The Influence of Fat Suppression Technique on Diffusion-weighted (DW) MRI in Lung Cancer

Purpose: To qualitatively and quantitatively investigate the effect of common vendor-related sequence variations in fat suppression techniques on the diagnostic performance of free-breathing DW protocols for lung imaging.Methods: 8 patients with malignant lung lesions were scanned in free breathing using two diffusion-weighted (DW) protocols with different fat suppression techniques: DWA used short-tau inversion recovery (STIR), and DWB used Spectral Adiabatic Inversion Recovery (SPAIR). Both techniques were obtained at two time points, between 1 hour and 1 week apart. Image quality was assessed using a 5-point scoring system. The number of lesions visible within lung, mediastinum and at thoracic inlet on the DW (b=800 s/mm2) images was compared. Signal-to-noise ratios (SNR) were calculated for lesions and para-spinal muscle. Repeatability of ADC values of the lesions was estimated for both protocols together and separately.Results: There was a signal void at the thoracic inlet in all patients with DWB but not with DWA. DWA images were rated significantly better than DWB images overall quality domains. (Cohens κ = 1). Although 8 more upper mediastinal/thoracic inlet lymph nodes were detected with DWA than DWB, this did not reach statistical significance (p = 0.23). Tumour ADC values were not significantly different between protocols (p=0.93), their ADC reproducibility was satisfactory (CoV=7.7%) and repeatability of each protocol separately was comparable (CoVDWA=3.7% (95% CI 2.5 7.1%) and CoVDWB=4.6% (95% CI 3.18.8%)).Conclusion: In a free-breathing DW-MRI protocol for lung, STIR fat suppression produced images of better diagnostic quality than SPAIR, while maintaining comparable SNR and providing repeatable quantitative ADC acceptable for use in a multicentre trial setting

Costs associated with febrile neutropenia in solid tumor and lymphoma patients - an observational study in Singapore.

BackgroundThe primary objective was to describe the total direct inpatient costs among solid tumor and lymphoma patients with chemotherapy-induced febrile neutropenia (FN) and the factors that were associated with higher direct cost. The secondary objective was to describe the out-of-pocket patient payments and the factors that were associated with higher out-of-pocket patient payments.MethodsThis was a single-center observational study conducted at the largest cancer center in Singapore. All of the adult cancer patients hospitalized due to FN from 2009 to 2012 were studied. The primary outcomes were the total hospital cost and the out-of-pocket patient payments (adjusted by government subsidy) per FN episode. Univariate analysis and multiple linear regression were conducted to identify the factors associated with higher FN costs.ResultsThree hundred and sixty seven adult cancer patients were documented with FN-related hospitalizations. The mean total hospital cost was US$4,193 (95$3,779-4,607) and the mean out-of-pocket patient payment was US$2,230 (95$1,976-2,484), per FN episode. The factors associated with a higher total hospital cost were longer length of stay, severe sepsis, and lymphoma as underlying cancer. The out-of-pocket patient payment was positively associated with longer length of stay, severe sepsis, lymphoma diagnosed as underlying cancer, the therapeutic use of granulocyte colony-stimulating factor (GCSF), the private ward class, and younger patients.ConclusionsThe total hospital cost and out-of-pocket patient payments of FN management in lymphoma cases were substantial compared with other solid tumors. Factors associated with a higher FN management cost may be useful for developing appropriate strategies to reduce the cost of FN for cancer patients

Results of the randomized phase IIB ARCTIC trial of low dose Rituximab in previously untreated CLL

ARCTIC was a multi-center, randomized-controlled, open, phase IIB non-inferiority trial in previously untreated Chronic Lymphocytic Leukemia (CLL). Conventional frontline therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). The trial hypothesized that including mitoxantrone with low-dose rituximab (FCM-miniR) would be non-inferior to FCR. 200 patients were recruited to assess the primary endpoint of complete remission (CR) rates according to IWCLL criteria. Secondary endpoints were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity, safety and cost-effectiveness. The trial closed following the pre-planned interim analysis. At final analysis, CR rates were 76% FCR vs 55% FCM-miniR [adjusted odds-ratio: 0.37; 95% CI: 0.19–0.73]. MRD-negativity rates were 54% FCR vs 44% FCM-miniR. More participants experienced Serious Adverse Reactions with FCM-miniR (49%) compared to FCR (41%). There are no significant differences between the treatment groups for PFS and OS. FCM-miniR is not expected to be cost-effective over a lifetime horizon. In summary, FCM-miniR is less well tolerated than FCR with an inferior response and MRD-negativity rate and increased toxicity, and will not be taken forward into a confirmatory trial. The trial demonstrated that oral FCR yields high response rates compared to historical series with intravenous chemotherapy

The multiple facets of the Hsp90 machine

International audienceThe Ninth International Conference on the Hsp90 Chaperone Machine concluded in October 2018, in Leysin, Switzerland. The program highlighted findings in various areas, including integrated insight into molecular mechanism of Hsp90, cochaperones, and clients’ structure and function.Heat shock protein-90 (Hsp90) is a molecular chaperone critical for the folding, stability, and activity of client proteins 1. Hsp90 and its orthologs, including bacterial HtpG, mitochondrial TRAP1 and endoplasmic reticulum Grp94, exist as dimers, hydrolyze ATP, and cycle between distinct conformational states. Hsp90 preferentially binds proteins in near native states facilitating their remodeling for protein interactions and signaling. At the 9th International Conference on the Hsp90 Chaperone Machine approximately one-third of the attendees shared their data on Hsp90 structure and function through short talks (Figure 1). Here, we distill and summarize their finding

Brain Imaging Studies in Pathological Gambling

This article reviews the neuroimaging research on pathological gambling (PG). Because of the similarities between substance dependence and PG, PG research has used paradigms similar to those used in substance use disorder research, focusing on reward and punishment sensitivity, cue reactivity, impulsivity, and decision making. This review shows that PG is consistently associated with blunted mesolimbic-prefrontal cortex activation to nonspecific rewards, whereas these areas show increased activation when exposed to gambling-related stimuli in cue exposure paradigms. Very little is known, and hence more research is needed regarding the neural underpinnings of impulsivity and decision making in PG. This review concludes with a discussion regarding the challenges and new developments in the field of neurobiological gambling research and comments on their implications for the treatment of PG

Mechanisms of Class II correction induced by the crown Herbst appliance as a single-phase Class II therapy : 1 year follow-up

Background The objective of this study is to evaluate the skeletal and dentoalveolar effects of the crown Herbst appliance used alone for a single phase of therapy followed by a 1-year observation period. Methods Forty patients (mean age 13.6 ± 1.3 years) with a stable Class I occlusion 1 year following the treatment with the crown Herbst appliance were selected from a prospective sample of 180 consecutively treated Class II patients. No other appliances were used during treatment or during the follow-up period. The dentoskeletal changes were compared with a matched sample of untreated Class II subjects (mean age 13.9 ± 1.6 years). Lateral cephalograms were taken before treatment, after Herbst treatment (1 year), and after 1-year follow-up. Overcorrection was avoided intentionally. Results Treatment produced an increase in mandibular length, a decrease in ANB angle, and a restriction in the vertical growth of posterior maxilla. The maxillary molars moved backward and tipped distally. The lower incisors proclined markedly, and the upper incisors became retroclined. During the follow-up period, the changes primarily were dentoalveolar in nature, with marked rebound of the upper molars and lower incisors, resulting in some increases in overbite and overjet. Conclusions The occlusal correction of Class II malocclusion observed 1 year after the crown Herbst appliance as a single-phase therapy was achieved primary due to the dentoalveolar changes and only limited skeletal change occurred.publishersversionPeer reviewe

New structural insights into the role of TROVE2 complexes in the on-set and pathogenesis of systemic lupus eythematosus determined by a combiantion of QCM-D and DPI

The final publication is available at link.springer.com.[EN] The mechanism of self-recognition of the autoantigen TROVE2, a common biomarker in autoimmune diseases, has been studied with a quartz crystal microbalance with dissipation monitoring (QCM-D) and dual polarization interferometry (DPI). The complementarity and remarkable analytical features of both techniques has allowed new insights into the onset of systemic lupus erythematosus (SLE) to be achieved at the molecular level. The in vitro study for SLE patients and healthy subjects suggests that anti-TROVE2 autoantibodies may undergo an antibody bipolar bridging. An epitope-paratope-specific binding initially occurs to activate a hidden Fc receptor in the TROVE2 tertiary structure. This bipolar mechanism may contribute to the pathogenic accumulation of anti-TROVE2 autoantibody immune complex in autoimmune disease. Furthermore, the specific calcium-dependent protein-protein bridges point out at how the TRIM21/TROVE2 association might occur, suggesting that the TROVE2 protein could stimulate the intracellular immune signaling via the TRIM21 PRY-SPRY domain. These findings may help to better understand the origins of the specificity and affinity of TROVE2 interactions, which might play a key role in the SLE pathogenesis. This manuscript gives one of the first practical applications of two novel functions (-df/dD and Delta h/molec) for the analysis of the data provided by QCM-D and DPI. In addition, it is the first time that QCM-D has been used for mapping hidden Fc receptors as well as linear epitopes in a protein tertiary structure.We would like to thank Sylvia Daunert for her invaluable help with the discussion of the paper. Furthermore, we acknowledge financial support from the Generalitat Valenciana (GVA-PROMETEOII/2014/040) as well as the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund under award numbers CTQ2013-45875-R and CTQ2013-42914-RJuste-Dolz, AM.; Do Nascimento, NM.; Monzó, IS.; Grau-García, E.; Roman-Ivorra, JA.; López-Paz, JL.; Escorihuela Fuentes, J.... (2019). New structural insights into the role of TROVE2 complexes in the on-set and pathogenesis of systemic lupus eythematosus determined by a combiantion of QCM-D and DPI. Analytical and Bioanalytical Chemistry. 411(19):4709-4720. https://doi.org/10.1007/s00216-018-1407-xS4709472041119Kakatia S, Teronpia R, Barmanb B. Frequency, pattern and determinants of flare in systemic lupus erythematosus: a study from North East India. Egypt Rheumatol. 2015;37:S55–9.Kuhn A, Wenzel J, Weyd H. Photosensitivity, apoptosis, and cytokines in the pathogenesis of lupus erythematosus: a critical review. 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Cue Reactivity in Active Pathological, Abstinent Pathological, and Regular Gamblers

Twenty-one treatment-seeking pathological gamblers, 21 pathological gamblers in recovery, and 21 recreational gamblers watched two video-taped exciting gambling scenarios and an exciting roller-coaster control scenario while their arousal (heart rate and subjective excitement) and urge to gamble were being measured. The gamblers did not differ significantly in cue-elicited heart rate elevations or excitement. However, the active pathological gamblers reported significantly greater urges to gamble across all cues compared to the abstinent pathological gamblers and, with marginal significance (p = 0.06), also compared to the social gamblers. Further exploration of these findings revealed that active pathological gamblers experience urges to gamble in response to exciting situations, whether or not they are gambling related, whereas abstinent and social gamblers only report urges to an exciting gambling-related cue. This suggests that for pathological gamblers excitement itself, irrespective of its source, may become a conditioned stimulus capable of triggering gambling behavior. Implications for treatment and future research are discussed

A Regional Reduction in Ito and IKACh in the Murine Posterior Left Atrial Myocardium Is Associated with Action Potential Prolongation and Increased Ectopic Activity.

BACKGROUND: The left atrial posterior wall (LAPW) is potentially an important area for the development and maintenance of atrial fibrillation. We assessed whether there are regional electrical differences throughout the murine left atrial myocardium that could underlie regional differences in arrhythmia susceptibility. METHODS: We used high-resolution optical mapping and sharp microelectrode recordings to quantify regional differences in electrical activation and repolarisation within the intact, superfused murine left atrium and quantified regional ion channel mRNA expression by Taqman Low Density Array. We also performed selected cellular electrophysiology experiments to validate regional differences in ion channel function. RESULTS: Spontaneous ectopic activity was observed during sustained 1Hz pacing in 10/19 intact LA and this was abolished following resection of LAPW (0/19 resected LA, P<0.001). The source of the ectopic activity was the LAPW myocardium, distinct from the pulmonary vein sleeve and LAA, determined by optical mapping. Overall, LAPW action potentials (APs) were ca. 40% longer than the LAA and this region displayed more APD heterogeneity. mRNA expression of Kcna4, Kcnj3 and Kcnj5 was lower in the LAPW myocardium than in the LAA. Cardiomyocytes isolated from the LAPW had decreased Ito and a reduced IKACh current density at both positive and negative test potentials. CONCLUSIONS: The murine LAPW myocardium has a different electrical phenotype and ion channel mRNA expression profile compared with other regions of the LA, and this is associated with increased ectopic activity. If similar regional electrical differences are present in the human LA, then the LAPW may be a potential future target for treatment of atrial fibrillation

To what extent can behaviour change techniques be identified within an adaptable implementation package for primary care? A prospective directed content analysis

Interpreting evaluations of complex interventions can be difficult without sufficient description of key intervention content. We aimed to develop an implementation package for primary care which could be delivered using typically available resources and could be adapted to target determinants of behaviour for each of four quality indicators: diabetes control, blood pressure control, anticoagulation for atrial fibrillation and risky prescribing. We describe the development and prospective verification of behaviour change techniques (BCTs) embedded within the adaptable implementation packages