Past, current, and future research on microalga-derived biodiesel: a critical review and bibliometric analysis

Abstract

Microalga-derived biodiesel plays a crucial role in the sustainable development of biodiesel in recent years. Literature related to microalga-derived biodiesel had an increasing trend with the expanding research outputs. Based on the Science Citation Index Expanded (SCI-Expanded) of the Web of Science, a bibliometric analysis was conducted to characterize the body of knowledge on microalga-derived biodiesel between 1993 and 2016. From the 30 most frequently used author keywords, the following research hotspots are extracted: lipid preparation from different microalga species, microalga-derived lipid and environmental applications, lipid-producing microalgae cultivation, microalgae growth reactor, and microalga harvest and lipid extraction. Other keywords, i.e., microalga mixotrophic cultivation, symbiotic system between microalga and other oleaginous yeast, microalga genetic engineering, and other applications of lipid-producing microalga are future focal points of research.

Graphical abstract

Association between serum autotaxin or phosphatidylserine-specific phospholipase A1 levels and melanoma

Abstract

Autotaxin (ATX), a producing enzyme for lysophosphatidic acids, was first identified from the medium of a melanoma cell line and has been considered to be one of the candidate targets to treat melanoma; however, the association between serum ATX and melanoma in human subjects has not been elucidated. Along with ATX, phosphatidylserine-specific phospholipase A1 (PS-PLA₁) is a producing enzyme for lysophosphatidylserine, a similar glycero-lysophospholipid mediator to lysophosphatidic acids. In the present study, we aimed to investigate the association between serum ATX or PS-PLA₁ levels and melanoma. We measured the serum levels of ATX, ATX isoforms and PS-PLA₁ in subjects with melanoma (n = 57) and healthy subjects (n = 58). We further investigated the existence of trends according to the clinical stages of melanoma. We observed that serum total ATX and classical ATX levels were significant higher and serum novel ATX levels tended to be higher in male subjects with melanoma, while no significant difference was observed between the two groups in female subjects. The trend test revealed that the serum total ATX and ATX isoforms were significantly associated with the clinical stages of female subjects with melanoma. Regarding PS-PLA₁, serum PS-PLA₁ levels were significantly higher in the melanoma subjects and associated with the clinical stages. The present study is the first study which revealed the association between ATX or PS-PLA₁ and melanoma, suggesting the possible involvement of ATX/lysophosphatidic acids or PS-PLA₁/lysophosphatidylserine axis in the pathogenesis of melanoma.

Case of punctate palmoplantar keratoderma type I treated with combination of low-dose oral acitretin and topical salicylic acid and steroid

Abstract

Palmoplantar keratodermas (PPK) are heterogeneous disorders characterized by abnormal keratinization. Especially, punctate PPK (PPPK), one of the subtypes of hereditary PPK, is a rare punctate keratoderma characterized by tiny "raindrop" keratoses having a tendency to coalesce on the edge of soles, which are exposed to sustained pressure. If typical punctate lesions are confined to the palms and soles and the patient has a family history and late onset, it can be considered as PPPK type I (PPKP1), also called Buschke–Fisher–Brauer disease. The exact etiology of PPPK has not been fully understood. Furthermore, no standardized treatment for PPPK has been established and treatment options are limited. Above all, traditional systemic retinoids have been used in several cases, but dose-related adverse effects are common. Therefore, combination of low-dose systemic retinoids and adjuvant topical therapy can be an alternative treatment option for PPPK. Herein, we report a case of PPKP1 treated with combination of low-dose oral acitretin (10 mg/day) and topical salicylic acid and steroid. Despite low capacity, low-dose acitretin showed excellent regression of the lesions by combined use of topical ointments. The supplementary topical therapy may be useful in reducing the dose of systemic retinoids and preventing potential toxicity.

Changes in salivary chromogranin A levels in adults with atopic dermatitis are correlated with changes in their condition

Abstract

Stress-induced scratching is an issue in patients with adult atopic dermatitis (AD). Symptoms of stress-induced AD are common in clinical practise. Salivary chromogranin A (CgA) level has research value as a possible index related to a patient's psychological stress. Using saliva, which is easily collectable, we compared two assessments of the severities of AD and stress with the levels of stress proteins in the saliva of 30 patients with AD in the Department of Dermatology of Shimane University between April 2015 and May 2017. The severities of AD and stress were assessed using the Scoring Atopic Dermatitis (SCORAD) score and State–Trait Anxiety Inventory score, respectively. Additionally, the assessments included those of personality using the Tokyo University Egogram (TEG)-II score and quality of life using the Dermatology Life Quality Index score. Simultaneously, we measured their salivary CgA levels. The change in salivary CgA per protein in patients with AD was correlated with their changes in SCORAD score (correlation coefficient, r = 0.596, P = 0.001) and objective SCORAD (r = 0.608, P < 0.001). The changes in CgA per protein correlated with those in TEG-II A (r = 0.370, P = 0.022), while the changes in SCORAD score correlated with those in DLQI (r = 0.309, P = 0.048). Our results suggest that changes in a patient's condition are reflective of the changes in the patient's stress. The changes in salivary CgA level in patients with AD correlated with the changes in their condition.

Cutaneous sarcoidosis in a patient with rheumatoid arthritis receiving tocilizumab

Splice site mutation in COL7A1 resulting in aberrant in-frame transcripts identified in a case of recessive dystrophic epidermolysis bullosa, pretibial

Abstract

Dystrophic epidermolysis bullosa (DEB), pretibial, a rare subtype of epidermolysis bullosa (EB), is characterized by recurrent blisters and erosions predominantly on the pretibial region. We report the case of a 60-year-old Japanese woman with persistent blistering eruptions and scar formation on the pretibial region and elbows. Mutational analysis revealed a previously reported c.5797C>T mutation in exon 70 (p.R1933X) and a novel c.6348+1G>A mutation in intron 76 of COL7A1. Reverse transcription polymerase chain reaction revealed that the c.6348+1G>A mutation resulted in the skipping of exon 76 (69 bp) and the retention of intron 76 (75 bp), and both transcripts were in-frame. From these results, we diagnosed the patient as having recessive DEB, pretibial. A review of previously reported mutations in DEB, pretibial, revealed that one-third of DEB, pretibial, cases showed a recessive inheritance pattern, and no case had a combination of premature termination codon (PTC)/PTC mutations. The DEB, pretibial, case described herein is the first reported case of a compound heterozygote with PTC/in-frame mutations. Although no special characteristic features of the mutations were identified, a high diversity of COL7A1 mutations was shown even in DEB, pretibial.

Whole genome analysis of six organophosphate-degrading rhizobacteria reveals putative agrochemical degradation enzymes with broad substrate specificity

Abstract

Six organophosphate-degrading bacterial strains collected from farm and ranch soil rhizospheres across the Houston-metropolitan area were identified as strains of Pseudomonas putida (CBF10-2), Pseudomonas stutzeri (ODKF13), Ochrobactrum anthropi (FRAF13), Stenotrophomonas maltophilia (CBF10-1), Achromobacter xylosoxidans (ADAF13), and Rhizobium radiobacter (GHKF11). Whole genome sequencing data was assessed for relevant genes, proteins, and pathways involved in the breakdown of agrochemicals. For comparative purposes, this analysis was expanded to also include data from deposited strains in the National Center for Biotechnology Information's (NCBI) database. This study revealed Zn-dependent metallo-β-lactamase (MBL)-fold proteins similar to OPHC2 first identified in P. pseudoalcaligenes as the likely agents of organophosphate (OP) hydrolysis in A. xylosoxidans ADAF13, S. maltophilia CBF10-1, O. anthropi FRAF13, and R. radiobacter GHKF11. A search of similar proteins within NCBI identified over 200 hits for bacterial genera and species with a similar OPHC2 domain. Taken together, we conclude from this data that intrinsic low-level OP hydrolytic activity is likely prevalent across the rhizosphere stemming from widespread OPHC2-like metalloenzymes. In addition, P. stutzeri ODKF13, P. putida CBF10-2, O. anthropi FRAF13, and R. radiobacter GHKF11 were found to harbor glycine oxidase (GO) enzymes that putatively possess low-level activity against the herbicide glyphosate. These bacterial GOs are reported to catalyze the degradation of glyphosate to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and suggest a possible link to AMPA that can be found in glyphosate-contaminated agricultural soil. The presence of aromatic degradation proteins were also detected in five of six study strains, but are attributed primarily to components of the widely distributed β-ketoadipate pathway found in many soil bacteria.

Modified purse-string closure: a lymphatic channel and tissue sparing technique for biopsy of suspicious pigmented lesions on extremities

Publication date: Available online 2 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): David Oberlin, Dennis A. Porto, Matteo Lopiccolo, Laurie L. Kohen

Inflammatory response and cytokine levels induced by intralesional photodynamic therapy and 630nm laser in a case series of basal cell carcinoma

Publication date: Available online 2 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): M.J. Suárez-Valladares, S. Calleja-Antolin, J.M. Ruíz-deMorales, M.A. Rodríguez-Prieto, J. Vega-Gutierrez

Patients prioritize local recurrence risk over other attributes for surgical treatment of facial melanomas - results of a stated preference survey and choice-based conjoint analysis

Publication date: Available online 2 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Jeremy R. Etzkorn, Scott D. Tuttle, Ilya Lim, Elea M. Feit, Joseph F. Sobanko, Thuzar M. Shin, Donald E. Neal, Christopher J. Miller
BackgroundSurgical treatment options for facial melanomas include conventional excision with postoperative margin assessment (CE-POMA), Mohs micrographic surgery with immunostains (MMS-I) or slow Mohs. Patient preferences for these surgical options have not been studied.ObjectivesTo evaluate patient preferences for surgical treatment of facial melanoma and to determine how patients value the relative importance of different surgical attributes.MethodsParticipants completed a two-part study consisting of a stated preference survey and a choice-based conjoint analysis (CBCA) experiment.ResultsPatients overwhelmingly (94.3%) rate local recurrence risk as "very important" and rank it as the most important attribute of surgical treatment for facial melanoma. Via CBCA, patients ranked the following surgical attributes from highest to lowest importance: local recurrence rate, out-of-pocket cost, chance of second surgical visit, timing of reconstruction, travel time, and time in office for the procedure. Consistent with their prioritization of low local recurrence rates, over 73% of respondents selected MMS-I or slow Mohs as their preferred treatment option for a facial melanoma.LimitationsData were obtained from a single health system.ConclusionPatients prefer surgical treatment options that minimize risk for local recurrence. Logistics for travel and treatment have less influence on patient preferences. Most survey participants chose MMS-I to maximize local cure and convenience of care.

Impact of Topical Fluorouracil Cream on Costs of Treating Keratinocyte Carcinoma (Nonmelanoma Skin Cancer) and Actinic Keratosis

Publication date: Available online 2 March 2018
Source:Journal of the American Academy of Dermatology
Author(s): Jean Yoon, Ciaran S. Phibbs, Adam Chow, Martin A. Weinstock
BackgroundIt is unknown whether treatment costs of Keratinocyte Carcinoma (KC) and Actinic Keratosis (AK) can be lowered by spending more on chemoprevention.ObjectiveWe examine the impact of one-course treatment of topical fluorouracil on the face and ears on KC and AK treatment costs over three years.MethodsThe VAKCC trial compared the efficacy of topical fluorouracil cream, 5%, vs vehicle control cream for reducing KC risk. Trial data and administrative data on costs and utilization were analyzed to measure post-randomization encounters and treatment costs for KC and AK care. Adjusted models were used to test for statistically significant differences between treatment arms for number of treatment encounters and costs.ResultsOne year after randomization, the control arm had higher mean number of treatment encounters for SCC (0.04) than the intervention arm (0.01) (P<0.01). At one year the intervention arm had lower treatment and dermatologic costs of $2,106 (SD=$2,079) compared to $2,444 (SD=$2,716) for control patients (P=0.02). After three years, the intervention arm incurred $771 less per patient.LimitationsCare not provided or paid by VA was not included. Results may not be generalizable to other payers.ConclusionWe found significant cost savings for patients treated with 5-FU.

Correction to: Multi-sensor temporal assessment of tropospheric nitrogen dioxide column densities over Pakistan

Abstract

The present address of Rabbia Murtaza is shown in this paper. (please tag the affiliation below, this is only for Rabbia Murtaza)

Cost analysis of enhanced recovery after surgery in microvascular breast reconstruction

Enhanced recovery after surgery (ERAS) pathways has been shown in multiple surgical speciaalties to decrease hospital length of stay (LOS) after surgery. ERAS in breast reconstruction has been found to decrease hospital length of stay and inpatient opioid use. ERAS protocols can facilitate a patient's recovery and is a systemwide improvement that can potentially increase the quality of care while decreasing costs.

Application of new instruments for beginner lymphatic supermicrosurgeon

Dear Sirs,

“Diagnostic accuracy of bioimpedance spectroscopy in patients with lymphedema - a retrospective cohort analysis”

Bioimpedance spectroscopy (BIS) is used by healthcare specialists to diagnose lymphedema. BIS measures limb fluid content by assessing tissue resistance to the flow of electric current. However, there is debate regarding the validity of BIS in diagnosing early lymphedema. Indocyanine green (ICG) lymphography has been established as the most accurate diagnostic modality to date for lymphedema diagnosis. In this retrospective study, we test the sensitivity, specificity, and diagnostic accuracy of BIS in diagnosing lymphedema by referencing its results with ICG lymphography.

Impact of Topical Fluorouracil Cream on Costs of Treating Keratinocyte Carcinoma (Nonmelanoma Skin Cancer) and Actinic Keratosis

It is unknown whether treatment costs of Keratinocyte Carcinoma (KC) and Actinic Keratosis (AK) can be lowered by spending more on chemoprevention.

Inflammatory response and cytokine levels induced by intralesional photodynamic therapy and 630nm laser in a case series of basal cell carcinoma

Modified purse-string closure: a lymphatic channel and tissue sparing technique for biopsy of suspicious pigmented lesions on extremities

Patients prioritize local recurrence risk over other attributes for surgical treatment of facial melanomas - results of a stated preference survey and choice-based conjoint analysis

Surgical treatment options for facial melanomas include conventional excision with postoperative margin assessment (CE-POMA), Mohs micrographic surgery with immunostains (MMS-I) or slow Mohs. Patient preferences for these surgical options have not been studied.

A novel method to prepare a magnetic carbon-based adsorbent with sugar-containing water as the carbon source and DETA as the modifying reagent

Abstract

A novel magnetic heavy metal adsorbent was prepared via diethylenetriamine (DETA) modification on magnetic hydrothermal carbon, with glucose and sugar-containing waste water as the carbon source. The prepared materials were characterized by FT-IR, SEM, TEM, EDXRF, TGA, elemental analysis, XPS, and magnetic moment determination. In this paper, the adsorption mechanism of the modified and unmodified adsorbents was well discussed. Four kinds of waste water (watermelon juice, expired sprite, sugar-pressing waste water, and confectionary waste water) were employed to produce heavy metal ion adsorbents; the chemical properties of hydrothermal carbon derived from the proposed sources were analyzed as well. The maximum uptake capacity for Cu²⁺, Pb²⁺, and Cd²⁺ of the adsorbent produced from glucose was 26.88, 103.09, and 25.38 mg g⁻¹, respectively. After 5 cycles, the adsorption ability was still well preserved. This work represents an efficient new direction for the treatment of heavy metal ions in water and the reuse of sugar-containing waste water.

Graphical abstract

The schemetic of DETA-modified magnetic carbon preparing from sugar-containing wastewater

Making Sense of Non-refuting Anomalies

Abstract

As emphasized by Larry Laudan in developing the notion of non-refuting anomalies (Laudan 1977; Nola and Sankey 2000), traditional analyses of empirical adequacy have not paid enough attention to the fact that the latter does not only depend on a theory's empirical consequences being true but also on them corresponding to the most salient phenomena in its domain of application. The purpose of this paper is to elucidate the notion of non-refuting anomaly. To this end, I critically examine Laudan's account and provide a criterion to determine when a non-refuting anomaly can be ascribed to the applicative domain of a theory. Unless this latter issue is clarified, no proper sense can be made of non-refuting anomalies, and no argument could be opposed to those cases where an arbitrary restriction in a theory's domain of application dramatically reduces the possibilities for its empirical scrutiny. In arguing for the importance of this notion, I show how several semanticist resources can help to reveal its crucial implications, not only for theory evaluation, but also for understanding the nature of a theory's applicative domain.

SLAM family member 8 is involved in oncogenic KIT-mediated signaling in human mastocytosis

Abstract

The signaling lymphocytic activation molecule family member 8 (SLAMF8)/CD353 is a member of the CD2 family of proteins. Its ligand has not been identified. SLAMF8 is expressed by macrophages and suppresses cellular functions. No study has yet explored SLAMF8 expression or function in human mastocytosis, which features oncogenic KIT-mediated proliferation of human mast cells. SLAMF8 protein was expressed in human mastocytosis cells, immunohistochemically. SLAMF8 expression was also evident in the human mast cell lines, HMC1.2 (expressing oncogenic KIT) and LAD2 (expressing wild-type KIT) cells. SLAMF8-knockdown significantly reduced the KIT-mediated growth of HMC1.2 cells but not that of LAD2 cells. SLAMF8-knockdown HMC1.2 cells exhibited significant attenuation of SHP-2 activation and oncogenic KIT-mediated RAS–RAF–ERK signaling. An interaction between SLAMF8 and SHP-2 was confirmed in HMC1.2 cells and all pathological mastocytosis specimens examined (19 of 19 cases, 100%). Thus, SLAMF8 is involved in oncogenic KIT-mediated RAS–RAF–ERK signaling and the subsequent growth of human neoplastic mast cells mediated by SHP-2. SLAMF8 is a possible therapeutic target in human mastocytosis patients.

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IL-26 in allergic contact dermatitis: resource in a state of readiness

Abstract

In this study, we investigated the role of IL-26 in allergic contact dermatitis (ACD), highlighting its contribute in the cytotoxic mechanism responsible of the tissue injury. IL-26 is a signature Th17 cytokine, and immune cells are its predominant sources. Recently, it has shown that Th17 cell-derived-IL-26 functions like an antimicrobial peptide. Here, we hypothesized that IL-26 could be involved in cytotoxicity mechanism, that underlies ACD. Indeed, we have attributed a role to IL-26 in this context, through PBMC cytotoxicity assays versus Hacat. In order to demonstrate that IL-26 was effectively involved in this activity, we performed the assay using transfected ACD PBMCs by siRNA for IL-26. Indeed, we demonstrated that these cells were less able to kill keratinocytes compared to ACD PBMC (p<0.01). In conclusion, our findings support the idea that this emergent cytokine, IL-26, is implicated in the killing mechanisms of KC observed during ACD.

This article is protected by copyright. All rights reserved.

Dermal fibroblasts can activate matrix metalloproteinase-1 independent of keratinocytes via plasmin in a 3D collagen model

Abstract

Photoaging of the skin is marked by obvious wrinkles and mainly depends on degradation of the extracellular matrix (ECM) in the dermis. Matrix metalloproteinase (MMP)-1 is one of the most important factors involved in degradation of the ECM, however, its mechanism of activation is not fully understood. It has been thought that MMP-1 is expressed by dermal fibroblasts as an inactive precursor protein that is activated by proteinases produced by keratinocytes in the epidermis. In this study, we constructed a 3D model of the dermis using collagen-embedded fibroblasts with or without ultraviolet (UV)-A exposure to mimic photoaging in the dermis. Collagen lattices embedded with UV-A irradiated fibroblasts miniaturized and collagen was degraded to a greater extent than collagen lattices embedded with non-irradiated fibroblasts. The results demonstrate that fibroblasts in this 3D model express activated-MMP-1 in the absence of keratinocytes. Moreover, the results confirm that activation of MMP-1 depends on increased plasmin activity in this model and lattice miniaturization was inhibited by the plasmin inhibitor tranexamic acid. Our results suggest that plasmin acts as an activator of MMP-1 and the inhibition of plasmin prevents collagen degradation.

This article is protected by copyright. All rights reserved.

Spatiotemporal variations in vegetation cover on the Loess Plateau, China, between 1982 and 2013: possible causes and potential impacts

Abstract

Vegetation is a key component of the ecosystem and plays an important role in water retention and resistance to soil erosion. In this study, we used a multiyear normalized difference vegetation index (NDVI) dataset (1982–2013) and corresponding datasets for observed climatic variables to analyze changes in the NDVI at both temporal and spatial scales. The relationships between NDVI, climate change, and human activities were also investigated. The annual average NDVI showed an upward trend over the 32-year study period, especially in the center of the Loess Plateau. NDVI variations lagged behind monthly temperature changes by approximately 1 month. The contribution of human activities to variations in NDVI has become increasingly significant in recent years, with human activities responsible for 30.4% of the change in NDVI during the period 2001–2013. The increased vegetation coverage has reduced soil erosion on the Loess Plateau in recent years. It is suggested that natural restoration of vegetation is the most effective measure for control of erosion; engineering measures that promote this should feature in the future governance of the Loess Plateau.

Long-Term Follow-Up After Baked Milk Introduction

Publication date: Available online 2 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Joan H. Dunlop, Corinne A. Keet, Kim Mudd, Robert A. Wood
BackgroundClinical trials of baked milk (BM) introduction have demonstrated accelerated resolution of milk allergy.ObjectiveLong-term data regarding real-world introduction of BM are lacking. We sought to characterize our experience of BM introduction.MethodsWe performed a retrospective chart review of consecutive BM oral food challenges performed in our clinic from 2009 to 2014, with a minimum follow-up of 24 months.ResultsOf the 206 patients challenged, 99 (48%) passed and 187 were sent home with detailed instructions to incorporate BM into their diets. After a median of 49 months of follow-up, 43% of the 187 had progressed to direct milk, 20% to less-cooked forms of milk, 10% remained ingesting BM, and 28% were strictly avoiding milk. Higher milk IgE levels were associated with decreased odds of passing a BM challenge and advancing to less-cooked forms of milk. Predictors of progressing to less-cooked forms of milk were passing the challenge and younger age. There were 79 reported milk reactions involving 68 patients (33% of total) during follow-up. Of these, 78% were classified as mild, 14% severe, and 6 patients developed eosinophilic esophagitis. Of 11 severe reactions, 4 were accidental exposures, 3 were planned escalations, and 4 occurred with previously tolerated doses.ConclusionsThe majority of patients who underwent a BM challenge, including those who failed their challenge, were able to progress to direct or less-cooked forms of milk. However, adverse reactions were common, and even a successful BM challenge does not guarantee future tolerance of BM or preclude later reactions, even to previously tolerated doses.

Diagnostic Value of Tryptase in Food Allergic Reactions: A Prospective Study of 160 Adult Peanut Challenges

Publication date: Available online 1 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Shelley Dua, James Dowey, Loraine Foley, Sabita Islam, Yvonne King, Pamela Ewan, Andrew T. Clark
BackgroundSerum tryptase is useful in diagnosing drug and venom anaphylaxis. Its utility in food anaphylaxis is unknown.ObjectiveThe objective of this study was to determine whether tryptase rises in food allergic reactions, optimal sampling time points, and a diagnostic cutoff for confirming a clinical reaction.MethodsCharacterized peanut allergic patients were recruited and underwent up to 4 peanut challenges and 1 placebo challenge each. Tryptase was measured serially on challenge days both before (baseline) and during the challenge. The peak percentage tryptase rise (peak/baseline) was related to reaction severity. Receiver operating characteristic (ROC) curves were generated establishing an optimal diagnostic cutoff.ResultsTryptase was analyzed in 160 reactive (9% anaphylaxis) and 45 nonreactive (placebo) challenges in 50 adults aged 18 to 39 years. Tryptase rose above the normal range (11.4 ng/mL) in 4 of 160 reactions. When compared with baseline levels, a rise was observed in 100 of 160 (62.5%) reactions and 0 of 45 placebo challenges. The median rise (95% confidence interval [CI]) for all reactions was 25% (13.3% to 33.3%) and 70.8% (33.3% to 300%) during anaphylaxis. Peak levels occurred at 2 hours and correlated with severity (P < .05). Moderate-to-severe respiratory symptoms, generalized erythema, dizziness, and hypotension were correlated with a higher peak/baseline tryptase (P < .05). ROC curve analysis demonstrated the optimal cutoff to identify a reaction as a 30% rise (sensitivity 0.53; specificity 0.85), area under the curve 0.72 (95% CI, 0.67-0.78).ConclusionsSerum tryptase measurement is valuable in food allergic reactions, and correlates with symptom severity. Comparing peak reaction levels at 2 hours with baseline is essential. A rise in tryptase of 30% is associated with food allergic reactions.

Asthma phenotypes defined from parameters obtained during recovery from a hospital-treated exacerbation

Publication date: Available online 1 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Rihuang Qiu, Jiaxing Xie, Kian Fan Chung, Naijian Li, Zhaowei Yang, Mengzhang He, Jing Li, Rongchang Chen, Nanshan Zhong, Qingling Zhang
BackgroundAsthma is a heterogeneous disease with diverse clinical manifestations and inflammatory pathologies that is punctuated by exacerbations.ObjectivesTo describe the clinical and inflammatory characteristics of asthma patients treated in hospital for an acute exacerbation.MethodsData from 320 adult patients receiving treatment for an acute exacerbation of asthma were obtained. In 218 with complete data , we used Ward's hierarchical clustering to obtain clusters. Pulmonary function, blood counts, sputum cell counts, serum IgE levels, and fractional exhaled nitric oxide were measured during the hospital admission. We selected 13 variables with which we performed Ward's minimum variance hierarchical clustering.ResultsFour clusters were defined. Clusters 1(24.5%) and 3(36.7%) were characterized by predominantly-female asthmatics with sputum neutrophilia, with Cluster 1 associated with small degree of airflow obstruction and early onset of asthma while Cluster 3 had a moderate degree of reduction in FEV1. Clusters 2(22.0%) and 4(16.5%) were associated with high sputum eosinophilia and severe airflow obstruction, but Cluster 4 was made up exclusively of male smoking subjects while Cluster 2 of predominantly female non-smoking subjects with the worst FEV1, FEF25-75 (% predicted) and arterial partial pressure of oxygen (PaO2) on admission. There were no differences between clusters in terms of atopy, serum IgE, prevalence of nasal disease, maintenance inhaled corticosteroids, or oral/systemic corticosteroid use and asthma exacerbations.ConclusionThe clusters during recovery from an exacerbation of asthma were distinguished by airflow obstruction and a neutrophilic, eosinophilic or mixed inflammation. Eosinophilic inflammation was found in smoking and non-smoking asthmatics during an exacerbation.

A multicenter evaluation of diagnosis and management of omega-5 gliadin allergy (also known as wheat-dependent exercise induced anaphylaxis) in 132 adults

Publication date: Available online 1 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Lucinda Kennard, Iason Thomas, Krzysztof Rutkowski, Vian Azzu, Patrick FK. Yong, Bogusia Kasternow, Hannah Hunter, Naeema MO. Cabdi, Alla Nakonechna, Annette Wagner
BackgroundOmega-5 gliadin allergy (also known as wheat-dependent exercise induced anaphylaxis) is a rare allergy to wheat which often presents with intermittent severe anaphylaxis in the context of a co-factor, such as exercise.ObjectivesTo undertake a detailed clinical characterisation of the largest cohort of omega 5-gliadin allergic patients to date.MethodsWe retrospectively analysed the demographics, presentation, investigation and management of 132 patients presenting to 4 UK centres with omega-5 gliadin allergy.ResultsThere are significant delays to diagnosis of 1-5 years (40% of patients) and over 5 years (29% of patients). The most common cofactors were exercise (80%), alcohol (25%) and NSAIDs (9%). A minority of patients (11%) present without an identifiable cofactor. The level of specific IgE to omega-5 gliadin does not predict the severity of allergic reactions. Patients adhering to either a gluten-free diet or who avoid wheat in combination with exercise achieve the largest reductions in subsequent allergic reactions by 67% and 69%, respectively.ConclusionsOmega-5 gliadin allergy is a rare wheat allergy that presents with severe anaphylaxis. The diagnosis is frequently delayed, therefore we recommend that all adult patients presenting with anaphylaxis of unclear cause should have omega-5 gliadin specific IgE tested. A gluten-free diet or avoidance of wheat based meals in combination with exercise (if the cofactor is exercise) helps to significantly decrease the risk of future allergic reactions. However, antihistamines and an epinephrine auto-injector must always be prescribed, as a third of patients continue to have allergic reactions despite dietary advice.

Treatment with the SQ house dust mite sublingual immunotherapy tablet may be initiated year-round

Publication date: Available online 1 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Hendrik Nolte, David I. Bernstein, Jörg Kleine-Tebbe, Peter A. Fejerskov, Qing Li, Susan Lu, Harrold S. Nelson

Disseminated abscesses due to Mycoplasma faucium in a patient with activated PI3Kδ syndrome type 2 (APDS2)

Publication date: Available online 1 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Nerea Dominguez-Pinilla, Luis M. Allende, Jérémie Rosain, Carmen Gallego Maria del, Fernando Chaves, Caroline Deswarte, Esther Viedma, Jaime de Inocencio Arocena, Jesús Ruiz-Contreras, Jacinta Bustamante, Luis Ignacio Gonzalez-Granado

A Survey of Caregiver Perspectives on Emergency Epinephrine Autoinjector Sharing

Publication date: Available online 1 March 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Marcus Shaker, Tsuzumi Kanaoka, Robert GP. Murray, Dana Toy, Susan Shaker, Aurora Drew

Comparison of gold nanoparticles biosynthesized by cell-free extracts of Labrys , Trichosporon montevideense , and Aspergillus

Abstract

Biosynthesis of gold nanoparticles (AuNPs) by microbes has received much attention as an efficient and eco-friendly process. However, the characteristics of AuNPs biosynthesized by different microbial cell-free extracts are rarely comparatively studied. In this study, three locally isolated strains, i.e., bacteria Labrys sp. WJW, yeast Trichosporon montevideense WIN, and filamentous fungus Aspergillus sp. WL-Au, were selected for AuNPs biosynthesis. UV-Vis absorption bands at 538, 539, and 543 nm confirmed the formation of AuNPs by these strains. Transmission electron microscopy and selected area electron diffraction analyses revealed that the as-synthesized AuNPs were crystalline with spherical or pseudo-spherical shapes. However, the average sizes of these AuNPs were diverse, which were 18.8, 22.2 and 9.5 nm, respectively. The biomolecules involved in nanoparticles stabilization were demonstrated by Fourier transform infrared spectroscopy analysis. Four common functional groups such as –N–H, –C=C, –N=O, and –S=O groups were detected in these AuNPs, while a distinct –C=O group was involved in WL-Au-AuNPs. The catalytic rate of WL-Au-AuNPs toward 4-nitrophenol reduction (0.37 min⁻¹) was much higher than those of others (WJW-AuNPs 0.27 min⁻¹ and WIN-AuNPs 0.23 min⁻¹). This research would provide useful information for exploring efficient microbial candidates to synthesize AuNPs with excellent performances.

Activation of RhoA, Smad2, c-Src, PKC-βII/δ and JNK in atopic dermatitis

Abstract

Atopic dermatitis is a multifactorial skin disease characterised by chronic and relapsing inflammation whose pathogenesis is incompletely understood. We found that the expression of TGFβR1 and the activation of SMAD2, RhoA, JNK, PKC-βII/δ and c-Src were upregulated in the infiltrated inflammatory cells, fibroblasts and vasculatures in the dermis and epidermis. In addition, increases in the expression of TGFβR1 and phosphorylation levels of JNK and c-Src were positively correlated with the inflammatory progression of atopic dermatitis severity.

The effect of template-based sequential (TBS) coding on an NHS plastic surgical practice

Publication date: Available online 1 March 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Ruben Y. Kannan, Catriona Neville, Tamsin Gwynn, Vanessa Venables, Raman Malhotra, Charles Nduka
IntroductionClinical coding is often a mystery to us surgeons but in actuality, it has a huge bearing on the financial sustainability of our services. Given the rapid innovations in plastic surgical procedures, clinical coders often struggle to decipher the extent of surgery. Meeting midway is the way forward here.MethodsIn a prospective audit over a six-month period, we analysed data from 2586 patients' in our practice; a combination of general plastic surgery and specialist facial reanimation services. This involved comparing data from the first three months' where coding was performed by clinical coders' based on operating notes per se (phase I) and the subsequent three months' when the operating surgeon filled in the OPCS 4.7 (version 2014) codes at the time of completing the operating notes and the clinical coders' then vetted this information (phase II) as part of a sequential TBS coding system.ResultsIn terms of out-patient income, there was a 3% increase in facial palsy income and 6% increase in general plastic services but the most significant improvement was in terms procedural income per case. General plastic surgery cases saw an increase of 49% while facial palsy income increased by 58% over the same period. Greater insight into OPCS and HRG codes also allowed for the calculation of the actual tariffs for specific procedures.ConclusionsHaving the operating surgeon as the primary coder, using a template, with subsequent vetting by the clinical coders, improves data capture which in turn, increases income. Future recommendations includes the use of proforma-based operating notes for workhorse procedures.

Cost analysis of enhanced recovery after surgery in microvascular breast reconstruction

Publication date: Available online 2 March 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Christine Oh, James Moriarty, Bijan J. Borah, Kristin C. Mara, William S. Harmsen, Michel Saint-Cyr, Valerie Lemaine
BackgroundEnhanced recovery after surgery (ERAS) pathways has been shown in multiple surgical speciaalties to decrease hospital length of stay (LOS) after surgery. ERAS in breast reconstruction has been found to decrease hospital length of stay and inpatient opioid use. ERAS protocols can facilitate a patient's recovery and is a systemwide improvement that can potentially increase the quality of care while decreasing costs.MethodsA standardized ERAS pathway was developed through multidisciplinary collaboration. It addressed all phases of surgical care for patients undergoing free-flap breast reconstruction utilizing an abdominal donor site. In this retrospective cohort study, clinical variables associated with hospitalization costs for patients who underwent free-flap breast reconstruction with the ERAS pathway were compared with those of historical controls, termed traditional recovery after surgery (TRAS). All patients included in the study underwent surgery between September 2010 and September 2014. Predicted costs of the study groups were compared using generalized linear modeling.ResultsA total of 200 patients were analyzed: 82 in the ERAS cohort and 118 in the TRAS cohort. Clinical variables found to have a statistically significant difference between groups that affected costs included unilateral versus bilateral procedure (p=0.04) and need for postoperative blood transfusion (p=0.03). The cost regression analysis on the two cohorts adjusted for these significant variables. Adjusted mean costs of ERAS patients were found to be $4,576 less than the TRAS control group ($38,688 versus $43,264).ConclusionsImplementation of the ERAS pathway was associated with significantly decreased costs when compared to historical controls. There has been a healthcare focus towards prudent resource allocation that dictates the need for plastic surgeons to recognize economic evaluation of clinical practice. The ERAS pathway can increase health care accountability by improving quality of care while simultaneously decreasing the costs associated with autologous breast reconstruction.

Assessment of quality of life in patients who underwent breast reduction using BREAST-Q

Publication date: Available online 1 March 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): M.P.D. Corrêa, M.T. Dornelas, E.N. de Carvalho, A. Barra, E.P. Venturelli, L.D. Corrêa, A. Chaoubah

A supermicrosurgery training model using the chicken mid and lower wing

Publication date: Available online 1 March 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Kota Hayashi, Yasunori Hattori, Dawn Sinn Yii Chia, Sotetsu Sakamoto, Abdelhakim Marei, Kazuteru Doi

Protective effects of PACAP in ischemia

Pituitary adenylate cyclase activating polypeptide (PACAP) is an ubiquitous peptide involved, among others, in neurodevelopment, neuromodulation, neuroprotection, neurogenic inflammation and nociception. Prese...

Role of percutaneous cholecystostomy for acute acalculous cholecystitis: clinical outcomes of 271 patients

Abstract

Objectives

To examine the outcomes of percutaneous cholecystostomy (PC) in patients with acute acalculous cholecystitis (AAC).

Methods

The study population comprised 271 patients (mean age, 72 years; range, 22–97 years, male, n=169) with AAC treated with PC with or without subsequent cholecystectomy. Clinical data from total 271 patients were analysed, and outcomes were assessed according to whether the catheter was removed or remained indwelling. Patient survival and recurrence rates were calculated.

Results

Symptom resolution and significant improvement of laboratory test values were achieved in 235 patients (86.7%) within 4 days after PC. Complications occurred in six patients (2.2%). Interval elective cholecystectomy was performed in 127 (46.8%) patients. Among the remaining 121 patients, successful removal of the PC catheter was achieved in 88 patients (72.7%) at a mean of 30 days (range, 4–365 days). Of the catheter removal group, 86/88 (97.7%) were successfully treated with the initial PC, whereas two (2.3%) experienced recurrence of cholecystitis. Cumulative recurrence rates were 1.1%, 2.7%, and 2.7% at 1, 2, and 8 years, respectively.

Conclusions

The good therapeutic outcomes of PC and low recurrence rate suggest that PC can be a definitive treatment option in the majority of AAC patients.

Key Points

• Many patients with AAC are too ill to undergo cholecystectomy.

• PC in AAC patients shows low complication and recurrence rate.

• PC solely can be a definitive treatment option in the majority of AAC patients

Discrepancies between coronary CT angiography and invasive coronary angiography with focus on culprit lesions which cause future cardiac events

Abstract

Objectives

To evaluate the clinical significance of discrepant lesions between coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) in a longitudinal study.

Methods

In 220 patients with suspected coronary artery disease (CAD) who underwent both 256-row CCTA and ICA, the obstructive CAD (≥ 50% stenosis) on CCTA was compared with that on ICA as the reference standard. We analysed the causes of the discrepancy between CCTA and ICA. During a 40-month follow-up period, major adverse cardiac events (MACE) were assessed.

Results

Discordance between CCTA and ICA was observed in 121 of the 3166 coronary artery segments (3.8%). Common causes were calcification (45.9%) and positive remodelling (PR) (29.6%) in 83 false positive lesions, and noise (40.0%) and motion artefact (37.8%) in 38 false negative lesions. MACE occurred in seven lesions among the discrepant lesions; six among the 29 PR lesions (20.7%) and one among the 53 calcified lesions (1.9%). With respect to the prediction power of MACE in an intermediate stenosis, the CCTA-related value including PR was higher than the ICA-related value.

Conclusions

PR was a frequent cause of MACE among the false positive lesions on CCTA. Therefore, the presence of PR on CCTA may suggest clinical significance, although it can be missed by ICA.

Key Points

• Compared to ICA, PR in CCTA may be cause of false positive lesion.

• CCTA-related value including PR shows higher prediction power of MACE than ICA-related value.

• PR reflects atherosclerotic burden that can be related to cardiac events.

• PR in CCTA should be observed carefully, even if it is false positive.

Image quality and radiation dose of coronary CT angiography performed with whole-heart coverage CT scanner with intra-cycle motion correction algorithm in patients with atrial fibrillation

Abstract

Objectives

To evaluate image quality, coronary evaluability and radiation exposure of coronary CT angiography (CCTA) performed with whole-heart coverage cardiac-CT in patients with atrial fibrillation (AF).

Materials and methods

We prospectively enrolled 164 patients with AF who underwent a clinically indicated CCTA with a 16-cm z-axis coverage scanner. In all patients CCTA was performed using prospective ECG-triggering with targeted RR interval. We evaluated image quality, coronary evaluability and effective dose (ED). Patients were divided in two subgroups based on heart rate (HR) during imaging. Group 1: 64 patients with low HR (<75 bpm), group 2: 100 patients with high HR (≥75 bpm). Written informed consent was obtained from all patients and the institutional ethics committee approved the study protocol.

Results

In a segment-based analysis, coronary evaluability was 98.4 % (2,577/2,620 segments) in the whole population, without significant differences between groups (1,013/1,024 (98.9 %) and 1,565/1,596 (98.1 %), for groups 1 and 2, respectively, p=0.15). Mean ED was similar in both groups (3.8±1.9 mSv and 3.9±2.1 mSv in groups 1 and 2, respectively, p=0.75)

Conclusions

The whole-heart-coverage scanner could evaluate coronary arteries with high image quality and without increase in radiation exposure in AF patients, even in the high HR group.

Key points

• Last-generation CT scanner improves coronary artery assessment in AF patients.

• The new CT scanner enables low radiation exposure in AF patients.

• Diagnostic ICA maybe avoided in AF patients with suspected CAD.

• Whole-heart coverage CT scanner enables low radiation exposure in AF patients.

The impact of MRI sequence on tumour staging and gross tumour volume delineation in squamous cell carcinoma of the anal canal

Abstract

Objectives

To compare maximum tumour diameter (MTD) and gross tumour volume (GTV) measurements between T₂-weighted (T₂-w) and diffusion-weighted (DWI) MRI in squamous cell carcinoma of the anal canal (SCCA) and assess sequence impact on tumour (T) staging. Second, to evaluate interobserver agreement and reader delineation confidence.

Methods

The staging MRI scans of 45 SCCA patients (25 females) were assessed retrospectively by two independent radiologists (0 and 5 years' experience of anal cancer MRI). MTD and GTV were delineated on both T₂-w and high-b-value DWI images and compared between sequences; T staging was derived from MTD. Interobserver agreement was assessed and delineation confidence scored (1 to 5) by each observer.

Results

GTV and MTD were significantly and systematically lower on DWI versus T₂-w sequences by 14.80%/9.98% (MTD) and 29.70%/12.25% (GTV) for each reader, respectively, causing T staging discordances in approximately a quarter of cases. Bland-Altman limits of agreement were narrower and intraclass correlation coefficients higher for DWI. Delineation confidence was greater on DWI: 40/42 cases were scored confidently (4 or 5) by each reader, respectively, versus 31/36 cases based on T₂-w images.

Conclusions

Sequence selection affects SCCA measurements and T stage. DWI yields higher interobserver agreement and greater tumour delineation confidence.

Key Points

• MTD and GTV measurements are significantly lower on DWI than on T ₂ -w MRI.

• Such differences cause T staging discordances in up to a quarter of cases.

• DWI results in higher agreement between inexperienced and experienced observers.

• DWI offers greater tumour delineation confidence to inexperienced readers.

Apparent diffusion coefficient of vertebral haemangiomas allows differentiation from malignant focal deposits in whole-body diffusion-weighted MRI

Abstract

Objectives

The aim of this study was to identify apparent diffusion coefficient (ADC) values for typical haemangiomas in the spine and to compare them with active malignant focal deposits.

Methods

This was a retrospective single-institution study. Whole-body magnetic resonance imaging (MRI) scans of 106 successive patients with active multiple myeloma, metastatic prostate or breast cancer were analysed. ADC values of typical vertebral haemangiomas and malignant focal deposits were recorded.

Results

The ADC of haemangiomas (72 ROIs, median ADC 1,085×10^-6mm²s^-1, interquartile range 927–1,295×10^-6mm²s^-1) was significantly higher than the ADC of malignant focal deposits (97 ROIs, median ADC 682×10^-6mm²s^-1, interquartile range 583–781×10^-6mm²s^-1) with a p-value < 10^-6. Receiver operating characteristic (ROC) analysis produced an area under the curve of 0.93. An ADC threshold of 872×10^-6mm²s^-1 separated haemangiomas from malignant focal deposits with a sensitivity of 84.7 % and specificity of 91.8 %.

Conclusions

ADC values of classical vertebral haemangiomas are significantly higher than malignant focal deposits. The high ADC of vertebral haemangiomas allows them to be distinguished visually and quantitatively from active sites of disease, which show restricted diffusion.

Key Points

• Whole-body diffusion-weighted MRI is becoming widely used in myeloma and bone metastases.

• ADC values of vertebral haemangiomas are significantly higher than malignant focal deposits.

• High ADCs of haemangiomas allows them to be distinguished from active disease.

Intraprocedural 3D perfusion measurement during chemoembolisation with doxorubicin-eluting beads in liver metastases of malignant melanoma

Abstract

Objectives

To study feasibility and validity of a new software application for intraprocedural assessment of perfusion during chemoembolisation of melanoma metastases.

Methodology

In a prospective phase-II trial, ten melanoma patients with liver-only metastases underwent chemoembolisation with doxorubicin-eluting beads (DEBDOX-TACE). Tumour perfusion was evaluated immediately before and after treatment at cone beam computer tomography (CBCT) using a new software application. For control and comparison, patients underwent perfusion measurement via contrast-enhanced multidetector CT (MDCT) before and after treatment.

Results

CBCT showed 94.7 % reduction in perfusion in metastases after DEBDOX-TACE, whereas MDCT showed 96.8 %. Reduction in perfusion after treatment was statistically significant (p < 0.01) for both methods. The additional time needed for data acquisition during treatment was 5 min per case or less; the post-processing data analysis was 10 min or less. Perfusion imaging was associated with additional contrast agent and patient exposure to radiation (dose-length product [DLP]): 18 ml and 394 mGy*cm in CBCT and 100 ml and 446 mGy*cm in MDCT, respectively.

Conclusions

Reduction in perfusion of melanoma metastases after DEBDOX-TACE can be reliably assessed during the intervention via perfusion software at CBCT. Data acquisition and analysis require additional time but can be easily performed during the treatment.

Key Points

• Tumour perfusion of melanoma metastases can be assessed at cone beam CT.

• The software shows a significant decrease of tumour perfusion after DEBDOX-TACE.

• Data acquisition and analysis require an acceptable additional time during the procedure.

• CBCT requires less radiation exposure and contrast for perfusion study than MSCT.

• This software can monitor the course of DEBDOX-TACE in melanoma metastases.

Conventional and synthetic MRI in multiple sclerosis: a comparative study

Abstract

Objectives

To compare the assessment of patients with multiple sclerosis (MS) using synthetic and conventional MRI.

Materials and methods

Synthetic and conventional axial images were prospectively acquired for 52 patients with diagnosed MS. Quantitative MRI (qMRI) was used for measuring proton density and relaxation times (T1, T2) and then, based on these parameters, synthetic T1W, T2W and FLAIR images were calculated. Image stacks were reviewed blindly, independently and in random order by two radiologists. The number and location for all lesions were documented and categorised. A combined report of lesion load and presence of contrast-enhancing lesions was compiled for each patient. Agreement was evaluated using kappa statistic.

Results

There was no significant difference in lesion detection using synthetic and conventional MRI in any anatomical region or for any of the three image types. Inter- and intra-observer agreements were mainly higher (p < 0.05) using conventional images but there was no significant difference in any specific region or for any image type. There was no significant difference in the outcome of the combined reports.

Conclusion

Synthetic MR images show potential to be used in the assessment of MS dissemination in space (DIS) despite a slightly lower inter- and intra-observer agreement compared to conventional MRI.

Key Points

• Synthetic MR images may potentially be useful in the assessment of MS.

• Examination times may be shortened.

• Inter- and intra-observer agreement is generally higher using conventional MRI.

Extracellular contrast agent-enhanced MRI: 15-min delayed phase may improve the diagnostic performance for hepatocellular carcinoma in patients with chronic liver disease

Abstract

Objectives

To determine the value of a 15-min delayed phase in extracellular contrast agent (ECA)-enhanced magnetic resonance imaging (MRI) for evaluation of hepatocellular carcinoma (HCC) in patients with chronic liver disease.

Methods

Between 2014 and 2015, 103 patients with chronic liver disease underwent ECA-enhanced MRI; 133 lesions consisting of 107 HCCs, 23 benign lesions and three non-HCC malignancies were identified with pathological or clinical diagnosis. MRI images were reviewed by two abdominal radiologists independently using the European Association for the Study of the Liver (EASL) and Liver Imaging Reporting and Data System (LI-RADS) criteria. Imaging features observed in the 15-min delayed phase were recorded.

Results

Of 107 HCCs, three or four additional HCCs were diagnosed according to the EASL criteria by adding the 15-min delayed phase, increasing sensitivity (Reviewer 1, from 69.2–72.0 % [P = 0.072]; Reviewer 2, from 75.7–79.4 % [P = 0.041]). Reviewers 1 and 2 upgraded one and four HCCs from LR-4 to LR-5 based on the LI-RADS, respectively. Among 23 benign lesions, no additional findings were observed in the 15-min delayed phase.

Conclusions

Including the 15-min delayed phase in ECA-enhanced MRI may improve the diagnostic performance for HCC in patients with chronic liver disease.

Key Points

• Additional acquisition of 15-min delayed phase (FDP) requires approximately 20 s.

• About 5 % of HCCs show washout or capsule appearance only in FDP.

• Including FDP improves the sensitivity of extracellular contrast agent-enhanced MRI for HCC.

• These results are applicable only to patients with chronic liver disease.

Medial temporal lobe atrophy ratings in a large 75-year-old population-based cohort: gender-corrected and education-corrected normative data

Abstract

Objectives

To find cut-off values for different medial temporal lobe atrophy (MTA) measures (right, left, average, and highest), accounting for gender and education, investigate the association with cognitive performance, and to compare with decline of cognitive function over 5 years in a large population-based cohort.

Methods

Three hundred and ninety 75-year-old individuals were examined with magnetic resonance imaging of the brain and cognitive testing. The Scheltens's scale was used to assess visually MTA scores (0–4) in all subjects. Cognitive tests were repeated in 278 of them after 5 years. Normal MTA cut-off values were calculated based on the 10th percentile.

Results

Most 75-year-old individuals had MTA score ≤2. Men had significantly higher MTA scores than women. Scores for left and average MTA were significantly higher in highly educated individuals. Abnormal MTA was associated with worse results in cognitive test and individuals with abnormal right MTA had faster cognitive decline.

Conclusion

At age 75, gender and education are confounders for MTA grading. A score of ≥2 is abnormal for low-educated women and a score of ≥2.5 is abnormal for men and high-educated women. Subjects with abnormal right MTA, but normal MMSE scores had developed worse MMSE scores 5 years later.

Key Points

• Gender and education are confounders for MTA grading.

• We suggest cut-off values for 75-year-olds, taking gender and education into account.

• Males have higher MTA scores than women.

• Higher MTA scores are associated with worse cognitive performance.

In memoriam Prof. Erik Boijsen

Detection of lung carcinoma with predominant ground-glass opacity on CT using temporal subtraction method

Abstract

Purpose

To evaluate the usefulness of the CT temporal subtraction (TS) method for the detection of the lung cancer with predominant ground-glass opacity (LC-pGGO).

Materials and methods

Twenty-five pairs of CT and their TS images in patients with LC-pGGO (31 lesions) and 25 pairs of those in patients without nodules were used for an observer performance study. Eight radiologists participated and the statistical significance of differences with and without the CT-TS was assessed by JAFROC analysis.

Results

The average figure-of-merit (FOM) values for all radiologists increased to a statistically significant degree, from 0.861 without CT-TS to 0.912 with CT-TS (p < .001). The average sensitivity for detecting the actionable lesions improved from 73.4 % to 85.9 % using CT-TS. The reading time with CT-TS was not significantly different from that without.

Conclusion

The use of CT-TS improves the observer performance for the detection of LC-pGGO.

Key Points

• CT temporal subtraction can improve the detection accuracy of lung cancer.

• Reading time with temporal subtraction is not different from that without.

• CT temporal subtraction improves observer performance for ground-glass/subsolid nodule detection.

Management of subcentimetre arterially enhancing and hepatobiliary hypointense lesions on gadoxetic acid-enhanced MRI in patients at risk for HCC

Abstract

Objectives

To investigate the significance of subcentimetre (≤1 cm) arterially enhancing and hepatobiliary hypointense lesions (SAELs) observed on gadoxetic acid-enhanced magnetic resonance imaging (MRI) of patients at risk of hepatocellular carcinoma (HCC).

Methods

A SAEL was defined as a subcentimetre hypervascular nodule exhibiting a hepatobiliary phase defect on gadoxetic acid-enhanced MRI. We included 52 SAELs from 46 patients in a HCC surveillance population. The HCC reference standard was pathologic confirmation or a nodule >1 cm with typical imaging features of HCC at follow-up imaging. The malignancy rate and HCC-favourable imaging findings of SAELs were evaluated.

Results

The malignancy rate among SAELs was 57.7% (30/52). At diagnosis, all SAELs that progressed to overt HCC were treatable with curative intention. Venous or late dynamic phase washout was more frequently observed with malignant SAELs than with benign SAELs (57.7% vs. 30.6%; P = 0.01). If SAELs exhibiting washout were considered as HCC, sensitivity, specificity, and positive predictive value was 83.3%, 50%, and 69.4%, respectively.

Conclusion

Among patients at risk of HCC, SAELs on gadoxetic acid-enhanced MRI exhibited high malignant potential. However, close observation may be an appropriate strategy for isolated SAELs. A washout appearance may be helpful for predicting malignancy.

Key Points

• Gadoxetic acid-enhanced MRI provides hepatobiliary phase (HBP) images.

• Screening frequently detects subcentimetre arterially enhancing and hepatobiliary hypointense lesions (SAELs).

• A majority of SAELs progressed to overt HCC within 2 years.

• A venous-phase washout appearance correlated significantly with malignancy in SAELs.

CAD-RADS – a new clinical decision support tool for coronary computed tomography angiography

Abstract

Coronary computed tomography angiography (CTA) has been established as an accurate method to non-invasively assess coronary artery disease (CAD). The proposed 'Coronary Artery Disease Reporting and Data System' (CAD-RADS) may enable standardised reporting of the broad spectrum of coronary CTA findings related to the presence, extent and composition of coronary atherosclerosis. The CAD-RADS classification is a comprehensive tool for summarising findings on a per-patient-basis dependent on the highest-grade coronary artery lesion, ranging from CAD-RADS 0 (absence of CAD) to CAD-RADS 5 (total occlusion of a coronary artery). In addition, it provides suggestions for clinical management for each classification, including further testing and therapeutic options. Despite some limitations, CAD-RADS may facilitate improved communication between imagers and patient caregivers. As such, CAD-RADS may enable a more efficient use of coronary CTA leading to more accurate utilisation of invasive coronary angiograms. Furthermore, widespread use of CAD-RADS may facilitate registry-based research of diagnostic and prognostic aspects of CTA.

Key points

• CAD-RADS is a tool for standardising coronary CTA reports.

• CAD-RADS includes clinical treatment recommendations based on CTA findings.

• CAD-RADS has the potential to reduce variability of CTA reports.

Histogram analysis of diffusion kurtosis imaging derived maps may distinguish between low and high grade gliomas before surgery

Abstract

Objective

To investigate the value of histogram analysis of diffusion kurtosis imaging (DKI) maps in the evaluation of glioma grading.

Methods

A total of 39 glioma patients who underwent preoperative magnetic resonance imaging (MRI) were classified into low-grade (13 cases) and high-grade (26 cases) glioma groups. Parametric DKI maps were derived, and histogram metrics between low- and high-grade gliomas were analysed. The optimum diagnostic thresholds of the parameters, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were achieved using a receiver operating characteristic (ROC).

Result

Significant differences were observed not only in 12 metrics of histogram DKI parameters (P<0.05), but also in mean diffusivity (MD) and mean kurtosis (MK) values, including age as a covariate (F=19.127, P<0.001 and F=20.894, P<0.001, respectively), between low- and high-grade gliomas. Mean MK was the best independent predictor of differentiating glioma grades (B=18.934, 22.237 adjusted for age, P<0.05). The partial correlation coefficient between fractional anisotropy (FA) and kurtosis fractional anisotropy (KFA) was 0.675 (P<0.001). The AUC of the mean MK, sensitivity, and specificity were 0.925, 88.5% and 84.6%, respectively.

Conclusions

DKI parameters can effectively distinguish between low- and high-grade gliomas. Mean MK is the best independent predictor of differentiating glioma grades.

Key points

• DKI is a new and important method.

• DKI can provide additional information on microstructural architecture.

• Histogram analysis of DKI may be more effective in glioma grading.

Subtraction multiphase CT angiography: A new technique for faster detection of intracranial arterial occlusions

Abstract

Objective

To describe and evaluate a novel technical development to improve detection of intracranial vessel occlusions using multiphase CT angiography (MPCTA).

Materials and methods

The institutional ethics committee approved the study. Fifty patients (30 consecutive distal (M2 or smaller) anterior circulation occlusions, ten M1 occlusions, ten cases without occlusion) presenting with suspected AIS who underwent MPCTA were included. Post-processing of MPCTA studies created "subtraction" and "delayed enhancement" (DE) datasets. Initially, non-contrast CT and MPCTA studies for each patient were evaluated. Readers' confidence, speed and sensitivity of detection of intracranial vessel occlusions were recorded. After an interval of at least 4 weeks, readers were provided with post-processed images and studies were re-evaluated.

Results

While the sensitivity of detection of intracranial vessel occlusions was equal for both conventional MPCTA and subMPCTA, the mean time taken to identify a vessel occlusion decreased by 64 % using subMPCTA (16 s vs. 45 s with conventional MPCTA) (p<0.001). In addition, confidence in interpretation improved (from 4.4 to 4.9) using subMPCTA (p<0.001).

Conclusion

SubMPCTA is a novel technique that aids in identifying small intracranial vessel occlusions in the suspected AIS patient. SubMPCTA increases confidence in interpretation and reduces the time taken to detect intracranial vessel occlusions.

Key Points

• SubMPCTA processes MPCTA data to better demonstrate intracranial arterial occlusions.

• SubMPCTA increases confidence and speed of interpretation of MPCTA studies.

• SubMPCTA may aid in rapidly differentiating acute ischaemic stroke from stroke mimics.

Secretin-stimulated ultrasound estimation of pancreatic secretion in cystic fibrosis validated by magnetic resonance imaging

Abstract

Objectives

Secretin-stimulated magnetic resonance imaging (s-MRI) is the best validated radiological modality assessing pancreatic secretion. The purpose of this study was to compare volume output measures from secretin-stimulated transabdominal ultrasonography (s-US) to s-MRI for the diagnosis of exocrine pancreatic failure in cystic fibrosis (CF).

Methods

We performed transabdominal ultrasonography and MRI before and at timed intervals during 15 minutes after secretin stimulation in 21 CF patients and 13 healthy controls. To clearly identify the subjects with reduced exocrine pancreatic function, we classified CF patients as pancreas-sufficient or -insufficient by secretin-stimulated endoscopic short test and faecal elastase.

Results

Pancreas-insufficient CF patients had reduced pancreatic secretions compared to pancreas-sufficient subjects based on both imaging modalities (p < 0.001). Volume output estimates assessed by s-US correlated to that of s-MRI (r = 0.56–0.62; p < 0.001). Both s-US (AUC: 0.88) and s-MRI (AUC: 0.99) demonstrated good diagnostic accuracy for exocrine pancreatic failure.

Conclusions

Pancreatic volume-output estimated by s-US corresponds well to exocrine pancreatic function in CF patients and yields comparable results to that of s-MRI. s-US provides a simple and feasible tool in the assessment of pancreatic secretion.

Key points

• Cystic fibrosis patients with affected pancreas have reduced pancreatic secretions.

• Secretin-stimulated sonography is a simple and feasible method to assess pancreatic output.

• Secretin-simulated MRI is a more precise method to assess pancreatic secretions.

• The sonographic and MRI methods yielded comparable pancreatic secretory output estimates.

Early US findings of biliary atresia in infants younger than 30 days

Abstract

Purpose

To investigate and compare ultrasound (US) findings for the diagnosis of biliary atresia (BA) in infants younger than 30 days with those of infants older than 30 days.

Materials and Methods

From 2000 to 2015, we reviewed hepatobiliary US images in 12 BA infants younger than 30 days (younger BA group) and 62 BA infants older than 30 days (older BA group) before Kasai procedure. Eight (67%) of younger BA group underwent follow-up US examinations before Kasai procedure. Our review of the images focused on triangular cord sign, gallbladder (GB) abnormalities, vascular changes, and signs of portal hypertension.

Results

The triangular cord sign was present in 17% of younger BA group and in 56% of older BA group (P=.024). GB abnormalities were commonly identified in both groups. The hepatic artery diameter was significantly smaller in younger BA group than in older BA group (P<.001). Signs of portal hypertension were less common in younger BA group (17%) than in older BA group (84%) (P<.001). Follow-up US of two infants in younger BA group showed a new appearance of the triangular cord sign.

Conclusion

BA infants younger than 30 days showed atypical US findings compared with those older than 30 days.

Key Points

• BA infants younger than 30 days show atypical US findings.

• GB abnormalities were common in both younger and older BA group.

• Subsequent US examination may be helpful to diagnose BA in young infants.

Accuracy of apparent diffusion coefficient in differentiating pancreatic neuroendocrine tumour from intrapancreatic accessory spleen

Abstract

Objectives

To evaluate and compare the accuracy of absolute apparent diffusion coefficient (ADC) and normalised ADC (lesion-to-spleen ADC ratio) in differentiating pancreatic neuroendocrine tumour (NET) from intrapancreatic accessory spleen (IPAS).

Methods

Study included 62 patients with the diagnosis of pancreatic NET (n=51) or IPAS (n=11). Two independent reviewers measured ADC on all lesions and spleen. Receiver operating characteristics (ROC) analysis to differentiate NET from IPAS was performed and compared for absolute and normalised ADC. Inter-reader reliability for the two methods was assessed.

Results

Pancreatic NET had significantly higher absolute ADC (1.431x10^-3 vs 0.967x10^-3 mm²/s; P<0.0001) and normalised ADC (1.59 vs 1.09; P<0.0001) compared to IPAS. An ADC value of ≥1.206x10^-3 mm²/s was 70.6% sensitive and 90.9% specific for the diagnosis of NET vs. IPAS. Lesion to spleen ADC ratio of ≥1.25 was 80.4% sensitive, and 81.8% specific while ratio of ≥1.29 was 74.5% sensitive and 100% specific in the differentiation. The area under the curve (AUCs) for two methods were similar (88.2% vs. 88.8%; P=0.899). Both methods demonstrated excellent inter-reader reliability with ICCs for absolute ADC and ADC ratio being 0.957 and 0.927, respectively.

Conclusion

Both absolute and normalised ADC allow clinically relevant differentiation of pancreatic NET and IPAS.

Key points

• Imaging overlaps between IPASs and pancreatic-NETs lead to unnecessary procedures including pancreatectomy.

• Uniquely low ADC of spleen allows differentiating IPASs from pancreatic NETs.

• Both absolute-ADC and normalised-ADC (lesion-to-spleen ADC-ratio) demonstrate high accuracy in differentiating IPASs from NETs.

• Both methods demonstrate excellent inter-reader reliability.

Correlation between the availability of dopamine transporter and olfactory function in healthy subjects

Abstract

Objectives

Olfactory dysfunction in Parkinson's disease is usually prodromal to other symptoms. In this study, we aimed to explore the association of olfactory function with the availabilities of striatal dopamine transporter (DAT) in healthy subjects.

Methods

Data used in the preparation of this article were obtained from Parkinson's Progression Markers Initiative database (www.ppmi-info.org/data). The study population consisted of healthy controls with screening ¹²³I-FP-CIT single photon emission tomography (SPECT). University of Pennsylvania Smell Identification Test (UPSIT) was assessed to evaluate the olfactory function. Results: Totally, 181 healthy subjects (117 male, 64 female) with ¹²³I-FP-CIT SPECT data were included in this study. Specific binding ratios (SBRs) of the caudate nucleus (rho = -0.4217, p < 0.0001), putamen (rho = -0.2292, p = 0.0019), and striatum (rho=-0.3425, p < 0.0001) showed a reduction with ageing. SBRs of the caudate nucleus, putamen, and striatum were positively correlated with UPSIT (rho = 0.3716, p < 0.0001; rho = 0.3655, p < 0.0001; rho = 0.3880, p < 0.0001). After controlling for age by partial correlation, SBRs of the caudate nucleus, putamen, and striatum showed an influence on UPSIT (rho = 0.3288, p < 0.0001; rho = 0.3374, p < 0.0001; rho = 0.3511, p < 0.0001).

Conclusion

Olfactory function is associated with the availability of striatal DAT independent of age in healthy subjects.

Key Points

• Olfactory dysfunction in Parkinson's disease is prodromal to other symptoms.

• The availability of dopamine transporter showed a reduction with ageing.

• Olfactory function is associated with the availability of dopamine transporter.

Political liberalism and autonomy education: Are citizenship-based arguments enough?

Abstract

Several philosophers of education argue that schooling should facilitate students' development of autonomy. Such arguments fall into two main categories: Student-centered arguments support autonomy education to help enable students to lead good lives; Public-goods-centered arguments support autonomy education to develop students into good citizens. Critics challenge the legitimacy of autonomy education—of the state imposing a schooling curriculum aimed at making children autonomous. In this paper, I offer a unified solution to the challenges of legitimacy that both arguments for autonomy education face. I first defend a particular construal of liberal legitimacy, and then consider each legitimacy challenge in light of that construal. I argue that the legitimacy challenges confronting both types of argument can be overcome. Further, I explain why we should pursue both arguments, rather than resting the entire case for autonomy education on one or the other. I conclude that each argument—if it can justify autonomy education at all—can justify autonomy education consistent with the requirements of liberal democratic legitimacy.

Editorial Board

Publication date: March 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 180

Cutaneous squamous cell carcinoma with epidermodysplasia verruciformis-like features in a patient with Schimke immune-osseous dysplasia (SIOD)

Schimke immune-osseous dysplasia¹ (SIOD) is an autosomal recessive disorder caused by mutations in the SMARCAL1 gene encoding an ATP-driven annealing helicase that stabilizes stalled replication forks and facilitates DNA repair during replication². The syndrome is characterized by spondyloepiphyseal dysplasia, steroid-resistant nephropathy and cellular immune deficiency.

Urban wastewater treatment by using Ag/ZnO and Pt/TiO 2 photocatalysts

Abstract

In this study, the treatment of wastewater coming from a river highly polluted with domestic and industrial effluents was evaluated. For this purpose, series of photocatalysts obtained by ZnO and TiO₂ modification were evaluated. The effect of metal addition and Ti precursor (in the case of the titania series) over the physicochemical and photocatalytic properties of the materials obtained was also analyzed. The evaluation of the photocatalytic activity showed that semiconductor modification and precursor used in the materials synthesis are important factors influencing the physicochemical and therefore the photocatalytic properties of the materials obtained. The water samples analyzed in the present work were taken from a highly polluted river, and it was found that the effectiveness of the photocatalytic treatment increases when the reaction time increases and for both, wastewater samples and isolated Escherichia coli strain follow the next order Pt/TiO₂ << ZnO. It was also observed that biochemical and chemical demand oxygen and turbidity significantly decrease after treatment, thus indicating that photocatalysis is a non-selective technology, which can lead to recover wastewater containing different pollutants.

Enhanced electro-reduction of NO to NH 3 on Pt cathode at electro-scrubber

Abstract

Besides cheaper electrodes used in NH₃ product formation during NO degradation by mediated electrochemical reduction (MER), a specific electrode that can perform direct electrochemical reduction (DER) and MER of NO is an added advantage. In the present study, a Pt electrode was used to examine NO degradation through NH₃ formation during the electro-scrubbing process. Initially, the DER of NO was tested on a Pt electrode to determine if the DER of NO is possible. The NO degradation by only absorption, DER on Pt, and MER using electrogenerated [Ni(I)(CN)₄]³⁻ showed that a combination of DER and MER increased the NO degradation efficiency. In addition, the online FTIR spectra obtained under different conditions showed that the product formed was NH₃, either from the DER or MER during electro-scrubbing. The feed gas flow rate and feed concentration results of NH₃ formation revealed an additional chemical reaction that was influenced by the Pt electrode in addition to the DER and MER processes. Furthermore, the degradation efficiency of NO when using the Pt electrode increased to 90% compared to that of the Cu electrode (65%), which showed that Pt follows a combination of DER and MER processes. Based on the gas-phase FTIR results of NH₃ formation during NO degradation, higher NH₃ production (0.32 mg/h) was obtained when using a Pt electrode than that using a Cu electrode (0.21 mg/h), highlighting the specificity of the Pt electrode in NH₃ formation during the degradation of NO gas.

MSR1 repeats modulate gene expression and affect risk of breast and prostate cancer

Abstract

Background

MSR1 repeats are a 36-38bp minisatellite element that have recently been implicated in the regulation of gene expression, through copy number variation (CNV).

Patients and methods

Bioinformatic and experimental methods were used to assess the distribution of MSR1 across the genome, evaluate the regulatory potential of such elements and explore the role of MSR1 elements in cancer, particularly non-familial breast cancer and prostate cancer.

Results

MSR1s are predominately located at chromosome 19 and are functionally enriched in regulatory regions of the genome, particularly regions implicated in short-range regulatory activities (H3K27ac, H3K4me1, and H3K4me3). MSR1-regulated genes were found to have specific molecular roles, such as serine-protease activity (P=4.80x10⁻⁷) and ion channel activity (P=2.7x10⁻⁴). The kallikrein locus was found to contain a large number of MSR1 clusters, and at least six of these showed CNV. An MSR1 cluster was identified within KLK14, with 9-copies and 11-copies being normal variants. A significant association with the 9-copy allele and non-familial breast cancer was found in two independent populations (P=0.004; P=0.03). In the white British population, the minor allele conferred an increased risk of 1.21 to 3.51-times for all non-familial disease, or 1.7 to 5.3-times in early-onset disease. The 9-copy allele was also found to be associated with increased risk of prostate cancer in an independent population (odds ratio = 1.27-1.56; P =0.009).

Conclusions

MSR1 repeats act as molecular switches that modulate gene expression. It is likely that CNV of MSR1 will affect risk of development of various forms of cancer, including that of breast and prostate. The MSR1 cluster at KLK14 represents the strongest risk factor identified to date in non-familial breast cancer and a significant risk factor for prostate cancer. Analysis of MSR1 genotype will allow development of precise stratification of disease risk and provide a novel target for therapeutic agents.

Genetic profiling using plasma-derived cell-free DNA in therapy-naïve hepatocellular carcinoma patients: a pilot study.

Abstract

Background

Hepatocellular carcinomas (HCCs) are not routinely biopsied, resulting in a lack of tumor materials for molecular profiling. Here we sought to determine if plasma-derived cell-free DNA (cfDNA) captures the genetic alterations of HCC in patients who have not undergone systemic therapy.

Patients and methods

Frozen biopsies from the primary tumor and plasma were synchronously collected from 30 prospectively recruited, systemic treatment-naïve HCC patients. Deep sequencing of the DNA from the biopsies, plasma-derived cfDNA and matched germline was performed using a panel targeting 46 coding and non-coding genes frequently altered in HCCs.

Results

In 26/30 patients, at least one somatic mutation was detected in biopsy and/or cfDNA. Somatic mutations in HCC-associated genes were present in the cfDNA of 63% (19/30) patients and could be detected 'de novo' without prior knowledge of the mutations present in the biopsy in 27% (8/30) patients. Mutational load and the variant allele fraction of the mutations detected in the cfDNA positively correlated with tumor size and Edmondson grade. Crucially, among the seven patients in whom the largest tumor was ≥5cm or was associated with metastasis, at least one mutation was detected 'de novo' in the cfDNA of 86% (6/7) cases. In these patients, cfDNA and tumor DNA captured 87% (80/92) and 95% (87/92) of the mutations, suggesting that cfDNA and tumor DNA captured similar proportions of somatic mutations.

Conclusion

In patients with high disease burden, the use of cfDNA for genetic profiling when biopsy is unavailable may be feasible. Our results support further investigations into the clinical utility of cfDNA in a larger cohort of patients.

Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol

Abstract

Background

Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in STAMPEDE: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC+AAP vs SOC+DocP.

Method

Recruitment to SOC+DocP and SOC+AAP overlapped Nov-2011─Mar-2013. SOC was long-term ADT or, for most non-metastatic cases, ADT for ≥2yrs and RT to the primary tumour. Stratified randomisation allocated pts 2:1:2 to SOC; SOC+docetaxel 75mg/m² 3-weekly x6 + prednisolone 10mg daily; or SOC+abiraterone acetate 1000mg + prednisolone 5mg daily. AAP duration depended on stage & intent to give radical RT. The primary outcome measure was death from any cause. Analyses used Cox proportional hazards & flexible parametric models, adjusted for stratification factors. This was not a formally-powered comparison. A hazard ratio (HR)<1 favours SOC+AAP, HR > 1 favours SOC+DocP.

Results

566 consenting patients were contemporaneously randomised: 189 SOC+DocP, 377 SOC+AAP. The patients, balanced by allocated treatment were: 342 (60%) M1; 429 (76%) Gleason 8-10; 449 (79%) WHO performance status 0; median age 66yr & median PSA 56ng/ml. With median follow-up 4 years, 149 deaths were reported. For overall survival, HR = 1·16 (95%CI 0·82-1·65); failure-free survival HR = 0·51 (95%CI 0·39-0·67); progression-free survival HR = 0·65 (95%CI 0·48-0·88); metastasis-free survival HR = 0·77 (95%CI 0·57-1·03); prostate cancer-specific survival HR = 1·02 (0·70-1·49); and symptomatic skeletal events HR = 0·83 (95%CI 0·55-1·25). In the safety population, the proportion reporting ≥1 grade 3, 4 or 5 adverse events ever was 36%, 13% and 1% SOC+DocP, & 40%, 7% and 1% SOC+AAP; prevalence 11% at 1 and 2yrs on both arms. Relapse treatment patterns varied by arm.

Conclusions

This direct, randomised comparative analysis of two new treatment standards for hormone-naïve prostate cancer (HNPC) showed no evidence of a difference in overall or prostate cancer-specific survival, nor in other important outcomes such as symptomatic skeletal events, suggesting that Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs.

Trial registration

Clinicaltrials.gov: NCT00268476