Risk Factors and Eating Behaviors in Peripheral Arterial Disease (PAD)

Dietary risk factors play a fundamental role in the prevention and progression of atherosclerosis and PAD (Peripheral Arterial Disease). The impact of nutrition, however, defined as the process of taking in food and using it for growth, metabolism and repair, remains undefined with regard to PAD. This article describes the interplay between nutrition and the development/progression of PAD. We reviewed 688 articles, including key articles, narrative and systematic reviews, meta-analyses and clinical studies. We analyzed the interaction between nutrition and PAD predictors, and subsequently created four descriptive tables to summarize the relationship between PAD, dietary risk factors and outcomes. We comprehensively reviewed the role of well-studied diets (Mediterranean, vegetarian/vegan, low-carbohydrate ketogenic and intermittent fasting diet) and prevalent eating behaviors (emotional and binge eating, night eating and sleeping disorders, anorexia, bulimia, skipping meals, home cooking and fast/ultra-processed food consumption) on the traditional risk factors of PAD. Moreover, we analyzed the interplay between PAD and nutritional status, nutrients, dietary patterns and eating habits. Dietary patterns and eating disorders affect the development and progression of PAD, as well as its disabling complications including major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Nutrition and dietary risk factor modification are important targets to reduce the risk of PAD as well as the subsequent development of MACE and MALE

Lipofibromatous hamartoma of the median nerve

Lipofibromatous hamartoma is a rare tumour of peripheral nerves which is characterised by an excessive infiltration of the epineurium and perineurium by fibroadipose tissue. To the best of our knowledge, only approximately 88 cases are reported in the literature. We report a rare case of lipofibromatous hamartoma of the median nerve causing secondary carpal tunnel syndrome in a 25 year old patient. This patient was treated conservatively with decompression and biopsy and experienced a complete resolution of symptoms post-operatively. Magnetic resonance imaging may be used to diagnose this lesion as it has very distinctive characteristics. Multiple conditions have been associated with this lesion and a greater understanding of these associations may clarify the pathogenesis. The architecture of the tumour makes excision very challenging and the surgical management remains controversial. A review of the literature regarding the etiology, pathogenesis and surgical management of lipofibromatous hamartoma is included

Value of Screening Asymptomatic Carotid Artery Stenosis Prior to Coronary Artery Bypass Grafting: Analysis of the E-CABG Registry

Background and aim: The aim of this study was to evaluate the prognostic impact of asymptomatic carotid artery stenosis(CAS) in patients undergoing isolated coronary artery bypass grafting(CABG). Methods:Patients from the multicenter, prospective E-CABG registry without history of stroke or transient ischemic attack and screened by duplex ultrasound for CAS before isolated CABG were included in this analysis. Results:Among 2813 patients screened by duplex ultrasound for asymptomatic CAS, 11.1% had a CAS of 50-59%, 6.0% of 60-69%, 3.1% of 70-79%, 1.4% of 80-89%, 0.5% of 90-99%, and 1.1% had carotid occlusion. Postoperative stroke occurred in 25 patients(0.9%). Lesions were bilateral in five patients(25%) and ipsilateral to a CAS 6550% in six patients(30%). In univariate analysis, the severity of CAS was associated with a significantly increased risk of stroke(p<0.0001). In multivariate analysis, a CAS of 90-99%(OR 12.03, 95%CI 1.34-108.23) and the presence of an occluded internal carotid artery(OR 8.783, 95%CI 1.820-42.40) were independent predictors of stroke along with urgency of the procedure, severe-massive bleeding according to the E-CABG classification and the presence of a porcelain ascending aorta. Conclusions: Among patients with asymptomatic CAS, the risk of stroke is significant only in patients with a stenosis 6590%. Since this condition has a low prevalence and when left untreated is associated with a relatively low rate of stroke, preoperative screening of asymptomatic CAS before CABG may not be justified. Instead, avoiding manipulation of diseased ascending aorta and prevention of excessive bleeding may be more effective measures to prevent stroke after CABG

Serum High Mobility Group Box-1 Levels Associated With Cardiovascular Events After Lower Extremity Revascularization: A Prospective Study of a Diabetic Population

Background: Peripheral arterial disease (PAD) is one of the most disabling cardiovascular complications of type 2 diabetes mellitus and is indeed associated with a high risk of cardiovascular and limb adverse events. High mobility group box-1 (HMGB-1) is a nuclear protein involved in the inflammatory response that acts as a pro-inflammatory cytokine when released into the extracellular space. HMBG-1 is associated with PAD in diabetic patients. The aim of this study was to evaluate the association between serum HMGB-1 levels and major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after lower-extremity endovascular revascularization (LER) in a group of diabetic patients with chronic limb-threatening ischemia (CLTI). Methods: We conducted a prospective observational study of 201 diabetic patients with PAD and CLTI requiring LER. Baseline serum HMGB-1 levels were determined before endovascular procedure. Data on cardiovascular and limb outcomes were collected in a 12-month follow-up. Results: During the follow-up period, 81 cases of MACE and 93 cases of MALE occurred. Patients who subsequently developed MACE and MALE had higher serum HMGB-1 levels. Specifically, 7.5 ng/mL vs 4.9 ng/mL (p \u3c 0.01) for MACE and 7.2 ng/mL vs 4.8 ng/mL (p \u3c 0.01) for MALE. After adjusting for traditional cardiovascular risk factors, the association between serum HMGB-1 levels and cardiovascular outcomes remained significant in multivariable analysis. In our receiver operating characteristic (ROC) curve analysis, serum HMGB-1 levels were a good predictor of MACE incidence (area under the curve [AUC] = 0.78) and MALE incidence (AUC = 0.75). Conclusions: This study demonstrates that serum HMGB-1 levels are associated with the incidence of MACE and MALE after LER in diabetic populations with PAD and CLTI

Development of a Biomarker Panel for Assessing Cardiovascular Risk in Diabetic Patients With Chronic Limb-Threatening Ischemia (Clti): A Prospective Study

BACKGROUND: Lower-extremity endovascular revascularization (LER) is often required for diabetic patients with chronic limb threatening ischemia (CLTI). During the post-revascularization period patients may unpredictably experience major adverse cardiac events (MACE) and major adverse limb events (MALE). Several families of cytokines are involved in the inflammatory process that underlies the progression of atherosclerosis. According to current evidence, we have identified a panel of possible biomarkers related with the risk of developing MACE and MALE after LER. The aim was to study the relationship between a panel of biomarkers - Interleukin-1 (IL-1) and 6 (IL-6), C-Reactive Protein (CRP), Tumor Necrosis Factor-α (TNF-α), High-Mobility Group Box-1 (HMGB-1), Osteoprotegerin (OPG), Sortilin and Omentin-1- at baseline, with cardiovascular outcomes (MACE and MALE) after LER in diabetic patients with CLTI. METHODS: In this prospective non-randomized study, 264 diabetic patients with CLTI undergoing endovascular revascularization were enrolled. Serum levels of each biomarker were collected before revascularization and outcomes\u27 incidence was evaluated after 1, 3, 6 and 12 months. RESULTS: During the follow-up period, 42 cases of MACE and 81 cases of MALE occurred. There was a linear association for each biomarker at baseline and incident MACE and MALE, except Omentin-1 levels that were inversely related to the presence of MACE or MALE. After adjusting for traditional cardiovascular risk factors, the association between each biomarker baseline level and outcomes remained significant in multivariable analysis. Receiver operating characteristics (ROC) models were constructed using traditional clinical and laboratory risk factors and the inclusion of biomarkers significantly improved the prediction of incident events. CONCLUSIONS: Elevated IL-1, IL-6, CRP, TNF-α, HMGB-1, OPG and Sortilin levels and low Omentin-1 levels at baseline correlate with worse vascular outcomes in diabetic patients with CLTI undergoing LER. Assessment of the inflammatory state with this panel of biomarkers may support physicians to identify a subset of patients more susceptible to the procedure failure and to develop cardiovascular adverse events after LER

Paracrine cellular senescence exacerbates biliary injury and impairs regeneration

Senescence has been suggested as causing biliary cholangiopathies but how this is regulated is unclear. Here, the authors generate a mouse model of biliary senescence by deleting Mdm2 in bile ducts and show that inhibiting TGFβ limits senescence-dependent aggravation of cholangiopathies

Transient mTOR Inhibition Facilitates Continuous Growth of Liver Tumors by Modulating the Maintenance of CD133+ Cell Populations

The mammalian target of the rapamycin (mTOR) pathway, which drives cell proliferation, is frequently hyperactivated in a variety of malignancies. Therefore, the inhibition of the mTOR pathway has been considered as an appropriate approach for cancer therapy. In this study, we examined the roles of mTOR in the maintenance and differentiation of cancer stem-like cells (CSCs), the conversion of conventional cancer cells to CSCs and continuous tumor growth in vivo. In H-Ras-transformed mouse liver tumor cells, we found that pharmacological inhibition of mTOR with rapamycin greatly increased not only the CD133+ populations both in vitro and in vivo but also the expression of stem cell-like genes. Enhancing mTOR activity by over-expressing Rheb significantly decreased CD133 expression, whereas knockdown of the mTOR yielded an opposite effect. In addition, mTOR inhibition severely blocked the differentiation of CD133+ to CD133- liver tumor cells. Strikingly, single-cell culture experiments revealed that CD133- liver tumor cells were capable of converting to CD133+ cells and the inhibition of mTOR signaling substantially promoted this conversion. In serial implantation of tumor xenografts in nude BALB/c mice, the residual tumor cells that were exposed to rapamycin in vivo displayed higher CD133 expression and had increased secondary tumorigenicity compared with the control group. Moreover, rapamycin treatment also enhanced the level of stem cell-associated genes and CD133 expression in certain human liver tumor cell lines, such as Huh7, PLC/PRC/7 and Hep3B. The mTOR pathway is significantly involved in the generation and the differentiation of tumorigenic liver CSCs. These results may be valuable for the design of more rational strategies to control clinical malignant HCC using mTOR inhibitors