Search

Room temperature ionic liquids (RTILs) are molten salts consisting entirely of ions and have over the past decades gained increased interest due to their high potential in applications. These structurally complex systems often display multiple relaxation modes in the response functions at lower frequencies, hinting to complex underlying mechanisms. While the existence of these multimodal spectra in the shear mechanical, dielectric, and light scattering response of RTILs has been confirmed multiple times, controversy still surrounds the origin. This paper, therefore, aims to provide additional insights into the multimodal spectra seen in RTILs by presenting new shear mechanical results on seven different RTILs: Pyr1n-TFSI with n = 4, 6, and 8; Pyr18-TFSI mixed with Li-TFSI in two high concentrations; and Cn-mim-BF4 with n = 3 and 8. Dynamic depolarized light scattering was also measured on one of the Pyr18-TFSI Li-salt mixtures. These specific cases were analyzed in detail and put into a bigger perspective together with an overview of the literature. Recent literature offers two specific explanations for the origin of the multimodal shear mechanical spectra: (1) cation-anion time scale separation or (2) combined cation-anion relaxation in addition to a dynamic signal from mesoscale aggregates at lower frequencies. However, neither of these two pictures can consistently explain all the results on different ionic liquids. Instead, we conclude that the origin of the multimodal spectrum is system specific. This underlines the complexity of this class of liquids and shows that great care must be taken when making general conclusions based on specific cases., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Cardiac allograft vasculopathy (CAV) is a leading cause of death following heart transplantation (HTx) and non-invasive prognostic methods in long-term CAV surveillance are needed. We evaluated the prognostic value of myocardial flow reserve (MFR) obtained by 82-rubidium ( 82 Rb) positron emission tomography (PET)., Methods: Recipients undergoing dynamic rest-stress 82 Rb PET between April 2013 and June 2017 were retrospectively evaluated in a single-center study. Evaluation by PET included quantitative myocardial blood flow and semiquantitative myocardial perfusion imaging. Patients were grouped by MFR (MFR ≤ 2.0 vs MFR > 2.0) and the primary outcome was all-cause mortality., Results: A total of 50 patients (68% men, median age 57 [IQR: 43 to 68]) were included. Median time from HTx to PET was 10.0 (6.7 to 16.0) years. In 58% of patients CAV was documented prior to PET. During a median follow-up of 3.6 (2.3 to 4.3) years 12 events occurred. Survival probability by Kaplan-Meier method was significantly higher in the high-MFR group (log-rank P = .02). Revascularization (n = 1), new CAV diagnosis (n = 1), and graft failure (n = 4) were more frequent in low-MFR patients. No retransplantation occurred., Conclusions: Myocardial flow reserve appears to offer prognostic value in selected long-term HTx recipients and holds promise as a non-invasive method for CAV surveillance possibly guiding management strategy., (© 2021. American Society of Nuclear Cardiology.)

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis. Multianalyte signatures, including liquid biopsy and traditional clinical variables, have shown promise for improving prognostication in other solid tumors but have not yet been rigorously assessed for PDAC., Materials and Methods: We performed a prospective cohort study of patients with newly diagnosed locally advanced pancreatic cancer (LAPC) or metastatic PDAC (mPDAC) who were planned to undergo systemic therapy. We collected peripheral blood before systemic therapy and assessed circulating tumor cells (CTCs), cell-free DNA concentration (cfDNA), and circulating tumor KRAS (ctKRAS)-variant allele fraction (VAF). Association of variables with overall survival (OS) was assessed in univariate and multivariate survival analysis, and comparisons were made between models containing liquid biopsy variables combined with traditional clinical prognostic variables versus models containing traditional clinical prognostic variables alone., Results: One hundred four patients, 40 with LAPC and 64 with mPDAC, were enrolled. CTCs, cfDNA concentration, and ctKRAS VAF were all significantly higher in patients with mPDAC than patients with LAPC. ctKRAS VAF (cube root; 0.05 unit increments; hazard ratio, 1.11; 95% CI, 1.03 to 1.21; P = .01), and CTCs ≥ 1/mL (hazard ratio, 2.22; 95% CI, 1.34 to 3.69; P = .002) were significantly associated with worse OS in multivariate analysis while cfDNA concentration was not. A model selected by backward selection containing traditional clinical variables plus liquid biopsy variables had better discrimination of OS compared with a model containing traditional clinical variables alone (optimism-corrected Harrell's C-statistic 0.725 v 0.681)., Conclusion: A multianalyte prognostic signature containing CTCs, ctKRAS, and cfDNA concentration outperformed a model containing traditional clinical variables alone suggesting that CTCs, ctKRAS, and cfDNA provide prognostic information complementary to traditional clinical variables in advanced PDAC.

Purpose: The role of plasma-based tumor mutation burden (pTMB) in predicting response to pembrolizumab-based first-line standard-of-care therapy for metastatic non-small cell lung cancer (mNSCLC) has not been explored., Experimental Design: A 500-gene next-generation sequencing panel was used to assess pTMB. Sixty-six patients with newly diagnosed mNSCLC starting first-line pembrolizumab-based therapy, either alone or in combination with chemotherapy, were enrolled (Clinicaltrial.gov identifier: NCT03047616). Response was assessed using RECIST 1.1. Associations were made for patient characteristics, 6-month durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS)., Results: Of 66 patients, 52 (78.8%) were pTMB-evaluable. Median pTMB was 16.8 mutations per megabase (mut/Mb; range, 1.9-52.5) and was significantly higher for patients achieving DCB compared with no durable benefit (21.3 mut/Mb vs. 12.4 mut/Mb, P = 0.003). For patients with pTMB ≥ 16 mut/Mb, median PFS was 14.1 versus 4.7 months for patients with pTMB < 16 mut/Mb [HR, 0.30 (0.16-0.60); P < 0.001]. Median OS for patients with pTMB ≥ 16 was not reached versus 8.8 months for patients with pTMB < 16 mut/Mb [HR, 0.48 (0.22-1.03); P = 0.061]. Mutations in ERBB2 exon 20, STK11, KEAP1 , or PTEN were more common in patients with no DCB. A combination of pTMB ≥ 16 and absence of negative predictor mutations was associated with PFS [HR, 0.24 (0.11-0.49); P < 0.001] and OS [HR, 0.31 (0.13-0.74); P = 0.009]., Conclusions: pTMB ≥ 16 mut/Mb is associated with improved PFS after first-line standard-of-care pembrolizumab-based therapy in mNSCLC. STK11/KEAP1/PTEN and ERBB2 mutations may help identify pTMB-high patients unlikely to respond. These results should be validated in larger prospective studies., (©2020 American Association for Cancer Research.)

Background: Takotsubo cardiomyopathy (TTC) is a syndrome of acute non-coronary heart failure with similar symptoms and electrocardiograms to acute anterior ST-elevation myocardial infarction (STEMI). Little is known about the pathophysiology of TTC. We assessed admission plasma concentrations of biomarkers reflecting neuroendocrine response (copeptin, mid-regional-pro-adrenomedullin, pro-atrial-natriuretic-peptide, soluble thrombomodulin (sTM), syndecan-1) and inflammation (suppression-of-tumorigenicity 2 (ST2), high-sensitive C-reactive-protein) in TTC patients and compared to patients with acute anterior STEMI. Materials and methods: Twenty TTC patients were matched with 40 STEMI patients by age, gender and left ventricular ejection fraction. Blood was sampled upon hospital admission immediately before acute coronary angiography. Results: The groups had similar comorbidities. TTC patients had higher plasma concentrations of sTM: 7.94 (5.89;9.61) vs. 6.42 (5.50;7.82)ng/ml, p  = 0.04 and ST2 (53 (32;157) vs. 45 (31;55)ng/ml, p  = 0.008) and higher heart rate: 101 ([Formula: see text]33) vs. 76([Formula: see text]14)bpm, p  = 0.0001, but lower concentrations of copeptin (10.4 (7.6;39) vs. 92.3 (13;197)pmol/l, p  < 0.05) and troponin T (348 (98;759) vs. 1190 (261;4105)ng/l, p  = 0.04). Conclusion: TTC patients had higher plasma concentrations of sTM and ST2, higher heart rate and lower copeptin and troponin T concentrations compared to acute anterior STEMI patients. This study contributes to the hypothesis that TTC patients have endothelial cell damage and are hemodynamically more stable than patients with acute anterior STEMI on admission.

Postmortem CT might provide valuable information in determining the cause of death and understanding disease processes, particularly when combined with traditional autopsy. Pediatric applications of postmortem imaging represent a new and rapidly growing field. We describe our experience in establishing a pediatric postmortem CT program and present a discussion of the distinct challenges in developing this type of program in the United States of America, where forensic practice varies from other countries. We give a brief overview of recent literature along with the common imaging findings on postmortem CT that can simulate antemortem pathology.

In part 2 of this two-part manuscript on takotsubo syndrome (TTS), we discuss typical biomarkers (particularly excess catecholamines and what kinds of electrocardiographic information operators should look for) and numerous complications the syndrome can cause. This consensus paper is the result of a multinational effort aiming to summarize the current state of the art on TTS. Several novel and unique sections are emphasized in this document, including the current state of the art on genetics of takotsubo syndrome, microRNAs (miRs), racial differences, role of cardiac spectroscopy and intracoronary imaging, as well as mechanical circulatory support. New structured algorithms are also proposed to aid clinicians in the decision-making process as well as future directions for research given the current lack of evidence-based medical approaches., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Takotsubo syndrome (TTS) is an acute cardiac condition independent of epicardial coronary obstruction that mimics acute coronary syndrome and is characterized by acute heart failure with reversible ventricular motion abnormalities. This consensus paper is the result of a multinational effort aiming to summarize the current state of the art on TTS. Experts in the field provide a thorough and detailed review of this syndrome. Several novel and unique sections are emphasized in this document, including the current state of the art on genetics of takotsubo syndrome, microRNAs (miRs), racial differences, role of cardiac spectroscopy and intracoronary imaging, as well as mechanical circulatory support. In part 1 of this two-part manuscript, we discuss how TTS came to be known, several patterns and forms it can take in patients, epidemiology and pathophysiology of the syndrome, and clinical presentation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: People living with HIV (PLWH) appear to be at increased risk of cardiovascular disease (CVD), and this is possibly more pronounced in women living with HIV (WLWH). In the general population, men are more likely to develop obstructive coronary artery disease (CAD), and women often present with a nonobstructive pattern with cardiac microvascular dysfunction. We investigated cardiac microvascular function in men and women living with HIV and tested for association with cytomegalovirus (CMV) immunoglobulin G (IgG), as this has been associated with CVD in PLWH., Methods: In a cross-sectional study, 94 PLWH on antiretroviral therapy were scanned with 82 Rb positron emission tomography/computed tomography at rest and during adenosine-induced stress, which enables the quantification of the myocardial flow reserve (MFR). CMV IgG was measured in plasma., Results: WLWH had significantly lower MFR compared with men living with HIV (MLWH; P = .003), and >45% of the women had an MFR indicative of cardiac microvascular dysfunction, whereas this was only true for 24% of men ( P = .03). CMV IgG concentrations were inversely associated with MFR among WLWH but not MLWH ( P = .05 for interaction)., Conclusions: In this first study comparing MFR in women and men living with HIV, we found that WLWH had significantly lower MFR than MLWH and 45% of the women had cardiac microvascular dysfunction despite younger age and lower cardiovascular risk. Furthermore, CMV IgG was inversely associated with MFR among women but not men. This calls for attention to CVD among young WLWH even with low cardiovascular risk.

Background: Determining infarct size and myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) is important when assessing the efficacy of new reperfusion strategies. We investigated whether rest 82 Rb-PET myocardial perfusion imaging can estimate area at risk, final infarct size, and myocardial salvage index when compared to cardiac SPECT and magnetic resonance (CMR)., Methods: Twelve STEMI patients were injected with 99m Tc-Sestamibi intravenously immediate prior to reperfusion. SPECT, 82 Rb-PET, and CMR imaging were performed post-reperfusion and at a 3-month follow-up. An automated algorithm determined area at risk, final infarct size, and hence myocardial salvage index., Results: SPECT, CMR, and PET were performed 2.2 ± 0.5, 34 ± 8.5, and 32 ± 24.4 h after reperfusion, respectively. Mean (± SD) area at risk were 35.2 ± 16.6%, 34.7 ± 11.3%, and 28.1 ± 16.1% of the left ventricle (LV) in SPECT, CMR, and PET, respectively, P = 0.04 for difference. Mean final infarct size estimates were 12.3 ± 15.4%, 13.7 ± 10.4%, and 11.9 ± 14.6% of the LV in SPECT, CMR, and PET imaging, respectively, P = .72. Myocardial salvage indices were 0.64 ± 0.33 (SPECT), 0.65 ± 0.20 (CMR), and 0.63 ± 0.28 (PET), (P = .78)., Conclusions: 82 Rb-PET underestimates area at risk in patients with STEMI when compared to SPECT and CMR. However, our findings suggest that PET imaging seems feasible when assessing the clinical important parameters of final infarct size and myocardial salvage index, although with great variability, in a selected STEMI population with large infarcts. These findings should be confirmed in a larger population.

Aims: Cardiac allograft vasculopathy (CAV) is a leading cause of death in orthotopic heart transplant (OHT) survivors. Effective non-invasive screening methods are needed. Our aim was to investigate the added diagnostic and prognostic value of myocardial blood flow (MBF) to standard myocardial perfusion imaging (MPI) with positron emission tomography (PET) for CAV detection., Methods and Results: We studied 94 OHT recipients (prognostic cohort), including 66 who underwent invasive coronary angiography and PET within 1 year (diagnostic cohort). The ISHLT classification was used as standard definition for CAV. Positron emission tomography evaluation included semiquantitative MPI, quantitative MBF (mL/min/g), and left ventricular ejection fraction (LVEF). A PET CAV severity score (on a scale of 0-3) was modelled on the ISHLT criteria. Patients were followed for a median of 2.3 years for the occurrence of major adverse events (death, re-transplantation, acute coronary syndrome, and hospitalization for heart failure). Sensitivity, specificity, positive, and negative predictive value of semiquantitative PET perfusion alone for detecting moderate-severe CAV were 83% [52-98], 82% [69-91], 50% [27-73], and 96% [85-99], respectively {receiver operating characteristic (ROC area: 0.82 [0.70-0.95])}. These values improved to 83% [52-98], 93% [82-98], 71% [42-92], and 96% [97-99], respectively, when LVEF and stress MBF were added (ROC area: 0.88 [0.76-0.99]; P = 0.01). There were 20 major adverse events during follow-up. The annualized event rate was 5%, 9%, and 25% in patients with normal, mildly, and moderate-to-severely abnormal PET CAV grading (P < 0.001), respectively., Conclusion: Multiparametric cardiac PET evaluation including quantification of MBF provides improved detection and gradation of CAV severity over standard myocardial perfusion assessment and is predictive of major adverse events., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Background: Respiratory motion due to breathing during cardiac positron emission tomography (PET) results in spatial blurring and erroneous tracer quantification. Respiratory gating might represent a solution by dividing the PET coincidence dataset into smaller respiratory phase subsets. The aim of our study was to compare the resulting imaging quality by the use of a time-based respiratory gating system in two groups administered either adenosine or dipyridamole as the pharmacological stress agent., Methods and Results: Forty-eight patients were randomized to adenosine or dipyridamole cardiac stress 82 RB-PET. Respiratory rates and depths were measured by a respiratory gating system in addition to registering actual respiratory rates. Patients undergoing adenosine stress showed a decrease in measured respiratory rate from initial to later scan phase measurements [12.4 (±5.7) vs 5.6 (±4.7) min -1 , P < .001] and tended to have a lower frequency of successful respiratory gating compared to dipyridamole (47% vs 71%, P = .12). As a result, imaging quality was superior in the dipyridamole group compared to adenosine., Conclusions: If respiratory gating is considered for use in cardiac PET, a dipyridamole stress protocol is recommended as it, compared to adenosine, causes a more uniform respiration and results in a higher frequency of successful respiratory gating and thereby superior imaging quality.

Background: Coronary microvascular function can be assessed by transthoracic Doppler echocardiography as a coronary flow velocity reserve (TTDE CFVR) and by positron emission tomography as a myocardial blood flow reserve (PET MBFR). PET MBFR is regarded the noninvasive reference standard for measuring coronary microvascular function but has limited availability. We compared TTDE CFVR with PET MBFR in women with angina pectoris and no obstructive coronary artery disease and assessed repeatability of TTDE CFVR., Methods: From a cohort of women with angina and no obstructive coronary artery stenosis at invasive coronary angiography, TTDE CFVR by dipyridamole induced stress and MBFR by rubidium-82 PET with adenosine was successfully measured in 107 subjects. Repeatability of TTDE CFVR was assessed in 10 symptomatic women and in 10 healthy individuals., Results: MBFR was systematically higher than CFVR. Median MBFR (interquartile range, IQR) was 2.68 (2.29-3.10) and CFVR (IQR) was 2.31 (1.89-2.72). Pearson's correlation coefficient was 0.36 (p<0.01). Limits of agreement (2·standard deviation) assessed by the Bland-Altman (confidence interval, CI) method was 1.49 (1.29;1.69) and unaffected by time-interval between examinations. Results were similar when adjusting for rate pressure product or focusing on perfusion of the left anterior descending artery region. Limits of agreement (CI) for repeated CFVR in 10 healthy individuals and in 10 women with angina was 0.44 (0.21;0.68) and 0.48 (0.22; 0.74), respectively., Conclusion: CFVR had a good repeatability, but the agreement between CFVR and MBFR was modest. Divergence could be due to methodology differences; TTDE estimates flow velocities whereas PET estimates myocardial blood flow., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Even in absence of obstructive coronary artery disease women with angina pectoris have a poor prognosis possibly due to coronary microvascular disease. Coronary microvascular disease can be assessed by transthoracic Doppler echocardiography measuring coronary flow velocity reserve (CFVR) and by positron emission tomography measuring myocardial blood flow reserve (MBFR). Diffuse myocardial fibrosis can be assessed by cardiovascular magnetic resonance (CMR) T1 mapping. We hypothesized that coronary microvascular disease is associated with diffuse myocardial fibrosis., Methods: Women with angina, a clinically indicated coronary angiogram with <50 % stenosis and no diabetes were included. CFVR was measured using dipyridamole (0.84 mg/kg) and MBFR using adenosine (0.84 mg/kg). Focal fibrosis was assessed by 1.5 T CMR late gadolinium enhancement (0.1 mmol/kg) and diffuse myocardial fibrosis by T1 mapping using a modified Look-Locker pulse sequence measuring T1 and extracellular volume fraction (ECV)., Results: CFVR and CMR were performed in 64 women, mean (SD) age 62.5 (8.3) years. MBFR was performed in a subgroup of 54 (84 %) of these women. Mean native T1 was 1023 (86) and ECV (%) was 33.7 (3.5); none had focal fibrosis. Median (IQR) CFVR was 2.3 (1.9; 2.7), 23 (36 %) had CFVR < 2 indicating coronary microvascular disease, and median MBFR was 2.7 (2.2; 3.0) and 19 (35 %) had a MBFR value below 2.5. No significant correlations were found between CFVR and ECV or native T1 (R 2  = 0.02; p = 0.27 and R 2  = 0.004; p = 0.61, respectively). There were also no correlations between MBFR and ECV or native T1 (R 2  = 0.1; p = 0.13 and R 2  = 0.004, p = 0.64, respectively). CFVR and MBFR were correlated to hypertension and heart rate., Conclusion: In women with angina and no obstructive coronary artery disease we found no association between measures of coronary microvascular disease and myocardial fibrosis, suggesting that myocardial ischemia induced by coronary microvascular disease does not elicit myocardial fibrosis in this population. The examined parameters seem to provide independent information about myocardial and coronary disease.

Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, allow for quantification of both structural and functional properties of this cardiac chamber. In echocardiography, only the maximal LA volume is included in the assessment of diastolic function at the current moment. Numerous studies, however, have shown that functional measures may be superior to the maximal LA volume in several aspects and to possess clinical value even in the absence of structural abnormalities. Such functional measures could prove particularly useful in the setting of predicting atrial fibrillation, which will be a point of focus in this review. Pivotal cardiac magnetic resonance imaging studies have revealed high correlation between LA fibrosis and risk of atrial fibrillation recurrence after catheter ablation, and subsequent multimodality imaging studies have uncovered an inverse relationship between LA reservoir function and degree of LA fibrosis. This has sparked an increased interest into the application of advanced imaging modalities, including both speckle tracking echocardiography and tissue tracking by cardiac magnetic resonance imaging. Even though increasing evidence has supported the use of functional measures and proven its superiority to the maximal LA volume, they have still not been adopted in clinical guidelines. The reason for this discrepancy may rely on the fact that there is little to no agreement on how to technically perform deformation analysis of the LA. Such technical considerations, limitations, and alternate imaging prospects will be addressed in this review., (© 2016 American Heart Association, Inc.)

Objectives: The study sought to investigate adrenergic activity in patients with takotsubo cardiomyopathy (TTC)., Background: TTC is a specific type of reversible heart failure possibly caused by excessive catecholamine stimulation of the myocardium. Scintigraphic iodine-123-meta-iodobenzylguanidine (mIBG) imaging of the heart and measurement of plasma catecholamines can be used to assess adrenergic activity in vivo. The authors hypothesized that sympathetic nerve activity is increased in the subacute state of TTC, and this study used cardiac mIBG imaging and plasma levels of norepinephrine and epinephrine as markers to assess this hypothesis., Methods: In this study, 32 patients with TTC and 20 controls were examined at admission and again on follow-up with echocardiography, mIBG scintigraphy, and plasma catecholamine measurements., Results: Ejection fraction (EF) was initially 36 ± 9% but increased to >60% (p = 0.0004) in all patients with TTC. In the control subjects EF was initially higher (51 ± 11%; p = 0.0004) than in the patients with TTC. However, EF of the patients with TTC exceeded that of the control subjects on follow-up (56 ± 8%; p = 0.0007). The mIBG imaging showed a lower late (4-h) heart-to-mediastinum ratio (H/Mlate) (2.00 ± 0.38) and a higher washout rate (WR) (45 ± 12%) in the subacute state of TTC, both when compared with follow-up (H/Mlate: 2.42 ± 0.45; p = 0.0004; WR: 33 ± 14%; p = 0.0004) and when compared with the control group in the subacute state (H/Mlate: 2.34 ± 0.60, p = 0.035; WR: 33 ± 19%, p = 0.026). On follow-up, no differences in mIBG parameters were observed between the TTC and control groups (H/Mlate: 2.41 ± 0.51, p = 0.93; WR: 30 ± 13%, p = 0.48) group. In the TTC group, plasma epinephrine levels were elevated in the subacute state (Log2[epinephrine]: 6.13 ± 1.04 pg/ml), both when compared with follow-up (5.25 ± 0.62 pg/ml; p = 0.0004) and when compared with the control group in the subacute state (5.46 ± 0.69 pg/ml; p = 0.044), and these levels remained elevated in the TTC group on follow-up compared with the control group (4.56 ± 0.95 pg/ml; p = 0.014). No significant differences in plasma norepinephrine levels were observed., Conclusions: The present study supports a possible role of adrenergic hyperactivity in TTC., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Takotsubo cardiomyopathy (TTC) is an acute cardiac syndrome, characterized by transient left ventricular dysfunction often following a stressful event in post-menopausal women. Symptoms are indistinguishable from myocardial infarction. However, TTC patients do not have a culprit lesion on acute angiography, and regional akinesia is not limited to a single vascular territory. As opposed to other cardiomyopathies TTC is completely reversible, albeit with a 5% mortality rate as well as a 10% re-occurrence rate. This article summarizes the current knowledge about aetiology, diagnostics and treatment.

Background: Coronary flow velocity reserve (CFVR) measured by transthoracic Doppler echocardiography of the LAD is used to assess microvascular function but validation studies in clinical settings are lacking. We aimed to assess feasibility, reproducibility and agreement with myocardial flow reserve (MFR) measured by PET in overweight and obese patients., Methods: Participants with revascularized coronary artery disease were examined by CFVR. Subgroups were examined by repeated CFVR (reproducibility) or Rubidium-82-PET (agreement). To account for time variation, results were computed for scans performed within a week (1-week) and for all scans regardless of time gap (total) and to account for scar tissue for patients with and without previous myocardial infarction (MI)., Results: Eighty-six patients with median BMI 30.9 (IQR 29.4-32.9) kg × m(-2) and CFVR 2.29 (1.90-2.63) were included. CFVR was feasible in 83 (97 %) using a contrast agent in 14 %. For reproducibility overall (n = 21) limits of agreement (LOA) were (-0.75;0.71), within-subjects coefficient of variation (CV) 11 %, and reliability 0.84. For reproducibility within 1-week (n = 13) LOA were (-0.33;0.25), within-subjects CV 5 %, and reliability 0.97. Agreement with MFR of the LAD territory (n = 35) was without significant bias and overall LOA were (-1.40;1.46). Agreement was best for examinations performed within 1-week of participants without MI of the LAD-territory (n = 12); LOA = (-0.68;0.88)., Conclusions: CFVR was highly feasible with a good reproducibility on par with other contemporary measures applied in cardiology. Agreement with MFR was acceptable, though discrepancy related to prior MI has to be considered. CFVR of LAD is a valid tool in overweight and obese patients.

Cardiac Rubidium-82 ((82)Rb) positron-emission-tomography (PET) is a good method for quantification of myocardial blood flow in man. Quantification of myocardial blood flow in animals to evaluate new treatment strategies or to understand underlying disease is also of great interest but raises some challenges. Animals, which have been anesthetized during PET acquisition, might react differently to used stress medications, and therefore difficulties might exist while evaluating the resulting PET images using standard software packages from commercial vendors optimized for human hearts. Furthermore propofol, used for anesthesia, can influence myocardial perfusion and coronary flow reserve due to its vasorelaxant effect, and interactions might exist between propofol and used stress agents, potentially affecting the result of the examination. We present cardiac (82)Rb-PET studies performed in propofol-anesthetized minipigs with normal and infarcted myocardium stressed with both adenosine and dipyridamole. Despite the mentioned challenges, we were able to trace the small minipig heart with software designed for human cardiac PET and to achieve blood flow measurements comparable with results in humans with both adenosine and dipyridamole. We found dipyridamole to be a superior stress agent for this experimental setup. Finally, we were able to clearly identify the myocardial perfusion defect after an induced myocardial infarction.

Background: Takotsubo cardiomypathy (TTC) causes acute reversible heart failure. Prior studies have indicated that the syndrome is associated with traits such as social inhibition, chronic psychological stress, and anxio-depressive disorders. The objective of this study was to further characterize key psychological/psychopathological traits of patients with TTC., Methods: A survey of three groups was conducted: I) Female post-recovery TTC patients admitted between October 1(st) 2009 and December 10(th) 2014, II) Age, gender and geographically matched ST-elevation myocardial infarction (STEMI) patients, and III) Age, gender and geographically matched individuals from the background population. The following questionnaires were used in the survey: the WHO-5 Well-Being Index, Eysenck's Neuroticism Scale, the Major Depression Inventory, and the anxiety subscale of Symptoms Checklist (SCL-90)., Results: In total, 173 of 230 invitees (75 %) participated in the study. In comparison to the background controls, TTC patients reported significantly less well-being, more neuroticism, more depression, and more anxiety. The levels of well-being, depression and neuroticism were comparable between TTC and STEMI patients, but the level of anxiety was higher in the TTC patients. There was a negative correlation between the time since TTC admission and the total scores on the psychopathology rating scales., Conclusions: Patients with TTC reported significantly higher anxiety levels compared to both STEMI patients and background controls. However, unlike the STEMI patients, the TTC patients appeared to improve psychologically during the post-recovery phase. This may be a consolation for TTC patients in acute psychological distress.

Aims/hypothesis: Coronary flow reserve (CFR) and coronary artery calcium (CAC) represent functional and structural aspects of atherosclerosis. We examined the prevalence of reduced CFR and high CAC scores in three predefined groups of participants without known cardiovascular disease: (1) patients with type 2 diabetes and albuminuria; (2) patients with type 2 diabetes and normoalbuminuria; and (3) non-diabetic controls., Methods: In a cross-sectional design, cardiac (82)Rb positron emission tomography/computed tomography was conducted in 60 patients with type 2 diabetes who were free of overt cardiovascular disease and who were stratified by normoalbuminuria (<30 mg/24 h) (n = 30; age [mean ± SD] 60.9 ± 10.1 years) and albuminuria (≥ 30 mg/24 h) (n = 30; age 65.6 ± 4.8 years), and in 30 healthy, non-diabetic controls (age 59.8 ± 9.9 years)., Results: In controls, normoalbuminuric and albuminuric patients, CFR was 3.0 ± 0.8, 2.6 ± 0.8 and 2.0 ± 0.5, respectively. Reduced CFR (<2.5) was observed in 16.7%, 40.0% and 83.3% of participants, respectively, and median (interquartile range) CAC scores were 0 (0-81), 36 (1-325) and 370 (152-1,025), respectively (p for trend <0.01). After adjustment, the difference in CFR and CAC between albuminuric patients and controls remained significant (p ≤ 0.001). There were trends towards lower CFR and higher CAC scores in normoalbuminuric patients vs controls (p ≤ 0.023) and towards higher CAC scores in albuminuric vs normoalbuminuric patients (p = 0.026). In multivariate regression analysis, a higher urinary albumin excretion rate (UAER) tended to predict reduced CFR in the total population (p = 0.045). When the CAC score was added, there was also a trend (p = 0.032) towards an inverse association with reduced CFR., Conclusions/interpretation: Type 2 diabetic patients who were free of overt cardiovascular disease had a high prevalence of coronary microvascular dysfunction, especially with concomitant albuminuria, suggesting a common microvascular impairment occurring in multiple microvascular beds. Prospective studies are needed to show the prognostic significance of this finding.

Aims: Takotsubo cardiomyopathy (TTC) is characterized by acute completely reversible regional left ventricle (LV) akinesia and decreased tracer uptake in the akinetic region on semi-quantitative perfusion imaging. The latter may be due to normoperfusion of the akinetic mid/apical area and basal hyperperfusion. Our aim was to examine abnormalities of perfusion in TTC, and we hypothesized that basal hyperperfusion is the primary perfusion abnormality in the acute state., Method and Results: Twenty-five patients were diagnosed with TTC due to (i) acute onset of symptoms, (ii) typical apical ballooning, (iii) absence of significant coronary disease, and (iv) complete remission on 4-month follow-up. The patients underwent coronary angiography (CAG), echocardiography, cardiac magnetic resonance imaging (CMR), and (13)NH3/(82)Rb positron emission tomography (PET) in the acute state and-except CAG-on follow-up. Patients initially had severe heart failure, mid/apical oedema but no infarction, and a rise in cardiac biomarkers. On initial perfusion PET imaging, eight patients appeared to have normal, whereas 17 patients had impaired LV perfusion. In the latter, flow in the basal region was increased in the acute state (1.5 ± 0.1 vs. 1.2 ± 0.1 mL/g/minRPP-corrected, P < 0.01), whereas midventricular (1.7 ± 0.1 vs. 1.6 ± 0.1 mL/g/minRPP-corrected, P = 0.21) and apical (1.4 ± 0.1 vs. 1.5 ± 0.1 mL/g/minRPP-corrected, P = 0.36) flow was unchanged between acute and follow-up, and within normal range., Conclusion: Our results suggest an abnormal LV perfusion distribution in the acute state of TTC with basal hyperperfusion and a normoperfused akinetic region. The proportion of patients without visualized perfusion abnormalities in the acute state may represent a subgroup with fast remission., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Studies have found HIV-infected patients to be at increased risk of myocardial infarction, which may be caused by coronary microvascular dysfunction. For the first time among HIV-infected patients, we assessed the myocardial flow reserve (MFR) by Rubidium-82 (82Rb) positron emission tomography (PET), which can quantify the coronary microvascular function. MFR has proved highly predictive of future coronary artery disease and cardiovascular events in the general population.In a prospective cross-sectional study, HIV-infected patients all receiving antiretroviral therapy (ART) with full viral suppression and HIV-uninfected controls were scanned using 82Rb PET/computed tomography at rest and adenosine-induced stress, thereby obtaining the MFR (stress flow/rest flow), stratified into low ≤1.5, borderline >1.5 to 2.0, or normal >2.0.Fifty-six HIV-infected patients and 25 controls were included. The HIV-infected patients had a mean age of 53 years (range 37-68 years) with 23% active smokers. The controls had a mean age of 52 years (range 36-68 years) and 26% active smokers. In the HIV-infected group 73% had a normal MFR, 17% borderline, and 10% low values of MFR. Among controls these values were 71%, 19%, and 10%, respectively (P = 0.99). However, the HIV-infected group had lower values of stress myocardial blood flow (MBF) (2.63 ± 0.09 mL/g/min vs 2.99 ± 0.14 mL/g/min; P = 0.03). We found no evidence of decreased MFR as assessed by 82Rb PET among HIV-infected patients on stable ART with full viral suppression compared with HIV-uninfected controls. We did notice a decreased MBF during stress.

Introduction: Several studies have investigated the ability of the twelve-lead electrocardiogram (ECG) to reliably distinguish Takotsubo cardiomyopathy (TC) from an acute anterior ST-segment elevation myocardial infarction (STEMI). In these studies, only ECG changes were required - ST-segment deviation and/or T-wave inversion - in TC whereas in acute anterior STEMI, ECGs had to meet STEMI criteria. In the majority of these studies, patients of both genders were used even though TC predominantly occurs in women. The aim of this study is to see whether TC can be distinguished from acute anterior STEMI in a predominantly female study population where all patients meet STEMI-criteria., Methods: Retrospective analysis of the ST-segment changes was done on the triage ECGs of 37 patients with TC (34 female) and was compared to the triage ECGs of 103 female patients with acute anterior STEMI. The latter group was divided into the following subgroups: 46 patients with proximal, 47 with mid and 10 with distal LAD occlusion. Three ST-segment based ECG features were investigated: (1) Existing criterion for differentiating anterior STEMI from TC: ST-segment depression >0.5mm in lead aVR+ST-segment elevation ≤1mm in lead V1, (2) frontal plane ST-vector and (3) mean amplitude of ST-segment deviation in each lead., Results: The existing ECG criterion was less accurate (76%) than in the original study (95%), with a large difference in sensitivity (26% vs. 91%). Only a frontal plane ST-vector of 60° could significantly distinguish TC from all acute anterior STEMI subgroups (p<0.01) with an overall diagnostic accuracy of 81%. The mean amplitude in inferior leads II and aVF was significantly higher for patients with TC compared to all patients with acute anterior STEMI (p<0.01 and p<0.05 respectively) and the mean amplitude in the precordial leads V1 and V2 was significantly lower compared to proximal and mid LAD occlusion (p<0.01)., Conclusions: Given the consequences of missing the diagnosis of an acute anterior STEMI the diagnostic accuracy of the ECG criteria investigated in this retrospective study were insufficient to reliably distinguish patients with TC from patients with an acute anterior STEMI. To definitely exclude the diagnosis of an acute anterior STEMI coronary angiography, which remains the gold standard, will need to be performed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In patients with heart failure (HF) due to coronary disease, a combined evaluation of perfusion and glucose metabolism by cardiac single photon emission computed tomography (SPECT)/positron emission tomography (PET) can be used to distinguish viable from non-viable myocardium, and current guidelines recommend cardiac SPECT and fluorodeoxyglucose (FDG) PET for viability assessment. Takotsubo cardiomyopathy (TTC) is a disease characterized by acute but reversible HF leaving no scarring. To explore how robust the semi-quantitative viability criteria used in cardiac SPECT and FDG PET stands their ground in a population with TTC. From 1 September 2009 to 1 October 2012, 24 patients suspected of TTC were enrolled in a multimodality cardiac imaging research project. Echocardiography, (99m)Tc SPECT, and (18)F FDG PET were performed during the acute admission and at follow-up 4 months later. Nineteen patients had a final diagnosis of TTC consistent with Mayo Clinic Diagnostic Criteria. Three of these patients were excluded from further analysis, since wall motion abnormalities were not persistent at the time of nuclear imaging. The remaining sixteen patients exhibited a distinct pattern with HF, "apical ballooning" and a perfusion-metabolism defect in the midventricular/apical region. When viability criteria were applied, they identified significant scarring/limited hibernation in the akinetic part of the left ventricle. However, full recovery was found in all TTC patients on follow-up. Using the current guideline-endorsed viability criteria for semiquantitative cardiac SPECT and FDG PET, these modalities failed to demonstrate the presence of viability in the acute state of TTC.

Aims: Takotsubo cardiomyopathy (TTC) is an entity mimicking acute myocardial infarction, characterized by transient severe systolic heart failure. Echocardiographic studies suggest that diastolic dysfunction is present in TTC at presentation; however, no reports exist regarding the time course of left ventricular (LV) recovery. This study describes the recovery of LV systolic and diastolic function in TTC. We hypothesized that, in TTC, there is diastolic dysfunction at admission, and that recovery is delayed compared with systolic function., Methods and Results: We enrolled (consecutively 2010-12) 16 patients (mean age 66, range 39-84 years) diagnosed with TTC and 20 healthy matched controls. We performed cardiac magnetic resonance imaging (CMR) at admission, pre-discharge, and 3-month follow-up. Diastolic function was assessed by LV peak filling rate (LVPFR) and left atrial (LA) emptying volumes. At admission, LV ejection fraction was low, increased at pre-discharge (37 ± 6 vs. 58 ± 6%, P < 0.001), and normalized at follow-up (to 65 ± 5%, P = 0.01). LVPFR did not increase during hospitalization (80 ± 3 vs. 89 ± 4 mL/s/m(2), P = 0.21), but was normalized at follow-up (to 206 ± 19, P < 0.001; controls, 214 ± 13, P = 0.23). During hospitalization, LA passive emptying volume remained low (6 ± 2 vs. 8 ± 3 mL/m(2), P = 0.05) and LA active emptying volume remained high (17 ± 3 vs. 16 ± 3 mL/m(2), P = 0.71), whereas LA conduit volume increased (7 ± 3 vs. 23 ± 4 mL/m(2), P < 0.001). T2-weighted imaging demonstrated non-coronary distributed apical oedema without contrast enhancement., Conclusion: Patients with TTC undergo fast systolic recovery. However, at discharge, profound diastolic dysfunction is demonstrated by CMR. At follow-up, both LV systolic and diastolic function is normalized in patients with recovered TTC., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Introduction: Aim was to compare absolute myocardial perfusion using cardiac magnetic resonance imaging (CMRI) based on Tikhonov's procedure of deconvolution and rubidium-82 positron emission tomography (Rb-82 PET)., Materials and Methods: Fourteen patients with coronary artery stenosis underwent rest and adenosine stress imaging by 1.5-Tesla MR Scanner and a mCT/PET 64-slice Scanner. CMRI were analyzed based on Tikhonov's procedure of deconvolution without specifying an explicit compartment model using our own software. PET images were analyzed using standard clinical software. CMRI and PET data was compared with Spearman's rho and Bland-Altman analysis., Results: CMRI results were strongly and significantly correlated with PET results for the absolute global myocardial perfusion differences (r=0.805, p=0.001) and for global myocardial perfusion reserve (MPR) (r=0.886, p<0.001). At vessel territorial level, CMRI results were also significantly correlated with absolute PET myocardial perfusion differences (r=0.737, p<0.001) and MPR (r=0.818, p<0.001). Each vessel territory had similar strong correlation for absolute myocardial perfusion differences (right coronary artery (RCA): r=0.787, p=0.001; left anterior descending artery (LAD): r=0.796, p=0.001; left circumflex artery (LCX): r=0.880, p<0.001) and for MPR (RCA: r=0.895, p<0.001; LAD: r=0.886, p<0.001; LCX: r=0.886, p<0.001)., Conclusion: On a global and vessel territorial basis, CMRI-measured absolute myocardial perfusion differences and MPR were strongly and significantly correlated with the Rb-82 PET findings., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: We aimed to study the prevalence of acute cardiac disorders in patients with suspected ST-segment elevation myocardial infarction (STEMI) and non-significant coronary artery disease (CAD)., Methods: From January to October 2012 we consecutively included patients admitted with suspected STEMI and non-significant CAD (coronary artery stenosis diameter <50%). Patients were diagnosed with acute cardiac disorder in the presence of elevated cardiac biomarkers (troponin T >50ng/l or creatine kinase MB >4μg/l) or dynamic ECG changes (ST-segment changes or T-wave inversion)., Results: Of the 871 patients admitted with suspected STEMI, 11% (n=95) had non-significant CAD. Of these, 67% (n=64) had elevated cardiac biomarkers or dynamic ECG changes and were accordingly diagnosed with acute cardiac disorders. In the remaining 33% (n=31) of patients, cardiac biomarkers were normal and ECG changes remained stationary., Conclusions: Acute cardiac disorders were diagnosed in two thirds of patients with suspected STEMI and non-significant CAD., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The autonomic nervous system plays an important role in the pathology of heart failure. The single-photon emission computed tomography tracer iodine-123-metaiodobenzylguanidine ((123) I-MIBG) can be used to investigate the activity of the predominant neurotransmitter of the sympathetic nervous system, norepinephrine. Also, positron emission tomography tracers are being developed for the same purpose. With (123) I-MIBG as a starting point, this brief review introduces the modalities used for cardiac sympathetic imaging., (© 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Many DNA viruses use powerful molecular motors to cleave concatemeric viral DNA into genome-length units and package them into preformed procapsid powered by ATP hydrolysis. Here we report the structures of the DNA-packaging motor gp2 of bacteriophage Sf6, which reveal a unique clade of RecA-like ATPase domain and an RNase H-like nuclease domain tethered by a regulatory linker domain, exhibiting a strikingly distinct domain arrangement. The gp2 structures complexed with nucleotides reveal, at the atomic detail, the catalytic center embraced by the ATPase domain and the linker domain. The gp2 nuclease activity is modulated by the ATPase domain and is stimulated by ATP. An extended DNA-binding surface is formed by the linker domain and the nuclease domain. These results suggest a unique mechanism for translation of chemical reaction into physical motion of DNA and provide insights into coordination of DNA translocation and cleavage in a viral DNA-packaging motor, which may be achieved via linker-domain-mediated interdomain communication driven by ATP hydrolysis.

In many DNA viruses, genome packaging is initiated by the small subunit of the packaging terminase, which specifically binds to the packaging signal on viral DNA and directs assembly of the terminase holoenzyme. We have experimentally mapped the DNA-interacting region on Shigella virus Sf6 terminase small subunit gp1, which occupies extended surface areas encircling the gp1 octamer, indicating that DNA wraps around gp1 through extensive contacts. High-resolution structures reveal large-scale motions of the gp1 DNA-binding domain mediated by the curved helix formed by residues 54-81 and an intermolecular salt bridge formed by residues Arg67 and Glu73, indicating remarkable structural plasticity underlying multivalent, pleomorphic gp1:DNA interactions. These results provide spatial restraints for protein:DNA interactions, which enable construction of a three-dimensional pseudo-atomic model for a DNA-packaging initiation complex assembled from the terminase small subunit and the packaging region on viral DNA. Our results suggest that gp1 functions as a DNA-spooling device, which may transform DNA into a specific architecture appropriate for interaction with and cleavage by the terminase large subunit prior to DNA translocation into viral procapsid. This may represent a common mechanism for the initiation step of DNA packaging in tailed double-stranded DNA bacterial viruses., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Aims: The efficacy and safety of insulin degludec (degludec), a new-generation ultra-long-acting basal insulin, was compared with insulin glargine (glargine) in people with Type 1 diabetes mellitus in a 16-week, open-label, randomized trial. Health status, an important aspect of effective diabetes management, was also assessed., Methods: Degludec (n = 59) or glargine (n = 59) were injected once daily, with insulin aspart at mealtimes. Health status assessment utilized the validated Short Form 36 Health Survey, version 2, which has two summary component scores for mental and physical well-being, each comprising four domains., Results: At study end, HbA(1c) reductions were comparable between groups, but confirmed nocturnal hypoglycaemia was significantly less frequent with degludec [relative rate 0.42 (95% CI 0.25-0.69)], and overall hypoglycaemia numerically less frequent [relative rate 0.72 (95% CI 0.52-1.00)]. After 16 weeks, a significant improvement in Short Form 36 Health Survey mental component score of +3.01 (95% CI 0.32-5.70) was obtained for degludec against glargine, attributable to significant differences in the social functioning [+8.04 (95% CI 1.89-14.18)] and mental health domains [+2.46 (95% CI 0.10-4.82)]. For mental component score, Cohen's effect size was 0.42, indicating a small-to-medium clinically meaningful difference. The physical component score [+0.66 (95% CI -2.30 to 3.62)] and remaining domains were not significantly different between degludec and glargine., Conclusions: In the context of comparable overall glycaemic control with glargine, degludec improved mental well-being as measured using the mental component score of the Short Form 36 Health Survey. The improvements in overall mental component score and the underlying social functioning and mental health domains with degludec compared with glargine may relate to the observed reduction in hypoglycaemic events., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

Aims: Fast-acting insulin analogues (FAIAs) reduce hypoglycaemia and improve administration flexibility compared with short-acting human insulin (SHI). This analysis examines whether these benefits translate into cost offsets when comparing the total treatment costs for FAIA versus SHI used as basal-bolus therapy for treating type 2 diabetes (T2D)., Methods: Registry data covering the Danish population including demographic variables, prescription, hospital and primary care data formed the basis for analysis. To capture patients on basal-bolus therapy only, inclusion criteria were ≥2 prescriptions of either long-acting insulin analogues (LAIAs) or neutral protamine Hagedorn (NPH) insulin (basal component), and ≥2 prescriptions for either an FAIA or SHI (bolus component) during the inclusion period (1 January-31 December 2005). Patients using LAIAs (n = 521) or NPH (n = 2695) were analysed separately. Within each basal cohort, patients using FAIAs or SHI were matched regarding observable variables using propensity scores. Healthcare costs were analysed for a follow-up period (maximum 2 years post-inclusion)., Results: Within each cohort, matching produced groups with similar observed covariates. Overall direct healthcare costs in the LAIA cohort were €4183 and €5289 for FAIA and SHI, respectively. In the NPH cohort, costs were €4940 and €4699 for FAIA and SHI, respectively. For both basal cohorts, cost differences between FAIA and SHI were not statistically significant., Limitations: As the propensity score model cannot account for unobserved variables, conclusions of causality cannot be made. Moreover, exclusion of indirect costs and application of hospital contact charges accrued in the discharge year only may result in an underestimation of overall healthcare costs., Conclusion: Using matched cohorts, treating patients with T2D using basal-bolus regimens containing FAIAs was no more costly to the Danish healthcare system than regimens using SHI. FAIAs provide a flexible administration and optimal glucose control for a similar cost.

Introduction: This retrospective study used data from a primary care database to compare two insulin products in routine clinical practice for the treatment of type 2 diabetes in the UK., Patients and Methods: Records were analyzed for patients with type 2 diabetes who had been initiated on biphasic insulin aspart 30 (BIAsp30) (n=632) or biphasic isophane human insulin 30 (BHI30) (n=762) and who had a glycated hemoglobin (HbA₁(c)) measurement at baseline (up to 6 months before the index date) and end of study (6-12 months after index date). Regression analyses were used to test for a statistically significant interaction between reduction in HbA₁(c) from baseline to end of study and the log-transformed average daily dose (logADD) of insulin., Results: With BIAsp30 a significantly lower dose of insulin (47.74 insulin units [IU]/day vs. 66.63 IU/day, P<0.0001) was required to obtain a similar HbA₁(c) reduction (1.71%-point vs. 1.55%-point, P=0.24). To achieve an additional reduction of 0.1 percentage points in HbA₁(c) (eg, reduction from 9% to 7.9% HbA₁(c) instead of from 9% to 8%), the dose of BIAsp30 would need to be increased by a factor of 1.15. For BHI30, a greater increase in dose would be needed to achieve the same additional HbA₁(c) reduction (dose increase by a factor of 1.74)., Conclusion: Clinically meaningful reductions in HbA₁(c) can be achieved at lower insulin doses with BIAsp30 treatment than with BHI30. Lower insulin doses may have important implications for medication costs.

Aims: To compare direct healthcare costs incurred by patients with type 2 diabetes in Denmark prescribed long-acting insulin analogues (LAIA) or intermediate-acting human insulin (NPH) in a basal-only regimen., Methods: Demographic and socio-economic patient characteristics, hospital utilisation data, primary care visits, specialist physician visits and prescription data were extracted from registers covering the Danish population. Patients receiving basal insulin were identified during a 1-year inclusion period (2005) and allocated to a LAIA (n=303) or NPH group (n=8523). LAIA patients were then matched with NPH patients using propensity scores based on observable covariates. Annual direct healthcare costs were determined during a <2-year analysis period (2005-2006)., Results: Direct healthcare costs, including prescription costs, were equivalent between groups. However, while most cost items were similar between groups, ambulatory visit costs were significantly lower in LAIA-treated patients (p=0.03), whereas insulin pharmacy costs were significantly lower in NPH-treated patients (p<0.001)., Conclusion: There was no difference in direct healthcare costs between patients using LAIAs or NPH insulin., (Copyright © 2010 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Introduction: The objective was to compare glycemic control, insulin utilization, and body weight in patients with type 2 diabetes (T2D) initiated on insulin detemir (IDet) or insulin glargine (IGlar) in a real-life setting in the Netherlands., Methods: Insulin-naïve patients with T2D, starting treatment with IDet or IGlar between January 1, 2004 and June 30, 2008, were selected from the PHARMO data network. Glycemic control (hemoglobin A1c [HbA1c]), target rates (HbA1c <7%), daily insulin dose, and weight gain were analyzed comparing IDet and IGlar for patients with available HbA1c levels both at baseline and at 1-year follow-up. Analysis of all eligible patients (AEP) and a subgroup of patients without treatment changes (WOTC) in the follow-up period were adjusted for patient characteristics, propensity scores, and baseline HbA1c., Results: A total of 127 IDet users and 292 IGlar users were included in the WOTC analyses. The mean HbA1c dropped from 8.4%-8.6% at baseline to 7.4% after 1 year. Patients at HbA1c goal increased from 9% at baseline to 32% for IDet and 11% to 35% for IGlar, which was not significantly different (OR 0.75, 95% CI 0.46, 1.24). Weight gain (n=90) was less among IDet users (+0.4 kg) than among IGlar users (+1.1 kg), albeit not significant. The AEP analysis (252 IDet + 468 IGlar users) showed similar results with 33%-36% at goal (OR 0.81, 95% CI 0.57, 1.16), and median daily insulin doses of 25 IU/day (P=0.70)., Conclusion: There was no significant difference between users of IDet and IGlar with respect to glycemic control and insulin dose in a real-life setting. The low proportion of patients on target at baseline may indicate that insulin therapy is initiated too late. Moreover, the observation that one-third of the patients reached HbA1c target at follow-up may indicate that basal insulin analogs are not titrated intensively enough.

Background: The Utah Psoriasis Initiative (UPI) is an expanding database that is being used to identify and characterize phenotypic variants of psoriasis and explore genotype-phenotype relationships. We recently reported distinct morphological variants of psoriasis that are characterized by thickness of lesions (induration) in the untreated state., Objectives: To explore the clinical relevance of these morphological variants., Methods: For these analyses, we used the phenotypic data from 282 additional subjects gathered at enrollment into the UPI and compared their phenotype with that of the original 500 patients reported previously. The analysis was further expanded via a longitudinal follow-up of 286 subjects from the original 500 case cohort., Results: Firstly, the initial findings were confirmed. Expansion of the cohort used for the original observation by about 50% and reanalysis showed that there was no alteration in the proportions of patients expressing thin- and thick-plaque disease phenotypes. Secondly, analysis of the larger cohort showed that this morphological phenotype had clinical relevance: those patients with thin-plaque disease were more likely to report a complete therapeutic response to topical corticosteroids and phototherapy. In contrast, plaque thickness did not appear to be a factor in response to systemic agents., Conclusions: Using a patient's baseline plaque morphology to choose a primary treatment modality may result in earlier disease improvement and reduce the cost of therapy.

Hospital cleaning is a neglected part of infection control. Due to financial constraints and lack of clinical evidence it has been cut down to the bare minimum and currently-used methods are unfit for the removal of microorganisms. Recent studies indicate that MRSA and other important pathogens may be transmitted to patients from the hospital environment. Furthermore, studies suggest that intensified cleaning may lower the risk of transmission. There is an urgent need for more clinical evidence and for development of standards and methods which focus on the removal of pathogens from the hospital environment.