Relationship Among Radiological Measurements of Anterior Mediastinal Fat and Outcomes of Lung Transplantation in Fibrotic Patients

ObjectiveLung transplantation (LT) for pulmonary fibrosis is related to higher mortality than other transplant indications. We aim to assess whether the amount of anterior mediastinal fat (AMF) was associated to early and long-term outcomes in fibrotic patients undergoing LT.MethodsRetrospective analysis of 92 consecutive single lung transplants (SLT) for pulmonary fibrosis over a 10-year period. AMF dimensions were measured on preoperative CT-scan: anteroposterior axis (AP), transverse axis (T), and height (H). AMF volumes (V) were calculated by the formula: AP × T × H × 3.14/6.According to the radiological AMF dimensions, patients were distributed into two groups: low-AMF (V < 20 cm³) and high-AMF (V > 20 cm³), and early and long-term outcomes were compared by univariable and multivariable analyses.ResultsThere were 92 SLT: 73M/19F, 53 ± 11 [14–68] years old. 30-Day mortality (low-AMF vs. high-AMF): 5 (5.4%) vs. 15 (16.3%), p = 0.014. Patients developing primary graft dysfunction within 72 h post-transplant, and those dying within 30 days post-transplant presented higher AMF volumes: 21.1 ± 19.8 vs. 43.3 ± 24.7 cm³ (p = 0.03) and 24.4 ± 24.2 vs. 56.9 ± 63.6 cm³ (p < 0.01) respectively. Overall survival (low-AMF vs. high-AMF) (1, 3, and 5 years): 85%, 81%, 78% vs. 55%, 40%, 33% (p < 0.001).Factors predicting 30-day mortality were: BMI (HR = 0.77, p = 0.011), AMF volume (HR = 1.04, p = 0.018), CPB (HR = 1.42, p = 0.002), ischaemic time (HR = 1.01, p = 0.009).Factors predicting survival were: AMF volume (HR = 1.02, p < 0.001), CPB (HR = 3.17, p = 0.003), ischaemic time (HR = 1.01, p = 0.001).ConclusionPreoperative radiological assessment of mediastinal fat dimensions and volumes may be a useful tool to identify fibrotic patients at higher risk of mortality after single lung transplantation.     

Metabolic manipulation in dilated cardiomyopathy: Assessing the role of trimetazidine

ObjectivesTo study the role of metabolic modulator (trimetazidine: TMZ) in dilated cardiomyopathy (DCM). Optimizing altered substrate metabolism in heart failure (HF) with metabolic modulators allows more efficacious energy production from glucose than from free fatty acids.Methods100 patients of DCM (47.7 years, NYHA class 2.17, LVEF 27.3%) were randomized to TMZ (20 mg tid, n = 50) vs conventional therapy (n = 50). Functional status, BNP and various echocardiographic parameters were assessed at 3–6 months.ResultsAt 3 months, TMZ group had significantly improved NYHA class (2.25 vs 1.85), 6 min walk test (349.7 vs 402 m), LVD-36 score (25.5 vs 21) and BNP (744.7 vs 248.3 pg/ml), all p 0.001. Significant improvement was also seen in LV end-systolic (LVESV, 87.1 ± 27.5 vs 78.5 ± 24.9 ml/m², p 0.001), LV end-diastolic volumes (LVEDV, 117.6 ± 29.3 vs 110.9 ± 27.4 ml/m², p 0.001), LVEF (27 vs 30.9%, p 0.001) and LV wall stress (90.2 ± 18.9 vs 71.1 ± 13.2 dyn/cm², p 0.0001). The % change in LVESV, LVEDV, LVEF and LV wall stress was −9.5%, −5.4%, +8.4% and −21.8%. Other echo parameters also improved after 3 months of TMZ (E/A ratio 1.9 vs 1.2, p = 0.001, E/A VTI 2.7 vs 1.6, p = 0.001, myocardial performance index, MPI 0.8 vs 0.7, p = 0.0001), Tissue Doppler parameters (E/E′ septal (19.7 vs 12.5, p = 0.001) and E/E′ lateral (13.3 vs 9.4, p = 0.0001)). Patients in control group had no change in NYHA class, LVD-36 scores, LV volumes or LVEF at 3 months although BNP and LV wall stress reduced to a slight extent. Patients on TMZ had further improvement in NYHA class, walk test, BNP levels and echocardiographic parameters at 6 months.ConclusionsMetabolic modulators (TMZ) may help in improving LV function in DCM. In this study, benefit was noted by 3 months with further improvement at 6 months.     

Effects of 12 weeks of probiotic supplementation on quality of life in colorectal cancer survivors: A double-blind,randomized, placebo-controlled trial

BackgroundProbiotics may help resolve bowel symptoms and improve quality of life. We investigated the effects of 12 weeks of probiotics administration in colorectal cancer patients.MethodsWe conducted a double-blind, randomized, placebo-controlled trial. The participants took probiotics (Lacidofil) or placebo twice a day for 12 weeks. The cancer-related quality of life (FACT), patient's health-9 (PHQ-9), and bowel symptom questionnaires were completed by each participant.ResultsWe obtained data for 32 participants in the placebo group and 28 participants in the probiotics group. The mean ages of total participants were 56.18 ± 8.86 years and 58.3% were male. Administration of probiotics significantly decreased the proportion of patients suffering from irritable bowel symptoms (0 week vs. 12 week; 67.9% vs. 45.7%, p = 0.03), improved colorectal cancer-related FACT (baseline vs. 12 weeks: 19.79 ± 4.66 vs. 21.18 ± 3.67, p = 0.04) and fatigue-related FACT (baseline vs. 12 weeks: 43.00 (36.50–45.50) vs. 44.50 (38.50–49.00), p = 0.02) and PHQ-9 scores (0 weeks vs. 12 weeks; 3.00 (0–8.00) vs. 1.00 (0–3.00), p = 0.01). We found significant differences in changes of the proportion of patients with bowel symptoms (p < 0.05), functional well-being scores (p = 0.04) and cancer-related FACT scores (p = 0.04) between the two groups.ConclusionProbiotics improved bowel symptoms and quality of life in colorectal cancer survivors.     

La técnica de superposición de cúspides en TAVI con dispositivo autoexpandible optimiza la profundidad del implante y reduce la necesidad de marcapasos permanente

Introduction and objectivesThis study aimed to determine the safety and efficacy of modifying the classic implantation technique for aortic transcatheter heart valve (THV) implantation to a cusp-overlap-projection (COP) technique to achieve a higher implantation depth and to reduce the burden of new permanent pacemaker implantation (PPMI) at 30 days. Aortic self-expanding THV carries an elevated risk for PPMI. A higher implantation depth minimizes the damage in the conduction system and may reduce PPMI rates.MethodsFrom March 2017, 226 patients were consecutively included: 113 patients were treated using the COP implantation technique compared with the previous 113 consecutive patients treated using the classic technique. In all patients, implantation depth was assessed by 3 methods (noncoronary cusp to the THV, mean of the noncoronary cusp and the left coronary cusp to the THV, and the deepest edge from the left coronary cusp and the noncoronary cusp to the THV).ResultsThe COP group had a lower implantation depth than the group treated with the classic technique (4.8 mm ± 2.2 vs 5.7 mm ± 3.1; P = .011; 5.8 mm ± 3.1 vs 6.5 mm ± 2.4; P = .095; 7.1 mm ± 2.8 vs 7.4 mm ± 3.2; P = .392). Forty patients (17.7%) required a new PPMI after the 30-day follow-up but this requirement was significantly lower in the COP group (12.4% vs 23%, P = .036). The COP implantation technique consistently protected against the main event (OR, 0.45; 95%CI, 0.21-0.97; P = .043), with similar procedural success rates and complications.ConclusionsThe COP implantation technique is a simple modification of the implantation protocol and provides a higher implantation depth of self-expanding-THV with lower conduction disturbances and PPMI rates.     

Albuminuria and VEGF as early markers of cardiovascular disturbances in young type 1 diabetic patients

AimsThe aim of the study was to assess myocardial perfusion by means of non-invasive diagnostic methods and measurement of the plasma concentration of vascular endothelial growth factor (VEGF) in patients with long-lasting type 1 diabetes.Methods and resultsThe study was performed on 41 Type 1 diabetic patients (23 females, 18 males), aged 30 ± 7.6 with a duration of disease 15.2 ± 5.5 years. 17 patients exhibited microalbuminuria (10 females, 7 males) and 24 subjects were without microalbuminuria (13 females, 11 males). The methods used included a 24-h ECG tape, an exercise treadmill test, echocardiological evaluation with dobutamine and atropine challenge and single photon emission computer tomography (SPECT) at rest, and after dipyridamol induction of ischemia. All the exercise and stress echocardiography tests were negative. There were significant differences between microalbuminuric and normoalbuminuric subjects in the duration of their exercise tests (586.9 ± 110.5 vs. 664.9 ± 133.2 s, p = 0.027), performed work (11.4 ± 1.6.vs. 12.6 ± 1.8 METs, p = 0.045), achieved pulse limit (89.1 ± 3.6 vs. 92.6 ± 5.2%, p = 0.037), rest ejection fraction (55.8 ± 8.7 vs. 62.0 ± 4.4%, p = 0.040), abnormal changes in SPECT (53 vs. 21%, p = 0.047) and VEGF concentration (101.5 ± 7.8 vs. 75.15 ± 16.5 pg/ml, p < 0.05). The presence of retinopathy increased 12-fold the probability of significant changes in the SPECT (OR 12.1, 95% CI 1.38–105.64, p = 0.02) and nephropathy (OR 4.27; 95%CI 1.09–16.83, p = 0.03).ConclusionAsymptomatic patients with long lasting type 1 diabetes may have disturbances in myocardial perfusion, especially these with microalbuminuria.     

Neutrophil,lymphocyte and platelet ratio as a predictor of mortality in septic-acute kidney injury patients

BackgroundAKI is frequent in critically ill patients, in whom the leading cause of AKI is sepsis. The role of intrarenal and systemic inflammation appears to be significant in the pathophysiology of septic-AKI. The neutrophils to lymphocytes and platelets (N/LP) ratio is an indirect marker of inflammation. The aim of this study was to evaluate the prognostic ability of N/LP ratio at admission in septic-AKI patients admitted to an intensive care unit (ICU).MethodsThis is a retrospective analysis of 399 septic-AKI patients admitted to the Division of Intensive Medicine of the Centro Hospitalar Universitário Lisboa Norte between January 2008 and December 2014. The Kidney Disease Improving Global Outcomes (KDIGO) classification was used to define AKI. N/LP ratio was calculated as: (Neutrophil count × 100)/(Lymphocyte count × Platelet count).ResultsFifty-two percent of patients were KDIGO stage 3, 25.8% KDIGO stage 2 and 22.3% KDIGO stage 1. A higher N/LP ratio was an independent predictor of increased risk of in-hospital mortality in septic-AKI patients regardless of KDIGO stage (31.59 ± 126.8 vs 13.66 ± 22.64, p = 0.028; unadjusted OR 1.01 (95% CI 1.00–1.02), p = 0.027; adjusted OR 1.01 (95% CI 1.00–1.02), p = 0.015). The AUC for mortality prediction in septic-AKI was of 0.565 (95% CI (0.515–0.615), p = 0.034).ConclusionsThe N/LP ratio at ICU admission was independently associated with in-hospital mortality in septic-AKI patients.     

Paraoxonase 1 gene (Gln192–Arg) polymorphism and the risk of coronary artery disease in type 2 diabetes mellitus

BackgroundParaoxonase 1 (PON1) is reported to have antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or type A/arginine (Arg) or type B polymorphism at position 192 of PON1 gene has been suggested with coronary artery disease (CAD) among patients with diabetes mellitus (DM). However, conflicting results have also been reported.ObjectivesTo investigate the relationship between PON1 gene (Gln¹⁹²–Arg) polymorphism and the presence, extent and severity of CAD in type 2 DM.MethodsThe study comprised 180 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD and DM into four groups: Group I (n = 40 patients) nondiabetic subjects without CAD, Group II (n = 45 patients) diabetic patients without CAD, Group III (n = 47 patients) nondiabetic patients with CAD and Group IV (n = 48 patients) diabetic patients with CAD. PON1(Gln¹⁹²–Arg) genotype was assessed using polymerase chain reaction (PCR) followed by AlwI digestion.ResultsThe frequency of Gln allele (type A) was significantly higher in Group I and Group II compared to Group III and Group IV (62.5%, 60% vs. 38.3%, 31.25%, respectively, p < 0.001) while the frequency of Arg allele (type B + type AB) was significantly higher in ischemic groups (III and IV) compared to nonischemic groups (I and II) (61.7%, 68.75% vs. 37.5%, 40%, respectively, p < 0.001). Patients with CAD and DM (Group IV) have significantly higher severity score and vessel score than those with CAD only (Group III) (9.7 ± 2.97, 2.44 ± 0.56 vs. 6.99 ± 3.71, 1.67 ± 0.89, respectively, p < 0.001) Patients with vessel score 3 had significantly higher severity score and higher Arg allele frequency than patients with vessel score 2, the latter group had also significantly higher severity score and Arg allele frequency than patients with vessel score 1 (8.9 ± 2.79 vs. 5.21 ± 2.13 and 80.49% vs. 67.86%), (5.21 ± 2.13 vs. 3.11 ± 0.89 and 67.86% vs. 53.85%), p < 0.001 for all. In multivariate logistic regression analysis of different variables for prediction of CAD, age [OR 2.99, CI (1.11–10.5), p < 0.01], smoking [OR 4.13, CI (1.37–11.7), p < 0.001], low-density lipoprotein (LDL) cholesterol > 100 mg/dL [OR 4.31, CI (1.25–12.5), p < 0.001], high-density lipoprotein (HDL) cholesterol < 40 mg/dL [OR 5.11, CI (1.79–16.33), p < 0.001] and PON1 192 Arg allele [OR 4.62, CI (1.67–13.57), p < 0.001] were significantly independent predictors of CAD.ConclusionArg allele of PON1 192 gene polymorphism is an independent risk factor for CAD and is associated not only with the presence of CAD but also with its extent and severity and its impact is clearly more pronounced in diabetic patients.     

Lung Function,Radiological Findings and Biomarkers of Fibrogenesis in a Cohort of COVID-19 Patients Six Months After Hospital Discharge

IntroductionImpairment in pulmonary function tests and radiological abnormalities are a major concern in COVID-19 survivors. Our aim is to evaluate functional respiratory parameters, changes in chest CT, and correlation with peripheral blood biomarkers involved in lung fibrosis at two and six months after SARS-CoV-2 pneumonia.MethodsCOVID-FIBROTIC (clinicaltrials.gov NCT04409275) is a multicenter prospective observational cohort study aimed to evaluate discharged patients. Pulmonary function tests, circulating serum biomarkers, chest radiography and chest CT were performed at outpatient visits.ResultsIn total, 313, aged 61.12 ± 12.26 years, out of 481 included patients were available. The proportion of patients with DLCO < 80% was 54.6% and 47% at 60 and 180 days. Associated factors with diffusion impairment at 6 months were female sex (OR: 2.97, 95%CI 1.74–5.06, p = 0.001), age (OR: 1.03, 95% CI: 1.01–1.05, p = 0.005), and peak RALE score (OR: 1.22, 95% CI 1.06–1.40, p = 0.005). Patients with altered lung diffusion showed higher levels of MMP-7 (11.54 ± 8.96 vs 6.71 ± 4.25, p = 0.001), and periostin (1.11 ± 0.07 vs 0.84 ± 0.40, p = 0.001). 226 patients underwent CT scan, of whom 149 (66%) had radiological sequelae of COVID-19. In severe patients, 68.35% had ground glass opacities and 38.46% had parenchymal bands. Early fibrotic changes were associated with higher levels of MMP7 (13.20 ± 9.20 vs 7.92 ± 6.32, p = 0.001), MMP1 (10.40 ± 8.21 vs 6.97 ± 8.89, p = 0.023), and periostin (1.36 ± 0.93 vs 0.87 ± 0.39, p = 0.001).ConclusionAlmost half of patients with moderate or severe COVID-19 pneumonia had impaired pulmonary diffusion six months after discharge. Severe patients showed fibrotic lesions in CT scan and elevated serum biomarkers involved in pulmonary fibrosis.     

Assessment of the acute impact of normobaric hypoxia as a part of an intermittent hypoxic training on heart rate variability

AimTo assess the dynamics of ANS by means of heart rate variability (HRV) during and after acute exposure to normobaric hypoxia, representing a single session of an intermittent hypoxic training protocol.Material and methodsTwenty four healthy males aged 28.0 ± 7.2 (mean ± SD) breathed hypoxic air (FIO2 = 12.3 ± 1.5%) for one hour delivered via hypoxicator (AltiPro 8850 Summit+, Altitude Tech, Canada). Pulse oximetry and HRV were measured before, during and after the hypoxic exposure.ResultsAt the end of the hypoxic session all of the tested subjects had higher low frequency (lnLF) (6.9 ± 1.1 ms² vs. 7.5 ± 1.1 ms²; p = 0.042), LF/HF (1.5 ± 0.8 vs. 3.3 ± 2.8; p = 0.007) and standard deviation 2 of the Poincaré plot (SD2) (92.8 ± 140.0 ms vs. 120.2 ± 54.2 ms; p = 0.005) as well as increase in the Total power (7.7 ± 1.1 ms² vs. 8.1 ± 1.2 ms²; p = 0.032) and the Standard deviation of normal-to-normal interbeat intervals (SDNN) (57.3 ± 31.0 ms vs. 72.3 ± 41.1 ms; p = 0.024) but lower Sample entropy (SampEn) (1.6 ± 0.2 vs. 1.4 ± 0.2; p = 0.010). Immediately after the hypoxic exposure LF/HF lowered (3.3 ± 2.8 vs. 2.2 ± 1.8; p = 0.001) but lnHF significantly increased (6.6 ± 1.4 ms² vs. 7.1 ± 1.3 ms²; p = 0.020).ConclusionAcute normobaric hypoxia as a part of a single session of an intermittent hypoxic training protocol leads to changes in the activity of the ANS. The sympathetic tone prevails during hypoxic exposure and parasympathetic tone increases immediately after the hypoxic factor is withdrawn.     

Effects of coffee consumption in chronic hepatitis C: A randomized controlled trial

BackgroundCoffee is associated with a reduced risk of hepatocellular carcinoma in patients with chronic C hepatitis. This prospective trial was aimed at assessing the mechanisms underlying coffee-related protective effects.MethodsForty patients with chronic hepatitis C were randomized into two groups: the first consumed 4 cups of coffee/day for 30 days, while the second remained coffee “abstinent”. At day 30, the groups were switched over for a second month.ResultsAt baseline, aspartate aminotransferase and alanine aminotransferase were lower in patients drinking 3–5 (Group B) than 0–2 cups/day (Group A) (56 ± 6 vs 74 ± 11/60 ± 3 vs 73 ± 7 U/L p = 0.05/p = 0.04, respectively). HCV-RNA levels were significantly higher in Group B [(6.2 ± 1.5) × 10⁵ vs (3.9 ± 1.0) × 10⁵ UI/mL, p = 0.05]. During coffee intake, 8-hydroxydeoxyguanosine and collagen levels were significantly lower than during abstinence (15 ± 3 vs 44 ± 16 8-hydroxydeoxyguanosine/10⁵ deoxyguanosine, p = 0.05 and 56 ± 9 vs 86 ± 21 ng/mL, p = 0.04). Telomere length was significantly higher in patients during coffee intake (0.68 ± 0.06 vs 0.48 ± 0.04 Arbitrary Units, p = 0.006). Telomere length and 8-hydroxydeoxyguanosine were inversely correlated.ConclusionIn chronic hepatitis C coffee consumption induces a reduction in oxidative damage, correlated with increased telomere length and apoptosis, with lower collagen synthesis, factors that probably mediate the protection exerted by coffee with respect to disease progression.     

Aortic stiffness is increased in patients with premature coronary artery disease: A tissue Doppler imaging study

BackgroundAtherosclerosis and arterial stiffening may coexist and the correlation of these parameters in patients with premature coronary artery disease (CAD) has not been well elucidated. Tissue Doppler imaging of the ascending aorta may be used in the assessment of elastic properties of the great arteries.ObjectiveTo investigate the correlation between aortic stiffness and premature CAD using parameters derived from two-dimensional and tissue Doppler imaging (TDI) echocardiography of the ascending aorta.MethodsFifty consecutive subjects younger than 40 years old who were hospitalized with diagnosis of acute coronary syndrome and had undergone coronary angiography were recruited. The control group included 70 age–sex matched individuals without a diagnosis of CAD. Aortic stiffness index (SI), aortic distensibility (D), and pressure-strain elastic modulus (E_p) were calculated from the aortic diameters measured by two-dimensional M-mode echocardiography and blood pressure obtained by sphygmomanometry. Aortic systolic velocity (S_Ao), and early (E_Ao) and late (A_Ao) diastolic velocities were determined by pulse-wave TDI from the anterior wall of ascending aorta 3 cm above the aortic cusps in parasternal long-axis view.ResultsStiffness index was higher [median 5.40, interquartile range (IQR) 5.98 vs. median 4.14 IQR 2.43; p = 0.03] and distensibility was lower (median 2.86 × 10⁻⁶ cm²/dyn, IQR 2.51 × 10⁻⁶ cm²/dyn vs. median 3.46 × 10⁻⁶ cm²/dyn, IQR 2.38 × 10⁻⁶ cm²/dyn; p = 0.04) in patients with CAD compared to the control group. E_Ao was significantly lower in the CAD group (7.2 ± 1.8 cm/s vs. 9.2 ± 2.4 cm/s, p < 0.01). The difference in E_Ao remained significant when CAD patients with a left ventricular ejection fraction >55% was compared to the control group. S_Ao and A_Ao velocities of ascending aorta were similar in control and CAD groups. There was a significant correlation between E_Ao velocity and aortic stiffness index (r = −0.28, p = 0.01), distensibility (r = 0.19, p = 0.04) and elastic modulus (r = −0.24, p = 0.01). In multivariate regression analysis, decreased levels of high-density lipoprotein cholesterol [odds ratio (OR): 1.12 95% CI 1.06–1.19; p = 0.01] and E_Ao (OR: 1.41 95% CI 1.12–1.79; p = 0.01) measurements remained as the variables independently correlated with premature CAD in the study group.ConclusionArterial stiffness is increased in patients with premature CAD. E_Ao of the anterior wall of ascending aorta measured with pulse-wave TDI echocardiography is correlated with arterial stiffening and is decreased in patients with premature CAD.     

Predictors of mortality in medically treated patients with congestive heart failure of nonrheumatic etiology and reduced systolic function

ObjectiveWe investigated the prognostic value of various parameters on the mortality of patients with nonrheumatic chronic heart failure and left ventricular (LV) systolic dysfunction.MethodsThis study included 132 consecutive patients with congestive heart failure and reduced LV systolic function without rheumatic valve disease. The primary outcome was mortality. Mean follow-up was 38 ± 6 months.ResultsDuring the follow-up period there were 47 deaths (35.6%). The age (64.1 ± 13.5 vs. 58.7 ± 11.8 years, P = 0.019), left bundle branch block (44.7% vs. 18.8%, P = 0.002), urea concentration (11.4 ± 5.3 vs. 8.9 ± 4.6 mmol/L, P = 0.006), LV end-diastolic and end-systolic dimensions (6.7 ± 0.8 vs. 6.4 ± 0.8 cm, P = 0.025 and 5.5 ± 0.8 vs. 4.9 ± 0.8 cm, P < 0.001, respectively), grade 3–4 mitral regurgitation (40.4 vs. 22.4%, P < 0.001), fractional shortening (16.7 ± 5.3% vs. 19.8 ± 5.7%, P = 0.002) and LV ejection fraction (32.9 ± 8.5% vs. 38.7 ± 11.3%, P = 0.003) were different between non-survivors and survivors. Multivariate analysis identified severity of mitral regurgitation (OR = 1.99, 95% CI 1.18–3.34; P = 0.009), age (OR = 1.07, 95% CI 1.02–1.12; P = 0.01) and LV end-systolic dimension (OR = 1.09, 95% CI 1.02–1.16; P = 0.014) as independent correlates of mortality.ConclusionsIn medically treated patients with nonrheumatic chronic heart failure and left ventricular systolic dysfunction, severity of mitral regurgitation, age and enlarged LV end-systolic dimension were independently associated with increased risk of death.     

Patterns of serum lipids derangements and cardiovascular risk assessment in patients with primary biliary cholangitis

Introduction and objectivesPrimary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease that disrupts the cholesterol metabolism. Our aim was to investigate the frequency of dyslipidemias and to evaluate the risk of cardiovascular events in a historic cohort of patients with PBC.PatientsAll patients attended from 2000 to 2009 with histological diagnosis of PBC were included and were compared with healthy controls. The 10-year cardiovascular risk was estimated by the Framingham risk score.ResultsFifty four patients with PBC were included and compared to 106 controls. Differences in total cholesterol (263.8 ± 123.9 mg/dl vs. 199.6 ± 40, p = 0.0001), LDL-cholesterol (179.3 ± 114.8 vs. 126.8 ± 34.7, p = 0.0001), HDL-cholesterol (62.4 ± 36.2 mg/dl vs. 47.3 ± 12.3, p = 0.0001) and triglycerides (149.1 ± 59.1 mg/dl vs. 126.4 ± 55.4, p = 0.001) were found. Hypercholesterolemia (>240 mg/dl) was found in 52.4% of the patients with PBC vs. 11% in the control group, high LDL-cholesterol (160–189 mg/dl) in 45.2% of the patients with PBC vs. 10% in controls and hyperalphalipoproteinemia (HDL-cholesterol >60 mg/dl) in 45.2% of the patients with PBC vs. 16% in controls. The 10-year cardiovascular risk was 5.3% ± 5.9 in the patients with PBC and 4.1% ± 5.7 in the control group (p = 0.723, IC 95% = 0.637–1.104). Only one cardiovascular event (stroke) in a patient with PBC was registered in a mean follow up time of 57.9 ± 36.5 months.ConclusionsMarked derangements in serum lipids and a high frequency of dyslipidemias are found in patients with PBC, however, these do not increase the risk of cardiovascular events.     

Independent relationship of serum uric acid levels with leukocytes and coronary atherosclerotic burden

Background and AimEpidemiological studies have shown that increased serum uric acid (SUA) level is associated with coronary artery disease (CAD). Leukocytes have been shown to play an important role in the atherosclerotic process. The aim of the study was to investigate whether there is any relationship among SUA, leukocyte counts and coronary atherosclerotic burden in patients who are suspected of having CAD.Method and resultsWe enrolled 690 eligible patients who had undergone coronary angiography between October 2005 and June 2006 in a consecutive manner. The relationship of SUA with total and differential leukocyte counts and CAD was investigated. Serum uric acid levels (5.57 ± 1.64 vs 4.63 ± 1.27 mg/dl, p < 0.001) and leukocytes were higher in patients with CAD than those with normal coronary arteries (NCA). When we divided the patients into four groups according to the quartiles of SUA, we found that the monocyte count was prominently related with SUA (478 ± 165, 553 ± 177, 565 ± 199 and 607 ± 229 mm⁻³, Q1–Q4, p < 0.001). In multivariate analysis, SUA was an independent predictor of CAD (OR, 1.270; 95% CI, 1.087–1.484, p = 0.003). When we performed multiple linear regression analyses to determine the independent predictors of inflammatory cells in blood, we found a strong, positive and independent relationship between SUA with neutrophils (β ± SE: 206 ± 60, p = 0.001) and monocytes (β ± SE: 35 ± 7, p < 0.001).ConclusionOur study results demonstrated that neutrophils and monocytes which play an important role in inflammation and atherosclerosis were independently related with SUA. This finding suggests an important epidemiologic relation and may provide a possible causative mechanism of SUA in atherosclerotic process.     

Association between circadian rhythm of blood pressure and glucose tolerance status in normotensive,non-diabetic subjects

AimsTo examine whether circadian rhythm of blood pressure (BP) is associated with glucose tolerance status in normotensive, non-diabetic subjects.MethodsA cross-sectional study recruited normotensive and non-diabetic subjects, aged 35–79 years. A 75 g oral glucose tolerance test (OGTT) and 24-h ambulatory blood pressure monitoring (24-h ABPM) were performed.ResultsAmong 31 impaired glucose tolerance (IGT) and 36 normal glucose tolerance (NGT) study subjects, the mean (±S.D.) diurnal–nocturnal differences of average systolic BP (SBP) were 7.1 ± 6.9 and 9.9 ± 6.2 mm Hg, respectively (p = 0.086). In a linear mixed-effects regression model, however, taking each measurement of BP as the outcome, nighttime reduction of SBP in the IGT group was 7.19 mm Hg, which was significantly smaller compared to a reduction of 9.80 mm Hg in the NGT group (p-value for IGT: nighttime interaction = 0.0014). The prevalence of non-dipping BP pattern was 77.4% in the IGT group which was significantly higher than 52.8% of the NGT group (p = 0.036). Logistic regression revealed a significant effect of IGT for predicting non-dipping pattern with an adjusted odds ratio of 3.71 (95% CI: 1.09, 12.66, p = 0.029).ConclusionsAmong normotensive, non-diabetic subjects, the decreased nocturnal BP reduction was associated with impaired glucose tolerance status.     

Desarrollo de un modelo murino de inflamación y remodelación de vías respiratorias en asma experimental

Background and ObjectiveExperimental animal models are necessary for studying asthma disease mechanisms and for identifying new therapeutic targets. We present a murine model of experimental asthma that allows integrated, quantitative assessment of airway inflammation and remodeling.Material and MethodsBALB/c mice were sensitized to ovalbumin (OVA) and challenged with OVA or vehicle 3 times per week for 12 weeks.ResultsOn bronchoalveolar lavage, the OVA-sensitized mice had significantly higher total leukocyte counts, with a median (Q25–Q75) of 670.0 cells/mL×10³ (376.2, 952.5) in comparison with 40.0 cells/mL×10³ (60.0–85.0) in controls (P=.001), and higher eosinophil and differential lymphocyte counts. In sagittal sections of lungs inflated to a standard pressure, the OVA-sensitized animals showed goblet cell hyperplasia in the respiratory epithelium (periodic acid-Schiff staining, 53.89 [36.26–62.84] cells/mm² vs 0.66 [0.00–1.06] cells/mm², P<.001), dense mononuclear and eosinophilic inflammatory infiltrates (hematoxylin-eosin, 32.87 [27.34–37.13] eosinophils/mm² vs 0.06 [0.00–0.20] eosinophils/mm², P=.002), subepithelial infiltration by mast cells (toluidine blue, 2.88 [2.00–3.28] mast cells/mm² vs 0.28 [0.15–0.35] mast cells/mm², P<.001), increased contractile tissue mass (immunofluorescence analysis for α-smooth-muscle actin, 2.60 [2.28–2.98] vs 1.08 [0.93–1.16], dimensionless, P<.001) and enhanced extracellular matrix deposition (Masson's trichrome, 2.18 [1.85–2.80] vs 0.50 [0.37–0.65], dimensionless, P<.001).ConclusionsOur dataset describes an experimental model of asthma which is driven by prolonged allergen exposure and in which airway inflammation and remodeling develop and are assessed together.     

Independent inverse relationship between serum lycopene concentration and arterial stiffness

ObjectiveEmerging evidence suggests a role of lycopene in the primary prevention of cardiovascular disease. This study aimed to investigate the association of serum lycopene concentration with brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness and markers of oxidative stress and inflammation.Methodshealthy women (n = 264, 31–75 yrs) were classified into tertiles according to serum lycopene concentration. Multivariate linear regression analyses were used to assess the relationship between serum lycopene and baPWV.ResultsSubjects in middle tertile (T2) and upper tertile (T3) had lower baPWV (1263 ± 23 and 1265 ± 14 cm/s vs. 1338 ± 21 cm/s; p = 0.009) and lower oxidized LDL (oxLDL) (53 ± 3 and 55 ± 3 U/L vs. 66 ± 3U/L; p < 0.001) than those in lower tertile (T1). Subjects in T3 showed higher LDL particle size (24.3 ± 0.08 nm vs. 24.0 ± 0.07 nm, p = 0.005) and lower C-reactive protein (hs-CRP) (0.80 ± 0.25 mg/dL vs. 1.27 ± 0.24 mg/dL, p = 0.015), compared with those in T1. Logistic regression analysis showed that baPWV decreased with the increment of lycopene concentration; log baPWV decreased by 0.21 cm/s (95% CI ?0.168;?0.045, p = 0.001) per unit change in lycopene. After adjustment for age, BMI, smoking, drinking, menopause and blood pressure, the estimated effect was attenuated by 35%, but remained statistically significant [?0.13 cm/s (95% CI ?0.112;?0.018, p = 0.006)]. Further adjustment for β-carotene, α-tocopherol, oxLDL, LDL particle size, and hs-CRP increased the strength of the association [β = ?0.221 (95% CI ?0.215;?0.012, p = 0.029)].ConclusionThis study supports the presence of an independent inverse relationship between circulating lycopene and baPWV. Additionally, reduced oxidative modification of LDL may be one of mediators on the mechanisms how lycopene reduces arterial stiffness.     

Metabolic syndrome and albuminuria show an additive effect in modulating glomerular filtration rate in patients with Type 2 Diabetes Mellitus

BackgroundAlthough metabolic syndrome (MetSyn) or albuminuria (MA) most often occurs in concomitance in Type 2 Diabetes Mellitus patients (T2DM), their mode of interaction in increasing the risk of low glomerular filtration rate (GFR) has been poorly investigated.ObjectiveWe evaluated in a cohort of 1659 T2DM patients the relationship between MetSyn and MA in modulating the risk for low GFR. The risk of developing low GFR by graded number of MetSyn traits was also evaluated.MethodsThis was a cross-sectional study where 1659 T2DM patients were studied. Low GFR was defined as estimated-GFR (e-GFR) <60 ml min^?1 × 1.73 m^?2 (modification of diet in renal disease, MDRD, formula).Resultse-GFR progressively decreased from 91 ± 25 of patients MetSyn?MA?, to 82 ± 27 of patients MetSyn?MA+, 81 ± 24 of patients MetSyn+MA? and 76 ± 30 ml min^?1 × 1.73 m^?2 of patients MetSyn+MA+ (adjusted p < 0.0001). A progressive gradient of the frequency of patients with low e–GFR with concomitance of MetSyn and MA was also observed [MetSyn?MA? (6.1%), MetSyn?MA+ (15.3%), MetSyn+MA?(16.6%), MetSyn+MA+ (26.8%); p < 0.0001]. As compared to patients with MetSyn?MA?, the risk progressively increased to 2.80 (95% C.I. 1.46–5.37; p = 0.002) in MetSyn+MA?, to 2.83 (95% C.I. 1.12–7.10; p = 0.027) in MetSyn?MA+ and to 5.73 (95% C.I. 2.99–10.9; p < 0.0001) in MetSyn+MA+ patients. Estimated-GFR progressively decreased by number of MetSyn traits in the whole population (adjusted p < 0.0001).ConclusionsMetSyn or MA has an additive effect in increasing the risk of having low GFR in patients with T2DM. Furthermore, e-GFR is negatively affected by graded number of MetSyn traits independently of albuminuria.     

Pilot trial of diabetes self-management education in the hospital setting

AimsDiabetes self-management education (DSME) is recommended for all patients with diabetes. Current estimates indicate that <50% of patients receive DSME, increasing risk for hospitalization which occurs more frequently with diabetes. Hospitalization presents opportunities to provide DSME, potentially decreasing readmissions. To address this, we investigated the feasibility of providing DSME to inpatients with diabetes.MethodsPatients hospitalized on four medicine units were randomized to receive DSME (Education Group) (n = 9) prescribed by a certified diabetes educator and delivered by a registered nurse, or Usual Care (n = 12). Participants completed Diabetes Knowledge Tests (DKT), Medical Outcomes Short Form (SF-36), Diabetes Treatment Satisfaction Questionnaire (DTSQ), and the DTSQ-inpatient (DTSQ-IP). Bedside capillary blood glucoses (CBG) on day of admission, randomization and discharge were compared.ResultsThere were no group differences in demographics, diabetes treatment, admission CBG (186 ± 93 mg/dL vs. 219 ± 84 mg/dL, p = 0.40), DKT scores (Education vs. Usual Care 48 ± 25 vs. 68 ± 19, p = 0.09), SF-36, and DTSQ scores (28 ± 6 vs. 25 ± 7, p = 0.41). Patients receiving education reported more satisfaction with inpatient treatment (83 ± 13 vs. 65 ± 19, p = 0.03), less hyperglycemia prior to (2.7 ± 4.5 vs. 4.5 ± 1.4, p = 0.03) and during hospitalization (3.9 ± 1.9 vs. 5.5 ± 1.2, p = 0.04); and had lower mean discharge CBG (159 ± 38 mg/dL vs. 211 ± 67 mg/dL, p = 0.02).ConclusionsInpatient diabetes education has potential to improve treatment satisfaction, and reduce CBG.     

Intestinal permeability is increased in children with non-alcoholic fatty liver disease,and correlates with liver disease severity

BackgroundIncreased intestinal permeability seems to play a major role in non-alcoholic liver disease development and progression.AimTo investigate the prevalence of altered intestinal permeability in children with non-alcoholic fatty liver disease, and to study its potential association with the stage of liver disease.MethodsWe performed a case–control study examining intestinal permeability in children using the lactulose–mannitol bowel permeability test.ResultsOverall, 39 consecutive patients (30 males, median age 12 years) and 21 controls (14 males, median age 11.8 years) were included. The lactulose/mannitol ratio resulted impaired in 12/39 patients (31%) and none of the controls. Intestinal permeability was higher in children with non-alcoholic fatty liver disease (lactulose/mannitol ratios: 0.038 ± 0.037 vs. 0.008 ± 0.007, p < 0.05). Within the non-alcoholic fatty liver disease group, intestinal permeability was increased in children with steatohepatitis compared to those with steatosis only (0.05 ± 0.04 vs. 0.03 vs. 0.03, p < 0.05). Pathological lactulose/mannitol ratio correlated with portal inflammation (p = 0.02), fibrosis (p = 0.0002), and ballooning of hepatocytes (p = 0.003). Blood lipopolysaccharides levels were higher in children with steatohepatitis (2.27 ± 0.68 vs. 2.80 ± 0.35, p < 0.05).ConclusionsIntestinal permeability is increased in children with non-alcoholic fatty liver disease, and correlates with the severity of the disease.