Serum Growth Arrest-Specific Protein 6 Levels are a Reliable Biomarker of Disease Activity in Systemic Lupus Erythematosus

Purpose

Growth arrest-specific protein 6 (Gas6) has been suggested to be a biomarker of disease activity in patients with systemic lupus erthematosus (SLE). We investigated the clinical significance of this protein in Korean SLE.

Methods

Blood samples were collected from 150 SLE patients and 50 normal controls (NC). In addition, follow-up samples were collected from 50 SLE patients.

Results

Serum Gas6 levels of SLE patients (43.01?±?28.02 ng/mL) were higher than those of NC (20.15?±?9.23 ng/mL, p?<?0.001). When evaluated sensitivity and specificity of the Gas6 for diagnosing SLE using ROC curves, the sensitivity and specificity were 72.7 % and 84 % with a cut-off value of 25.3 ng/mL. In the ROC analysis of Gas6, anti-dsDNA antibody, ESR, complement 3 and complement 4 to identify patients with active lupus, area under the curve (AUC) of Gas6 was highest with 0.763. Serum Gas6 levels were significantly higher in the patients with serositis (70.04?±?30.85 ng/mL) and renal disorder (65.66 ±32.28 ng/mL) compared to those without (41.88?±?27.44 ng/mL, p?=?0.033, 40.3?±?26.33 ng/mL, p?=?0.001, respectively). Gas6 levels were correlated positively with anti-dsDNA antibody (r?=?0.199, p?=?0.015), ESR (r?=?0.204, p?=?0.013) and SLEDAI (r?=?0.512, p?<?0.001). In addition, serum Gas6 levels were correlated negatively with hemoglobin (r?=??0.165, p?=?0.043), lymphocyte count (r?=??0.165, p?=?0.043), complement 3 (r?=??0.343, p?<?0.001) and complement 4 (r?=??0.316, p?<?0.001). Furthermore, change in serum Gas6 levels was correlated with change in SLEDAI levels in the SLE patients that were followed up (r?=?0.524, p?<?0.001).

Conclusion

These results suggest that serum Gas6 can be a reliable clinical marker for monitoring disease activity and treatment response in SLE.     

Prolactin and Autoimmunity

Evidence points to an association of prolactin to autoimmune diseases. We examined the correlation between hyperprolactinemia and disease manifestations and activity in a large patient cohort. Age- and sex-adjusted prolactin concentration was assessed in 256 serum samples from lupus patients utilizing the LIASON prolactin automated immunoassay method (DiaSorin S.p.A, Saluggia, Italy). Disease activity was defined as present if European Consensus Lupus Activity Measurement (ECLAM)?>?2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)?>?4. Lupus manifestations were grouped by organ involvement, laboratory data, and prescribed medications. Hyperprolactinemia was presented in 46/256 (18%) of the cohort. Hyperprolactinemic patients had significantly more serositis (40% vs. 32.4%, p?=?0.03) specifically, pleuritis (33% vs. 17%, p?=?0.02), pericarditis (30% vs. 12%, p?=?0.002), and peritonitis (15% vs. 0.8%, p?=?0.003). Hyperprolactinemic subjects exhibited significantly more anemia (42% vs. 26%, p?=?0.02) and marginally more proteinuria (65.5% vs. 46%, p?=?0.06). Elevated levels of prolactin were not significantly associated with other clinical manifestations, serology, or therapy. Disease activity scores were not associated with hyperprolactinemia. Hyperprolactinemia in lupus patients is associated with all types of serositis and anemia but not with other clinical, serological therapeutic measures or with disease activity. These results suggest that dopamine agonists may be an optional therapy for lupus patients with hyperprolactinemia.     

Correlation of methicillin-resistant Staphylococcus aureus vancomycin minimal inhibitory concentration results by Etest and broth microdilution methods with population analysis profile: lack of Etest overestimation of the MIC

Methicillin-resistant Staphylococcus aureus (MRSA) vancomycin minimum inhibitory concentrations (V-MICs) are sometimes reported to be higher according to Etest versus broth microdilution (BMD). These observations are often interpreted as an Etest overestimation of the actual MIC. We measured V-MIC of 484 MRSA blood isolates using Etest, BMD, and a modified BMD (M-BMD) with incremental dilutions parallel to the Etest scale, correlated the results with population analysis profile–area under the curve (PAP-AUC). All MIC tests were done in parallel. The mean V-MIC was comparable (1.83?±?0.44 [Etest], 1.88?±?0.67 [BMD] and 1.75?±?0.57 mg/L [M-BMD]; p?=?0.9 [ANOVA]). The V-MICs/PAP-AUC correlation coefficient was 0.555 (Etest), 0.513 (BMD), and 0.586 (M-BMD). Etest MICs were equal (44.2 %), one dilution higher (21.9 %), two dilutions higher (2.5 %), one dilution lower (29.8 %), and two dilutions lower (1.6 %) than BMD MICs and were equal (61.5 %), one dilution higher (28.3 %), two dilutions higher (0.4 %), one dilution lower (9.5 %), and two dilutions lower (0.2 %) than M-BMD MICs. The mean PAP-AUC for Etest vs M-BMD among isolates with similar Etest/M-BMD MIC values was 0.25?±?0.15 vs 0.35?±?0.13 (p?=?0.8), 0.46?±?0.16 vs 0.50?±?0.17 (p?=?0.8), 0.64?±?0.19 vs 0.67?±?0.21 (p?=?0.9), and 0.90?±?0.31 vs 0.88?±?0.25 (p?=?1.0) for isolates with V-MIC of ≤1, 1.5, 2, and ≥3 mg/L respectively. These results suggest that Etest might not overestimate V-MIC in comparison to M-BMD or BMD; Etest and M-BMD tests depict comparable PAP-AUC and have a higher correlation with PAP-AUC than the conventional BMD, probably because of the more detailed results. Etest may be more suitable than conventional BMD for MIC outcome assessment because of the more detailed MICs.     

Activity of ethanol and daptomycin lock on biofilm generated by an in vitro dynamic model using real subcutaneous injection ports

Vancomycin lock solution (LS) is recommended for the conservative treatment of subcutaneous injection port (SIP)-related infections, but may be associated with failure. We used an in vitro dynamic model of biofilm formation in an SIP, based on a continuous flow circulating via a real SIP, to assess the effectiveness of vancomycin (5 mg/ml), daptomycin (5 mg/ml) and ethanol 40 % LS in eradicating a pre-established Staphylococcus epidermidis biofilm. Heparin, Ringer’s lactate and enoxaparin sodium LS were used as controls. The logarithmic reductions of colony-forming units (CFU) were compared by Student’s t-test. After 24 h of exposure, the vancomycin LS did not exert a greater bactericidal effect than the heparin LS control (mean logarithmic reduction: 2.27?±?0.58 vs. 1.34?±?0.22, respectively, p?=?0.3). The mean logarithmic reduction was greater with daptomycin LS (5.45?±?0.14 vs. 0.39?±?0.12, p?<?0.01) and ethanol LS (6.79?±?1.03 vs. 1.43?±?0.54, p?=?0.02). Bacterial revival after exposure to 24 h of LS was assessed. The mean viable bacteria count was significantly higher for vancomycin LS (9.36?±?0.10 log₁₀CFU) and daptomycin LS (9.16?±?0.02 log₁₀CFU) than for ethanol LS (2.95?±?1.65 log₁₀CFU). Ethanol appeared to be the most attractive option to treat SIP-related infection, but its poor ability to entirely disrupt the biofilm structure may require its use in association with a dispersal agent to avoid renewal of the biofilm.     

The association of urinary interferon-gamma inducible protein-10 (IP10/CXCL10) levels with kidney allograft rejection

Background

Interferon-gamma inducible protein-10 (IP-10/CXCL10) is a chemokine involved in the alloimmune response against kidney allograft. We aimed to investigate the association of urinary CXCL10 protein levels with rejection in renal transplant patients.

Methods

A total of 273 urine samples from (biopsy-proven) rejection and non-rejection patients and controls were included in this study. CXCL10 levels were analyzed for association with rejection.

Results

The data showed statistically significant differences in the CXCL10 levels between rejection vs. non-rejection (p?<?0.001). Among the rejection groups, statistically significant differences for CXCL10 levels were found between ACR vs. NAD (p?<?0.001), ACR vs. BLR (p?=?0.019) and AVR vs. NAD (p?=?0.009). Receiver Operating Characteristic (ROC) curve analysis of CXCL10 showed an area under the curve (AUC) of 0.74 with 72% sensitivity and 71% specificity at 27.5 pg/ml between rejection and non-rejection group. Kaplan–Meier curve analysis among different levels of CXCL10 showed a better rejection-free graft survival in patients with <100 pg/ml when compared to >200 pg/ml (38?±?6 vs. 12?±?1.0 weeks; log-rank p?<?0.001) and 100–200 pg/ml (38?±?6 vs. 22?±?9 weeks; log-rank p?=?0.442) concentration.

Conclusion

The results indicate significantly increased levels of CXCL10 protein in the urine at the time of allograft rejection. This association of urinary CXCL10 protein levels with rejection could provide an additional tool for the non-invasive monitoring of allograft rejection.

     

White Blood Cell Subtypes after STEMI: Temporal Evolution, Association with Cardiovascular Magnetic Resonance��Derived Infarct Size and Impact on Outcome

The evolution of white blood cells after ST elevation myocardial infarction (STEMI) and their association with infarct size and major adverse cardiac events (MACE) remains unclear. Two hundred eleven patients underwent CMR after STEMI. Infarct mass (grams) was determined. Neutrophil, lymphocyte, and monocyte counts (×1,000 cells/ml) were measured upon arrival and at 12, 24, 48, 72, and 96 h. Patients with large infarctions (3rd tertile????28.5 g vs. 1st and 2nd tertiles?<?28.5 g) showed a larger neutrophil count at 12 h (14.8?±?4.8 vs. 11.4?±?3.3, p?<?0.0001) and an increased monocyte count (maximum at 24 h (0.65[0.50?C0.91] vs. 0.55[0.42?C0.71], p?=?0.004)) but no difference in lymphocyte count. Neutrophil count at 12 h independently predicted large infarctions (OR 1.14, 95%CI [1.04?C1.26], p?=?0.008). During follow-up (median 504 days), 25 MACE occurred. Neutrophil count at 96 h independently predicted MACE (HR 1.2, 95%CI [1.1?C1.4], p?=?0.003). Large infarctions show a marked neutrophil peak and an increasing monocyte count. Neutrophil count independently predicts large infarctions and MACE.     

The influence of ice slurry ingestion on maximal voluntary contraction following exercise-induced hyperthermia

The purpose of this study was to determine whether ingestion of a small bolus of ice slurry (1.25?g?kg^?1) could attenuate the reduction in maximal voluntary isometric contraction (MVC) torque output during a 2-min sustained task following exercise-induced hyperthermia. On two separate occasions, 10 males (age: 24?±?3?years, $ \dot{V}{\text{O}}_{{ 2 {\text{peak}}}} $ : 49.8?±?4.7?ml?kg^?1?min^?1) ran to exhaustion at their first ventilatory threshold in a hot environment (34.1?±?0.1°C, 49.5?±?3.6% RH). Prior to and after exercise, subjects performed a 2-min sustained MVC of the right elbow flexors in a thermoneutral environment (24.6?±?0.8°C, 37.2?±?4.5% RH). The post exercise MVC was performed immediately following the ingestion of either 1.25?g?kg^?1 of ice slurry (?1°C; ICE) or warm fluid (40°C; CON), in a counterbalanced and randomised order. Run time to exhaustion (42.4?±?9.5 vs. 41.7?±?8.7?min; p?=?0.530), and rectal (39.08?±?0.30 vs. 39.08?±?0.30°C; p?=?0.934) and skin temperatures (35.26?±?0.65 vs. 35.28?±?0.67°C; p?=?0.922) and heart rate (189?±?5 vs. 189?±?6 beats?min^?1; p?=?0.830) at the end of the run were similar between trials. Torque output during the post-exercise 2-min sustained MVC was significantly higher (p?=?0.001) following ICE (30.75?±?16.40?Nm) compared with CON (28.69?±?14.88?Nm). These results suggest that ice slurry ingestion attenuated the effects of exercise-induced hyperthermia on MVC, possibly via internal thermoreceptive and/or temperature-related sensory mechanisms.     

A study on the antioxidant defense system of psoriasis patients in the ethnic population of Kashmir-India

The study was designed to evaluate the role of antioxidant defense system in the etiology of psoriasis, a chronic skin disorder of complex etiology and pathology. Hospital-based case–control study was carried out in major referral hospital in Kashmir, North India. Cases (N?=?40) were composed of patients with psoriasis vulgaris, and controls (N?=?20) were healthy volunteers. Study included estimation in plasma of both patients and controls of glutathione (GSH) levels, superoxide dismutase (SOD) activity, and total antioxidant potential (AOP) as indices of antioxidant defense system and malondialdehyde (MDA) as a measure of lipid peroxidation (LP), an indicator of oxidative stress. The GSH levels, SOD activity, AOP, and malondialdehyde levels in plasma of psoriasis patients were 2.58?±?0.22 μM/l, 5.24?±?0.69 U/ml, 0.020?±?.011?nmol^?1/ml?h, and 0.88?±?0.20 nmol/ml and were 4.76?±?0.52 μM/l, 4.14?±?0.56U/ml, 0.042?±?0.018 nmol^?1/ml?h, and 0.53?±?0.16 nmol/ml in healthy voluntary controls, respectively. A significant decrease in GSH levels (p?<?0.005) and AOP (p?<?0.005) and significant increase in SOD activity (p?<?0.01) MDA levels (p?<?0.005) as an indicator of LP was observed.     

Role of serum pro-hepcidin and GSTM1 and GSTT1 null polymorphisms for estimation of the risk of myocardial siderosis in children and “young adults” with β-thalassemia major

This study aims to evaluate the serum pro-hepcidin level in β-thalassemia patients, to clarify its relation with serum level of ferritin and to assess the possible role of null polymorphisms of glutathione S-transferase genes, GSTM1 and GSTT1, for susceptibility to β-thalassemia and myocardial siderosis. The serum level of pro-hepcidin was assessed in 31 patients [16 children (52 %) and 15 young adults (48 %)] with β-thalassemia and nine healthy individuals [four children (44 %) and five young adults (56 %)] applying ELISA method. Genotyping for the null polymorphisms of GSTM1 and GSTT1 was performed successfully by multiplex PCR in 17 patients and in 40 healthy individuals, which were enrolled in the case–control study for assessment of the role of these polymorphisms as risk factors for β-thalassemia. The mean serum level of pro-hepcidin in patients did not differ significantly (159.12?±?70.12 ng/ml) from that in controls (144.64?±?53.30 ng/ml). We found a significant positive correlation with the serum ferritin (R?=?0.371, p?=?0.039). In addition, there was an association between the serum pro-hepcidin and the type of chelating therapy. The frequency of GSTT1 null genotypes was significantly higher in patients than in controls (0.29 vs. 0.07, p?=?0.025). We observed tendencies for a higher serum ferritin and lower value of ejection fraction of the left ventricle (EFLV) of the patients carrying GSTT1 null genotypes than those with non-null GSTT1 genotypes. The serum levels of pro-hepcidin is not the most precise markers of iron overload and organ dysfunction, but it could be considered as a relatively good alternative of the serum ferritin as an index of iron stores. In addition, we suggest that GSTT1 null genotype could be considered as a predisposing factor for β-thalassemia, myocardial siderosis, and dysfunction in patients with this disease.     

Serum C-reactive Protein Level and Distribution in Chronic Obstructive Pulmonary Disease Versus Healthy Controls: a Case–Control Study from Iran

Inflammation has a contributive role in the development and progression of chronic obstructive pulmonary disease (COPD).The present study was designed to determine the level and the distribution of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in COPD compared with controls. Ninety patients with COPD presented to an outpatient hospital clinic and 50 controls who were selected among personals of the same hospital entered the study. Serum high sensitive CRP (hs-CRP) was measured by immunoturbidimetric method and the ESR by Westergren method. Receiver operating characteristic curve was applied to determine a cutoff point for differentiation of the COPD and control group. In statistical analysis, the patients and controls were compared regarding levels and distribution of hs-CRP and ESR. Mean age of patients and controls was 67?±?11.6 and 51.3?±?6.7 years, respectively (p?=?0.001). Mean hs-CRP was significantly higher (4.76?±?5.6 vs 1.72?±?1.68 mg/L, p?=?0.001) but mean ESR was nonsignificantly higher (9.1?±?11.2 vs 7.2?±?7.4 m/h, p?=?0.95) in patients than control. Serum hs-CRP at 1.55 mg/L, differentiated patients and controls at sensitivity of 77.3 % and specificity of 60 %. Serum hs-CRP >3 mg/L was observed in 39 (44.3 %) patients and 9 (18 %) controls (p?=?0.001) and >6 mg/L in 22 (25 %) patients and 2 (4 %) controls (p?=?0.001).Serum hs-CRP was significantly correlated with ESR in patient but not in control group (Spearman correlation coefficient?=?0.516, p?=?0.001). Serum hs-CRP and ESR was not correlated with age, weigh, smoking, and the severity of COPD. The results of this study indicated a systemic inflammatory process in COPD. Since inflammation has an important contribution in development of future pulmonary and extrapulmonary complications, serum CRP assessment will provide additional information beyond that achieved by conventional method of pulmonary function test.     

Selenium and lipid subfractions in Egyptian type 2 diabetes patients

The purpose of this study was to examine the relationship between serum selenium (Se) levels and lipid subfraction among Egyptian type 2 diabetes patients and their association with the severity of the disease. The study was conducted on 60 type 2 diabetic adults with BMI <30 divided according to disease duration into two groups: group 1 with disease duration less than 5 years and group 2 with a disease duration more than 5 years. Thirty age- and sex-matched apparently healthy volunteers were considered as the control group. Serum selenium was measured by atomic absorption spectrometry lipid subfractions including small dense low density lipoprotein (sd LDL) which was measured by enzyme-linked immunosorbent assay and glycated hemoglobin (HbA1c) by high-performance liquid chromatography. All participants do not receive Se supplementation. The mean serum Se level in participants with diabetes was as follows: group 2?=?62.70?±?5.73, group 1?=?70.58?±?4.158, and control subjects?=?79.80?±?5.37 μg/l (p?=?0.00). Se was found to be an independent protective factor with an OR of 0.29 and 95 % CI of 0.06–1.3. Mean serum sd LDL in participants with diabetes was as follows: group 2?=?43.81?±?13.70, group 1?=?25.77?±?5.28, and control group?=?15.99?±?5.32 (p?=?0.00). Correlation study, between studied parameters, revealed positive correlation between sd LDL and apolipoprotein B (Apo B) (r?=?0.730, p?=?0.001). On the other hand, negative correlation was encountered between apolipoprotein A (Apo A) and Apo B (r?=??0.514, p?=?0.001) as well as Apo A and sd LDL (r?=??0.697, p?=?0.001). Selenium correlated negatively with both Apo B (r?=??0.669, p?=?0.001) and sd LDL (r?=??0.671, p?=?0.001) and positively with Apo A (r?=?0.513, p?=?0.001). In a sample of the Egyptian population, low serum Se levels were positively associated with the prevalence of diabetes. Until findings from prospective studies and randomized controlled trials are available, Se intake, including Se supplementation, should be recommended for primary or secondary diabetes prevention in populations with inadequate selenium status.     

Clinical presentation of Puumala virus infections in southern Austria in the peak year 2012

In 2012, an extraordinary rise in Puumala infections causing nephropathia epidemica (NE) was observed in southern Austria. We investigated differences in epidemiology, clinical presentation, laboratory results, treatment parameters, and outcome between patients in 2012 and previous years (2007–2011). All patients diagnosed with Puumala virus infections between 2007 and 2012 using a point of care Puumala IgM test at the microbiology laboratory, Department of Internal Medicine, Medical University of Graz, were included. In 2012, 42 and in 2007–2011 a total of 40 patients were diagnosed with NE. In 2007–2011, patients presented more frequently with arthromyalgias (25 % vs 7 %, p?=?0.027), while lower back pain was reported more often in 2012 (21 % vs 5 %, p?=?0.029). Other symptoms occurred at the same rate. In 2012, patients were diagnosed significantly faster (time from first contact with a physician to diagnosis 1.3?±?0.2 vs 2.7?±?0.4 days, p?=?0.01). Significantly fewer patients required haemodialysis in 2012 (2.4 % vs 20 %, p?=?0.01). There were no significant differences in laboratory parameters between the two groups. In the peak year 2012, patients were diagnosed faster and fewer patients required haemodialysis possibly because of the earlier diagnosis and earlier onset of therapy.     

Impact of Helicobacter pylori eradication on refractory thrombocytopenia in patients with chronic HCV awaiting antiviral therapy

The possibility of delaying treatment of HCV due to severe thrombocytopenia is challenging. This study aimed to detect the prevalence of active helicobacter infection as a claimed cause of thrombocytopenia in a cohort of Egyptian patients with chronic active HCV awaiting combined anti-viral therapy. The study included 400 chronic HCV patients with thrombocytopenia. Laboratory investigations included liver function tests, real time quantitative PCR, reticulocytic count, ESR, ANA, bone marrow aspiration, measurement of anti-helicobacter antibodies, and helicobacter stool antigen. Positive cases for active H. pylori were given the standard triple therapy for 2 weeks. Helicobacter stool antigen was detected 4 weeks after termination of therapy and the change in platelet count was detected 1 month after eradication. A total of 248 out of 281 seropositive patients for H. pylori (88.3 %) showed positive stool antigen (p?=?0.01). Eradication was achieved in 169 (68.1 %) patients with platelet mean count 114.9?±?18.8?×?10³/μl with highly significant statistical difference from pretreatment value (49.7?±?9.2?×?10³/μl, p?=?0.000). Seventy-nine patients were resistant to conventional triple therapy and given a 7-day course of moxifloxacin-based therapy; 61 patients responded (77.1 %) with mean platelet improvement from 76.4?±?17.4?×?10³/μl to 104.2?±?15.2?×?10³/μl (p?=?0.000). The non-responders showed no improvement in their platelet count (74.6?±?20.5 vs. 73.6?±?15.3?×?10³/ul, P?=?0.5). Eradication of active H. pylori in HCV augments platelet count and enhances the early start of antiviral therapy.     

Differences in clotting parameters between species for preclinical large animal studies of cardiovascular devices

Several species of domestic animals are used in preclinical studies evaluating the safety and feasibility of medical devices; however, the relevance of animal models to human health is often not clear. The purpose of this study was to compare the clotting parameters of animal models to determine which animals most adequately mimic human clotting parameters. The clotting parameters of the different species were assessed in whole blood by in vitro thromboelastography using the clotting activators, such as tissue factor (extrinsic clotting screening test, EXTEM^®) and partial thromboplastin phospholipid (intrinsic clotting screening test, IINTEM^®). The measurements were performed using normal blood samples from humans (n?=?13), calves (n?=?18), goats (n?=?56) and pigs (n?=?8). Extrinsic clotting time (CT) and the intrinsic CT were significantly prolonged in calves compared to humans (249.9?±?91.3 and 376.4?±?124.4 s vs. 63.5?±?11.8 and 192.5?±?29.0 s, respectively, p?<?0.01). The maximum clot firmness (MCF) in domestic animals (EXTEM^®: 77–87 mm, IINTEM^®: 66–78 mm) was significantly higher than that of humans (EXTEM^®: 59.1?±?6.0 mm, IINTEM^®: 58.8?±?1.5 mm, p?<?0.01), and calves and goats exhibited longer time to MCF (MCF-t) than did humans and pigs (p?<?0.01). Our results show that there are relevant differences in the four species’ extrinsic and intrinsic clotting parameters. These cross-comparisons indicate that it is necessary to clarify characteristics of clotting properties in preclinical animal studies.     

Asthma and Hypogammaglobulinemia: an Asthma Phenotype with Low Type 2 Inflammation

Purpose

Little is known about hypogammaglobulinemia (HGG) in asthma patients. No data are available on the characteristics of adult patients with asthma and HGG.

Methods

We conducted a retrospective monocentric study between January 2006 and December 2012. Asthma patients with a serum immunoglobulin (Ig) quantitative analysis were included and classified into two groups depending on their serum IgG concentration: presence or absence of HGG. Clinical, biological, functional, and radiologic characteristics were compared in univariate and multivariate analysis, using a logistic regression model.

Results

In univariate analysis, asthma patients with HGG (n?=?25) were older (58 years old?±?18 vs 49?±?18, p?=?0.04) and more frequently active or former smokers as compared to patients with normoglobulinemia (n?=?80) (56.0 vs 35.0 %, p?=?0.01). Total IgE?<?30 kUI/L was more frequently observed in patients with HGG (53.0 vs 18.3 %, p?=?0.01). HGG asthma patients had lower fraction of exhaled nitric oxide (p?=?0.02), blood eosinophilia (p?=?0.0009), and presented with more severe composite score for bronchiectasis (p?=?0.01). In multivariate analysis, asthma patients with HGG had increased risk of being smokers [OR?=?6.11 (IC 95 %?=?1.16–32.04)], having total IgE concentration?<?30 kUI/L [OR?=?12.87 (IC 95 %?=?2.30–72.15)], and a more severe composite score of bronchiectasis [OR?=?20.65 (IC 95 %?=?2.13–199.74)].

Conclusion

Asthma patients with HGG are older and more often tobacco smoker than asthma patients without HGG. These patients have low type-2 inflammation markers.

     

Altered ventriculo-arterial coupling during exercise in athletes releasing biomarkers after endurance running

Exercise can lead to release of biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), a poorly understood phenomenon proposed to especially occur with high-intensity exercise in less trained subjects. We hypothesised that haemodynamic perturbations during exercise are larger in athletes with cTnT release, and studied athletes with detectable cTnT levels after an endurance event (HIGH; n?=?16; 46?±?9?years) against matched controls whose levels were undetectable (LOW; n?=?11; 44?±?7?years). Echocardiography was performed at rest and at peak supine bicycle exercise stress. Left ventricular (LV) end-systolic elastance (E _LV a load-independent measure of LV contractility), effective arterial elastance (E _A a lumped index of arterial load) and end-systolic meridional wall stress were calculated from cardiac dimensions and brachial blood pressure. Efficiency of cardiac work was judged from the ventriculo-arterial coupling ratio (E _A/E _LV: optimal range 0.5–1.0). While subgroups had similar values at rest, we found ventriculo-arterial mismatch during exercise in HIGH subjects [0.47 (0.39–0.58) vs. LOW: 0.73 (0.62–0.83); p?<?0.01] due to unopposed increase in E _LV (p?<?0.05). In LOW subjects, a greater increase occurred in E _A during exercise (+81?±?67?% vs. HIGH: +39?±?32?%; p?=?0.02) which contributed to a maintained coupling ratio. Subjects with higher baseline NT-proBNP had greater systolic wall stress during exercise (R ²?=?0.39; p?<?0.01) despite no correlation at rest (p?=?ns). In conclusion, athletes with exercise-induced biomarker release exhibit ventriculo-arterial mismatch during exercise, suggesting non-optimal cardiac work may contribute to this phenomenon.     

Proximal tubule specific knockout of the Na+/H+ exchanger NHE3: effects on bicarbonate absorption and ammonium excretion

The existing NHE3 knockout mouse has significant intestinal electrolyte absorption defects, making this model unsuitable for the examination of the role of proximal tubule NHE3 in pathophysiologic states in vivo. To overcome this problem, we generated proximal convoluted tubule-specific KO mice (NHE3-PT KO) by generating and crossing NHE3 floxed mice with the sodium-glucose transporter 2 Cre transgenic mice. The NHE3-PT KO mice have >80 % ablation of NHE3 as determined by immunofluorescence microscopy, western blot, and northern analyses, and show mild metabolic acidosis (serum bicarbonate of 21.2 mEq/l in KO vs. 23.7 mEq/l in WT, p?<?0.05). In vitro microperfusion studies in the isolated proximal convoluted tubules demonstrated a ～36 % reduction in bicarbonate reabsorption (J _HCO3?=?53.52?±?4.61 pmol/min/mm in KO vs. 83.09?±?9.73 in WT) and a ～27 % reduction in volume reabsorption (J _v ?=?0.67?±?0.07 nl/min/mm in KO vs. 0.92?±?0.06 nl/min/mm in WT) in mutant mice. The NHE3-PT KO mice tolerated NH₄Cl acid load well (added to the drinking water) and showed NH₄ excretion rates comparable to WT mice at 2 and 5 days after NH₄Cl loading without disproportionate metabolic acidosis after 5 days of acid load. Our results suggest that the Na⁺/H⁺ exchanger NHE3 plays an important role in fluid and bicarbonate reabsorption in the proximal convoluted tubule but does not play an important role in NH₄ excretion.     

Quality of documentation on antibiotic therapy in medical records: evaluation of combined interventions in a teaching hospital by repeated point prevalence survey

This study aimed to improve the quality of documentation on antibiotic therapy in the computerized medical records of inpatients. A prospective, uncontrolled, interrupted time series (ITS) study was conducted by repeated point prevalence survey (PPS) to audit the quality of documentation on antibiotic therapy in the medical records before and after a combined intervention strategy (implementation of guidelines, distribution of educational materials, educational outreach visits, group educational interactive sessions) from the antimicrobial stewardship team (AST) in the academic teaching hospital (CHU) of Liège, Belgium. The primary outcome measure was the documentation rate on three quality indicators in the computerized medical records: (1) indication for treatment, (2) antibiotics prescribed, and (3) duration or review date. Segmented regression analysis was used to analyze the ITS. The medical records of 2306 patients receiving antibiotics for an infection (1177 in the pre-intervention period and 1129 in the post-intervention period) were analyzed. A significant increase in mean percentages in the post-intervention period was observed as compared with the pre-intervention period for the three quality indicators (indication documented 83.4?±?10.4 % vs. 90.3?±?6.6 %, p?=?0.0013; antibiotics documented 87.9?±?9.0 % vs. 95.6?±?5.1 %, p?<?0.0001; and duration or review date documented 31.9?±?15.4 % vs. 67.7?±?15.2 %, p?<?0.0001). The study demonstrated the successful implementation of a combined intervention strategy from the AST. This strategy was associated with significant changes in the documentation rate in the computerized medical records for the three quality indicators.     

Peri-Infarct Zone Characterized by Cardiac Magnetic Resonance Imaging is Directly Associated with the Inflammatory Activity During Acute Phase Myocardial Infarction

Enhanced systemic inflammatory activity (SIA) during myocardial infarction (MI) and the extent of the peri-infarct zone characterized by cardiac magnetic resonance imaging (CMRi) are both associated with increased risk of life-threatening arrhythmias and sudden cardiac death. The present study investigated the existence of association between these two phenomena in 98 patients (55?±?10 years) with ST segment elevation MI. Plasma levels of C-reactive protein (CRP), interleukin-2 (IL-2), and tumor necrosis factor (TNF) were measured on admission (D1) and on the fifth day post-MI (D5). CMRi was performed 2 weeks after MI to quantify peri-infarct zone (PIZ). Between D1 and D5, the increase in CRP (6.0 vs. 5.6 times; p?=?0.02), IL-2 (3.6 vs. 3.4 times; p?=?0.04) and tumor necrosis factor type α (TNF-α; 4.6 vs. 3.9 times; p?=?0.001) were higher in patients with PIZ above the median than in the counterparts. PIZ was correlated with CRP-D5 (r?=?0.69), delta-CRP (r?=?0.7), IL-2-D5 (r?=?0.5), delta-IL-2 (r?=?0.6), TNF-α (r?=?0.5), delta-TNF-α (r?=?0.4; p?=?0.0001). Enhanced activation of SIA during the acute phase of MI is directly related with generation of PIZ.