Darby S.C.,University of Oxford |
Ewertz M.,University of Southern Denmark |
McGale P.,University of Oxford |
Bennet A.M.,Karolinska Institutet |
And 12 more authors.
New England Journal of Medicine | Year: 2013
Background: Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of ischemic heart disease is uncertain. Methods: We conducted a population-based case-control study of major coronary events (i.e., myocardial infarction, coronary revascularization, or death from ischemic heart disease) in 2168 women who underwent radiotherapy for breast cancer between 1958 and 2001 in Sweden and Denmark; the study included 963 women with major coronary events and 1205 controls. Individual patient information was obtained from hospital records. For each woman, the mean radiation doses to the whole heart and to the left anterior descending coronary artery were estimated from her radiotherapy chart. Results: The overall average of the mean doses to the whole heart was 4.9 Gy (range, 0.03 to 27.72). Rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per gray (95% confidence interval, 2.9 to 14.5; P<0.001), with no apparent threshold. The increase started within the first 5 years after radiotherapy and continued into the third decade after radiotherapy. The proportional increase in the rate of major coronary events per gray was similar in women with and women without cardiac risk factors at the time of radiotherapy. Conclusions: Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent rate of ischemic heart disease. The increase is proportional to the mean dose to the heart, begins within a few years after exposure, and continues for at least 20 years. Women with preexisting cardiac risk factors have greater absolute increases in risk from radiotherapy than other women. (Funded by Cancer Research UK and others.). Copyright © 2013 Massachusetts Medical Society.
Arendt-Nielsen L.,University of Aalborg |
Nie H.,University of Aalborg |
Laursen M.B.,Aalborg Hospital |
Laursen B.S.,Aalborg Hospital |
And 3 more authors.
Pain | Year: 2010
Pain is the dominant symptom in osteoarthritis (OA) and sensitization may contribute to the pain severity. This study investigated the role of sensitization in patients with painful knee OA by measuring (1) pressure pain thresholds (PPTs); (2) spreading sensitization; (3) temporal summation to repeated pressure pain stimulation; (4) pain responses after intramuscular hypertonic saline; and (5) pressure pain modulation by heterotopic descending noxious inhibitory control (DNIC). Forty-eight patients with different degrees of knee OA and twenty-four age- and sex-matched control subjects participated. The patients were separated into strong/severe (VAS ≥ 6) and mild/moderate pain (VAS < 6) groups. PPTs were measured from the peripatellar region, tibialis anterior (TA) and extensor carpi radialis longus muscles before, during and after DNIC. Temporal summation to pressure was measured at the most painful site in the peripatellar region and over TA. Patients with severely painful OA pain have significantly lower PPT than controls. For all locations (knee, leg, and arm) significantly negative correlations between VAS and PPT were found (more pain, more sensitization). OA patients showed a significant facilitation of temporal summation from both the knee and TA and had significantly less DNIC as compared with controls. No correlations were found between standard radiological findings and clinical/experimental pain parameters. However, patients with lesions in the lateral tibiofemoral knee compartment had higher pain ratings compared with those with intercondylar and medial lesions. This study highlights the importance of central sensitization as an important manifestation in knee OA. © 2010.
Laurberg P.,Aarhus University Hospital |
Berman D.C.,Aalborg Hospital |
Pedersen I.B.,Aarhus University Hospital |
Andersen S.,Aarhus University Hospital |
Carle A.,Aarhus University Hospital
Journal of Clinical Endocrinology and Metabolism | Year: 2012
Context: Population-based data on the incidence and clinical presentation of moderate to severe Graves' orbitopathy (GO) are scarce, and virtually nothing is known on the effect of an iodization program on the incidence and presentation of GO. Objective: The objective of the study was to characterize incident moderate to severe GO in North Jutland County, Denmark, during the period 1992-2009, beforeandafter the Danish salt iodization program. Design and Patients: The design of the study was a prospective register of patients with incident moderate to severe GO in a population during 8.9 million persons x years of observation. Setting: The study was conducted at a thyroid-eye clinic of university hospital. Main Outcome Measures: Clinical presentation and incidence before and after the year 2000 initiation of the mandatory Danish iodization of salt were measured. The incidence of GO was related to the incidence of Graves' hyperthyroidism (GH) in the same population. Results:The incidence rate of moderate to severe GO was 16.1/million per year (women: 26.7; men: 5.4), with no change associated with iodization of salt. The moderate to severe GO incidence was 4.9% of the incidence of GH. The incidence rate ratio between women and men with GO (4.9) was not different from the ratio in GH. Compared with GH, only a few patients (<2%) suffered from moderate and severe GO below the age of 40 yr, whereas GO was relatively common in age groups 40-60 yr (∼8%). Conclusions: Approximately 5% of the patients with Graves' disease develop moderate to severe GO, with a similar risk in women and men with Graves' disease. The risk of GO is much higher in patients aged 40-60 yr than in young patients with Graves' disease. Salt iodization was not associated with a change in the incidence of GO. Copyright © 2012 by The Endocrine Society.
Brugmann A.,Aalborg Hospital |
Sorensen B.S.,Aarhus University Hospital
Future Oncology | Year: 2011
In breast cancer, HER2-targeted therapy with trastuzumab has gained significant attention, owing to the dramatic response observed in a subset of HER2-positive patients. The mechanisms of action are complex and not fully understood, and much effort has been spent in order to identify responders. Good patient management, side effects of the humanized monoclonal antibody and socioeconomics all demand that the drug should be administered only to the patients who will benefit from it. This has been a difficult task and contributions to solve it have been proposed from a variety of research. In this article we describe some of these contributions based on the literature and provide our viewpoint as to which identifiers will emerge in the following decade. © 2011 Future Medicine Ltd.
Rix T.A.,Aalborg Hospital |
Christensen J.H.,Aarhus University Hospital |
Schmidt E.B.,Aalborg Hospital
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2013
Purpose of Review: There are suggestions of effects of marine omega-3 polyunsaturated fatty acids (PUFAs) in relation to ventricular arrhythmia and sudden cardiac death and, more recently, also of possible effects related to atrial fibrillation. Recent Findings: On the basis of the recently published human studies, this article not only focusses primarily on recent developments and current knowledge on the effect of marine omega-3 PUFAs on atrial fibrillation, but also provides a status for their effects on ventricular arrhythmias. Summary: Marine omega-3 PUFAs may protect against ventricular arrhythmias, and there is growing evidence for an effect of marine omega-3 PUFAs in the prevention and treatment of atrial fibrillation. Further studies are needed to establish which patients are more likely to benefit from omega-3 PUFAs, the timing of treatment, and the dosages. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Christiansen O.B.,Rigshospitalet |
Christiansen O.B.,Aalborg Hospital
Molecular Immunology | Year: 2013
Much research has been done to investigate why the fetus in most pregnancies, in spite of being semi-allogenic, is not rejected by the immune system. Experiments in transgenic mice have suggested that dysfunctions in both the innate immune system (NK cells) and the adaptive immune system (T-cells and T regulatory cells) result in increased fetal loss rate.Many studies have suggested that women with pathological pregnancies such as recurrent miscarriages have signs of generally exaggerated inflammatory immune responses both before and during pregnancy and signs of breakage of tolerance to autoantigens and fetal antigens. In addition, several abnormalities of innate immune responses seem to characterize women with pathological pregnancies. These abnormalities involve disadvantageous interactions between uterine NK cells and HLA-G and HLA-C on the trophoblast that may have pro-inflammatory effects. Also, humoral factors belonging to the innate immune system such as mannose-binding lectin seem to be associated with pregnancy outcome probably by modifying the level of inflammation at the feto-maternal interface. The pro-inflammatory conditions at the feto-maternal interface characterizing pathological pregnancy are suggested to predispose to adaptive immunological processes against alloantigens on the trophoblast that may further increase the risk of pathological pregnancy outcome. The best documented adaptive immune reaction against fetal alloantigens is directed against male-specific minor histocompatibility (HY) antigens. Anti-HY immunity seems to play a role especially in women with secondary recurrent miscarriage. © 2012 Elsevier Ltd.
Larsen E.C.,Copenhagen University |
Christiansen O.B.,Copenhagen University |
Kolte A.M.,Copenhagen University |
Macklon N.,Copenhagen University |
And 3 more authors.
BMC Medicine | Year: 2013
Sporadic miscarriage is the most common complication of early pregnancy. Two or three consecutive pregnancy losses is a less common phenomenon, and this is considered a distinct disease entity. Sporadic miscarriages are considered to primarily represent failure of abnormal embryos to progress to viability. Recurrent miscarriage is thought to have multiple etiologies, including parental chromosomal anomalies, maternal thrombophilic disorders, immune dysfunction and various endocrine disturbances. However, none of these conditions is specific to recurrent miscarriage or always associated with repeated early pregnancy loss. In recent years, new theories about the mechanisms behind sporadic and recurrent miscarriage have emerged. Epidemiological and genetic studies suggest a multifactorial background where immunological dysregulation in pregnancy may play a role, as well as lifestyle factors and changes in sperm DNA integrity. Recent experimental evidence has led to the concept that the decidualized endometrium acts as biosensor of embryo quality, which if disrupted, may lead to implantation of embryos destined to miscarry. These new insights into the mechanisms behind miscarriage offer the prospect of novel effective interventions that may prevent this distressing condition. © 2013 Larsen et al.; licensee BioMed Central Ltd.
Andersen J.C.,Aalborg Hospital
Danish medical journal | Year: 2012
In order to elaborate evidence-based, national Danish guidelines for the treatment of diverticular disease the literature was reviewed concerning the epidemiology, staging, diagnosis and treatment of diverticular disease in all its aspects. The presence of colonic diverticula, which is considered to be a mucosal herniation through the intestinal muscle wall, is inversely correlated to the intake of dietary fibre. Other factors in the genesis of diverticular disease may be physical inactivity, obesity, and use of NSAIDs or acetaminophen. Diverticulosis is most common in Western countries with a prevalence of 5% in the population aged 30-39 years and 60% in the part of the population > 80 years. The incidence of hospitalization for acute diverticulitis is 71/100,000 and the incidence of complicated diverticulitis is 3.5-4/100,000. Acute diverticulitis is conveniently divided into uncomplicated and complicated diverticulitis. Complicated diverticulitis is staged by the Hinchey classification 1-4 (1: mesocolic/pericolic abscess, 2: pelvic abscess, 3: purulent peritonitis, 4: faecal peritonitis). Diverticulitis is suspected in case of lower left quadrant abdominal pain and tenderness associated with fever and raised WBC and/or CRP; but the clinical diagnosis is not sufficiently precise. Abdominal CT confirms the diagnosis and enables the classification of the disease according to Hinchey. The distinction between Hinchey 3 and 4 is done by laparoscopy or, when not possible, by laparotomy. Uncomplicated diverticulitis is treated by conservative means. There is no evidence of any beneficial effect of antibiotics in uncomplicated diverticulitis, but antibiotics may be used in selected cases depending on the overall condition of the patients and the severity of the infection. Abscess formation is best treated by US- or CT-guided drainage in combination with antibiotics. When the abscess is < 3 cm in diameter, drainage may be unnecessary, and only antibiotics should be instituted. The surgical treatment of acute perforated diverticulitis has interchanged between resection and non-resection strategies: The three-stage procedure dominating in the beginning of the 20th century was later replaced by the Hartmann procedure or, alternatively, resection of the sigmoid with primary anastomosis. Lately a non-resection strategy consisting of laparoscopy with peritoneal lavage and drainage has been introduced in the treatment of Hinchey stage 3 disease. Evidence so far for the lavage regime is promising, comparing favourably with resection strategies, but lacking in solid proof by randomized, controlled investigations. In recent years, morbidity has declined in complicated diverticulitis due to improved diagnostics and new treatment modalities. Recurrent diverticulitis is relatively rare and furthermore often uncomplicated than previously assumed. Elective surgery in diverticular disease should probably be limited to symptomatic cases not amenable to conservative measures, since prophylactic resection of the sigmoid, evaluated from present evidence, confers unnecessary risks in terms of morbidity and mortality to the individual as well as unnecessary costs to society. Any recommendation for routine resection following multiple cases of diverticulitis should await results of randomized studies. Laparoscopic resection is preferred in case of need for elective surgery. When malignancy is ruled out preoperatively, a sigmoid resection with preservation of the inferior mesenteric artery, oral division of colon in soft compliant tissue and anastomosis to upper rectum is recommended. Fistulae to bladder or vagina, or stenosis of the colon may be dealt with according to symptoms and comorbidity. Resection of the diseased segment of colon is preferred when possible and safe; alternatively, a diverting stoma can be the best solution.
Rasmussen M.M.,Aalborg Hospital
Danish medical journal | Year: 2012
The treatment of spinal nerve root cysts is not uniform. In the past decades, microsurgical resection to preserve nervous tissue has been reported. We report on our microsurgical method and present the clinical results in relation to surgical outcome. Retrospective review of a consecutive series of patients who underwent surgical cyst closure from 2006 to 2010. Twelve patients, all female, with a total of 23 cysts underwent surgery for 20 symptomatic cysts. The mean age was 45 (range 13-75) years. Following treatment with this procedure, 95% of the cysts were closed and 5% had notably diminished at post-operative magnetic resonance imaging. Clinical improvement was seen in 67% of the patients; one improved temporarily, two remained unchanged and one had worsened at the last follow-up. The mean post-operative follow-up period was 11 (range 3-19) months. Clinical outcome was associated with none of the pre-operative parameters, i.e. pain-provoking postural position, cyst size, number of treated cysts, educational level or pre-operative sick leave. We find that our surgical technique is suit-able for closure of spinal nerve root cysts; however, the clinical outcome after surgery was sub-optimal according to preoperative clinical judgement. Consequently, we have established a dedicated outpatient clinic that performs extensive pre-operative assessment and investigation of patients with symptomatic spinal nerve root cysts. We hereby hope to improve surgical outcome in the future.
Graversen C.,Aalborg Hospital
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference | Year: 2012
Diabetes mellitus (DM) is a multi-factorial and complex disease causing autonomic neuropathy and gastrointestinal symptoms in some patients. The neural mechanisms behind these symptoms are poorly understood, but it is believed that both peripheral and central mechanisms are involved. To gain further knowledge of the central mechanisms, the aim of this study was to identify biomarkers for the altered brain activity in type-1 DM patients compared to healthy volunteers (HV), and to correlate the obtained biomarkers to clinical patient scores. The study included 14 DM patients and 15 HV, with brain activity recorded as multi-channel electroencephalography evoked brain potentials (EPs) elicited by painful electrical stimulations in the esophagus. The single-sweep EPs were decomposed by an optimized discrete wavelet transform (DWT), and averaged for each channel. The DWT features from the DM patients were discriminated from the HV by a support vector machine (SVM) applied in regression mode. For the optimal DWT, the discriminative features were extracted and the SVM regression value representing the overall alteration of the EP was correlated to the clinical scores. A classification performance of 86.2% (P=0.01) was obtained by applying a majority voting scheme to the 5 best performing channels. The biomarker was identified as decreased theta band activity. The regression value was correlated to symptoms reported by the patients (P=0.04). The methodology is an improvement of the present approach to study central mechanisms in diabetes mellitus, and may provide a future application for a clinical tool to optimize treatment in individual patients.