Association of serum bilirubin with oxidant damage of human atherosclerotic plaques and the severity of atherosclerosis

Bilirubin has protective effects against atherosclerotic cardiovascular diseases hypothetically due to its antioxidant–antilipoperoxidative properties. Thus, we investigated whether serum bilirubin is associated with oxidant damage, namely lipid peroxidation, of human atherosclerotic plaques and the severity of atherosclerosis. In this regard, we correlated the levels of serum total bilirubin (STB), direct (conjugated) bilirubin (SDB) and indirect (unconjugated) bilirubin (SIB) with those of fluorescent damage products of lipid peroxidation (FDPL) and lipid hydroperoxides (LOOH) of 32 endarterectomy-derived carotid atherosclerotic plaques. Moreover, we compared the levels of serum bilirubin and plaque lipoperoxides between two groups of patients of the study population with different severity of atherosclerosis as judged by the carotid stenosis degree, i.e., <90% (group A, n = 23) and ≥90% (group B, n = 9). Remarkably, the levels of STB were strongly inversely correlated with those of plaque FDPL (rS = ?0.70, P < 0.0001) and LOOH (rS = ?0.66, P < 0.0001), as were those of SIB (FDPL: rS = ?0.68, P < 0.0001; LOOH: rS = ?0.63, P < 0.0001). SDB had a weaker association with plaque FDPL (rS = ?0.41, P < 0.05) and LOOH (rS = ?0.35, P < 0.05). Moreover, the levels of STB, SDB and SIB were lower and those of plaque lipoperoxides higher in group B than in group A, pointing to the association of serum bilirubin and plaque oxidant burden with the severity of atherosclerosis. In conclusion, lowered serum bilirubin is associated with oxidant damage of human atherosclerotic plaques and the severity of atherosclerosis.     

Open-Source Radiation Exposure Extraction Engine (RE3) with Patient-Specific Outlier Detection

We present an open-source, picture archiving and communication system (PACS)-integrated radiation exposure extraction engine (RE3) that provides study-, series-, and slice-specific data for automated monitoring of computed tomography (CT) radiation exposure. RE3 was built using open-source components and seamlessly integrates with the PACS. RE3 calculations of dose length product (DLP) from the Digital imaging and communications in medicine (DICOM) headers showed high agreement (R ²?=?0.99) with the vendor dose pages. For study-specific outlier detection, RE3 constructs robust, automatically updating multivariable regression models to predict DLP in the context of patient gender and age, scan length, water-equivalent diameter (D _w), and scanned body volume (SBV). As proof of concept, the model was trained on 811 CT chest, abdomen + pelvis (CAP) exams and 29 outliers were detected. The continuous variables used in the outlier detection model were scan length (R ² ?=?0.45), D _w (R ²?=?0.70), SBV (R ²?=?0.80), and age (R ²?=?0.01). The categorical variables were gender (male average 1182.7?±?26.3 and female 1047.1?±?26.9 mGy cm) and pediatric status (pediatric average 710.7?±?73.6 mGy cm and adult 1134.5?±?19.3 mGy cm).     

Activated CD4+ and CD8+ T Cell Proportions in Multiple Sclerosis Patients

The goal of this study was to trace the course of multiple sclerosis (MS) by evaluating the lymphocyte subpopulation counts and the levels of CD4+ and CD8+ T cell activation using flow cytometry. Samples obtained from healthy subjects (N?=?40) and patients with MS (N?=?290) were analyzed. Lymphocytes were labeled for the surface markers CD4+, CD8+, CD3+, CD16+, CD19+, CD45+, and CD53+ and the activation marker HLA-DR+. Cell counts were then determined using flow cytometry. A high degree of inter-individual variability was observed in the counts of all lymphocyte subtypes in the MS group. A significantly lower proportion of CD3+ T cells (69?±?14 % in healthy subjects and 60?±?17 % as a percent of total lymphocytes in MS patients), CD4+ T cells (41?±?11 and 28?±?18 %, respectively), and a significantly higher proportion of NK T cells (12?±?5 and 25?±?21 %, respectively) were observed in patients with MS than in healthy subjects. These differences led to a lowered CD4+/CD8+ T cell ratio. Furthermore, a significantly lower proportion of activated CD4+ T cells (HLA-DR+ CD4+; from 48?±?10 to 38?±?15 % as a percent of CD4+ cells) was observed in patients with MS than in healthy subjects. The high level of inter-individual variability in lymphocyte cell counts and the counts of activated T cells suggest that MS is a complex and heterogeneous disease.     

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.     

Influence of blood flow velocity on arterial distensibility of carotid artery in healthy men

Decreased distensibility of carotid artery is independently associated with the incidence of cardiovascular and cerebrovascular events. Arterial distensibility is determined by vascular tone. Since shear stress is an important driving force of vasodilatory substances production form endothelial cells, we hypothesized that local basal (i.e., resting) arterial blood flow velocity is associated with regional arterial distensibility. To test this hypothesis, we determined the influence of local blood flow velocity on carotid arterial distensibility in cross-sectional study design. In a total of 73 apparent healthy men (18–64 years), carotid arterial properties, including measures of carotid arterial distensibility and BFV at rest, were evaluated via B-mode and Doppler ultrasound imaging and applanation tonometry system. Carotid arterial peak BFV and the absolute and normalized pulsatile BFV significantly correlated with age (r = ?0.453 to ?0.600, p < 0.0001), whereas mean and minimum BFV were not influenced by age. Distensibility coefficient of carotid artery correlated with peak BFV (r = 0.305, p < 0.01) and more strongly with pulsatile (i.e., systolic minus end-diastolic) BFV (r = 0.406, p < 0.0001) and the normalized pulsatile BFV by time-averaged velocity (r = 0.591, p < 0.0001). Multi-regression analysis revealed that age (β = ?0.57, p < 0.0001) was the primary independent determinant for distensibility coefficient. In addition with this, carotid lumen diameter (β = ?0.202, p < 0.01) and the normalized pulsatile BFV (β = 0.237, p < 0.05) were significant independent determinants of distensibility coefficient. Qualitatively similar results (although inverse in direction) were obtained by use of β-stiffness index. These results suggest that greater gradient of blood flow velocity during a cardiac cycle are favorably associated with distensibility of carotid artery.     

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.     

Effect of Kalpaamruthaa on immunosuppression of both humoral and cell-mediated immunity in DMBA-induced mammary tumours of rats

The present study was carried out to elucidate the protective effect of Kalpaamruthaa on improving 7,12-dimethylbenz(a)anthracene (DMBA)-induced immunosuppression of both humoral and cell-mediated immunity in mammary carcinoma-induced rats. Breast cancer was induced in rats by administering DMBA orally (25 mg/rat) as a single dose. After 90 days of induction, SA (200 mg/kg body weight) and KA (300 mg/kg body weight) were administered for 14 days, by gastric intubation. Several immunotoxicological assays such as T cell rosette delayed type hypersensitivity (DTH) response, migration inhibition factor (MIF) assay, lymphocyte proliferation assay, plaque forming cell (PFC) assay and haemagglutination assay, plaque forming cell (PFC) assay, serum soluble immune complex and cytokine production, T and B cell mitogenesis induced by Con A and nonspecific cell-mediated immunity were evaluated using phagocytosis activity and NBT reduction. In cancer-induced animals (group II), the leukocyte migration inhibition declined markedly (p?<?0.001), the levels of cytokines IFN-γ and IL-2 were significantly decreased (p?<?0.001) and also the antibody titre level (p?<?0.001) was significantly reduced when compared with control rats. A marked decline in PFC (p?<?0.001) and serum soluble immune complex (PEG) formation (p?<?0.001) was also observed. Hence, the present study clearly demonstrates the immunoprotective effect of KA.     

Infective endocarditis in patients with hepatic diseases

Few data have been published regarding the epidemiology and outcome of infective endocarditis (IE) in patients with chronic hepatic disease (CHD). A retrospective analysis of the Studio Endocarditi Italiano (SEI) database was performed to evaluate the epidemiology and outcome of CHD+ patients compared with CHD? patients. The diagnosis of IE was defined in accordance with the modified Duke criteria. Echocardiography, diagnosis, and treatment procedures were in accordance with current clinical practice. Among the 1722 observed episodes of IE, 300 (17.4 %) occurred in CHD+ patients. The cause of CHD mainly consisted of chronic viral infection. Staphylococcus aureus was the most common bacterial species in CHD+ patients; the frequency of other bacterial species (S. epidermidis, streptococci, and enterococci) were comparable among the two groups. The percentage of patients undergoing surgery for IE was 38.9 in CHD+ patients versus 43.7 in CHD? patients (p?=?0.06). Complications were more common among CHD+ patients (77 % versus 65.3 %, p?<?0.001); embolization (43.3 % versus 26.1 %, p?<?0.001) and congestive heart failure (42 % versus 34.1 %, p?=?0.01) were more frequent among CHD+ patients. Mortality was comparable (12.5 % in CHD? and 15 % in CHD+ patients). At multivariable analysis, factors associated with hospital-associated mortality were having an infection sustained by S. aureus, a prosthetic valve, diabetes and a neoplasia, and CHD. Being an intravenous drug user (IVDU) was a protective factor and was associated with a reduced death risk. CHD is a factor worsening the prognosis in patients with IE, in particular in patients for whom cardiac surgery was required.     

The correlation between <Emphasis Type="Italic">Toxoplasma gondii</Emphasis> infection and prenatal depression in pregnant women

Previous studies have demonstrated that latent toxoplasmosis is associated with neuropsychiatric disorders. We evaluated the correlation between Toxoplasma gondii infection and prenatal depression. In this case–control study, we enrolled 116 depressed pregnant women and 244 healthy controls. The Edinburgh Postpartum Depression Scale (EPDS) was used to evaluate the depression symptom severity in study participants. All participants were screened for the anti-Toxoplasma IgG by enzyme-linked immunosorbent assay. Seroprevalence of T. gondii did not significantly differ between the depressed pregnant women and healthy controls (OR?=?1.4; 95 % CI?=?0.9–2.19; P?=?0.142). T. gondii IgG titer was significantly higher in depressed women (18.6?±?10.9 IUs) than those in the control group (13.6?±?8.1 IUs) (z?= ?5.36, P?<?0.001). The T. gondii–positive depressed women showed a positive correlation of T. gondii IgG titer with the EPDS scores (r?=?0.52; P?<?0.01). The mean EPDS score was also significantly higher in the T. gondii–positive depressed women (20.7?±?2.7) compared with the controls (18.36?±?2.7) (P?<?0.001). The results obtained from the current study revealed that T. gondii infection might affect susceptibility to depression and severity of depressive symptoms in pregnant women, particularly in those patients who have high antibody titers. Further study is required to fully elucidate the characteristics and mechanisms of this association.     

Effects of two dietary exogenous multi-enzyme supplementation,Natuzyme<Superscript>®</Superscript> and beta-mannanase (Hemicell<Superscript>®</Superscript>), on growth and blood parameters of Caspian salmon (<Emphasis Type="Italic">Salmo trutta caspius</Emphasis>)

Recent increases in feed ingredient costs have motivated the fisheries industry to identify technologies that will improve feed utilisation and reduce the cost per pound of gain. The effects of two supplemental exogenous enzymes (Natuzyme® and Hemicell®) on the growth performance in Caspian salmon (Salmo trutta caspius) were examined over an 8-week feeding trial. After the experimental period, the survival rate ranged from 91.33?±?1.15 % in controls to 96.67?±?1.15 % in the group that received 0.5 g Natuzyme® kg^?1?+?0.5 g Hemicell® kg^?1 (NH) in their diet and there was a statistical difference between experimental and control groups (p?<?0.05). Growth rate was significantly higher in the NH group (1.01?±?0.01) than the other groups (Sig.?=?0.00). The best feed conversion rate (0.64?±?0.01) was in the NH group and it was significantly lower than the control group, the 0.5 g Natuzyme® kg^?1 group, and the 0.25 g Hemicell® kg^?1 group (Sig.?=?0.03). The best final body weight (80.68?±?5.27) was observed in the NH group. Also, WBC count (7,716.67?±?348.80 N/mm³) was significantly higher in the NH group compared to the control (6,916.67?±?194.10 N/mm³; p?<?0.05). No difference was observed in haematocrit%, haemoglobin, red blood cell, mean corpuscular volume, mean corpuscular haemoglobin, and mean corpuscular haemoglobin concentration (p?>?0.05). The results suggested that enzyme supplementation caused significant improvement on growth performance and feed utilisation in Caspian salmon.     

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.

     

Haematological and acute-phase response of dogs with experimental skin <Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> infection to treatment with antibiotic and parthenolide

Changes in white blood cells, leukogram patterns, the positive acute-phase protein (APP) fibrinogen and negative APPs (albumin and arylesterase) were monitored to evaluate their potential as sensitive indicators throughout the course of therapy in canine skin Pseudomonas aeruginosa infection. The study was performed on 15 male mixed-breed dogs, divided in three groups of 5 dogs each. Dogs from group A were injected subcutaneously with P. aeruginosa bacterial culture (1?×?10⁸ CFU/mL) at a dose of 0.3 mL/kg and treated with enrofloxacin (5 mg/kg, s.c.) on post infection hour 48 for 10 consecutive days. Dogs from group B were infected and treated with a combination of enrofloxacin (at above-mentioned dose and intervals) and parthenolide (feverfew extract 90 mg, 0.7 % parthenolide). The schedule consisted of daily oral intake of two capsules of feverfew beginning on post infection hour 4 and continued for 6 days. The control group C included healthy dogs, injected s.c. with 0.3 mL/kg physiological saline. The haematological indices and APPs were assayed before infection and on 4th, 24th, 48th and 72nd hours and on 7th, 10th and 14th days after infection. Infected and antibiotic-treated dogs responded with significant leukocytosis, left shift, eosinopaenia and lymphopaenia between hours 24 and 72. In this group, fibrinogen increased substantially by post infection hours 24 (p?<?0.01 vs 0 h; p?<?0.05 vs group C), 48 (p?<?0.001 vs 0 h; p?<?0.05 vs group C) and 72 (p?<?0.001 vs 0 h; p?<?0.01 vs group C) while albumin reduction was marked by hours 48 (p?<?0.05 vs 0 h) and 72 (p?<?0.05 vs 0 h; p?<?0.001 vs group C) and day 7 (p?<?0.01 vs 0 h; p?<?0.001 vs group C). The combination of enrofloxacin and parthenolide modified, at a significant extent, the deviations in studied parameters except for eosinophil percentage, which persisted low.     

Effect of improved navigation performance on the accuracy of implant placement in total hip arthroplasty with a CT-based navigation system

A computed tomography (CT)-based navigation system is one of the support tools to place implant with appropriate alignment and position in total hip arthroplasty (THA). To determine whether the higher performance of the navigation would further improve the accuracy of implant placement in the clinical setting, we retrospectively compared the navigation accuracy of two different versions of a navigation system. The newer version of the navigation system had an upgraded optical sensor with superior positional accuracy. Navigation accuracy, defined as differences between postoperative measurements on CT images and intraoperative records on the navigation system, of 49 THAs performed with the newer version of the navigation system was compared with that of 49 THAs performed with the older version. With the newer version, the mean absolute accuracy (95% limits of agreement) of implant alignment was 1.2° (±?3.3°) for cup inclination, 1.0° (±?2.4°) for cup anteversion, 2.0° (±?4.9°) for stem anteversion, and 1.1° (±?2.4°) for stem valgus angle. The accuracy of the implant position was 1.5 mm (±?3.1 mm), 1.3 mm (±?3.0 mm), and 1.5 mm (±?3.1 mm) for cup x-, y-, and z-axes, respectively, 1.6 mm (±?3.2 mm), 1.4 mm (±?2.9 mm), and 1.5 mm (±?2.7 mm) for stem x-, y-, and z-axes, respectively, and 2.4 mm (±?4.5 mm) for leg length discrepancy. The values for the newer version were significantly more accurate with less variation compared to those of the older version. With upgraded navigation performance, more accurate implant placement was demonstrated in the clinical setting.     

Effekte einer adaptiven Servoventilation auf Herzrhythmusstörungen bei Patienten mit chronischer Herzinsuffizienz und schlafbezogenen Atmungsstörungen

Background

In patients with chronic heart failure with reduced left ventricular ejection fraction (HFrEF) sleep-disordered breathing (SDB) is linked with an increased risk for nocturnal cardiac arrhythmias. SDB can be effectively treated with adaptive servo-ventilation (ASV). Therefore, we tested the hypothesis that ASV therapy reduces nocturnal arrhythmias and heart rate in patients with HFrEF and SDB.

Methods

In a non-prespecified subanalysis of a multicenter randomized-controlled trial (ISRCTN04353156) twenty consecutive patients with stable HFrEF (age 67 ± 9 y; left ventricular ejection fraction 32 ± 7?%) and SDB (apnea-hypopnea index, AHI 48 ± 20/h) were randomized to either ASV (n = 10; Philips Respironics, Murrysville, PA, USA) or optimal medical treatment alone (control, n = 10). Polysomnography (PSG) with centralized scoring and blinded analysis where obtained at baseline and 12 weeks. The electrocardiograms (ECG) of the PSGs were analyzed with 24 h-Holter electrocardiography software (Pulse Biomedical Inc., QRS-Card^TM Cardiology Suite, USA).

Results

There was a decrease in ventricular ectopic beats (VEBs) per hour recording time in the ASV-group compared to the control group (?8.1 ± 42.4 versus +9.8 ± 63.7/h, p = 0.356). ASV reduced the number of ventricular couplets as well as non-sustained ventricular tachycardias (nsVT) compared to the control-group (?2.3 ± 6.9 versus +2.1 ± 12.7/h, p = 0.272, and ?0.1 ± 0.5 versus +0.1 ± 1.1/h, p = 0.407, respectively). Mean nocturnal heart rate decreased in the ASV group compared to the control-group (?2.0 ± 2.7 versus +3.9 ± 11.5/minute, p = 0,169). Described changes were not significantly different between groups.

Conclusions

In HFrEF patients with SDB ASV treatment may reduce nocturnal ventricular ectopic beats, couplets, nsVT and mean nocturnal heart rate. Findings underscore the need for further analyses in larger studies.

     

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.

     

Effects of adaptive servo-ventilation on ventricular arrhythmias in patients with stable congestive heart failure and sleep-disordered breathing

Background

Congestive heart failure patients with reduced left ventricular ejection fraction (HFrEF) and sleep-disordered breathing (SDB) are at an increased risk of nocturnal cardiac arrhythmias. SDB can be effectively treated with adaptive servo-ventilation (ASV). Therefore, we tested the hypothesis that ASV therapy reduces nocturnal arrhythmias and heart rate in patients with HFrEF and SDB.

Methods

In a non-prespecified subanalysis of a multicenter randomized controlled trial (ISRCTN04353156), 20 consecutive patients with stable HFrEF (age 67 ± 9 years; left ventricular ejection fraction, LVEF 32 ± 7?%) and SDB (apnea–hypopnea index, AHI 48 ± 20/h) were randomized to either an ASV therapy (n = 10) or an optimal medical treatment alone group (controls, n = 10). Polysomnography (PSG) with blinded centralized analysis and scoring was performed at baseline and at 12 weeks. The electrocardiograms (ECG) of the PSGs were analyzed with long-term (24-h) Holter ECG software (QRS-Card? Cardiology Suite; Pulse Biomedical Inc., King of Prussia, PA, USA).

Results

There was a decrease in ventricular extrasystoles (VES) per hour of recording time in the ASV group compared to the control group (?8.1 ± 42.4 versus +9.8 ± 63.7/h, p = 0.356). ASV reduced the number of ventricular couplets and nonsustained ventricular tachycardias (nsVT) compared to the control group (?2.3 ± 6.9 versus +2.1 ± 12.7/h, p = 0.272 and ?0.1 ± 0.5 versus +0.1 ± 1.1/h, p = 0.407, respectively). Mean nocturnal heart rate decreased in the ASV group compared to the controls (?2.0 ± 2.7 versus +3.9 ± 11.5/min, p = 0.169). The described changes were not significantly different between the groups.

Conclusion

In HFrEF patients with SDB, ASV treatment may reduce nocturnal VES, couplets, nsVT, and mean nocturnal heart rate. The findings of the present pilot study underscore the need for further analyses in larger studies.

     

Laboratory automation reduces time to report of positive blood cultures and improves management of patients with bloodstream infection

The impact on time to results (TTR) and clinical decisions was evaluated for mono-microbial positive blood cultures (BC) processed using the BD Kiestra Work Cell Automation (WCA) system. Positive BC were processed by the WCA system by full-automatic subculture on solid media and digital imaging after 8 h of incubation (8-h method) followed by identification (ID) and antimicrobial susceptibility testing (AST). To evaluate the accuracy of the 8-h method, ID and AST from 8-h and overnight incubated colonies were compared for the same organisms. To evaluate its clinical impact, results from 102 BC processed by the 8-h method (cases) were compared with those from 100 BC processed by overnight incubation method (controls) in a comparable period. Identification after 8-h and overnight incubation gave concordant results in 101/102 (99.0%) isolates. Among a total of 1379 microorganism-antimicrobial combinations, categorical agreement was 99.4% (1371/1379); no very major error, 7 major errors, and one minor error were observed. TTR in cases (32.8 h?±?8.3 h) was significantly (p?<?0.001) shorter than in controls (55.4 h?±?13.3 h). A significant reduction was observed for duration of empirical therapy (cases 54.8 h ± 23.3 h vs controls 86.9 h?±?34.1 h, p?<?0.001) and 30-day crude mortality rate (cases 16.7% vs controls 29.0%, p?<?0.037). Automation and 8-h digital reading of plates from positive BC, followed by ID and AST, greatly reduce TTR and shorten the duration of antimicrobial empiric therapy, possibly improving outcome in patients with mono-microbial bloodstream infections.     

Time to positivity of blood culture and its prognostic value in bloodstream infection

The purpose of this study was to investigate the relationship between the time to positivity (TTP) of blood cultures and outcome in patients with bloodstream infections (BSIs). Between January 1st, 2011 and December 31st, 2013, the blood cultures of inpatients with BSI or catheter-related BSI were collected at Peking University Third Hospital. The TTP of different isolates was analyzed, and the relationship between the TTP of isolates and outcome of patients with Enterobacter BSI was retrospectively analyzed. We analyzed the TTP of 886 isolates. Escherichia coli has the shortest (11.97?±?10.06 h) and Candida has the longest first TTP (61.62?±?42.77 h). 68.01 % of isolates reached positivity within 24 h and 88.33 % within 48 h. Over 90 % of E. coli isolates reached positivity within 24 h. Over 50 % of Candida isolates reached positivity within 48 h. The TTP differed significantly between cultures that were single or double positive for coagulase-negative staphylococci isolates, Enterobacteriaceae, and Pseudomonas aeruginosa, and between aerobic and anaerobic cultures of E. coli (p?<?0.05). However, the TTP did not differ significantly between coagulase-negative staphylococci (double positivity) and Staphylococcus aureus. The best TTP threshold for prediction of mortality from Enterobacter species BSI was 16.3 h [area under the curve (AUC) 0.730, 95 % confidence interval (CI) 0.557, 0.864, sensitivity 100 %, specificity 44.4 %]. The TTP of clinical isolates may represent a valuable marker of the clinical significance of BSIs. Laboratories and clinics should consider using the TTP to predict the prognosis of patients with BSI by bacteria, including Enterobacter and other species.     

Estimation of flavoniods,antimicrobial, antitumor and anticancer activity of <Emphasis Type="Italic">Carissa opaca</Emphasis> fruits

Background

Carissa opaca Stapf ex Hanes fruits is traditionally used in the treatment of asthma, hepatitis and microbial infections. The present study was arranged to investigate the antimicrobial, cytotoxic and antitumor activity of various fractions of C. opaca extract and its bioactive metabolites responsible for that activity.

Methods

To characterize various fractions of C.opaca antibacterial, antifungal, cytotoxic and antitumor assays are used. Eight strains of bacteria including Bacillus subtilis, Enterobactor aerogenes, Escherichia coli, Klebsiella pneumoniae, Micrococcus luteus, Pseudomonas aeroginosa, Salmonella typhy, and Staphylococcus aureus and four strains of fungal viz: Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger and Fusarium solani are used. Brine shrimps and potato dics are used for anticancer and antitumor potency of extract. High performance liquid chromatography (HPLC) is utilized for determination of bioactive metabolites responsible for the activity.

Results

HPLC chromatogram revealed the presence of orientin, isoquercetin, myricetin and apigenin. Various fractions of C. oapca showed significant antibacterial, antitumor and anticancer activity. In case of C. opaca fruit inhibition growth of Aspergillus niger was ranged between 23.2?±?1.36% to 43.3?±?2.39%, Aspergillus flavus ranged between 27.6?±?1.39% to 65.6?±?3.44%, Aspergillus fumigatus ranged between 13.2?±?1.00% to 52.4?±?1.54% and Fusarium solani ranged between 10.5?±?1.02% to 14.6?±?1.74%.

Conclusion

It can be concluded that, various fractions of C.opaca are accessible source of ethno pharmacy as they are consumed in different areas of Pakistan with ultimate health compensations.