Evaluating the Optimal Timing of Revascularisation in Patients with Transient ST-Segment Elevation Myocardial Infarction: Rationale and Design of the TRANSIENT Trial

Patients with chest pain and a prehospital ST-segment elevation myocardial infarction (STEMI) are preferably treated with immediate percutaneous coronary intervention (PCI). However, patients with normalization of symptoms and ST-segment elevation upon hospital arrival (transient STEMI) received inconsistent therapy due to logistic reasons and the absence of evidence or explicit guidelines. In this trial, the optimal timing of coronary angiography and subsequent revascularisation is investigated in patients presenting with transient STEMI. In this prospective, multicentre, randomized controlled clinical trial, 142 consecutive patients with initially acute chest pain and STEMI, whose symptoms and ST-segment elevation resolve upon admission, are randomized to immediate intervention or a delayed intervention. Primary outcome is infarct size measured at 4 days determined by cardiovascular magnetic resonance. Secondary outcomes are left ventricular function and volumes, myocardial salvage and microvascular injury at baseline; the change in left ventricular function, volumes and infarct size at 4 months; and major adverse cardiac events at 4 and 12 months. The TRANSIENT Trial evaluates whether a delayed invasive strategy (according to NSTEMI-guidelines) is superior to an immediate invasive strategy (according to STEMI-guidelines) in patients with a transient STEMI.     

Transforming growth factor (TGF)-β levels and unprovoked recurrent venous thromboembolism

Prediction of recurrence in patients with unprovoked venous thromboembolism (VTE) remains a challenge. Studies of atherosclerosis suggest a protective role of transforming growth factor (TGF)-β. However, the role of TGF-β has not been studied in VTE. The aim of this study was to investigate TGF-β as a predictive marker of recurrent VTE in patients with a first episode of unprovoked VTE. Patients in the Malmö Thrombophilia Study (MATS) were followed after the discontinuation of anticoagulant treatment until the diagnosis of recurrent VTE or the end of the study in December 2008 (mean ± SD 38.5 months ± 27). Among patients with a first episode of unprovoked VTE, we identified 42 patients with recurrent VTE during the follow-up period. Two age- and sex-matched control subjects without recurrent VTE were selected for each patient (n = 84). Plasma levels of the three isoforms of TGF-β (TGF-β1, TGF-β2 and TGF-β3) were quantified simultaneously by TGF-β 3-plex immunoassay. Compared to controls, plasma levels of TGF-β1 and TGF-β2 were significantly lower in patients with recurrent VTE (p < 0.05), whereas no difference was found for TGF-β3. In a multivariate Cox regression analyses, adjusted for inherited thrombophilia, age, sex and BMI, low levels of TGF-β1 [hazard ratio (HR) = 2.2, 95 % confidence interval (CI) 1.1–4.3; p = 0.02] and TGF-β2 (HR = 2.4, 95 % CI 1.2–4.7; p = 0.01) were independently associated with a higher risk of recurrent VTE. We propose TGF-β1 and TGF-β2 as potential predictive markers for recurrence in patients with unprovoked VTE.     

Alpha- and beta-cell abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes

New recommendations for the use of glycated haemoglobin A1c (HbA1c) to diagnose prediabetes and type 2 diabetes have changed the constitution of the two populations. We aimed to investigate the pathophysiological characteristics of individuals with HbA1c-defined prediabetes and type 2 diabetes, respectively. Ten subjects with HbA1c-defined prediabetes, i.e. HbA1c from 5.7 to 6.4 % (39–46 mmol/mol), eight newly diagnosed patients with HbA1c-defined type 2 diabetes [HbA1c ≥6.5 % (≥48 mmol/mol)], and ten controls with HbA1c lower than 5.7 % (<39 mmol/mol), were studied. Blood was sampled over 4 h on two separate days after a 75 g-oral glucose tolerance test and an isoglycaemic intravenous glucose infusion, respectively. Blood was analysed for glucose, insulin, C-peptide, glucagon, and incretin hormones. Insulinogenic index, disposition index, glucagon suppression, and incretin effect were evaluated. Subjects with HbA1c-defined prediabetes showed significantly lower insulinogenic index (P = 0.02), disposition index (P = 0.001), and glucagon suppression compared with controls; and similar (P = NS) insulinogenic index and glucagon suppression and higher disposition index (P = 0.02) compared to HbA1c-diagnosed type 2 diabetic patients. The patients with type 2 diabetes showed lower insulinogenic index (P = 0.0003), disposition index (P < 0.0001), and glucagon suppression compared with the controls. The incretin effect was significantly (P < 0.05) reduced in patients with HbA1c-defined type 2 diabetes compared to subjects with HbA1c-defined prediabetes and controls. Plasma levels of incretin hormones were similar across the three groups. HbA1c associated negatively with insulinogenic index, disposition index, and incretin effect. Our findings show clear alpha- and beta-cell dysfunction in HbA1c-defined type 2 diabetes compatible with the previously described pathophysiology of plasma glucose-defined type 2 diabetes. Furthermore, in HbA1c-defined prediabetes, we show defective insulin response in combination with inappropriate suppression of glucagon, which may constitute new targets for pharmacological interventions.     

Prognostic implications of left ventricular regional function heterogeneity assessed with two-dimensional speckle tracking in patients with ST-segment elevation myocardial infarction and depressed left ventricular ejection fraction

The aim of the current study was to evaluate the prognostic implications of myocardial tissue heterogeneity assessed with two-dimensional speckle-tracking echocardiography in patients three months after first ST-segment elevation myocardial infarction (STEMI) with left ventricular ejection fraction (LVEF) ≤35 %. For this purpose, a total of 79 patients with first STEMI and LVEF ≤35 % at three months postinfarction were evaluated. Based on left ventricular (LV) speckle-tracking longitudinal strain echocardiography, the infarct core, border zone, and remote zone at baseline and three months’ follow-up were defined. Patients were followed for the occurrence of the composite end point of appropriate implantable cardioverter-defibrillator (ICD) therapy and/or cardiac mortality. During a median follow-up of 46 months, 13 patients (17 %) reached the composite end point. At baseline, patients with and without events showed comparable values of LV longitudinal strain at the infarct, border, and remote zones. However, at three months’ follow-up, patients with events showed significantly more impaired longitudinal strain at the border zone (?6.8 ± 3.1 % vs. ?10.5 ± 4.9 %, P = 0.002), whereas LVEF was comparable (28 ± 6 % vs. 31 ± 4 %, P = 0.09). The median three-month LV longitudinal strain at the border zone was ?9.4 %. Multivariate Cox regression analysis demonstrated that three-month longitudinal strain >?9.4 % at the border zone was independently associated with the composite end point (hazard ratio 3.94, 95 % confidence interval 1.05–14.70; P = 0.04). In conclusion, regional longitudinal strain at the border zone three months post-STEMI is associated with appropriate ICD therapy and cardiac mortality.     

Time to treatment—door-to-balloon time is not everything

International guidelines for the management of patients with ST-elevation myocardial infarction (STEMI) recommend various performance measures to monitor the quality of STEMI systems of care. Door-to-balloon (D2B) time (arrival at hospital to percutaneous coronary intervention, PCI) and overall health care system delay (first medical contact to reperfusion) are acknowledged as valuable performance measures when treating patients with primary percutaneous coronary intervention (PPCI). However, there is confusion regarding the exact definition of these performance measures, and moreover system delay and PCI-related delay (the extra delay acceptable to perform PPCI instead of fibrinolysis) are often used synonymously, which add confusion when considering reperfusion strategy. The present paper calls for a consensus regarding the use and definition of objective performance measures when treating patients with STEMI, and exemplifies why it is insufficient just to focus on D2B time.     

Influence of gender on the risk of death and adverse events in patients with acute myocardial infarction undergoing pharmacoinvasive strategy

Pharmacoinvasive treatment is an acceptable alternative for patients with ST-segment elevation myocardial infarction (STEMI) in developing countries. The present study evaluated the influence of gender on the risks of death and major adverse cardiovascular events (MACE) in this population. Seven municipal emergency rooms and the Emergency Mobile Healthcare Service in São Paulo treated STEMI patients with tenecteplase. The patients were subsequently transferred to a tertiary teaching hospital for early (<24 h) coronary angiography. A total of 469 patients were evaluated [329 men (70.1 %)]. Compared to men, women had more advanced age (60.2 ± 12.3 vs. 56.5 ± 11 years; p = 0.002); lower body mass index (BMI; 25.85 ± 5.07 vs. 27.04 ± 4.26 kg/m²; p = 0.009); higher rates of hypertension (70.7 vs. 59.3 %, p = 0.02); higher incidence of hypothyroidism (20.0 vs. 5.5 %; p < 0.001), chronic renal failure (10.0 vs. 8.8 %; p = 0.68), peripheral vascular disease (PVD; 19.3 vs. 4.3 %; p = 0.03), and previous history of stroke (6.4 vs. 1.3 %; p = 0.13); and higher thrombolysis in myocardial infarction risk scores (40.0 vs. 23.7 %; p < 0.001). The overall in-hospital mortality and MACE rates for women versus men were 9.3 versus 4.9 % (p = 0.07) and 12.9 versus 7.9 % (p = 0.09), respectively. By multivariate analysis, diabetes (OR 4.15; 95 % CI 1.86–9.25; p = 0.001), previous stroke (OR 4.81; 95 % CI 1.49–15.52; p = 0.009), and hypothyroidism (OR 3.75; 95 % CI 1.44–9.81; p = 0.007), were independent predictors of mortality, whereas diabetes (OR 2.05; 95 % CI 1.03–4.06; p = 0.04), PVD (OR 2.38; 95 % CI 0.88–6.43; p = 0.08), were predictors of MACE. In STEMI patients undergoing pharmacoinvasive strategy, mortality and MACE rates were twice as high in women; however, this was due to a higher prevalence of risk factors and not gender itself.     

Efficacy and safety of rivaroxaban versus low-molecular-weight heparin therapy in patients with lower limb fractures

Thromboprophylaxis with rivaroxaban has proved effective and safe in patients undergoing hip and knee replacement surgery. As it is unclear whether it is also effective and safe in fracture patients, the aim of the present study was to evaluate the efficacy and safety of rivaroxaban in patients with lower limb fractures. We performed a retrospective cohort study of 2,050 consecutive patients treated for lower limb fractures at our trauma center, comparing rates of venous thromboembolism (VTE), bleeding and surgical complications, and the length of hospital stay for 608 patients who received rivaroxaban and 717 who received a low-molecular-weight heparin (LMWH). Rates of symptomatic VTE were 4.9 and 8.6 % in the rivaroxaban and LMWH groups, respectively (p = 0.008), and distal VTE rates were 1.8 and 5.7 %, respectively (p = 0.036). The incidence of major bleeding events in the rivaroxaban group was also lower than in the LMWH group (0.2 vs 0.6 %), but the difference between the groups was not statistically significant. The mean length of hospital stay was significantly shorter in the rivaroxaban group (12.2 vs 13.1 days, respectively; p = 0.016). This retrospective cohort study is the first report documenting the efficacy and safety of rivaroxaban in patients with lower extremity fractures. In comparison with LMWH, rivaroxaban reduced the incidence of VTE by 45 % without increasing the risk of bleeding. However, prospective, randomized controlled trials comparing rivaroxaban and LMWH are needed to confirm our findings.     

The value of plasma D-dimer level on admission in predicting no-reflow after primary percutaneous coronary intervention and long-term prognosis in patients with acute ST segment elevation myocardial infarction

D-dimer is a final product of fibrin degradation and gives an indirect estimation of the thrombotic burden. We aimed to investigate the value of plasma D-dimer levels on admission in predicting no-reflow after primary percutaneous coronary intervention (p-PCI) and long-term prognosis in patients with ST segment elevation myocardial infarction (STEMI). We retrospectively involved 569 patients treated with p-PCI for acute STEMIs. We prospectively followed up the patients for a median duration of 38 months. Angiographic no-reflow was defined as postprocedural thrombolysis in myocardial infarction (TIMI) flow grade <3 or TIMI 3 with a myocardial blush grade <2. Electrocardiographic no-reflow was defined as ST-segment resolution <70 %. The primary clinical end points were mortality and major adverse cardiovascular events (MACE). The incidences of angiographic and electrocardiographic no-reflow were 31 and 39 % respectively. At multivariable analysis, D-dimer was found to be an independent predictor of both angiographic (p < 0.001), and electrocardiographic (p < 0.001) no-reflow. Both mortality (from Q1 to Q4, 5.7, 6.4, 11.3 and 34.1 %, respectively, p < 0.001) and MACE (from Q1 to Q4, 17.9, 29.3, 36.9 and 52.2 %, respectively, p < 0.001) rates at long-term follow-up were highest in patients with admission D-dimer levels in the highest quartile (Q4), compared to the rates in other quartiles. However, Cox proportional hazard model revealed that high D-dimer on admission (Q4) was not an independent predictor of mortality or MACE. In contrast, electrocardiographic no-reflow was independently predictive of both mortality [Hazard ratio (HR) 2.88, 95 % confidence interval (CI) 1.04–8.58, p = 0.041] and MACE [HR 1.90, 95 % CI 1.32–4.71, p = 0.042]. In conclusion, plasma D-dimer level on admission independently predicts no-reflow after p-PCI. However, D-dimer has no independent prognostic value in patients with STEMI.     

Clinical characteristics and lung function in chronic obstructive pulmonary disease complicated with impaired peripheral oxygenation

During exercise testing, patients with chronic obstructive pulmonary disease (COPD) often present with ventilatory limitations and various combinations of impaired peripheral oxygenation (IPO) to the exercising muscles. The entities of IPO include anemia, circulation impairment and deconditioning. COPD-IPO is not widely accepted as being a subgroup of COPD. Therefore, the aim of this study was to evaluate the clinical features of COPD-IPO patients. Forty-seven COPD patients underwent cardiopulmonary exercise testing. COPD-IPO was identified when all IPO variables had abnormal values. The patients who did not meet the COPD-IPO criteria were defined as the NIPO group. The variables with abnormal values included peak oxygen uptake ( \( {\dot{\text{V}}\text{O}}_{ 2} \) ) <85 % predicated, anaerobic threshold <40 % \( {\dot{\text{V}}\text{O}}_{{ 2 {\text{max}}}} \) pred, \( {\dot{\text{V}}\text{O}}_{ 2} \) -work rate slope <8.6 ml/watt, oxygen pulse <80 %pred, and ventilatory equivalents for O₂ and CO₂ at nadir (>31 and >34, respectively). Anthropometrics, biochemistry, and lung function were compared between the groups. Forty-six COPD patients were enrolled after excluding one patient who had technical difficulties in performing the exercise tests. Despite FEV₁ and FVC being similarly reduced (p = NS) between the groups, the COPD-IPO (n = 13, 28 %) patients had lower body mass index and were taller, and had impaired diffusing capacity and larger total lung capacity and air-trapping (all p < 0.05). We concluded that COPD patients with all six variables having abnormal values are a unique subgroup and that identification of these patients is worthwhile for further investigations and management such as exercise training and nutritional supplements.     

Left-sided primary tumors are associated with favorable prognosis in patients with KRAS codon 12/13 wild-type metastatic colorectal cancer treated with cetuximab plus chemotherapy: an analysis of the AIO KRK-0104 trial

Purpose

AIO KRK-0104 investigated first-line therapy of metastatic colorectal cancer (mCRC) with cetuximab, capecitabine and irinotecan versus cetuximab, capecitabine and oxaliplatin. This analysis investigated the impact of primary tumor location on outcome of patients.

Patients and methods

Left-sided primary tumors were defined as tumors from rectum to left flexure, while tumors in the remaining colon were regarded right sided. Overall survival (OS), progression-free survival (PFS) and response rate were correlated with primary tumor location. A Cox regression model was used to evaluate interaction between primary tumor location and KRAS mutation.

Results

Of 146 patients of the AIO KRK-0104 trial, 100 patients presented left-sided (of those 68 KRAS codon 12/13 wild-type) and 46 patients right-sided primary tumors (of those 27 KRAS codon 12/13 wild-type). Left-sided tumors were associated with significantly longer OS (p = 0.016, HR = 0.63) and PFS (p = 0.02, HR = 0.67) as compared to right-sided tumors. These effects were present in the KRAS codon 12/13 wild-type population (HR OS: 0.42; HR PFS: 0.54), while no impact of primary tumor location was evident in patients with KRAS codon 12/13 mutant tumors (HR OS: 1.3; HR PFS: 1.01). A significant interaction of KRAS status and primary tumor location concerning OS and PFS was observed.

Conclusion

Our findings suggest that primary tumor location and KRAS codon 12/13 mutational status interact on the outcome of patients with mCRC receiving cetuximab-based first-line therapy. Left-sided primary tumor location might be a predictor of cetuximab efficacy.     

Health-related quality of life and persistent symptoms in relation to (R-)CHOP14, (R-)CHOP21, and other therapies among patients with diffuse large B-cell lymphoma: results of the population-based PHAROS-registry

The increasing number of longer-living patients with diffuse large B-cell lymphoma (DLBCL) and serious side effects of treatment urged us to study the health-related quality of life (HRQoL) and persistent (treatment-related) symptoms in unselected patients after different treatment modalities and compare HRQoL of patients with a normative population. The population-based Eindhoven Cancer Registry was used to select all patients diagnosed with DLBCL from 2004 to 2010. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) was completed twice, with a 1-year interval. Detailed data on treatment were extracted from the Population-based HAematological Registry for Observational Studies. Two hundred fifty-six patients responded (84 %, T1). Compared to patients treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days ((R-)CHOP21), those who underwent (R-)CHOP14 more often reported tingling in the hands and feet (27 vs 42 %, p?=?0.02) and fatigue (35 vs 46 %, p?=?0.03) and reported a lower global health status/HRQoL. Mean HRQoL was statistically and clinically relevantly lower among DLBCL patients compared to a normative population (p?DLBCL patients is needed and may help to avoid lasting negative influence on their HRQoL.     

BRCA1 promoter methylation is a marker of better response to platinum–taxane-based therapy in sporadic epithelial ovarian cancer

Background

The aim of the current study was to investigate the role of BRCA1 promoter methylation as predictive factor of response to platinum–taxane-based therapy in sporadic ovarian cancer.

Patients and methods

BRCA1 promoter methylation was analyzed in 42 sporadic epithelial ovarian cancers. The results were validated in a second cohort of 137 ovarian cancer patients.

Results

BRCA1 promoter methylation was observed in 35.7 % of patients in the first group and in 33.6 % in the second group. BRCA1 promoter methylation was associated with significant increase in median progression-free survival (PFS) of ovarian cancer patients receiving adjuvant platinum–taxane-based chemotherapy (P = 0.008). Multivariate analysis revealed that BRCA1 promoter methylation remains a favorable factor in regard to PFS (HR 0.52; 95 % CI 0.32–0.85, P = 0.009) after adjustment for other prognostic factors. Under the patients with recurrent disease, BRCA1 promoter methylation was associated with significant longer median PFS of 18.5 months in comparison with 12.8 months PFS for patients without BRCA1 promoter methylation.

Conclusions

BRCA1 promoter methylation is predictive for better response to platinum–taxane-based therapy in EOC.     

Correlations between A1c,fasting glucose, 2h postload glucose,and β-cell function in the Chinese population

This study was aimed to assess the associations of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and 2h postload plasma glucose (2hPG) with β-cell function in the Chinese population. A total of 913 subjects underwent 75-g oral glucose tolerance test (OGTT) and HbA1c testing. According to OGTT, isolated impaired fasting glucose (i-IFG) was defined as 5.6 mmol/l ≤ FPG < 7.0 mmol/l and 2hPG < 7.8 mmol/l; isolated impaired glucose tolerance (i-IGT) was defined as FPG < 5.6 mmol/l and 7.8 mmol/l ≤ 2hPG < 11.1 mmol/l. HbA1c 5.7–6.4 % was used to identify subjects with prediabetes. Insulin release was calculated by basal homeostasis model assessment of insulin secretion (HOMA-β), early-phase InsAUC₃₀/GluAUC₃₀, and total-phase InsAUC₁₂₀/GluAUC₁₂₀. β-cell function relative to insulin sensitivity was expressed as disposition index (DI). All indices of insulin sensitivity and β-cell function gradually decreased with increasing HbA1c, FPG, and 2hPG (all p < 0.01). β-cell function decreased precipitously when HbA1c exceeded 5.5 %. Compared with HbA1c, FPG showed stronger correlations with HOMA-β, InsAUC₃₀/GluAUC₃₀, InsAUC₁₂₀/GluAUC₁₂₀, DI₃₀, and DI₁₂₀ (all p < 0.05), and 2hPG was more closely related to DI₃₀ and DI₁₂₀ (all p < 0.01). Moreover, FPG was more strongly related to HOMA-β and InsAUC₃₀/GluAUC₃₀ than 2hPG (all p < 0.05). The combination of i-IFG and HbA1c 5.7–6.4 % showed the greatest reduction in DI₃₀ and DI₁₂₀ compared with HbA1c 5.7–6.4 % alone, i-IGT, or i-IFG (p < 0.05). In conclusion, HbA1c could be used as a marker to identify subjects with impaired β-cell function, but OGTT performs better than HbA1c. The combination of HbA1c and FPG is a simple and sensitive method to evaluate β-cell function.     

PTEN Upregulation May Explain the Development of Insulin Resistance and Type 2 Diabetes with High Dose Statins

Purpose

Statins increase the incidence of new onset diabetes. Prolonged statin therapy upregulates PTEN expression. PTEN levels are also elevated in diabetic animals. Activation of protein kinase A by cAMP decreases PTEN expression. We assessed whether prolonged treatment with rosuvastatin (ROS) induces glucose intolerance by upregulating Phosphatase and Tensin Homologue on Chromosome 10 (PTEN) in mice receiving normal (ND) or Western Diet (WD) and whether concomitant treatment with cilostazol (CIL, a phosphodiesterase-3 inhibitor) attenuates the effects.

Methods

PTEN^loxp/cre or PTEN^+/? mice received ND or WD without or with ROS (10 mg/kg/day). Wild-type mice received ND or WD without or with ROS, CIL (10 mg/kg/day), or ROS+CIL for 30 days. Fasting insulin and glucose tolerance test were measured as well as PTEN and P-AKT levels in skeletal muscle.

Results

Serum glucose after intraperitoneal injection of glucose was higher in PTEN^loxp/cre mice receiving WD or ROS and especially WD+ROS. Levels were lower in PTEN^+/? mice compared to PTEN^loxp/cre in each treatment group. CIL decreased glucose levels in mice receiving WD, ROS and their combination. Insulin levels were higher in the WD+ROS group. CIL decreased insulin in mice receiving WD+ROS. WD, ROS and especially their combination increased PTEN and decreased P-AKT levels. CIL attenuated the effect of WD, ROS and their combination.

Conclusions

Long-term ROS can induce diabetes by upregulating PTEN. CIL attenuates these changes. Partial knockdown of PTEN also ameliorates ROS-induced insulin resistance. Further studies are needed to assess the effects of increasing cAMP levels to prevent the induction of diabetes by statins.     

Oxacillin-susceptible methicillin-resistant Staphylococcus aureus (OS-MRSA), a hidden resistant mechanism among clinically significant isolates in the Wessex region/UK

Purpose

Methicillin-resistant Staphylococcus aureus (MRSA) is defined as S. aureus genetically having the mecA or mecC genes or phenotypically showing minimum inhibitory concentration (MIC) of oxacillin higher than 2 mg/L. However, recently, cefoxitin/oxacillin-susceptible mecA-positive S. aureus (OS-MRSA) has been reported worldwide. Little is known about the prevalence and virulence of these strains among clinically significant isolates in the UK. The aims were to (1) investigate the prevalence of OS-MRSA in seven major hospitals in the Wessex region/UK from a cohort of 500 clinically significant phenotypically identified MSSA isolates, (2) genetically characterise OS-MRSA strains by pulsed-field gel electrophoresis (PFGE) and compare these to common UK epidemic strains; and (3) to determine Panton-Valentine leukocidin (PVL; lukFS) gene carriage rates among these isolates.

Results

OS-MRSA was found in six isolates (1.2 %) of phenotypically identified and reported MSSA isolates by conventional methods. PFGE showed OS-MRSA strains to be genetically diverse and distinct from the common UK epidemic strains EMRSA-15 and EMRSA-16. None of these OS-MRSA stains carried the genes encoding PVL; however, overall positivity rate for PVL was 4.4 %, much higher than the nationally reported rates of 2 % in the UK.

Conclusion

There are still many unknowns regarding phenotypic and/or genetic characterization of the emerging OS-MRSA isolates in the UK and worldwide. Data regarding their epidemiology and optimal therapy for infection are limited and need further investigation not only in the UK, but also worldwide, as it is likely to have an impact on the empirical treatment of S. aureus infections.     

Transthoracic echocardiographic and cardiopulmonary exercise testing parameters in Eisenmenger’s syndrome

Objective

The six-minute walk test (6MWT) evaluates the functional exercise capacity in patients with cardiopulmonary disease. We aimed to investigate the association between 6MWT distance and transthoracic echocardiographic (TTE) findings as well as cardiopulmonary exercise testing (CPET) parameters in Eisenmenger’s syndrome (ES) patients waiting for heart–lung transplantation on their initial admission to our center.

Patients and methods

A total of 23 patients with ES (12 women, 11 men; mean age, 28.2?±?8.1 years) were included in the study. The correlation between 6MWT distance and CPET and TTE findings was retrospectively analyzed.

Results

The most frequent underlying heart diseases were ventricular septal defect (VSD) with complex congenital heart disease (n?=?10, 43?%) and isolated VSD (n?=?7, 30?%). The 6MWT distance was 349.7?±?77.4 m in the study group. An inverse correlation was found between 6MWT distance and systolic pulmonary arterial pressure (SPAP) measured with TTE (r?=???0.445; p?=?0.03). All patients underwent CPET at the first visit. Mean VO₂ max was 14.9?±?3.3 ml/kg/min and the VE/VCO₂ rate was 50.4?±?9.2?%. No significant correlation was observed between 6MWT and CPET findings. SPAP, which did not display any correlation with CPET findings, was the only independent predictor of 6MWT distance.

Conclusion

We suggest that 6MWT distance may be more suitable than CPET in the follow-up of ES patients. Further prospective, randomized, controlled trials are necessary to make more robust interpretations of this issue.     

ABO blood group influences transfusion and survival after cardiac surgery

ABO dependent variation in von Willebrand factor (vWf) and procoagulant factor VIII (FVIII) is a plausible mechanism for modulating perioperative hemostasis and bleeding. Group AB has the highest and group O the lowest vWf and FVIII levels. Therefore, we tested the hypothesis that ABO blood group is associated with perioperative transfusion and subsequent survival after coronary revascularization. This retrospective study combined demographic, operative, and transfusion data, including follow-up for a median of 2,096 days, for consecutive aortocoronary bypass (CABG) and CABG/valve procedures from 1996–2009 at a tertiary referral University Heart Center. Between group differences were compared by a Kruskall Wallis test, and hazard ratios [95 % confidence intervals] are reported for mortality risk-adjusted Cox proportional hazards regression analysis. From 15,454 patients, follow-up records were available for 13,627 patients: 6,413 group O, 5,248 group A, 1,454 group B, and 435 group AB. Packed red blood cells were the most commonly transfused blood product (3 [0–5] units), while group AB received 2 [0–5] units (Kruskall Wallis Chi squared value for between group differences = 8.2; p = 0.04). Group AB favored improved long-term, postoperative survival (Hazard ratio = 0.82 [95 %CI 0.68–0.98]; p = 0.03), which became evident approximately a year after surgery. In conclusion, the procoagulant phenotype of blood group AB is associated with fewer transfusions and improved late survival after cardiac surgery. Whether this finding is related to fewer perioperative transfusions, a reduction in later bleeding or other mechanisms remains speculative.     

Comparative analysis of different enzyme immunoassays for assessment of phosphatidylserine-dependent antiprothrombin antibodies

Phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) were strongly correlated with the presence of lupus anticoagulant showing a high specificity for the diagnosis of antiphospholipid syndrome. However, the main criticism for the clinical applicability of aPS/PT testing is the lack of reproducibility of the results among laboratories. In this study, we measured IgG and IgM aPS/PT using our original in-house enzyme-linked immunosorbent assays (ELISA) and commercial ELISA kits to assess the assay performance and to evaluate the accuracy of aPS/PT results. The study included 111 plasma samples collected from patients and stored at our laboratory for aPS/PT assessment. Sixty-one samples were tested for IgG aPS/PT using two assays: (1) aPS/PT in-house ELISA and (2) QUANTA Lite? aPS/PT IgG ELISA kit (INOVA Diagnostics, Inc., USA). Fifty samples were evaluated for IgM aPS/PT using two assays: (1) aPS/PT in-house ELISA and (2) QUANTA Lite? aPS/PT IgM ELISA kit (INOVA Diagnostics). Ninety-eight percent of samples yielded concordant results for IgG aPS/PT and 82 % for IgM aPS/PT. There was an excellent agreement between the IgG aPS/PT assays (Cohen κ = 0.962) and moderate agreement between the IgM aPS/PT assays (κ = 0.597). Statistically significant correlations in the aPS/PT results were obtained from both IgG and IgM aPS/PT assays (r = 0.749, r = 0.622, p < 0.001, respectively). In conclusion, IgG and IgM detection by ELISA is accurate. The performance of aPS/PT is reliable, and concordant results can be obtained using different ELISA methods.     

Serum alkaline phosphatase differentiates prostate-specific antigen flare from early disease progression after docetaxel chemotherapy in castration-resistant prostate cancer with bone metastasis

Purpose

A transient rise in prostate-specific antigen (PSA) after the initiation of chemotherapy, called as PSA flare, has been frequently reported in patients with castration-resistant prostate cancer (CRPC) but there has been no way to differentiate PSA rises in CRPC. We investigated whether bone-related serum markers differentiate PSA flare from progression in CRPC patients with bone metastasis.

Methods

We reviewed CRPC patients with bone metastasis who received systemic chemotherapy from 2002 to 2008. Pretreatment baseline and follow-up data including age, performance score, PSA, Gleason score, alkaline phosphatase (ALP), calcium level, and hemoglobin were evaluated. Pretreatment parameters and follow-up serum parameters after the first cycle of chemotherapy were included in statistical analyses.

Results

PSA increased in 38 patients (45.8 %) at the first evaluation after chemotherapy. Among the PSA rises, PSA increased continuously or did not decrease to the stabilization level by the third evaluation in 22 (26.5 %) patients, while PSA decreased to the stabilization or response level by the third evaluation in 16 (19.3 %). PSA flare occurred in 17 (20.5 %). The univariate analyses showed that no baseline parameters were associated with PSA flare, but the initial ALP decrease, changed ALP ratio, and median calcium level were significantly associated with PSA flare (p = 0.001, p = 0.008 and p = 0.012, respectively). Multivariate logistic regression analysis showed that a change in the ALP level is an independent predictive factor for PSA flare (p = 0.017).

Conclusions

ALP is a useful biomarker to differentiate PSA flare from early PSA progression during docetaxel chemotherapy in CRPC patients with bone metastasis.     

Less but better: cardioprotective lipid profile of patients with GCK-MODY despite lower HDL cholesterol level

Patients with diabetes caused by single-gene mutations generally exhibit an altered course of diabetes. Those with mutations of the glucokinase gene (GCK-MODY) show good metabolic control and low risk of cardiovascular complications despite paradoxically lowered high-density lipoprotein (HDL) cholesterol levels. In order to investigate the matter, we analyzed the composition of low-density lipoprotein (LDL) and HDL subpopulations in such individuals. The LipoPrint^© system (Quantimetrix, USA) based on non-denaturing, linear polyacrylamide gel electrophoresis was used to separate and measure LDL and HDL subclasses in fresh-frozen serum samples from patients with mutations of glucokinase or HNF1A, type 1 diabetes (T1DM) and healthy controls. Fresh serum samples from a total of 37 monogenic diabetes patients (21 from GCK-MODY and 16 from HNF1A-MODY), 22 T1DM patients and 15 healthy individuals were measured in this study. Concentrations of the small, highly atherogenic LDL subpopulation were similar among the compared groups. Large HDL percentage was significantly higher in GCK-MODY than in control (p = 0.0003), T1DM (p = 0.0006) and HNF1A-MODY groups (p = 0.0246). Patients with GCK-MODY were characterized by significantly lower intermediate HDL levels than controls (p = 0.0003) and T1DM (p = 0.0005). Small, potentially atherogenic HDL content differed significantly with the GCK-MODY group showing concentrations of that subfraction from control (p = 0.0096), T1DM (p = 0.0193) and HNF1A-MODY (p = 0.0057) groups. Within-group heterogeneity suggested the existence of potential gene–gene or gene–environment interactions. GCK-MODY is characterized by a strongly protective profile of HDL cholesterol subpopulations. A degree of heterogeneity within the groups suggests the existence of interactions with other genetic or clinical factors.