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News Article | May 5, 2017
Site: www.eurekalert.org

Vienna, Austria: Lung cancer patients who are treated with radiotherapy can develop an inflammation of the lung tissue called pneumonitis; this can limit the dose of radiation they can receive and severe forms of pneumonitis, if left untreated, can be fatal. Now researchers have found that it is possible to adapt radiation treatment so that it targets the tumour much more precisely. "This has resulted in a significant decrease in the incidence of radiation pneumonitis in patients with advanced lung cancer, while still slowing and controlling the growth of the cancer," Dr Azza Khalil, a clinical oncologist at Aarhus University Hospital, Denmark, told the ESTRO 36 conference today (Saturday). "Previously, the radiation therapist would set up the patient on the radiotherapy machines using the bone structures in the chest and skin tattoos to mark the area to be treated. We have already shown that during the course of radiotherapy the anatomical structure can differ and the cancer change position inside the chest," explained Dr Khalil. "For this study the radiation therapists used a daily 3D image of the tumour to adjust the patient's position under the radiotherapy machine, and if they discovered any change during the course of radiotherapy, doctors and physicists were able to adapt the radiation treatment. This meant they could target the tumour area more accurately, leaving smaller margins so that less healthy tissue was irradiated." Dr Khalil and her colleagues analysed data from 108 patients with locally advanced lung cancer (cancer that had started to spread from where it started to nearby tissue or lymph nodes) who had received adaptive radiation treatment (ART) with smaller margins after April 2013. They matched them with a control group of 102 patients who had been treated prior to April 2013 without the adaptive strategy, using the older method for planning the treatment, which involved leaving larger margins. They followed the patients for a median average of 20 months (ranging from two to 56 months). "We found that the incidence of radiation pneumonitis that was serious enough to require treatment (grade 2 and above) decreased significantly from 50% of patients in the group treated without adaptive radiation treatment to 33% in the group that did receive adaptive radiation treatment," said Dr Khalil. "However, there was no difference between the two groups in the rates of recurrence of cancer or the failure of the radiotherapy to control tumour growth." Thirty-two percent of patients treated with ART had a recurrence of cancer at the site of the original tumour compared to 36% of patients in the non-ART group. Failure to control tumour growth (loco-regional failure) occurred in 45% of the ART group and 48% of the non-ART group. The researchers have not followed the patients for long enough to assess the rates of overall survival between the two groups. However, the average amount of time that patients lived without their disease progressing was similar between the two groups: 16 months for the ART group and 19 months for the non-ART group. Dr Khalil said: "These are important findings for this group of patients who have limited treatment options. Adaptive radiation treatment has resulted in fewer and less pronounced pulmonary symptoms and other side effects, which makes a significant difference to the patients' quality of life." Adaptive radiation treatment has been introduced into routine clinical practice in Dr Khalil's department and she believes her findings are applicable to clinics elsewhere. She and her colleagues are continuing their research into ART. "The outcome of patients with locally advanced lung cancer is compromised by a high rate of local failure where the cancer comes back in the same area we have treated. As we reduced the tumour margin using this adaptive strategy, we are testing whether we would be able now to increase the treatment doses to the tumour without affecting the incidence of the radiation pneumonitis, and hence have a better outcome," she concluded. The incidence of radiation pneumonitis that produces some symptoms in lung cancer patients varies between 25-50% depending on the study. Severe radiation pneumonitis (grade 3 and above) varies between 10-20%. Untreated severe pneumonitis can be fatal. In a previous study Dr Khalid and her colleagues found that overall survival time was shorter in patients who developed severe pneumonitis. President of ESTRO, Professor Yolande Lievens, head of the department of radiation oncology at Ghent University Hospital, Belgium, said: "This study shows significant reductions in radiation pneumonitis when adaptive radiation treatment is used to target the tumour more precisely, and it is a good example of how we are working constantly to refine and improve radiation therapy so that patients can be treated effectively with fewer side effects. These are impressive decreases in toxicity and we look forward to seeing whether overall survival for patients treated in this way is as good as or better than for patients not treated with ART." Abstract no: OC-0143, "Lung" proffered papers session at 16.30-17.30 hrs (CEST) on Saturday, 6 May, Auditorium.


News Article | April 18, 2017
Site: www.eurekalert.org

The commonly used antibiotic azithromycin is not linked to an increased risk of ventricular arrhythmia, an often life-threatening rapid, irregular heartbeat, according to a large study published in CMAJ (Canadian Medical Association Journal). Azithromycin is an antibiotic commonly used to treat bacterial infections -- mostly respiratory and urinary tract infections -- in people of all ages. It belongs to a class of drugs known as macrolides, of which at least one other drug, erythromycin, is known to disrupt the heart's normal rhythm, leading to a condition known as ventricular arrhythmia. Several recent studies have reported conflicting results over whether azithromycin is linked to an increased risk of death from ventricular arrhythmia in people taking the antibiotic. To provide clarity among these conflicting findings, a team of European researchers looked at data on nearly 29 million people in health care databases from Italy, the United Kingdom, Germany, the Netherlands and Denmark to determine if there is a link between azithromycin and ventricular arrhythmia. Of the more than 14 million new antibiotic users, 0.1% (12 874) people developed ventricular arrhythmia, of whom 30 were new users of azithromycin. When compared to amoxicillin, another commonly used antibiotic, from the penicillin class of drugs, there was no increased risk of this heart condition in people using azithromycin. However, there was an increased risk of ventricular arrhythmia in people taking azithromycin compared to people not using antibiotics at all. "This finding suggests that the risk of ventricular arrhythmia is more likely to be due to a person's poor health and caused by their infection, rather than to azithromycin itself," says Dr. Gianluca Trifirò, Department of Biomedical and Dental Sciences and Morpho-functional Imaging, University of Messina, Italy. "This finding was confirmed in several sensitivity analyses and replicated in single databases participating in the study." The authors note these findings may not be applied in hospital settings as the health of patients and use of antibiotics is quite different in community settings, from which the data were drawn. "Current azithromycin use was associated with an increased risk of ventricular arrhythmia when compared with nonuse of antibiotics, but not when compared with current amoxicillin use. The decreased risk with an active comparator suggests significant confounding by indication," the authors conclude. The study was conducted by researchers from Erasmus University, Rotterdam, Netherlands; University of Messina, Messina, Italy; Italian College of General Practitioners, Florence, Italy; PHARMO Institute for Drug Outcomes Research, Utrecht, Netherlands; Leibniz Institute for Prevention Research and Epidemiology - BIPS Gmbh, Bremen, Germany; University of Bologna, Italy; Aarhus University Hospital, Aarhus, Denmark; and King's College, London, United Kingdom.


News Article | May 2, 2017
Site: www.eurekalert.org

Electroconvulsive therapy (ECT) is a highly effective treatment for severe depression and other mental disorders, but the procedure is feared by many. A study headed by researchers from Aarhus University in Denmark documents that this fear is unfounded. Electroconvulsive therapy (ECT) is a highly effective treatment for severe depression and other mental disorders, but the procedure is feared by many. A recent study headed by researchers from Aarhus University in Denmark documents that this fear is unfounded. There is no shortage of frightening images of electroconvulsive therapy (ECT) in movies - most notably in "One flew Over the Cuckoo's Nest", in which the main character Randle McMurphy (Jack Nicholson) is given electroconvulsive therapy (ECT) at a psychiatric hospital in Oregon, USA in the 1970s. It has turned out to be difficult to move on from the associations between ECT and pain, the exercise of power and danger. Even though "One flew Over the Cuckoo's Nest" is 43 years old, the negative image of ECT remains intact for many people. This is emphasised by the fact that every fifth respondent to a British survey expressed a fear of dying from ECT. This is an unfortunate statistic according to Associate Professor Søren D. Østergaard from Aarhus University Hospital - Risskov, which is part of the Department of Clinical Medicine at Aarhus University in Denmark. "In the psychiatric field we have had a clear impression that the fear of dying due to ECT was unfounded, but we have lacked a large-scale study on the topic. We have therefore conducted a systematic review of the literature that contains information about so-called ECT-related deaths, that is deaths where ECT represents the most likely cause of death," explains Søren D. Østergaard. Søren D. Østergaard is senior author of the article "The mortality rate of Electroconvulsive Therapy (ECT): A systematic review and pooled analysis", which was recently published in the journal Acta Psychiatrica Scandinavica. The most significant result in the article is that only one ECT-related death has been reported for the 414.747 ECT treatments that are registered in studies published after 2001. "The risk is very small and even many elderly patients with comorbid medical illnesses can be safely treated with ECT," says Søren D. Østergaard. The systematic review covered 15 studies with data from 32 countries published in the period from 1976 to 2014. For this entire period, the ECT-related mortality was estimated at 2.1 per 100,000 treatments. By comparison, the number of death caused by surgery under general anaesthesia was recently estimated at 3.4 per 100,000 surgeries. "The idea of an electric current running through the head is unpleasant, and some patients find it difficult to forget the frightening portrayals of ECT from movies. But these have little resemblance with reality," says Søren D. Østergaard. "One Flew Over the Cuckoo's Nest is a great movie, but it has been detrimental to psychiatry, because ECT was shown as being a form of punishment. That could hardly be farther from reality," explains Søren D. Østergaard. ECT is still portrayed very negatively in movies. This was the main conclusion in the review "Based on a true story? The Portrayal of ECT in International Movies" from 2016. For instance, ECT is often portrayed as a treatment that is given without anaesthesia, despite the fact that ECT treatment is only carried out under general anaesthesia in developed countries and with the use of muscle relaxants, so that the convulsions are minimal. "These frightening images cause great harm because in addition to being a very safe procedure, ECT is a highly effective treatment for many patients suffering from severe psychosis, mania or depression," says Søren D. Østergaard. He describes how extremely tormented patients can - during the course of just 2-3 treatments over a week - go from being in the deepest depression, being unable to take care of themselves, to gradually become their old selves again. Most often 8-12 treatments are required before a patient gets well. "Typically, you can see the improvement caused by ECT in the patient's eyes, facial expression and posture already before talking to him or her about the mood. Prior to the treatment these individuals are often not able to eat or take a shower because they are so extremely ill, and then a couple of weeks later they sit in front of you with their chin up and a completely different intensity in their eyes. That leaves a great positive impression on you," says Søren D. Østergaard. As with most forms of treatments, ECT has side effects. Some of the most common are headache and nausea, but memory impairment is probably the most feared side effect of ECT. "Memory impairment is a side effect for some patients, but for the majority the impairment is temporary. In addition, it is essential to weigh the side effects against the highly beneficial effects of ECT on the mental disorder being treated. Patients receiving ECT are often so ill that they do not want to live anymore. For these individuals, ECT can be life saving," says Søren D. Østergaard. "Close to 800,000 people die from suicide every year. I strongly believe that many of these suicides could have been prevented had these individuals received ECT in due time," says Søren D. Østergaard. The article based on the study is published in Acta Psychiatrica Scandinavica: http://onlinelibrary. Authors: Nina Tørring (Psychosis Research Unit, Aarhus University Hospital - Risskov), Sohag N. Sanghani & Georgios Petrides (The Zucker Hillside Hospital, Northwell Health System, Glen Oaks, NY, USA), Charles H. Kellner (Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA) and Søren D. Østergaard (Psychosis Research Unit, Aarhus University Hospital - Risskov) The study is supported by a grant from the Lundbeck Foundation


In patients with ST-segment elevation myocardial infarction (STEMI), delay between contact with the health care system and initiation of reperfusion therapy (system delay) is associated with mortality, but data on the associated risk for congestive heart failure (CHF) among survivors are limited. To evaluate the association between system delay and the risk for readmissions or outpatient contacts due to CHF after primary percutaneous coronary intervention (PPCI) in patients with STEMI. Historical follow-up study using population-based medical registries. Western Denmark. Patients with STEMI who were transported by emergency medical service from 1 January 1999 to 7 February 2010 and treated with PPCI within 12 hours of symptom onset and who had a system delay of 6 hours or less (n = 7952). The median duration of follow-up was 3.1 years. Cumulative incidence of readmissions or outpatient contacts due to CHF was determined by using competing-risk regression analysis, with death as the competing risk. Crude and adjusted cause-specific hazard ratios for readmissions or outpatient contacts due to CHF were determined for system delay and other covariates. System delays of 60 minutes or less (n = 451), 61 to 120 minutes (n = 3457), 121 to 180 minutes (n = 2655), and 181 to 360 minutes (n = 1389) corresponded with long-term risks for readmissions or outpatient contacts due to CHF of 10.1%, 10.6%, 12.3%, and 14.1%, respectively (P < 0.001). In multivariable analysis, system delay was an independent predictor of readmissions or outpatient contacts due to CHF (adjusted hazard ratio per hour increase in delay, 1.10 [95% CI, 1.02 to 1.17]). In any nonrandomized study, there are risks for selection bias and residual confounding. In patients with STEMI, shorter delay to PPCI is associated with lower risk for readmissions or outpatient contacts due to CHF during follow-up.


Sundvall L.,Aarhus University Hospital
Human reproduction (Oxford, England) | Year: 2013

How consistent is the time-lapse annotation of dynamic and static morphologic parameters of embryo development, within and between observers? The assessment of dynamic parameters is characterized by almost perfect agreement within and between observers. The commonly employed method used to assess embryos in IVF treatments is based on static evaluation of morphology in a microscope, but this is limited by substantial intra- and inter-observer variation. Time-lapse imaging has been proposed as a method to refine embryo selection by adding new dynamic predictors of viability to the assessment. Yet, there are no data regarding the consistency of estimates of the time-lapse parameters. Infertile patients were recruited at the Fertility Clinic, Arhus University Hospital from February 2011 to June 2012. All embryos were cultured for 6 days in a time-lapse incubator (EmbryoScope(™)). Automated image recording was performed every 20 min. In total, 158 fertilized embryos from 20 different patients were annotated. Three observers made independent annotations on time-lapse recordings. One observer performed the assessment twice. Twenty-five parameters were annotated and the inter- and intra-observer agreement was assessed by calculating intra-class correlation coefficients (ICCs). Extremely close agreement (ICC 0.99) was found for dynamic parameters including the timing of the following: pronuclei breakdown, completion of blastocyst hatching and the appearance and disappearance of the first nucleus after the first division. Observations of cleavage divisions were strongly correlated (ICC > 0.8), indicating close agreement. Measurements of the static morphologic parameters, i.e. multi-nucleation and evenness of blastomeres at 2-cell stage showed fair-to-moderate agreement (ICC ≤ 0.5). The study was conducted at a single clinic. Only embryos with a good prognosis were included. The influence of training sessions was not measured. Consistency is crucial to the validity of embryo scoring and selection. All of the time-lapse parameters suggested by the literature showed in our study high intra- and inter-observer correlation, thus validating the precision of time-lapse annotations. This provides the basis for further investigation of embryo assessment and selection by time-lapse imaging in prospective trials. Research at the Fertility Clinic was funded by an unrestricted grant from Ferring and MSD. The authors have no competing interests to declare. NCT01139268.


Bek T.,Aarhus University Hospital
Progress in Retinal and Eye Research | Year: 2013

Disturbances in the retinal vascular supply are involved in the pathophysiology of the most frequent diseases causing visual impairment and blindness in the Western World. These diseases are diagnosed by noting how morphological lesions in the retina vary in shape, size, location and dynamics, and subsequently concluding the presence of a specific disease entity. This diagnostic approach can be used to identify the site of a retinal vascular occlusion, to assess whether retinal diseases are primarily due to changes in the larger retinal vessels or the microcirculation, and to differentiate the relative involvement of the choroidal and the retinal vascular systems. However, a number of morphological manifestations of retinal vascular disease cannot presently be related to the underlying pathophysiology. The review concludes that there is a need for developing new methods for assessing vascular structure and function in the ciliary vascular system supplying the choroid and the optic nerve head. Presently, the study of these structures relies on imaging techniques with limited penetration and resolution into the tissue. Secondly, there is a need for studying oscillations in retinal vascular function occurring within days to weeks, and for studying regional manifestations of retinal vascular disease. This may constitute the basis for future research in retinal vascular pathophysiology and for the development of new treatment modalities to reduce blindness secondary to retinal vascular disease. © 2013 Elsevier Ltd.


Norskov-Lauritsen N.,Aarhus University Hospital
Clinical Microbiology Reviews | Year: 2014

The aim of this review is to provide a comprehensive update on the current classification and identification of Haemophilus and Aggregatibacter species with exclusive or predominant host specificity for humans. Haemophilus influenzae and some of the other Haemophilus species are commonly encountered in the clinical microbiology laboratory and demonstrate a wide range of pathogenicity, from life-threatening invasive disease to respiratory infections to a nonpathogenic, commensal lifestyle. New species of Haemophilus have been described (Haemophilus pittmaniae and Haemophilus sputorum), and the new genus Aggregatibacter was created to accommodate some former Haemophilus and Actinobacillus species (Aggregatibacter aphrophilus, Aggregatibacter segnis, and Aggregatibacter actinomycetemcomitans). Aggregatibacter species are now a dominant etiology of infective endocarditis caused by fastidious organisms (HACEK endocarditis), and A. aphrophilus has emerged as an important cause of brain abscesses. Correct identification of Haemophilus and Aggregatibacter species based on phenotypic characterization can be challenging. It has become clear that 15 to 20% of presumptive H. influenzae isolates from the respiratory tracts of healthy individuals do not belong to this species but represent nonhemolytic variants of Haemophilus haemolyticus. Due to the limited pathogenicity of H. haemolyticus, the proportion of misidentified strains may be lower in clinical samples, but even among invasive strains, a misidentification rate of 0.5 to 2% can be found. Several methods have been investigated for differentiation of H. influenzae from its less pathogenic relatives, but a simple method for reliable discrimination is not available. With the implementation of identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry, the more rarely encountered species of Haemophilus and Aggregatibacter will increasingly be identified in clinical microbiology practice. However, identification of some strains will still be problematic, necessitating DNA sequencing of multiple housekeeping gene fragments or full-length 16S rRNA genes. © 2014, American Society for Microbiology. All Rights Reserved.


Donskov F.,Aarhus University Hospital
Seminars in Cancer Biology | Year: 2013

The clinical relevance of the interaction between human cancer and neutrophils has recently begun to emerge. This review will focus on recently published articles regarding immunomonitoring of neutrophils in blood and tumor tissue in clinical trials comprising the main human tumor types, with a strong emphasis on independent prognostic relevance assessed by multivariate analyses.The prognostic role of tumor-infiltrating neutrophils, elevated blood neutrophils and elevated blood neutrophil/lymphocyte ratio has been associated with poor clinical outcome in several human cancers, most notably in renal cell carcinoma, melanoma, colorectal cancer, hepatocellular carcinoma, cholangiocarcinoma, glioblastoma, GIST, gastric, esophageal, lung, ovarian and head and neck cancer. A striking finding is the notion that high baseline neutrophil count in either tumor or blood, or both, was identified as strong, independent risk factor for poor outcome in multivariate analyses, and the negative prognostic impact of neutrophils was not eliminated by increasing the dose of cytokines, chemotherapy, or targeted therapy. For several cancers, patients benefit most from therapy if baseline neutrophil was low. Thus, baseline neutrophils over-ride nadir counts in prognostic significance.In summary, a proportion of patients who do not experience benefit from surgery or medical intervention may be associated with a worst prognosis because they are characterized by baseline tumor-related neutrophilia protecting them from benefit from therapy. Further research to unraveling the cancer biology and new treatment options is encouraged. © 2013 Elsevier Ltd.


Finnerup N.B.,Aarhus University Hospital
Pain | Year: 2013

Individuals with spinal cord injury (SCI) often have chronic pain, which may have a major impact on their quality of life. The purpose of this article is to present an update on the classification of SCI pain, recent advances in the understanding of underlying mechanisms, and current evidence-based treatment of SCI pain. The paper also discusses difficulties in assessing pain after SCI, both in the clinic and in preclinical research. While we continue to increase our understanding of underlying mechanisms, treatment is still unsatisfactory, and there is an unmet need to improve pain relief. We need to improve preclinical assessment of pain-like behavior in central pain models, and improve the clinical assessment of pain and our understanding of the interaction with cognitive, emotional, and social factors. In future studies on mechanisms and treatment, we need to acknowledge the different phenotypes of chronic SCI pain. © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.


Background: The importance of tumour hypoxia for the outcome of radiotherapy has been under investigation for decades. Numerous clinical trials modifying the hypoxic radioresistance in squamous cell carcinoma of the head and neck (HNSCC) have been conducted, but most have been inconclusive, partly due to a small number of patients in the individual trial. The present meta-analysis was, therefore, performed utilising the results from all clinical trials addressing the specific question of hypoxic modification in HNSCC undergoing curative intended primary radiotherapy alone. Methods: A systematic review of published and unpublished data identified 4805 patients with HNSCC treated in 32 randomized clinical trials, applying, normobaric oxygen or carbogen breathing (5 trials); hyperbaric oxygen (HBO) (9 trials); hypoxic radiosensitizers (17 trials) and HBO and radiosensitizer (1 trial). The trials were analysed with regard to the following endpoints: loco-regional control (32 trials), disease specific survival (30 trials), overall survival (29 trials), distant metastases (12 trials) and complications to radiotherapy (23 trials). Results: Overall hypoxic modification of radiotherapy in head and neck cancer did result in a significant improved therapeutic benefit. This was most dominantly observed when using the direct endpoint of loco-regional control with an odds ratio (OR) of 0.71, 95% cf.l. 0.63-0.80; p < 0.001), but this was almost mirrored in the disease specific survival (OR: 0.73, 95% cf.l. 0.64-0.82; p < 0.001), and to a lesser extent in the overall survival (OR: 0.87, 95% cf.l. 0.77-0.98; p = 0.03). The risk of distant metastases was not significantly influenced although it appears to be less in the tumours treated with hypoxic modification (OR: 0.87, 95% cf.l. 0.69-1.09; p = 0.22), whereas the radiation related late complications were not influenced by the overall use of hypoxic modifications (OR: 1.00, 95% cf.l. 0.82-1.23; p = 0.96). The improvement in loco-regional control was found to be independent of the type of hypoxic modification. The trials have used different fractionation schedules, including large doses per fraction, which may result in relatively more hypoxia and greater benefit. However, analysis of HNSCC trials using conventional fractionation only, showed that the significant effect of hypoxic modification was maintained. Conclusion: The meta-analysis thus demonstrates that there is level 1a evidence in favour of adding hypoxic modification to radiotherapy of squamous cell carcinomas of the head and neck. © 2011 Elsevier Ltd. All rights reserved.

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