Effects of dual pulse gastric electrical stimulation on gastric tone and compliance in dogs

BackgroundGastric electrical stimulation (GES) with short pulses improves nausea and vomiting in patients with gastroparesis, whereas GES with long pulses improves gastric motility.AimsTo assess the effects of a novel method of GES using dual pulse (both short and long pulses) on gastric tone, compliance and sympathovagal activity in dogs.Materials and methodsThe study was performed in 7 dogs implanted with a gastric cannula and a pair of gastric serosal electrodes for dual pulse GES. The study was composed of a number of sessions on different days with different stimulation parameters, including variations in the number of short pulses and stimulation amplitude.Results(1) Dual pulse GES of one short pulse and one long pulse with various amplitudes inhibited gastric tone (p < 0.05) but did not alter sympathetic or vagal activity. (2) Dual pulse GES with five short pulses and one long pulse not only inhibited gastric tone, but also reduced sympathetic activity and increased vagal activity (p < 0.05). (3) Dual pulse GES with five short pulses and one long pulse significantly increased gastric compliance.ConclusionsDual pulse GES reduces gastric tone and increases gastric compliance. The variation in the number of short pulse affects the sympathetic and vagal activities, whereas, the increase in stimulation strength enhances its effects on gastric tone.     

Prevalence of gastroparesis-related symptoms in an unselected cohort of patients with Type 1 diabetes

BackgroundThe prevalence of diabetic gastroparesis is not well defined because of discrepancy between objective measurements, i.e. gastric emptying time, and symptoms experienced by patients. Furthermore most studies have been performed on small selected cohorts.ObjectiveTo determine the prevalence of clinical symptoms of diabetic gastroparesis in a large unselected cohort of out-patients with Type 1 diabetes.Methods1028 patients with Type 1 diabetes attending a specialized diabetes clinic were mailed a validated questionnaire; “patient assessment of upper gastrointestinal disorders-symptom severity index”, in which a subset of questions measures symptoms of gastroparesis (GCSI; Gastroparesis Cardinal Symptom Index). Response rate was 74.4% (n = 765). All patients were classified according to presence or absence of late diabetic complications and clinical and paraclinical data were obtained.ResultsA GCSI Total Score ≥ 1.90 signified definite symptoms of gastroparesis (n = 102) and patient charts were investigated for concomitant illness and/or medication influencing gastric emptying. In 30 patients an alternative etiology was revealed, leaving 72 (9.8%) patients with symptoms related to diabetic gastroparesis. Only 8 patients were previously diagnosed. HbA_1c levels were significantly higher in patients with diabetic gastroparesis (8.4 ± 1.3 vs. 8.2 ± 1.2 respectively, p = 0.02). Furthermore, patients with diabetic gastroparesis had more retinopathy (p = 0.006) and peripheral polyneuropathy (16.7% vs. 6.7%, p < 0.001) and there was a trend for diabetic nephropathy being more common (p = 0.08).ConclusionsSymptoms of diabetic gastroparesis affect approximately 10% of patients with Type 1 diabetes in a specialized diabetes clinic and are associated with poor glycemic control and other late diabetic complications.     

Type 2 diabetes mellitus and chronic hepatitis C: Which is worse? Results of a long-term retrospective cohort study

BackgroundThe long-term outcome in patients with chronic hepatitis C and type 2 diabetes mellitus treated with interferon and ribavirin is unclear. We compared incidence of liver-related events and mortality rates between hepatitis C virus-positive patients with or without diabetes mellitus, and the incidence of diabetes-related events between diabetic patients with and without hepatitis C.MethodsRetrospective study of 309 patients with chronic hepatitis C. Incidence of liver-related events, diabetes-related events and mortality rates were assessed over a mean follow-up of 11.02 ± 4.9 years.Results50 (16%) chronic hepatitis C patients had diabetes mellitus. Diabetics showed a higher number of diabetes- and liver-related events than non-diabetics (10% vs 1.5%, p = 0.006; 18% vs 5.7%, p = 0.007, respectively) with a mortality of 14% vs 1.5% (p = 0.0003). Baseline cirrhosis (p = 0.002) and non-sustained virological response (p = 0.01) were independent risk factors for liver events; diabetes mellitus (p = 0.01) and hypertension (p = 0.0017) were independent factors for diabetes-related events.ConclusionsIn patients with chronic hepatitis C, comorbidity with diabetes mellitus was associated with a higher mortality rate and incidence of liver/diabetes-related events. Independent risk factors for liver-related events were the non-response to antiviral therapy and cirrhosis at baseline.     

Effect of free fatty acid inhibition on silent and symptomatic myocardial ischemia in diabetic patients with coronary artery disease

ObjectiveFree fatty acid inhibition with trimetazidine (TMZ) improves myocardial metabolism and myocardial ischemia in patients with coronary artery disease (CAD). Because of its effect on myocardial glucose utilization TMZ may represent a therapeutic option in diabetic patients with CAD. Aim of the present study was to evaluate whether the metabolic effect of TMZ may improve episodes of myocardial ischemia in diabetic patients with CAD.Research design and methodsWe assessed the effect of TMZ on 24 h ambulatory ECG monitoring (AEM) in 30 patients (22 males and 8 females, mean (SE) age 67 ± 6.5 years) with NIDDM and ischemic cardiomyopathy. Patients were randomized to receive on top of standard therapy either TMZ (20 mg, tds) or placebo (tds) and were evaluated at baseline and after 6 months.ResultsPatients randomized to TMZ or placebo were comparable regarding demographic data, distribution of CAD, and glicated haemoglobin levels. TMZ significantly reduced the number of episodes of transient myocardial ischemia (− 24% compared to baseline, p < 0.01; − 27% compared to placebo, p < 0.01), and Total Ischemic Burden (− 28% compared to baseline, p < 0.01; − 29% compared to placebo, p < 0.01). TMZ also significantly reduced the number of silent episodes of myocardial ischemia (− 42% compared to baseline and − 39% compared to placebo, p < 0.01) and the time of silent myocardial ischemia/24 h (− 37% compared to baseline and − 35% compared to placebo, p < 0.01). No significant changes in heart rate were detected between baseline, placebo and TMZ evaluations.ConclusionsTMZ is effective in reducing silent and symptomatic episodes of transient myocardial ischemia in diabetic patients with CAD on standard anti-anginal therapy.     

Long-term cardiac rehabilitation and exercise training programs improve metabolic parameters in metabolic syndrome patients with and without coronary heart disease

Background and aimsThe effectiveness of long-term cardiac rehabilitation and exercise training programs on metabolic parameters was evaluated in metabolic syndrome subjects with and without coronary heart disease (CHD).Methods and resultsFifty-nine CHD and 81 non-coronary patients with metabolic syndrome (59 ± 8 vs 56 ± 9 years) were identified retrospectively at entry into identical cardiac rehabilitation and exercise-training programs. Metabolic syndrome was defined using modified Adult Treatment Panel III criteria. Exercise training occurred approximately twice per week. Metabolic and exercise testing data were collected at baseline and after 12 months during the course of the program. Mean duration of cardiac rehabilitation and exercise training programs was over one year in both coronary and non-coronary patients (366 ± 111 vs 414 ± 102 days for CHD and non-coronary CHD cohorts respectively, p < 0.01). Significant improvements in bodyweight, body mass index, blood lipids, triglyceride/HDL ratio and exercise tolerance were noted in both cohorts. At the end of follow-up, 31% of CHD and 20% of non-CHD subjects no longer possessed diagnostic criteria for metabolic syndrome (p < 0.0001 and p < 0.001 respectively).ConclusionsA long-term cardiac rehabilitation program reduces metabolic syndrome prevalence in CHD patients and results in a similar improvement in risk factor control for metabolic syndrome patients without CHD.     

Five-year survival and prognostic factors in a cohort of hospitalized nonagenarians

BackgroundThe number of hospitalized nonagenarians is increasing. Only a few studies have evaluated long-term predictors of survival in these patients. The aim of this study was to determine the 5-year outcome of a cohort of hospitalized nonagenarians, and to identify predictors of long-term survival.MethodsIn 124 consecutive medical hospitalized patients older than 89 years, and followed up during 5 years, the following variables were prospectively recorded: sociodemographic characteristics, main diagnoses, Charlson comorbidity index, Barthel index, Lawton–Brody test, Mini-Mental State Examination, Short Portable Mental Status Questionnaire of Pfeiffer, Mini Nutritional Assessment, albumin levels, and the 5-year survival.ResultsOut of the 124 patients, 109 died (87.9%) during the follow-up. The probability of being alive at 1, 3 and 5 years was 45%, 22% and 12%, respectively. A worse 5-year survival was significantly related to the diagnoses of pneumonia (p = 0.037), heart failure (p = 0.045), higher Charlson index (p = 0.026), poorer functional status measured by the Barthel index (p = 0.003), and the Lawton–Brody test (p = 0.007), cognitive impairment measured by the Pfeiffer test (p = 0.011), and lower levels of albumin (p = 0.028). In the multivariate analysis, the Charlson index (p < 0.001), and the Barthel index (p = 0.003) were independently related to 5-year survival. These two variables were also 5-year survival prognostic factors in the subgroup of discharged patients. A prognostic index using these two variables was created: PI = (0.2 × Charlson index + 0.6 × Barthel index) × 0.92.ConclusionsIn hospitalized nonagenarian patients, poor scores in the Barthel Index and a higher comorbidity evaluated by the Charlson index are independently related to 5-year survival.     

A meta-analysis of randomized trials and adjusted observational studies of drug-eluting stents versus coronary artery bypass grafting for unprotected left main coronary artery disease

BackgroundAcute coronary syndrome (ACS) is an independent risk factor for late stent thrombosis which might be related to the impaired vascular healing after drug-eluting stent (DES) due to the disruption of plaques and thrombus formation. Therefore, we investigated the vascular response after various DES implantations between ACS and stable angina pectoris (SAP) using optical coherence tomography (OCT).MethodsNinety-one patients [49 ACS: 20 sirolimus-eluting (SES), 12 paclitaxel-eluting (PES) and 17 zotarolimus eluting stent (ZES) and 42 SAP: 15 SES, 12 PES and 15 ZES] underwent OCT at 9 months after stent implantation. Neointimal coverage and malapposition were evaluated in 21,939 struts in 2269-mm stented segments.ResultsIn the ACS group, the incidence of uncovered and malapposed struts was significantly higher (8.9 ± 13.7 vs 2.9 ± 6.2%, p = 0.01 and 2.2 ± 5.6 vs 0.5 ± 2.0%, p = 0.02). Among the three DESs tested, SES showed a significantly higher rate of uncovered struts in the ACS group (17.3 ± 13.4 vs 4.4 ± 6.2%, p = 0.003). PES had a trend toward higher rate of uncovered and malapposed struts in the ACS groups (6.7 ± 7.6 vs 4.0 ± 9.0%, p = 0.13) while ZES was similar in both groups.ConclusionThe patterns of neointimal coverage and malapposition at 9 months after DES implantation were different between ACS and SAP, and variable among the DES type between two groups. Therefore, the present study suggests that vascular response after DES implantation might be influenced by both clinical presentation and type of DES.     

Being older as a risk factor for vomiting in those undergoing spinal anesthesia

PurposeTo explore the effect of older age (≥ 65 years) as a risk factor for nausea and vomiting in the context of spinal anesthesia by assessing patient-, surgery- and anesthesia-related variables.MethodsThis is an observation study using a survey instrument in a tertiary general hospital. Patients scheduled to undergo surgery with spinal anesthesia were surveyed by questionnaire and record review to prospectively and consecutively study all patients consenting to spinal anesthesia for surgery during the intraoperative and 24-hour postoperative periods. Risk factors were examined via univariate and multivariate analysis.ResultsOf the 903 patients (69.7% were men) scheduled to undergo surgery with spinal anesthesia, 421 of them (46.6%) were older than 65 years of age. During the intraoperative and postoperative 24-hour observation period, 87 patients (28.1%) experienced nausea and 55 (17.7%) vomited. The incidence of nausea did not differ between elderly (≥ 65 years) and nonelderly patients. However, being elderly was a risk factor for vomiting (24.7% vs. 15.6%, p < 0.0001). After adjustment, being elderly was an independent risk factor for vomiting (adjusted odds ratio = 1.84, 95% confidence interval 1.26–2.68).ConclusionIn patients undergoing spinal anesthesia, the proportion of those complaining of nausea does not differ between elderly and non-elderly patients, but older patients do have a higher risk for vomiting.     

Knowledge of cardiovascular risk factors and awareness of non-pharmacological approach for risk prevention in young survivors of acute myocardial infarction. The cardiovascular risk prevention project "Help Your Heart Stay Young"

Background and aimsKnowledge of cardiovascular disease (CVD) risk factors in young patients who experienced myocardial infarction (MI) is poorly described.Methods and resultsKnowledge of traditional CVD risk factors, non-fatal cardiovascular events and of non-pharmacological factors able to reduce CVD risk and education level were evaluated by questionnaires in subjects who visited their family doctors. Sixty-one participants with history of MI in age <50 years (MI+) were compared with 3749 subjects with age <50 years, from the same population source, but without history of MI (MI−). MI+ were more frequently men (p < 0.01), did not have significantly higher prevalences of family history of CVD, diabetes and hypertension. MI+ individuals reported previous non-fatal stroke (13% vs. 0.5%, p < 0.001), overweight, diabetes, and hypercholesterolemia (all p < 0.001) more frequently than controls, whereas prevalence of arterial hypertension, smoking habit and physical inactivity did not differ between the two groups; MI+ and MI− individuals did not differ in terms of the proportion of those who were unaware of being hypertensive, diabetic or hypercholesterolemic. MI+ participants reported more frequently lower education level than controls (p < 0.05). Knowledge of non-pharmacological approach for CVD risk reduction was similar in MI+ and MI−. In a logistic multivariate analysis, male gender (adjusted odds ratio = 5.8) and high cholesterol level (adjusted odds ratio 2.8, both p < 0.01) were independent correlates of MI+. CVD risk factors distribution was similar between participants with juvenile MI+ and MI in age ≥50 years (n = 167) extracted from the same population source; however, stroke was reported more frequently in juvenile MI+ than in those who had MI at age ≥50 years/old (13% vs. 4%, p < 0.01).ConclusionsJuvenile non-fatal MI was associated with metabolic CVD risk factors, with higher cerebrovascular co-morbidity and lower education level.     

Cognitive performance is impaired in coeliac patients on gluten free diet: a case-control study in patients older than 65 years of age

IntroductionRetrospective studies and case reports suggest an association between coeliac disease and impaired cognitive function.AimTo evaluate functional and cognitive performances in coeliac disease vs. control patients older than 65 years.MethodEighteen coeliac disease patients (75 ± 4 years, group A) on gluten free diet since 5.5 ± 3 years and 18 age-sex matched controls (76 ± 4 years, group B) were studied using a battery of neuropsychological tests. Results of functional and cognitive tests are expressed as “row scores” and as “equivalent scores” by relating “raw scores” to reference rank categories.ResultsBarthel Index of functional performance was similar in the 2 groups. “Raw score” was significantly lower in coeliac disease than controls for Mini Mental Test Examination (p = 0.02), Trail Making Test (p = 0.001), Semantic Fluency (p = 0.03), Digit Symbol Test (p = 0.007), Ideo-motor apraxia (p < 0.001) and Bucco-facial apraxia (p < 0.002). “Equivalent score” was also lower in coeliac disease than controls for Semantic memory (p < 0.01) and for Ideo-motor apraxia (p = 0.007).ConclusionCognitive performance is worse in elderly coeliac disease than control patients, despite prolonged gluten avoidance in coeliacs. Awareness on the increasing phenomenon of late-onset coeliac disease is important to minimize diagnostic delay and prolonged exposure to gluten that may adversely and irreversibly affect cognitive function.     

Urine α-Glutathione S-transferase, systemic inflammation and arterial function in juvenile type 1 diabetes

BackgroundDespite marked improvement in therapy and monitoring of patients with insulin-dependent (type 1) diabetes, diabetic nephropathy remains a serious complication, with subsequent end-stage renal disease in about 20% of cases.ObjectiveTo investigate in young patients with type 1 diabetes whether urine α-Glutathione S-transferase to creatinine ratio (α-GST:crea) relates to markers of systemic inflammation and subclinical vasculopathy.DesignChildren and adolescents (median age and diabetes duration 14 and 6 years, respectively) with type 1 diabetes screened in a previous study for proximal tubular (urine α-GST:crea ratio) and renal (plasma creatinine, cystatin C glomerular filtration rate (GFR), and timed urine albumin excretion rate (AER)) function were, within the same timeframe, also investigated for vascular (blood pressure, carotid artery intima–media thickness (IMT) and compliance (CAC), brachial artery flow-mediated dilatation (FMD) and plasma cyclic guanosine monophosphate (cGMP) and inflammatory (C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α)) profiles. Exposure to environmental tobacco smoke (ETS) was assessed through questionnaire (n = 67 respondents).ResultsNone of the patients (n = 69) had overt renal insufficiency. AER correlated with age (p = 0.01, r = 0.3), diabetes duration (p = 0.02, r = 0.3), FMD (p = 0.04, r = ? 0.3, n = 52), CAC (p = 0.03, r = ? 0.3, n = 62) and cGMP (p = 0.01, r = ? 0.3, n = 59). α-GST:crea was lower (p = 0.03) in patients than in controls. α-GST:crea appeared to be particularly lower in older patients (p = 0.004, r = ? 0.34 vs age), in those with worse diabetic control (p = 0.03, r = ? 0.26 vs HbA1c), and in those with lower carotid artery elasticity (p = 0.017, r = 0.3 vs CAC). Although ETS had no direct significant impact on α-GST:crea, α-GST:crea correlated with FMD only in patients with ETS (r = 0.5, p = 0.009, n = 13). α-GST:crea showed positive association with TNF-α (p = 0.01, r = 0.3).ConclusionIn children and adolescents with type 1 diabetes, lower levels of urine excretion of α-GST:crea appear to be associated with decreasing elasticity and endothelial vasomotor function of peripheral arteries, especially in patients with ETS. In contrast, higher levels of α-GST:crea are more common in patients with elevated markers of systemic inflammation. Large scale prospective studies are needed to clarify the meaning and mechanisms of this association.     

Effects of soybean D-LeciVita product on serum lipids and fatty acid composition in type 2 diabetic patients with hyperlipidemia

Background and aimHyperlipidemia is one of the major risk factors of cardiovascular complication in diabetes. High intake of soy product has been suggested to prevent cardiovascular disease. The purpose of this study was to evaluate if dietary supplement of soybean D-LeciVita product, rich in polyunsaturated phospholipids (with 12% lecithin, 35% soy protein) affects serum lipids and serum and erythrocyte phospholipid fatty acid composition in type 2 diabetic patients.Methods and resultsForty-seven patients (men and post-menopausal women) with isolated hypertriglyceridemia (IHTG) and combined hyperlipidemia (CHL), aged 43–70 years, were given 15 g of D-LeciVita powder as a water suspension in a single evening dose during the follow-up period of 12 weeks. Patients kept their diabetic diet relatively constant. Treatment was associated with a significant (p ≤ 0.001) decrease in serum total cholesterol and triglyceride levels by 12% and 22%, respectively. LDL-cholesterol decreased by 16% and HDL-cholesterol increased by 11% (p ≤ 0.001). Our study shows a 27% decrease in LDL-cholesterol (p ≤ 0.001) and a 12% increase in HDL-cholesterol (p ≤ 0.01) in CHL type 2 diabetic patients. Triglyceride levels decreased in type 2 diabetic patients with IHTG and CHL by 29% and 13%, respectively (p ≤ 0.01 and p ≤ 0.05). Our results show decrease in SFA and increase in n-6 and n-3 PUFA in serum and erythrocyte phospholipids. SFA decreased and n-3 PUFA increased in serum and erythrocyte phospholipids in IHTG and CHL groups.ConclusionThe present study indicated that added to a regular diet, soybean D-LeciVita product (combination of soy protein and lecithin) is associated not only with lipid-lowering effects but also with more favorable serum phospholipids fatty acid profile in type 2 diabetic patients with hyperlipidemia.     

C-reactive protein is directly related to plasminogen activator inhibitor type 1 (PAI-1) levels in diabetic subjects with the 4G allele at position -675 of the PAI-1 gene

Background and aimsC-reactive protein (CRP) has been identified as a possible factor able to promote atherosclerosis. “In vitro” studies have demonstrated that CRP induces plasminogen activator inhibitor type 1 (PAI-1) expression, suggesting a hypofibrinolytic role for CRP. As CRP and PAI-1 levels increase in type 2 diabetic subjects, we decided to study the relationship between CRP and PAI-1, and the role of the 4G/5G polymorphism of the PAI-1 gene on this relationship in a diabetic population without complications.Methods and resultsTwo hundred and ninety-five type 2 diabetic patients (age 60.9 ± 10.5 years) and 290 healthy controls (age 59.2 ± 11.5 years) were enrolled. A significant correlation between PAI-1 and CRP in diabetic subjects was found (r = 0.45, p < 0.001), whereas no relationship was evident in the control subjects between these inflammatory markers. Multiple regression analysis highlighted that CRP is the only one significant variable of PAI-1 antigen in diabetic subjects (partial r = 0.31, p < 0.01). Stratifying by genotype, a positive correlation between PAI-1 and CRP in 4G/4G (partial r = 0.64 p < 0.001) and 4G/5G (partial r = 0.47, p < 0.001) subjects was found, whereas no correlation in 5G/5G was present. Multiple regression analysis confirmed the presence of this correlation in 4G/4G (partial r = 0.45, p < 0.001) and in 4G/5G (partial r = 0.34, p = 0.007) diabetic patients.ConclusionsThese findings demonstrate that CRP plays an important role in the complex mechanism regulating PAI-1 antigen in 4G diabetic carriers.     

A primary care register for impaired glucose handling (IGH): impact on cardiometabolic profile

ObjectiveDiet and exercise reduce the incidence of diabetes in high-risk individuals as does Metformin, although less dramatically. Here we evaluated if lifestyle and pharmacological intervention, for people at risk of diabetes, resulted in an improvement in their cardiometabolic risk profile.Research design/methodsIn a primary care based study, 92 individuals screened opportunistically and identified to have impaired glucose handling were offered detailed lifestyle advice, at 6 monthly intervals, with targeting of cardiovascular risk factors. Duration of follow-up was 4 years. The relation between fasting and 2 h glucose with different cardio-metabolic risk factors over time was assessed using multi-level modeling.ResultsThere was no significant weight reduction. At 24 months, mean fasting glucose level (6.4 mmol/L (95% CI 6.0–6.8)) was slightly lower than at baseline (6.6 mM (95% CI: 6.4–6.9), F = 3.67; p < 0.001). For men and women combined, systolic blood pressure (mean difference = ?6 mmHg, p = 0.013), total cholesterol (?0.66 mmol/L, p < 0.0001) and triglycerides (?0.13 mmol/L, p = 0.133) fell, whilst HDL-cholesterol (0.12 mmol/L, p = 0.047) rose. Diabetes developed in 18/92 participants during follow-up (up to 4 years).Five per cent of participants were started on Metformin, 88.5% on lipid lowering agents and 85.4% on anti-hypertensive agents. After adjusting for age, sex and BMI, 2 h glucose was independently and negatively associated with HDL-cholesterol (β = ?2.17, p = 0.041), and positively with systolic BP (β = 0.24, p = 0.004, per 5 mmHg).ConclusionsTargeted intervention had an effective role in improving lipid and BP profile in individuals with impaired glucose handling, with limited impact on glycaemia and no impact on weight. More work needs be done to evaluate the potential benefit of insulin sensitizing agents in this setting.     

Clinical outcome of lamivudine-resistant chronic hepatitis B patients with compensated cirrhosis under adefovir salvage treatment.: Importance of HCC surveillance

BackgroundData concerning the outcome of lamivudine-resistant (LAM-R) chronic hepatitis B (CHB) patients with compensated cirrhosis under adefovir (ADV) treatment are limited. The aim of our study was to evaluate the medium term outcome of these, high-risk for fatal events, patients.Methods31 LAM-R patients with compensated cirrhosis who had been treated with ADV monotherapy (n = 8) or ADV plus LAM (n = 23) for a mean of 27.6 months, were evaluated. Virological response (VR) was defined as HBV-DNA levels < 10⁴ copies/ml within the first year of treatment.ResultsTwenty-three patients (74.19%) achieved VR. Six patients (19.35%) developed ADV-related mutations (annual incidence 11%). Liver-related death, liver decompensation and hepatocellular carcinoma (HCC) were observed in 12.9%, 16.12% and 16.12% of patients, respectively. HCC (annual incidence 9.1%) was the main cause of liver decompensation (4/5, 80%) and of liver-related deaths (3/4, 75%). HCC development was not related to patients' age (p = 0.440), HBeAg status (p = 0.245), HBV genotype (p = 0.598), baseline ALT levels (p = 0.981), baseline viral load (p = 0.464), VR (p = 0.504) as well as emergence of ADV resistance (p = 0.871).ConclusionsADV suppresses viral replication in more than 70% of LAM-R cirrhotic patients during the first year of treatment. Despite that, HCC is frequently observed in these high-risk patients, irrespective of virological response or emergence of ADV resistance.     

Circumferential evaluation of the neointima by optical coherence tomography after ABSORB bioresorbable vascular scaffold implantation: Can the scaffold cap the plaque?

ObjectiveTo quantify the circumferential healing process at 6 and 12 months following scaffold implantation.BackgroundThe healing process following stent implantation consists of tissue growing on the top of and in the space between each strut. With the ABSORB bioresorbable vascular scaffold (BVS), the outer circumference of the scaffold is detectable by optical coherence tomography (OCT), allowing a more accurate and complete evaluation of the intra-scaffold neointima.MethodsA total of 58 patients (59 lesions), who received an ABSORB BVS 1.1 implantation and a subsequent OCT investigation at 6 (n = 28 patients/lesions) or 12 (n = 30 patients with 31 lesions) months follow-up were included in the analysis. The thickness of the neointima was calculated circumferentially in the area between the abluminal side of the scaffold and the lumen by means of an automated detection algorithm. The symmetry of the neointima thickness in each cross section was evaluated as the ratio between minimum and maximum thickness.ResultsThe neointima area was not different between 6 and 12 months follow-up (1.57 ± 0.42 mm² vs. 1.64 ± 0.77 mm²; p = 0.691). No difference was also found in the mean thickness of the neointima (median [IQR]) between the two follow-up time points (210 μm [180–260]) vs. 220 μm [150–260]; p = 0.904). However, the symmetry of the neointima thickness was higher at 12 than at 6 months follow-up (0.23 [0.13–0.28] vs. 0.16 [0.08–0.21], p = 0.019).ConclusionsA circumferential evaluation of the healing process following ABSORB implantation is feasible, showing the formation of a neointima layer, that resembles a thick fibrous cap, known for its contribution to plaque stability.     

Type 1 diabetes in Cheshire: cardiometabolic risk factor trends (2004-2009)

AimsIn the context of changes in the last 10 years in treatment strategies for type 1 diabetes we evaluated longitudinal trends in cardiometabolic risk factor profiles in a population from North-West England.MethodsWe retrospectively examined longitudinal case records for the period for 291 adult patients followed up between 2004 and 2009 (age range 16–85). Data search was performed through the EMIS^® software provider using data held in primary care.ResultsLongitudinal analysis of individually followed patients indicated a mean 0.4% reduction in HbA1c from 8.3% (67 mmol/mol) at baseline (p = 0.002). The proportion of patients with an HbA1c ≥10% (86 mmol/mol) at baseline had a significant reduction over time from 14.0% to 9.5% (χ² = 9.4, p = 0.002). BMI remained unchanged (28.3 vs 28.4 kg/m²). However total cholesterol fell by 12.5% from 4.8 mM to 4.2 mM, (p < 0.0001) with a corresponding 23% reduction in LDL-cholesterol from 3.0 mm to 2.3 mM (p < 0.0001). There was a significant fall in diastolic BP (78–74 mmHg, p = 0.0016). In a mixed longitudinal regression model, HbA1c was associated with LDL-C (β = 0.28, p < 0.001) and age (β = 0.02, p = 0.001), independent of BMI, gender and systolic BP.DiscussionIn spite of intensive work to improve glycaemic control in type 1 diabetes, mean HbA1c remains above target for many people in our area, highlighting the difficulty of achieving glycaemic targets in type 1 diabetes. The significant reduction in diastolic BP, LDL and total cholesterol may have long-term benefit in cardiovascular event rate reduction.     

Protein and glutamine kinetics during counter-regulatory failure in type 1 diabetes

Background and aimsHealthy individuals counteract insulin-induced hypoglycaemia by increasing glutamine utilization but not proteolysis. Glucagon is important to this response because it increases glutamine uptake. In type 1 diabetes (T1DM) glucagon and epinephrine responses to hypoglycaemia are defective. We investigated whether glutamine and amino acid utilization during hypoglycaemia is altered in T1DM with defective counter-regulatory responses.Methods and resultsEight T1DM patients (duration of diabetes 14 ± 4 years and therefore with presumed defective counter-regulatory response) and eight controls (CON) received a 3 h hypoglycaemic hyperinsulinaemic (0.65 mU/kg per min) clamp coupled to [6,6-²H₂]glucose, [1-¹³C]leucine and [2-¹⁵N]glutamine to trace the relative kinetics.Post-absorptive plasma glucose and glucose uptake were increased in T1DM (9.09 ± 0.99 vs 5.01 ± 0.22 mmol/l and 19.5 ± 0.9 vs 12.6 ± 0.8 μmol/kg per min, p < 0.01). During the clamp T1DM but not CON required exogenous glucose (4.4 ± 1.7 μmol/kg per min) to maintain the hypoglycaemic plateau because the endogenous glucose production was significantly suppressed (p < 0.01). In T1DM the leucine and phenylalanine concentrations were less suppressed from basal (p < 0.05) despite a similar insulin suppression of proteolysis (−16 ± 2 vs −20 ± 4%, p = ns) indicating a defective stimulation of leucine metabolic clearance from basal (+18 ± 3% vs +55 ± 9%, p < 0.01). Glutamine concentration remained unchanged from basal (−7 ± 3% vs −35 ± 3%, p < 0.01) and the clearance of glutamine was markedly defective in T1DM (+6 ± 2%) in comparison with controls (+22 ± 4%; p = 0.02).ConclusionsIn T1DM, the counter-regulatory failure to hypoglycaemia seems to be associated with a defective glutamine utilization. The failure to clear circulating amino acids, specifically glutamine, during hypoglycaemia may adversely affect gluconeogenesis.     

Gender specific associations between matrix metalloproteinases and inflammatory markers in post myocardial infarction patients

ObjectiveAtherothrombotic disease in the coronary arteries leads to myocardial infarction (MI) through plaque rupture or erosion of the endothelium, the former mechanism predominating in men and the latter in women. Inflammation is a key feature of these processes, and the interplay between inflammation and matrix metalloproteinases (MMPs) in this context is not fully understood. In this study, we investigated the association between inflammatory markers and MMPs in men and women.MethodsBlood samples were drawn 3 months after a first MI in 387 patients and 387 sex- and age-matched controls (82% men). C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, -18, tumour necrosis factor-α (TNF-α), macrophage chemoattractant protein-1 (MCP-1), MMP-1, -3 and -9 were measured. Coronary angiography was performed in 243 of the patients, and they were classified into 0-, 1-, 2- or 3-vessel disease groups.ResultsCRP, IL-6, -8, -18 and TNF-α were higher, and MMP-3 and -9 were lower, in patients than in controls. A greater proportion of women (49%) had 0-vessel disease than men (16%, p < 0.0001). A gender specific pattern of associations between inflammatory markers and MMPs was found as IL-6 (r_S = 0.29, p < 0.05), IL-18 (r_S = 0.34, p < 0.01) and MCP-1 (r_S = 0.35, p < 0.01) correlated with MMP-3 in female patients, whereas CRP (r_S = 0.23, p < 0.0001), IL-6 (r_S = 0.13, p < 0.05) and IL-8 (r_S = ?0.21, p < 0.01) correlated with MMP-9 in male patients.ConclusionsThe present study demonstrates different patterns of association between inflammatory markers and MMPs in men and women, strengthening the hypothesis of gender specific differences in pathophysiological mechanisms of MI.     

Both long-term HIV infection and highly active antiretroviral therapy are independent risk factors for early carotid atherosclerosis

ObjectiveThere is controversy over whether or not chronic HIV infection contributes to atherosclerosis. We investigated the relationship between HIV infection, antiretroviral medication and ultrasound evidence of early atherosclerosis in the context of vascular risk factors.DesignA case–control design with 292 HIV-positive subjects and 1168 age- and sex-matched controls.MethodsWe assessed vascular risk factors, blood pressure, serum lipids and carotid intima media thickness (IMT) in cases and controls. With multivariate regression models, we investigated the effects of HIV status and antiretroviral medication on IMT.ResultsThe common carotid artery (CCA) IMT value was 5.70% (95% confidence interval [3.08–8.38%], p < 0.0001) or 0.044 mm [0.021–0.066 mm] (p = 0.0001) higher in HIV-positives, adjusted for multiple risk factors. In the carotid bifurcation (BIF), the IMT values were 24.4% [19.5–29.4%] or 0.250 mm [0.198–0.303 mm] higher in HIV patients (p < 0.0001). An investigation of antiretroviral substances revealed higher CCA- and BIF-IMT values in patients receiving combination antiretroviral therapy (HAART).ConclusionsHIV infection and HAART are independent risk factors for early carotid atherosclerosis. Assuming a risk ratio similar to that in large population-based cohorts, the observed IMT elevation suggests that vascular risk is 4–14% greater and the “vascular age” 4–5 years higher in HIV-positive subjects. The underlying mechanisms remain to be clarified.