Roux-en-Y versus one-anastomosis gastric bypass (RYSA study): weight loss, metabolic improvements, and nutrition at 1 year after surgery, a multicenter randomized controlled trial.

OBJECTIVE: Although it has been suggested that one-anastomosis gastric bypass (OAGB) is metabolically superior to the "gold standard," i.e., Roux-en-Y gastric bypass (RYGB), there is little robust evidence to prove it. Because this result may arise from the typically longer length of bypassed intestine in OAGB, here, the authors standardized the bypass length in RYGB and OAGB and compared weight loss and metabolic outcomes in a randomized controlled trial. METHODS: The authors randomized 121 bariatric patients to RYGB (n = 61) or OAGB (n = 60) in two Finnish University Hospitals and measured weight; body composition; metabolic features (insulin sensitivity, lipids, inflammation, nutrition); and comorbidities before and 6 and 12 months after the operation. RESULTS: Total weight loss was similar in RYGB and OAGB at 6 months (mean: 21.2% [95% CI: 19.4-23.0] vs. 22.8% [95% CI: 21.5-24.1], p = 0.136) and 12 months (25.4% [95% CI: 23.4-27.5] vs. 26.1% [95% CI: 24.2-28.9], p = 0.635). Insulin sensitivity, lipids, and inflammation improved similarly between the groups (p > 0.05). Remission of type 2 diabetes and hypercholesterolemia was marked and similar (p > 0.05) but the use of antihypertensive medications was lower (p = 0.037) and hypertension tended to improve more (p = 0.053) with RYGB versus OAGB at 12 months. Higher rates of vitamin D-25 deficiency (p < 0.05) and lower D-25 levels were observed with OAGB versus RYGB throughout the follow-up (p < 0.001). No differences in adverse effects were observed. CONCLUSIONS: RYGB and OAGB were comparable in weight loss, metabolic improvement, remission of diabetes and hypercholesterolemia, and nutrition at 1-year follow-up. Vitamin D-25 deficiency was more prevalent with OAGB, whereas reduction in antihypertensive medications and hypertension was greater with RYGB. There is no need to change the current practices of RYGB in favor of OAGB.

LAPAROSCOPIC BARIATRIC SURGERY IN ADOLESCENTS: EARLY AND FIVE- YEAR CLINICAL AND LABORATORY ASSESSMENT.

BACKGROUND: Obesity has reached epidemic proportions among adolescents. Methods, such as bariatric surgery, have become the most effective treatment for patients with classes III and IV obesity. AIM: To evaluate weight loss, comorbidity remission, and long-term results of bariatric surgery in adolescents. METHODS: Study with adolescent patients undergoing bariatric surgery, evaluating laboratory tests, comorbidities, and the percentage of excess weight loss in the preoperative period and at one, two, and five years postoperatively. RESULTS: A total of 65 patients who met the inclusion criteria, with a mean age of 18.6 years, were included in the analysis. In the preoperative period, 30.8% of hypercholesterolemia, 23.1% of systemic arterial hypertension, and 18.4% of type 2 diabetes were recorded, with remission of these percentages occurring in 60, 66.7 and 83.4%, respectively. The mean percentage of excess weight loss was 63.48% after one year of surgery, 64.75% after two years, and 57.28% after five years. The mean preoperative total cholesterol level was 180.26 mg/dL, and after one, two, and five years, it was 156.89 mg/dL, 161.39 mg/dL, and 150.97 mg/dL, respectively. The initial mean of low-density lipoprotein was 102.19mg/dL and after five years the mean value reduced to 81.81 mg/dL. The mean preoperative glycemia was 85.08 mg/dL and reduced to 79.13 mg/dL after one year, and to 76.19 mg/dL after five years. CONCLUSIONS: Bariatric surgery is safe and effective in adolescents, with low morbidity, resulting in a loss of excess weight and long-term stability, improving laboratory tests, and leading to remission of comorbidities, such as diabetes mellitus, hypercholesterolemia, and systemic arterial hypertension.

Dihydroartemisinin improves hypercholesterolemia in ovariectomized mice via enhancing vectorial transport of cholesterol and bile acids from blood to bile.

The increase of concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the serum of postmenopausal women is the important risk factor of the high morbidity of cardiovascular diseases of old women worldwide. To test the anti-hypercholesterolemia function of dihydroartemisinin (DHA) in postmenopausal women, ovariectomized (OVX) mice were generated, and DHA were administrated to OVX mice for 4 weeks. The blood and liver tissues were collected for biochemical and histological tests respectively. The mRNA and protein expression levels of genes related to metabolism and transport of cholesterol, bile acid and fatty acid in the liver or ileum were checked through qPCR and western blot. DHA could significantly reduce the high concentrations of TC and LDL-C in the serum and the lipid accumulation in the liver of ovariectomized mice. The expression of ABCG5/8 was reduced in liver of OVX mice, and DHA could up-regulate the expression of them. Genes of transport proteins for bile salt transport from blood to bile, including Slc10a1, Slco1b2 and Abcb11, were also significantly up-regulated by DHA. DHA also down-regulated the expression of Slc10a2 in the ileum of OVX mice to reduce the absorption of bile salts. Genes required for fatty acid synthesis and uptake, such as Fasn and CD36, were reduced in the liver of OVX mice, and DHA administration could significantly up-regulate the expression of them. These results demonstrated that DHA could improve hypercholesterolemia in OVX mice through enhancing the vectorial transport of cholesterol and bile acid from blood to bile.

Familial Hypercholesterolemia Genetic Variations and Long-Term Cardiovascular Outcomes in Patients with Hypercholesterolemia Who Underwent Coronary Angiography.

BACKGROUND: Familial hypercholesterolemia (FH) has been associated with early coronary artery disease (CAD) and increased risk of atherosclerotic cardiovascular disease. However, the prevalence of FH and its long-term outcomes in a CAD-high-risk cohort, defined as patients with hypercholesteremia who underwent coronary angiography, remains unknown. Besides, studies regarding the impact of genetic variations in FH on long-term cardiovascular (CV) outcomes are scarce. METHODS AND RESULTS: In total, 285 patients hospitalized for coronary angiography with blood low-density lipoprotein cholesterol (LDL-C) levels ≥ 160 mg/dL were sequenced to detect FH genetic variations in LDL receptors apolipoprotein B and proprotein convertase subtilisin/kexin type 9. Risk factors associated with long-term CV outcomes were evaluated. The prevalence of FH was high (14.4%). CAD and early CAD were significantly more prevalent among FH variation carriers than non-carriers, despite comparable blood LDL-C levels. Moreover, the FH variation carriers also underwent more revascularization after a mean follow-up of 6.1 years. Multivariate logistic regression demonstrated that FH genetic variation was associated with increased incidence of cardiovascular disease and mortality (odds ratio = 3.17, p = 0.047). Two common FH variants, LDLR c.986G>A and LDLR c.268G>A, showed the most significant impacts on high blood LDL-C levels and early-onset CAD. CONCLUSIONS: Our results indicate that FH genetic variants may exhibit differential effects on early-onset CAD and revascularization risks in patients undergoing coronary angiography. FH genetic information might help identify high-risk patients with typical CAD symptoms for appropriate intervention.

Carotid sheath xanthoma: A rare manifestation of lipid disorders.

Xanthomas are visibly deformed cholesterol deposits that are commonly associated with lipid disorders, such as familial hypercholesterolemia (FH) or rare sitosterolemia. We present the first report of two cases of carotid sheath xanthomas in patients with lipid disorders. Case 1 involved a 26-year-old woman presenting with two heterogeneous mutations on the ABCG5 gene-as noted on genetic testing-who was finally diagnosed with sitosterolemia. Ultrasonography (US) revealed hypoechoic masses centered in the bilateral carotid sheath, which gradually reduced in size after diet control and the use of ezetimibe. Case 2 involved a 27-year-old man who was diagnosed with possible FH and had recurrent bilateral buttock xanthomas, as well as bilateral carotid sheath masses detected by US. Postoperative pathological examination of the resected right neck mass confirmed a xanthoma with proliferation of multinucleated giant cells and deposition of cholesterol clefts.

Down-regulation of microsomal prostaglandin E2 synthase-1 in the infrapatellar fat pad of osteoarthritis patients with hypercholesterolemia.

BACKGROUND: While epidemiological studies have reported a potential role for hypercholesterolemia (HCE) in osteoarthritis (OA), the association between HCE and OA has yet to be clarified. Adipose tissue is a primary locus for cholesterol metabolism and the presence of HCE reportedly causes adipose dysfunction. The knee joint contains adipose tissue in the form of the infrapatellar fat pad (IPFP), which has been shown to contribute to the pathophysiology of OA in the knee via the secretion of inflammatory mediators. However, the effect of HCE on the expression of inflammatory mediators in the IPFP has not been elucidated. METHODS: IPFP and synovial tissues (ST) were extracted from 145 subjects with OA, diagnosed by radiography, during total knee arthroplasty. OA patients were divided into three groups according to their total cholesterol levels (Desirable, Borderline high and High) based on the National Cholesterol Education Program Adult Treatment Panel III (NCEPATP III). We examined the expression of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES1), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 using real-time polymerase chain reaction and compared results among the Desirable, Borderline high and High groups. RESULTS: The mRNA expression levels of TNF-α, IL-1ß, and IL-6 in ST and the IPFP were not significantly different among the three groups. COX-2 mRNA expression in ST and IPFP was likewise not different among the three groups. While the mRNA expression level of mPGES1 in ST was also not significantly different, that of mPGES1 in the IPFP was significantly lower in the High group than in the Desirable and Borderline high groups. CONCLUSION: mRNA levels of mPGES-1 are reduced in the IPFP of knee OA patients with HCE. Additional studies are need to clarify the effect of mPGES-1 down-regulation in OA pathology.

[Risk factors generally neglected in oral surgery and implantology: the high LDL-cholesterol and the insufficient level of vitamin D]. / Des facteurs de risque généralement négligés en chirurgie orale et en implantologie : le taux élevé de LDL-cholestérol et le taux insuffisant de la vitamine D.

INTRODUCTION: Vitamin D deficiency is widespread throughout the world. Vitamin D has an important role in the regulation of phosphocalcic metabolism as well as in a large number of biological and metabolic processes. According to some studies, there is a correlation between vitamin D and LDL-cholesterol levels. A deficiency of vitamin D and / or a high level of LDL-cholesterol could represent risk factors for bone healing and osteointegration of dental implants. The purpose of our study is to demonstrate the reality of the problem of deficiency or deprivation in vitamin D in a population of patients requiring oral and / or implant surgery. MATERIAL AND METHODS: 46 cases of patients having undergone oral surgery together with preoperative blood test were analyzed. The results of the dosages of 25-hydroxy-vitamin D (25-OH-D), total cholesterol, LDL-cholesterol, HDL-cholesterol were collected and compared with reference values. Statistical tests were performed to determine the possible correlations between the 25-OH-D level and other blood parameters. RESULTS: 38 patients out of 46 (82.6 %) are defective in vitamin D, and 7 patients out of 46 (15.2 %) are deficient. LDL-cholesterol levels were high in 15 patients out of 33 (45.5 %). There was a non-significant correlation between LDLcholesterol and vitamin D levels. Total cholesterol was high in 42 % of patients. We observed a significant correlation between total cholesterol and vitamin D levels. CONCLUSION: According to our study, it appears that a preoperative assessment including the dosage of vitamin D, total cholesterol and LDLcholesterol may be of interest in patients requiring oral and / or implant surgery by correcting if necessary blood parameters and promoting bone metabolism.

INTRODUCTION: La déficience en vitamine D est largement répandue dans le monde. Or la vitamine D a un rôle important dans la régulation du métabolisme phosphocalcique ainsi que dans un grand nombre de processus biologiques et métaboliques. Selon certaines études, il existerait une corrélation entre le taux de vitamine D et le taux de LDL-cholestérol. Une déficience en vitamine D et/ou un taux élevé de LDL-cholestérol pourraient représenter des facteurs de risques de cicatrisation osseuse et d'ostéointégration d'implants dentaires. Le but de notre étude est d'objectiver, dans une population de patients devant bénéficier d'une chirurgie orale et/ou implantaire, la réalité du problème de déficience ou de carence en vitamine D. Matériel et méthode : 46 dossiers de patients ayant bénéficié d'une intervention chirurgicale buccodentaire et d'une prise de sang ont été analysés. Les résultats du dosage de 25-hydroxyvitamine D (25-OH-D), cholestérol total, LDL-cholestérol, HDL-cholestérol ont été recueillis et comparés aux valeurs de références. Des tests statistiques ont été réalisés afin d'établir les corrélations éventuelles entre le taux de 25-OH-D et les autres paramètres sanguins. Résultats : 38 patients sur 46 (82,6 %) sont déficients en vitamine D, et 7 patients sur 46 (15,2 %) sont carencés. Le taux de LDLcholestérol est élevé chez 15 patients sur 33 (45,5 %). Il existe une corrélation non significative entre le taux de LDL-cholestérol et le taux de vitamine D. Le taux de cholestérol total est élevé chez 42 % des patients. Nous observons une corrélation significative entre le taux de cholestérol total et le taux de vitamine D. CONCLUSION: D'après notre étude, il apparaît qu'un bilan préopératoire incluant le dosage de la vitamine D, du cholestérol total et du LDLcholestérol pourrait s'avérer intéressant afin de corriger si nécessaire ces paramètres sanguins et favoriser le métabolisme osseux dans un contexte de chirurgie orale et/ou implantaire.

The effect of simvastatin on periprosthetic bone mineral density in the hypercholesterolaemic patients after total hip arthroplasty.

OBJECTIVE: The purpose of this study was to investigate the effect of simvastatin on periprosthetic bone mineral density (BMD) in hypercholesterolaemic patients after total hip arthroplasty. METHODS: From January 2012 to December 2015, a total of 42 consecutive hypercholesterolaemic patients with total hip arthroplasty were recruited for this study. The simvastatin group was 21 patients (15 males, 6 females) with average age of 69.4 ± 6.6 years treated with simvastatin for one year post-operatively, and the control group was the other 21 patients (12 males, 9 females) who did not take simvastatin. These parameters of the periprosthetic bone mineral density after total hip arthroplasty were collected by dual energy X-ray absorptiometry(DEXA) one week and three, six, 12 months post-operatively. RESULTS: In the control group patients showed significant loss of periprosthetic BMD in ROIs 1, 2, 6, and 7 throughout the study period. The loss of BMD in ROIs 3 and 5 was only significantly observed at three months follow-up and recovered thereafter. There were no significant detected changes of BMD in ROI 4. In the Simvastatin group, the percentage of BMD loss was significantly less (P < 0.05) in ROI 1, 2, 6 and 7 throughout the study period than the control group. The percentage of BMD loss were significant observed in ROI 3 and 5 at three months follow-up, which were also significantly less (P < 0.05) than in the control group. A slight gain of BMD was measured in ROI 4 at 12 months follow-up (1.419%, P < 0.05). CONCLUSION: Simvastatin administered for one year post-operatively can effectively prevent periprosthetic bone loss after total hip arthroplasty.

Optical Coherence Tomography Assessment of Glucose Fluctuation Impact on the Neointimal Proliferation After Stent Implantation in a Diabetic/Hypercholesterolemic Swine Model.

The aim of the present study was to investigate the effects of glucose fluctuation on neointimal proliferation after stent implantation by optical coherence tomography (OCT) in a diabetic/hypercholesterolemic (DM/HC) swine model.A total of 24 everolimus-eluting stents (EES) were implanted in the right coronary artery (RCA) of the animals using a 20% overstretch ratio. The 24 swines were divided into a DM-high glucose fluctuation (HGF) group (n = 8), DMlow glucose fluctuation (LGF) group (n = 8), and a control group (n = 8). Percent diameter stenosis (%DS), late loss (LL), percent area stenosis (%AS), and neointimal thickness (NIT) were analyzed. The differences in neointimal characteristics and circulating oxidative stress and inflammation biomarkers were assessed and measured.At 28 days, the highest values of %DS, LL, %AS, and NIT were achieved in the HGF group followed by the LGF group (P < 0.05) and the control group (P < 0.05). The highest frequency of the heterogeneous pattern was in the HGF group followed by the LGF group (P < 0.05) and the control group (P < 0.05). This was also the case for the oxidative stress and inflammation biomarkers.DM might have a deleterious impact on neointimal proliferation after EES implantation in this DM/HC swine model. The extent of glucose fluctuation may be related to the degree of neointimal proliferation and this needs to be further confirmed by long-term follow-up and histology.

The impact of high total cholesterol and high low-density lipoprotein on avascular necrosis of the femoral head in low-energy femoral neck fractures.

BACKGROUND: Avascular necrosis of the femoral head (AVNFH) typically constitutes 5 to 15% of all complications of low-energy femoral neck fractures, and due to an increasingly ageing population and a rising prevalence of femoral neck fractures, the number of patients who develop AVNFH is increasing. However, there is no consensus regarding the relationship between blood lipid abnormalities and postoperative AVNFH. The purpose of this retrospective study was to investigate the relationship between blood lipid abnormalities and AVNFH following the femoral neck fracture operation among an elderly population. METHODS: A retrospective, comparative study was performed at our institution. Between June 2005 and November 2009, 653 elderly patients (653 hips) with low-energy femoral neck fractures underwent closed reduction and internal fixation with cancellous screws (Smith and Nephew, Memphis, Tennessee). Follow-up occurred at 1, 6, 12, 18, 24, 30, and 36 months after surgery. Logistic multi-factor regression analysis was used to assess the risk factors of AVNFH and to determine the effect of blood lipid levels on AVNFH development. Inclusion and exclusion criteria were predetermined to focus on isolated freshly closed femoral neck fractures in the elderly population. The primary outcome was the blood lipid levels. The secondary outcome was the logistic multi-factor regression analysis. RESULTS: A total of 325 elderly patients with low-energy femoral neck fractures (AVNFH, n = 160; control, n = 165) were assessed. In the AVNFH group, the average TC, TG, LDL, and Apo-B values were 7.11 ± 3.16 mmol/L, 2.15 ± 0.89 mmol/L, 4.49 ± 1.38 mmol/L, and 79.69 ± 17.29 mg/dL, respectively; all of which were significantly higher than the values in the control group. Logistic multi-factor regression analysis showed that both TC and LDL were the independent factors influencing the postoperative AVNFH within femoral neck fractures. CONCLUSIONS: This evidence indicates that AVNFH was significantly associated with blood lipid abnormalities in elderly patients with low-energy femoral neck fractures. The findings of this pilot trial justify a larger study to determine whether the result is more generally applicable to a broader population.

Angiotensin II type 1 receptor blockers suppress neointimal hyperplasia after stent implantation in carotid arteries of hypercholesterolemic rabbits.

OBJECTIVES: The purpose of this study was to examine whether oral administration of an angiotensin II type 1 receptor blocker (ARB) inhibited in-stent neointimal hyperplasia in carotid arteries of hypercholesterolemic rabbits. METHODS: Eleven male New Zealand white rabbits were subjected to endothelial injuries of the right common carotid arteries using a balloon catheter and then received chow containing 1% cholesterol for 6 weeks. A balloon-expandable stainless steel stent was subsequently inserted at the injured sites of the arteries. After stenting, five rabbits were randomly treated with an oral ARB, candesartan cilexetil (5 mg/kg per day orally), while the remaining six rabbits acted as untreated controls. Four weeks after the implantation, the rabbits were killed, followed by collection of the arteries including the stents. After careful removal of the stents, tissue sections were prepared and analyzed by morphometric and immunohistochemical methods. RESULTS: The mean thickness of the neointima was 53.6 ± 17.0 µm in the ARB-treated group, which was significantly reduced compared to 95.9 ± 16.7 µm in the control group (P = 0.0012). Immunohistochemistry showed a decrease in accumulation of macrophages and tenascin-C expression in the arterial wall in the ARB-treated animals. DISCUSSION: This study suggested that systemic administration of an ARB suppressed neointimal hyperplasia in the carotid artery following stent implantation by the anti-inflammatory effects, although the animal cohort tested was rather small. This finding implies that ARBs may be useful and practical agents for protection against in-stent restenosis in humans, and warrants further basic and clinical studies.

Mid-term results of laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass in adolescent patients.

The prevalence and severity of obesity in children and adolescents has been increasing in recent years at an unprecedented rate. Morbidly obese children will almost certainly develop severe comorbidities as they progress to adulthood, and bariatric surgery may provide the only alternative for achieving a healthy weight. The aim of this study was to assess the long-term outcomes and safety of laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB) as new treatment modalities for morbidly obese adolescents. We conducted a retrospective review of a prospectively collected database of all adolescent patients who underwent LSG and RYGB under IRB protocol at the Bariatric and Metabolic Institute in Cleveland Clinic Florida between 2002 and 2011. Patients were also contacted by phone, adhering to HIPAA regulations, and were asked to answer a survey. Eighteen adolescents had a bariatric procedure performed at this institution. The mean age was 17.5 years, the average weight was 293.1 lbs, and the average BMI was 47.2 kg/m2. The mean follow-up period consisted of 55.2 months. The postoperative weight at 55 months follow-up was 188.4 lbs and average BMI was 30.1 kg/m2. Fifteen of the patients were available for follow-up. Thirteen out of 16 (81%) comorbidities in patients available for follow-up were in remission following rapid weight loss. The long-term follow-up and perioperative morbidity shown in this study suggest that LSG and LRYGB appear to be safe and effective operations in morbidly obese adolescents.

Application of scanning electron microscopy and X-ray microanalysis: FE-SEM, ESEM-EDS, and EDS mapping for studying the characteristics of topographical microstructure and elemental mapping of human cardiac calcified deposition.

To explore the pathogenic mineral formation in a huge cardiolith isolated from the left heart atrium of an 80-year-old male patient, field emission scanning electron microscopy (FE-SEM) was used to analyze the topographic microstructure and perform elemental mapping in a cross-section of the cardiac calcified deposit after dissection. Environmental SEM equipped with an energy dispersive X-ray spectrometer (EDS) was also used to investigate the composition and spatial distribution of elements in the cross-section, and fiberoptic Raman spectroscopy was used to reidentify the chemical composition of designated positions. The results indicated that calcium hydroxyapatite and cholesterol were the main components of the cardiac calculus. The plate-like structures of calcium hydroxyapatite were unevenly spread over the cholesterol of the cardiac calculus. The calcium hydroxyapatite-rich area exhibited higher amounts of C, O, P, and Ca elements as well as trace amounts of N, Na, Mg, and Al, whereas the major concentration of C, minor concentrations of N and O, and trace amounts of P and Ca were observed in the cholesterol-rich area. Hypercholesterolemia associated with calcification of this cardiac calculus was proposed. Both FE-SEM and ESEM energy dispersive X-ray microanalyses were performed directly, for the first time, to provide useful information on the microstructural characteristics and spatial distribution of elements on the surface of human cardiac calculi.

Statin intake is associated with decreased insulin sensitivity during cardiac surgery.

OBJECTIVE: Surgical trauma impairs intraoperative insulin sensitivity and is associated with postoperative adverse events. Recently, preprocedural statin therapy is recommended for patients with coronary artery disease. However, statin therapy is reported to increase insulin resistance and the risk of new-onset diabetes. Thus, we investigated the association between preoperative statin therapy and intraoperative insulin sensitivity in nondiabetic, dyslipidemic patients undergoing coronary artery bypass grafting. RESEARCH DESIGN AND METHODS: In this prospective, nonrandomized trial, patients taking lipophilic statins were assigned to the statin group and hypercholesterolemic patients not receiving any statins were allocated to the control group. Insulin sensitivity was assessed by the hyperinsulinemic-normoglycemic clamp technique during surgery. The mean, SD of blood glucose, and the coefficient of variation (CV) after surgery were calculated for each patient. The association between statin use and intraoperative insulin sensitivity was tested by multiple regression analysis. RESULTS: We studied 120 patients. In both groups, insulin sensitivity gradually decreased during surgery with values being on average ∼20% lower in the statin than in the control group. In the statin group, the mean blood glucose in the intensive care unit was higher than in the control group (153 ± 20 vs. 140 ± 20 mg/dL; P < 0.001). The oscillation of blood glucose was larger in the statin group (SD, P < 0.001; CV, P = 0.001). Multiple regression analysis showed that statin use was independently associated with intraoperative insulin sensitivity (ß = -0.16; P = 0.03). CONCLUSIONS: Preoperative use of lipophilic statins is associated with increased insulin resistance during cardiac surgery in nondiabetic, dyslipidemic patients.

Oversized vein grafts develop advanced atherosclerosis in hypercholesterolemic minipigs.

BACKGROUND: Accelerated atherosclerosis is the main cause of late aortocoronary vein graft failure. We aimed to develop a large animal model for the study of pathogenesis and treatment of vein graft atherosclerosis. METHODS: An autologous reversed jugular vein graft was inserted end-to-end into the transected common carotid artery of ten hypercholesteroemic minipigs. The vein grafts were investigated 12-14 weeks later with ultrasound and angiograpy in vivo and microscopy post mortem. RESULTS: One minipig died during follow up (patent vein graft at autopsy), and one vein graft thrombosed early. In the remaining eight patent vein grafts, the mean (standard deviation) intima-media thickness was 712 µm (276 µm) versus 204 µm (74 µm) in the contralateral control internal jugular veins (P < .01). Advanced atherosclerotic plaques were found in three of four oversized vein grafts (diameter of graft > diameter of artery). No plaques were found in four non-oversized vein grafts (P < .05). CONCLUSIONS: Our model of jugular vein graft in the common carotid artery of hypercholesterolemic minipigs displayed the components of human vein graft disease, i.e. thrombosis, intimal hyperplasia, and atherosclerosis. Advanced atherosclerosis, the main cause of late failure of human aortocoronary vein grafts was only seen in oversized grafts. This finding suggests that oversized vein grafts may have detrimental effects on patient outcome.

The profile of the extracellular matrix changes in the aorta after sympathectomy in the hypercholesterolemic rats.

We previously showed that sympathectomy induces thickened intima and decreases the expression of cytoskeletal proteins associated with a differentiated smooth muscle cell (SMC) phenotype in hypercholesterolemic rats. In the present study, we sought to determine the effect of sympathectomy on various components of the extracellular matrix (ECM) in the aorta from these animals, since the state of SMC differentiation depends on the nature of ECM components. Collagen types I and III, previously reported to be associated with SMC dedifferentiation, and collagen VI, elastin, laminin and elastin-laminin receptor (E/L-R), previously reported to be associated with SMC differentiation, were analyzed by western immunoblot and confocal microscopy in abdominal aortae from sham rats and hypercholesterolemic rats sympathectomized with guanethidine. Both western immunoblot and immunohistological analysis showed an increase in collagens I and III (more for collagen I), with abundant labeling in the media, adventitia and thickened intima in sympathectomized aortae. Collagen IV labeling was decreased in the media and adventitia and was weak in the thickened intima in sympathectomised aortae. The E/L-R increased and was abundantly labeled in the media and weakly in the thickened intima in sympathectomized aortae. Elastin and laminin decreased and appeared less labeled in the media in the sympathectomised aortae. In the thickened intima, laminin was slightly labeled while elastin was not obviously labeled. These data show that sympathectomy favors the ECM features reported in association with a dedifferentiated/immature SMC phenotype and intimal thickening, probably by actions on both SMCs and fibroblasts.

Paediatric liver transplantation for metabolic disorders. Part 1: Liver-based metabolic disorders without liver lesions.

Liver-based metabolic disorders account for 10 to 15% of the indications for paediatric liver transplantation. In the last three decades, important progress has been made in the understanding of these diseases, and new therapies have emerged. Concomitantly, medical and surgical innovations have lead to improved results of paediatric liver transplantation, patient survival nowadays exceeding 80% 10-year after surgery with close to normal quality of life in most survivors. This review is a practical update on medical therapy, indications and results of liver transplantation, and potential future therapies, for the main liver-based metabolic disorders in which paediatric liver transplantation may be considered. Part 1 focuses on metabolic based liver disorders without liver lesions, and part 2 on metabolic liver diseases with liver lesions.

Statin use and the risk of surgical site infections in elderly patients undergoing elective surgery.

OBJECTIVE: To examine whether preoperative statin use is associated with a reduced risk of surgical site infections. DESIGN, SETTING, AND PATIENTS: Population-based retrospective cohort study of all elderly patients undergoing elective surgery in Ontario from April 1, 1992, through March 31, 2006. Preoperative statin use was identified using provincewide pharmacy records. Procedure and patient characteristics were derived from hospital and physician claims databases within Canada's single-payer universal health care system. MAIN OUTCOME MEASURE: The 30-day risk of surgical site infection was derived from the initial admission, outpatient consultations, and hospital readmissions. RESULTS: The cohort included 469,349 distinct elderly patients undergoing elective surgery, of whom 68,387 (14.6%) were statin users. The primary analysis included 53,565 statin users matched to 53,565 statin nonusers undergoing the same procedure in the same hospital by the same surgeon. Unadjusted analysis revealed a slight increase in the risk of surgical site infection among statin users compared with nonusers (8.9% vs 8.7%; P < .001), which disappeared after adjustment for demographics, health care utilization variables, comorbidities, and concurrent medication therapy (odds ratio, 1.00; 95% confidence interval, 0.95-1.04; P = .85). A similar lack of association was seen when matching was extended to include propensity scores (odds ratio, 0.99; 95% confidence interval, 0.94-1.05; P = .82). The lack of association persisted across pharmacologic, patient, and procedure subgroups. CONCLUSIONS: Statin use is not associated with an altered risk of surgical site infection. Prevention efforts should be directed toward other evidence-based strategies.

Enhanced external counterpulsation promotes growth cytokines-mediated myocardial angiogenesis in a porcine model of hypercholesterolemia.

BACKGROUND: Enhanced external counterpulsation (EECP) improves ischemia in patients with refractory angina pectoris, but the mechanism remains unclear. To explore the mechanisms of EECP action, we detected progenitor cells presenting any of the following markers CD34(+), CD29(+), and CD106(+). METHODS: Growth cytokines-mediated progenitor cell mobilization and associated angiogenesis potential were assessed in a porcine model of hypercholesterolemia. Twenty-four male domestic swines were randomly assigned to 4 groups: normal diet (control, n = 6), hypercholesterolemic diet (CHOL, n = 6), hypercholesterolemic diet with administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) (rhG-CSF, n = 6), and hypercholesterolemic diet with EECP treatment (EECP, n = 6). EECP was applied 2 hours every other day for a total of 36 hours. Serum levels of vascular endothelial growth factor (VEGF) and granulocyte colony-stimulating factor (G-CSF), peripheral blood progenitor cell counts, level of regional angiogenesis, and expression of VEGF and stromal cell derived factor 1alpha (SDF-1alpha) in porcine myocardium were assessed, respectively. RESULTS: A porcine model of hypercholesterolemia-induced arteriosclerosis was successfully established. There was no significant difference in serum levels of VEGF among the four groups. The serum levels of G-CSF in the EECP group increased significantly at week 15 and week 18 ((38.3 +/- 5.6) pg/ml at week 15 vs (26.2 +/- 3.7) pg/ml at week 12, P < 0.05, and (46.9 +/- 6.1) pg/ml at week 18 vs (26.2 +/- 3.7) pg/ml at week 12, P < 0.01). The serum levels of G-CSF in group 3 increased also significantly after receiving rhG-CSF injection for five days ((150 +/- 13.9) pg/ml at week 18 vs (24.8 +/- 5.4) pg/ml at week 12, P < 0.01). Compared to other groups and other time points, progenitor cell counts increased significantly after 2-hour EECP treatment (108 +/- 13 vs 26 +/- 6 per 10(5) leukocytes, P < 0.01), but not at week 18. The progenitor cell counts also increased significantly after subcutaneous injection of rhG-CSF for five days compared to the week 12 (baseline) (180 +/- 21 vs 25 +/- 7 per 10(5) leukocytes, P < 0.01). There was no significant difference among the four groups at other time points. Moreover, the expression of VEGF and SDF-1alpha and the level of regional angiogenesis in myocardium increased significantly in both EECP and rhG-CSF groups. CONCLUSIONS: The results demonstrated that EECP could facilitate angiogenesis in the myocardium of atherosclerotic swines by increasing endogenous G-CSF, inducing an enhanced mobilization of progenitor cells and augmenting myocardial expression of VEGF and SDF-1alpha.