Publications by authors named "Volkert D Siersma"

22 Publications

  • Page 1 of 1

Chronic hyperglycemia, hypercholesterolemia, and metabolic syndrome are associated with risk of tendon injury.

Scand J Med Sci Sports 2021 May 8. Epub 2021 May 8.

Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery M, Copenhagen University Hospital - Bispebjerg and Frederiksberg and Center for Healthy Aging, Institute of Sports Medicine Copenhagen, University of Copenhagen, Copenhagen, Denmark.

Tendon injury is a considerable problem affecting both physically active and sedentary people. The aim of this study was to examine the relationship between markers for metabolic disorders (hyperglycemia, hypercholesterolemia, and metabolic syndrome) and the risk of developing tendon injuries requiring referral to a hospital. The Copenhagen City Heart Study is a prospective study of diabetic and non-diabetic individuals from the Danish general population with different physical activity levels. The cohort was followed for 3 years via national registers with respect to tendon injuries. Data from 5856 individuals (median age 62 years) were included. The overall incidence of tendon injury in both upper and lower extremities that required an out-patient or in-house visit to a hospital was ~5.7/1000 person years. Individuals with elevated HbA1c (glycated hemoglobin) even in the prediabetic range (HbA1c>5.7%) had a ~3 times higher risk of tendon injury in the lower extremities only, as compared to individuals with normal HbA1C levels. Hypercholesterolemia (total cholesterol>5 mmol/L) increased risk of tendon injury in the upper extremities by ~1.5 times, and individuals with metabolic syndrome had ~2.5 times higher risk of tendon injury in both upper and lower extremities. In conclusion, these data demonstrate for the first time in a large cohort with different physical activity levels that the indicators for metabolic syndrome are a powerful systemic determinant of tendon injury, and two of its components, hyperglycemia and hypercholesterolemia, each independently make tendons susceptible for damage and injury.
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http://dx.doi.org/10.1111/sms.13984DOI Listing
May 2021

Association between perioperative hyperoxia and cerebrovascular complications after laparotomy-A post-hoc follow-up study.

Acta Anaesthesiol Scand 2019 02 31;63(2):164-170. Epub 2018 Jul 31.

Department of Anaesthesia and Intensive Care, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark.

Background: Perioperative hyperoxia has been linked to increased long-term mortality. Vasoconstrictive and cellular side effects to hyperoxia have been suggested to increase the risk of coronary and cerebral ischemia. The aim of this post-hoc analysis of a large randomized trial was to compare the effects of 80% vs 30% perioperative oxygen on the long-term risk of stroke or transient cerebral ischemia (TCI) in patients undergoing abdominal surgery.

Methods: A total of 1386 patients were randomized to 80% or 30% perioperative oxygen during acute or elective open abdominal surgery. Median follow-up was 3.9 years. Primary outcome was a composite of the long-term occurrence of stroke or TCI. Secondary outcomes included long-term mortality without stroke or TCI, and incidences of neurological admission, psychiatric admission, and dementia. Outcomes were analyzed in Cox regression models.

Results: Stroke or TCI occurred in 20 (3.0%) patients given 80% oxygen vs 22 (3.2%) patients given 30% oxygen with an adjusted hazard ratio (HR) of 0.96 [95% CI 0.52-1.76]. Composite secondary outcome of death, stroke, or TCI had a HR of 1.21 [95% CI 1.00-1.47] for 80% compared to 30% oxygen. HRs for secondary outcomes were HR 1.14 [95% CI 0.79-1.64] for neurological admission, 1.34 [95% CI 0.95-1.88] for psychiatric admission and 0.54 [95% CI 0.16-1.80] for dementia.

Conclusion: Stroke or TCI did not seem related to perioperative inspiratory oxygen fraction. Due to few events, this study cannot exclude that perioperative hyperoxia increases risk of mortality, stroke, or TCI after abdominal surgery.
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http://dx.doi.org/10.1111/aas.13235DOI Listing
February 2019

BRAF mutations in conjunctival melanoma: investigation of incidence, clinicopathological features, prognosis and paired premalignant lesions.

Acta Ophthalmol 2016 Aug 24;94(5):463-70. Epub 2016 Mar 24.

Department of Pathology - Rigshospitalet, Copenhagen, Denmark.

Purpose: To investigate incidence, clinicopathological features and prognosis of BRAF-mutated conjunctival melanoma in Denmark. Furthermore, to determine BRAF mutations in paired premalignant lesions and evaluate immunohistochemical BRAF V600E oncoprotein detection.

Methods: Data from 139 patients with conjunctival melanoma (1960-2012) were collected. Archived conjunctival melanoma samples and premalignant lesions were analysed for BRAF mutations using droplet digital polymerase chain reaction (PCR). Results were associated with clinicopathological features and compared with BRAF V600E oncoprotein stainings.

Results: The overall incidence of conjunctival melanoma (0.5 cases/1 000 000/year) increased during the study period with 0.13 cases/1 000 000/10 years. The increase comprised a higher proportion of patients aged >65 years, epibulbar tumours and tumours developed from a primary acquired melanosis with atypia. BRAF mutations were identified in 39 of 111 (35%) cases. The rate ratio of BRAF-mutated versus BRAF-wild-type melanoma did not change over time. BRAF mutations were associated with T1 stage (p = 0.007), young age (p = 0.001), male gender (p = 0.02), sun-exposed location (p = 0.01), mixed/non-pigmented tumour colour (p = 0.02) and nevus origin (p = 0.005), but did not associate with prognosis. BRAF status in conjunctival melanoma and paired premalignant lesions corresponded in 19 of 20 cases. Immunohistochemistry detected BRAF V600E mutations with a sensitivity of 0.94 and a specificity of 1.00 in newer conjunctival melanoma samples (2000-2012, n = 47).

Conclusion: The incidence of conjunctival melanoma increased in Denmark over 50 years. The proportion of BRAF-mutated conjunctival melanoma was constant. BRAF mutations were identified as early events in conjunctival melanoma, associated with a distinct clinicopathological profile, similar to BRAF-mutated cutaneous melanoma. Immunohistochemical detection of BRAF can be used to assess BRAF V600E mutations.
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http://dx.doi.org/10.1111/aos.13007DOI Listing
August 2016

The excess mortality of patients with diabetes and concurrent psychiatric illness is markedly reduced by structured personal diabetes care: A 19-year follow up of the randomized controlled study Diabetes Care in General Practice (DCGP).

Gen Hosp Psychiatry 2016 Jan-Feb;38:42-52. Epub 2015 Oct 19.

The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, DK-1014 Copenhagen K, Denmark. Electronic address:

Objective: To assess the effectiveness of an intervention in Type 2 diabetic patients with concurrent psychiatric illness (PI) and compare this with the effectiveness in patients without PI.

Method: In the Diabetes Care in General Practice trial, 1381 patients newly diagnosed with Type 2 diabetes were randomized to 6 years of structured personal diabetes care or routine diabetes care (ClinicalTrials.gov NCT01074762). In this observational post-hoc analysis, the effectiveness of the intervention for diabetes in 179 patients with concurrent PI was analyzed.

Results: During the 19-year follow-up period, patients with PI in the structured personal care group experienced a lower risk for all-cause mortality [105.3 vs. 140.4 events per 1000 patient-years; hazard ratio (HR): 0.63, P=0.023, multivariably adjusted], diabetes-related death (66.0 vs. 95.1; HR: 0.57, P=0.015), any diabetes-related endpoint (169.5 vs. 417.5; HR: 0.47, P=0.0009) and myocardial infarction (54.1 vs. 104.4; HR: 0.48, P=0.013), compared to patients with PI in the routine care group. This translates into a number needed to treat over 10 years of three or lower for these outcomes.

Conclusion: These findings suggest that in primary care, structured diabetes care allowing for individualization was highly effective among diabetic patients with co-occurring PI.
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http://dx.doi.org/10.1016/j.genhosppsych.2015.10.001DOI Listing
October 2016

A Retrospective Review of Conjunctival Melanoma Presentation, Treatment, and Outcome and an Investigation of Features Associated With BRAF Mutations.

JAMA Ophthalmol 2015 Nov;133(11):1295-303

Eye Pathology Institute, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark4Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark.

Importance: Large studies investigating clinical presentation and treatment in primary conjunctival melanoma (CM) are rare. Clinicopathological characteristics of BRAF-mutated CM have not been studied thoroughly.

Objectives: To determine the associations of clinicopathological tumor features and treatment with local recurrence, metastasis, and mortality and to determine the association of BRAF mutations with these features.

Design, Setting, And Participants: Population-based cohort study at the Eye Pathology Institute, Copenhagen, Denmark. Participants included 139 patients with primary CM in Denmark from January 1, 1960, to December 31, 2012. For BRAF analysis, all patients with available formalin-fixed, paraffin-embedded tumor samples from January 1, 1994, to December 31, 2012, were included.

Main Outcomes And Measures: BRAF mutations, local recurrence, regional and distant metastasis, melanoma-related mortality, and all-cause mortality were examined.

Results: A poor prognosis of tumors involving the extrabulbar conjunctiva and adjacent tissue structures was confirmed in multivariable Cox proportional hazards regression models. Patients undergoing incisional biopsy more frequently developed metastasis (hazard ratio [HR], 2.46; 95% CI, 1.08-5.58; P = .03). Excision without adjuvant treatment was associated with local recurrence (HR, 1.97; 95% CI, 0.11-3.48; P = .02), metastatic disease (HR, 2.51; 95% CI, 1.07-5.91; P = .03), and all-cause mortality (HR, 1.80; 95% CI, 1.05-3.08; P = .03). BRAF mutations were identified in 19 of 47 primary CMs (40.4%) and were more frequent in younger patients (P = .005), less frequent in the extrabulbar conjunctiva (P = .05), more frequently classified as T1 tumors (P = .03), and rarely manifested with primary acquired melanosis (P = .001) or with a uniformly pigmented lesion (P = .006). Distant metastases developed in 6 of 19 BRAF-mutated CMs (31.6%) as opposed to 1 of 28 BRAF wild-type CMs (3.6%). No definitive association with distant metastasis was seen in multivariable Cox proportional hazards regression models.

Conclusions And Relevance: Incisional biopsy and excision without adjuvant therapy were associated with a poor outcome in patients with CM. Extrabulbar location was also associated with a poor outcome in multivariable analysis. BRAF-mutated CMs were frequent in younger patients and were rare in tumors involving the extrabulbar conjunctiva. Despite a more favorable location, BRAF-mutated tumors may be associated with more frequent distant metastasis.
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http://dx.doi.org/10.1001/jamaophthalmol.2015.3200DOI Listing
November 2015

Is thrombocytosis a valid indicator of advanced stage and high mortality of gynecological cancer?

Gynecol Oncol 2015 Nov 25;139(2):312-8. Epub 2015 Sep 25.

The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

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http://dx.doi.org/10.1016/j.ygyno.2015.09.017DOI Listing
November 2015

Increased health-care utilisation in international adoptees.

Dan Med J 2015 Aug;62(8):A5111

Department of Public Health, Section of General Practice, Unit of Women and Gender Research in Medicine, University of Copenhagen, P.O. Box 2099, 1014 Copenhagen, Denmark.

Introduction: Several studies have documented that international adoptees have an increased occurrence of health problems and contacts to the health-care system after arriving to their new country of residence. This may be explained by pre-adoption adversities, especially for the period immediately after adoption. Our study aimed to the assess health-care utilisation of international adoptees in primary and secondary care for somatic and psychiatric diagnoses in a late post-adoption period. Is there an increased use of the health-care system in this period, even when increased morbidity in the group of international adoptees is taken into consideration?

Methods: This was a Danish register-based cohort study examining health-care utilisation in a multivariable two-part model. The prevalence of selected outcomes and the quantity of use were assessed in a late (year three, four and five) post-adoption period. The cohort comprised internationally adopted children (n = 6,820), adopted between 1994 and 2005, and all non-adopted children (n = 492,374) who could be matched with the adopted children on sex, age, municipality and family constellation at the time of adoption.

Results: International adoption increased the use of all services in primary care, while in secondary care only few areas showed an increased long-term morbidity.

Conclusion: International adoptees use medical services in primary care at a higher rate than non-adoptees some years after adoption. Excess use of services in secondary care is also present, but only exists in selected areas.

Funding: none.

Trial Registration: not relevant.
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August 2015

Micronucleus frequency in Danish schoolchildren and their mothers from the DEMOCOPHES population.

Mutagenesis 2016 Jan 17;31(1):1-8. Epub 2015 Jul 17.

Laboratory of Cell Genetics), Faculty of Science and Bio-Engineering, Free University of Brussels (VUB), Pleinlaan 2, 1050 Brussel, Belgium.

Micronucleus (MN) frequency is a biomarker for early genetic effects which is often used in human biomonitoring studies. Increased frequency of micronuclei has been associated with high levels of traffic exposure. Further high MN frequency was found predictive for cancer development in several studies of adults. In the present study, the MN frequency in blood samples from the Danish participants of the European pilot project DEMOCOPHES was analysed and related to the area of residence, self-reported and calculated exposure to road traffic as well as to mercury in hair and blood concentrations of persistent organic pollutants and dioxin-like activity measured in the same participants. The MN frequency analysis was performed with the cytokinesis-block micronucleus (CBMN) assay and included 100 children and 119 mothers. We found a significant correlation between mothers and children in the levels of micronuclei in 1000 binucleated T lymphocytes (‰MNBN) and in the proliferation index. Further the levels of ‰MNBN were significantly higher in mothers compared with their children. No significant associations were found for ‰MNBN for traffic related exposure in neither children nor their mothers. In children, a 2.5 times higher micronuclei in mononuclear T lymphocytes were found in children living within 50 m of a busy road, however, this was not found in mothers or in MNBN and the effect of exposure to road traffic on MN frequency needs further investigation. No significant associations were found between MN frequencies and the other biomarkers measured in the same participants.
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http://dx.doi.org/10.1093/mutage/gev054DOI Listing
January 2016

Association of the blood eosinophil count with hematological malignancies and mortality.

Am J Hematol 2015 Mar 16;90(3):225-9. Epub 2015 Jan 16.

Department of Hematology, Roskilde University Hospital, Roskilde, Denmark; The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

Blood eosinophilia (≥0.5 × 10(9) /l) may be an early sign of hematological malignancy. We investigated associations between levels of blood eosinophils and risks of hematological malignancies and mortality in order to provide clinically derived cut-offs for referral to specialist hematology care. From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356,196 individuals with at least one differential cell count encompassing the eosinophil count during 2000-2007 and matched these laboratory data with Danish nationwide health registers. We used multivariable logistic regression to calculate odds ratios (ORs) for the 4-year incidences of hematological malignancies and mortality between the eosinophil counts and a reference count of 0.16 × 10(9) /l which was the median eosinophil count in our data. Risks of hematological malignancies and mortality increased above the median eosinophil count. At the 99th percentile, corresponding to an eosinophil count of 0.75 × 10(9) /l, risks of hematological malignancies were increased more than twofold with OR (95% C.I.) of 2.39 (1.91-2.99). Interestingly, risks reached a plateau around an eosinophil count of 1.0 × 10(9) /l. Risks also increased when the eosinophil count approached zero. Here, counts associated relatively more with acute myeloid leukemia and myelodysplastic syndromes whereas counts above 0.16 × 10(9) /l associated more with myeloproliferative neoplasms. Eosinophil counts associate with hematological malignancies and mortality even below the definition of eosinophilia. The observed plateau of risks around 1.0 × 10(9) /l is important for physicians encountering patients with eosinophilia since even mild-to-moderate eosinophilia according to traditional definitions confers maximally increased risks of subsequent/subclinical hematological malignancy.
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http://dx.doi.org/10.1002/ajh.23916DOI Listing
March 2015

The Danish contribution to the European DEMOCOPHES project: A description of cadmium, cotinine and mercury levels in Danish mother-child pairs and the perspectives of supplementary sampling and measurements.

Environ Res 2015 Aug 14;141:96-105. Epub 2014 Oct 14.

Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, Spain.

Human biomonitoring (HBM) is an important tool, increasingly used for measuring true levels of the body burdens of environmental chemicals in the general population. In Europe, a harmonized HBM program was needed to open the possibility to compare levels across borders. To explore the prospect of a harmonized European HBM project, DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) was completed in 17 European countries. The basic measurements performed in all implemented countries of DEMOCOPHES included cadmium, cotinine and phthalate metabolites in urine and mercury in hair. In the Danish participants, significant correlations between mothers and children for mercury in hair and cotinine in urine were found. Mercury in hair was further significantly associated with intake of fish and area of residence. Cadmium was positively associated with BMI in mothers and an association between cadmium and cotinine was also found. As expected high cotinine levels were found in smoking mothers. For both mercury and cadmium significantly higher concentrations were found in the mothers compared to their children. In Denmark, the DEMOCOPHES project was co-financed by the Danish ministries of health, environment and food safety. The co-financing ministries agreed to finance a number of supplementary measurements of substances of current toxicological, public and regulatory interest. This also included blood sampling from the participants. The collected urine and blood samples were analyzed for a range of other persistent and non-persistent environmental chemicals as well as two biomarkers of effect. The variety of supplementary measurements gives the researchers further information on the exposure status of the participants and creates a basis for valuable knowledge on the pattern of exposure to various chemicals.
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http://dx.doi.org/10.1016/j.envres.2014.07.028DOI Listing
August 2015

PFAS concentrations in plasma samples from Danish school children and their mothers.

Chemosphere 2015 Jun 18;129:203-9. Epub 2014 Aug 18.

Section of Environmental Health, Department of Public Health, University of Copenhagen, 1410 Copenhagen K, Denmark.

Perfluoroalkyl substances (PFASs) are accumulating in our environment and human exposure to these potentially harmful chemicals are of growing concern. In the present study, 116 children aged 6-11 and 143 mothers in two locations in Denmark donated blood samples as a supplement to their participation in the large European human biomonitoring project, DEMOCOPHES (Demonstration of a study to COordinate and Perform Human Biomonitoring on a European Scale). The blood samples were analyzed by LC-MS/MS for the concentration of six PFASs: PFOA, PFHxS, PFNA, PFDA, br-PFOS and n-PFOS. All measured compounds were above the detection limit in both mothers and children except for PFHxS in one child. There was a significant correlation between the levels in children and their mothers, indicating a family-related exposure pattern. However, we also found that the levels of PFOA, PFNA, PFDA, br-PFOS and total-PFOS were significantly higher in children compared to their mothers. This may be due to higher exposure in children through for example dust and soil, and due to the fact that children are smaller in body size and blood volume and hence have a lower storage capacity. Furthermore, we found an association between plasma levels and the age of the mothers and higher levels of plasma PFASs in mothers with low parity. There were no associations between PFAS concentrations and residential area, dietary habits of the participants or with respect to the birth order of the children. The levels are comparable to concentrations found in other Western countries.
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http://dx.doi.org/10.1016/j.chemosphere.2014.07.018DOI Listing
June 2015

Follicular lymphoma of the ocular adnexal region: a nation-based study.

Acta Ophthalmol 2015 Mar 13;93(2):184-91. Epub 2014 Aug 13.

Department of Neuroscience and Pharmacology, Eye Pathology Institute, University of Copenhagen, Copenhagen, Denmark.

Purpose: To characterize the clinicopathological features of follicular lymphoma of the ocular adnexal region.

Methods: Retrospective nation-based study of Danish patients with ocular adnexal follicular lymphoma from January 1st 1980 through December 31st 2009.

Results: Twenty-four patients with ocular adnexal follicular lymphoma were identified. Fourteen (58%) of the patients were females. The median age was 63 years (range: 42-96 years). Eleven (46%) of the patients had primary ocular adnexal lymphoma, seven (29%) had an ocular adnexal lesion in conjunction with a concurrent systemic lymphoma and six patients (25%) presented with an ocular adnexal relapse. The most frequently affected sites were the lacrimal gland (38%) and the orbit (33%). Thirteen patients (54%) presented with Ann Arbor stage IE lymphoma, four (17%) had stage IIE, two patients (8%) stage IIIE, and five patients (21%) had stage IV lymphoma. Radiotherapy was primarily used in patients with primary lymphoma and those with a stage IE/IIE relapse (82%), while stage IIIE/IV lymphomas most frequently received alkylating chemotherapy (67%). Complete remission was observed in 19 of the patients (79%), but of these 11(58%) had a relapse. The 10-year overall survival for the entire cohort was 59%. The translocation t(14;18) was detected in 16 patients (16/24, 76%). Recurrence was only observed in patients with the t(14;18) (p=0.05, log-rank).

Conclusions: Ocular adnexal follicular lymphoma is more commonly found in elderly female patients. The lacrimal gland is relatively frequently involved. Radiotherapy is the treatment of choice for localized ocular adnexal follicular lymphoma providing a favourable prognosis for majority of patients.
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http://dx.doi.org/10.1111/aos.12525DOI Listing
March 2015

PCB concentrations and dioxin-like activity in blood samples from Danish school children and their mothers living in urban and rural areas.

Basic Clin Pharmacol Toxicol 2014 Jul 14;115(1):134-44. Epub 2014 Mar 14.

Section of Environmental Health, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

Human exposure to persistent organic pollutants (POPs) is of major concern due to a diversity of adverse effects from prolonged exposure and bioaccumulation. Manufacturing of polychlorinated biphenyls (PCBs), a subgroup of POPs, has been prohibited for many decades; however, human exposure still occurs due to the persistent nature of the chemicals. The concentrations of the dioxin-like PCB congeners 105, 118 and 156 and the non-dioxin-like PCB congeners 28, 52, 101, 138, 153 and 180, p,p'-DDE, p,p'-DDT, o,p'-DDE, o,p'-DDT, HCB and β-HCH as well as the dioxin-like activity using the AhR transactivity assay were analysed in blood samples from Danish schoolchildren and their mothers in the European framework of the DEMOCOPHES/COPHES projects. The participants were selected from an urban and a rural area, respectively. The PCB concentrations and the AhR-TEQ (TCDD toxic equivalent) were significantly higher in schoolchildren living in the urban area compared with the rural, and for AhR-TEQ, a strong correlation between the mothers and children was observed. We found a significant negative correlation between BMI and PCB concentrations in the children. Finally, in the mothers, there was a positive association between age and PCB concentration. These results show that both PCBs and dioxin-like activity can be measured as biomarkers of exposure and effects in blood samples from children and women. The results indicate that people living in urban areas may be exposed to higher concentrations of PCBs, dioxins and dioxin-like chemicals, which may lead to a greater risk of adverse effects for urban populations.
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http://dx.doi.org/10.1111/bcpt.12214DOI Listing
July 2014

MicroRNA expression analysis and Multiplex ligation-dependent probe amplification in metastatic and non-metastatic uveal melanoma.

Acta Ophthalmol 2014 Sep 24;92(6):541-9. Epub 2013 Dec 24.

Eye Pathology Institute, University of Copenhagen, Copenhagen, Denmark.

Purpose: To determine the association of microRNA expression and chromosomal changes with metastasis and survival in uveal melanoma (UM).

Methods: Thirty-six patients with UM were selected based on the metastatic status, and clinicopathological data were collected. Multiplex ligation-dependent probe amplification (MLPA) was used to identify chromosomal changes. Chromosomal changes and clinicopathological data were correlated with survival and metastasis. The microRNA expression was analysed in 26 of the 36 archived UM samples. Unsupervised analysis, differential expression analysis and Cox regression analysis were performed to determine the association with metastasis and survival.

Results: Metastasis and metastatic death occurred in 20 patients, two patients died of other causes and one patient of unknown causes. A significant association between increasing size category (p = 0.002, log-rank), extraocular extension (p = 0.001), chromosome 3 loss (p = 0.033) and 1p loss (p = 0.030) and development of metastases was observed. Tumour, node, metastasis (TNM) staging showed a significant association with survival (p < 0.0001, log-rank). Adjusting for gender and age TNM size category T4 (p = 0.016, Cox regression analysis), mixed (p = 0.029) and epithelioid (p = 0.0058) cell types, chromosome 3 loss (p = 0.014) and 8q gain (p = 0.010) were significant prognosticators for a poor survival. Hierarchical clustering divided the UM into three groups based on microRNA expression. The clusters showed no association with clinical or histopathological features, TNM staging, metastasis or survival. Differential expression analysis did not reveal microRNAs related to metastasis or survival.

Conclusions: The prognostic significance of chromosome 3 loss and 8q gain identified by MLPA analysis was confirmed in archived UM samples. The value of microRNA expression as a predictor of metastasis and survival in UM could not be confirmed.
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http://dx.doi.org/10.1111/aos.12322DOI Listing
September 2014

Family matters: parental-acquired brain injury and child functioning.

NeuroRehabilitation 2013 ;32(1):59-68

Department of Psychology, University of Copenhagen, DK-1353 Copenhagen, Denmark.

Objectives: To relate illness related to and family factors to emotional and behavioural problems in school-age children (7-14 years old) of parents with acquired brain injury and their healthy spouses.

Participants, Materials/methods: Members of 35 families in which a parent had been diagnosed with acquired brain injury participated. Family and brain injury characteristics were reported by the ill and healthy parents. Children self-reported post-traumatic stress symptoms (PSS) using the Child Impact of Events revised (CRIES). Emotional and behavioural problems among the children were also identified by the parents using the Achenbach's Child Behaviour Checklist (CBCL).

Results: The family stress variables relating to the healthy spouse in all six comparisons were significant (p <= 0.05) or nearly so (p = 0.07) in each case showing higher scores for spouses to be associated with higher CRIES and CBCL total scores for the children. For the adjusted associations, we again found the family stress variables in the healthy spouse to be related to the risk of emotional and behavioral problems in the children.

Conclusions: The present results suggest that in ABI families, the children's emotional functioning depends upon family factors and primarily on the level of parental stress in the healthy parent.
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http://dx.doi.org/10.3233/NRE-130823DOI Listing
August 2013

Diabetic foot disease: impact of ulcer location on ulcer healing.

Diabetes Metab Res Rev 2013 Jul;29(5):377-83

Department of Internal Medicine, Subdivision of Endocrinology, Maastricht University Medical Centre, P. Debeyelaan 25, Maastricht, the Netherlands.

Background: Healing of heel ulcers in patients with diabetes is considered to be poor, but there is relatively little information on the influence of ulcer location on ulcer healing.

Methods: The influence of ulcer location on time to healing of diabetic foot ulcers was analysed by multivariate Cox regression analysis for 1000 patients included in the Eurodiale study, a prospective cohort study of patients with diabetic foot disease.

Results: Median time to healing was 147 days for toe ulcers [(95% confidence interval (CI) 135-159 days)], 188 days for midfoot ulcers (95% CI 158-218 days) and 237 days for heel ulcers (95% CI 205-269 days) (p < 0.01). The median time to healing for plantar ulcers was 172 days (95% CI 157-187 days) and 155 days (95% CI 138-172 days) for nonplantar ulcers (p = 0.71). In multivariate Cox regression analysis, the hazard ratio for ulcer healing for midfoot and heel ulcers compared with toe ulcers was 0.77 (95% CI 0.64-0.92) and 0.62 (95% CI 0.47-0.83), respectively; the hazard ratio for ulcer healing for plantar versus nonplantar ulcers was 1 (95% CI 0.84-1.19). Other factors significantly influencing time to healing were the duration of diabetes, ulcer duration, the presence of heart failure and the presence of peripheral arterial disease.

Conclusions: Time to ulcer healing increased progressively from toe to midfoot to heel, but did not differ between plantar and nonplantar ulcers. Our data also indicate that risk factors for longer time to healing differ from factors that affect the ultimate number of ulcers that heal (healing rate).
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http://dx.doi.org/10.1002/dmrr.2400DOI Listing
July 2013

Diffuse large B-cell lymphoma of the ocular adnexal region: a nation-based study.

Acta Ophthalmol 2013 Mar 2;91(2):163-9. Epub 2012 May 2.

Department of Neuroscience and Pharmacology, Eye Pathology Institute, University of Copenhagen, Denmark.

Purpose: To characterize the clinicopathological features of diffuse large B-cell lymphoma (DLBCL) of the ocular adnexal region.

Methods: The present series of orbital and adnexal DLBCLs were found by searching the Danish Registry of Pathology between 1980 and 2009. Histological specimens were re-evaluated using a panel of monoclonal antibodies. Clinical files from all patients with confirmed DLBCL were collected.

Results: A total of 34 patients with DLBCL of the ocular adnexal region were identified. Eighteen of the patients were men. The patients had a median age of 78 years (range 35-97 years). Ninety-seven per cent of the patients had unilateral ocular adnexal region involvement, and the orbit (76%) was the most frequently affected site. Nineteen patients (56%) presented with Stage I lymphoma. Of these, 18 were diagnosed with primary lymphoma. Four patients (12%) had Stage II, one patient (3%) had Stage III and ten patients (29%) presented with Stage IV lymphoma. The 5-year overall survival (OS) rate for the whole study group was 20%. The patients with Stage I lymphoma had a significantly better 5-year OS rate (28%) than patients in Stage II-IV (5-year OS rate, 9%). In Cox regression analysis, concordant bone marrow involvement and the International Prognostic Index (IPI) score were prognostic factors for OS.

Conclusions: Diffuse large B-cell lymphoma of the ocular adnexal region is mainly prevalent in elderly patients. Most patients had unilateral orbital involvement. The overall prognosis is poor. Concordant bone marrow involvement and the IPI score were independent prognostic factors for mortality.
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http://dx.doi.org/10.1111/j.1755-3768.2011.02337.xDOI Listing
March 2013

Short-term practice effects and variability in cognitive testing in a healthy elderly population.

Exp Gerontol 2012 Jun 26;47(6):432-6. Epub 2012 Mar 26.

Section of Surgical Pathophysiology, Rigshospitalet, University of Copenhagen, Denmark.

Background: Cognitive decline in the elderly is a subject of intense focus. However, there is a lack of consensus regarding definition of significant decline in connection with repeated testing and the interpretation of cognitive tests results must take into account the practice effect and variability in test performance. The aim of this study was to collect cognitive test results with repeated testing in an elderly healthy population.

Methods: 161 healthy controls ≥60 years were included. Cognitive testing was performed upon entry into the study, at 1 week and 3 months. Practice effect was evaluated on 7 neuropsychological measures and reference values of clinically important changes were calculated according to z-scores above 1.96.

Results: Test scores improved significantly (p<0.05) in 2 of 7 measures between baseline and 2nd test and in 6 of 7 measures between baseline and 3rd test session. No significant correlation was found between magnitude of practice effect and age or educational status.

Conclusion: Practice effect and variability in cognitive testing in the elderly are important to consider when evaluating changes in cognitive performance over a short period of time.
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http://dx.doi.org/10.1016/j.exger.2012.03.011DOI Listing
June 2012

Malignant lymphoma of the lacrimal gland: a nation-based study.

Arch Ophthalmol 2011 Oct;129(10):1275-80

Department of Neuroscience and Pharmacology, Section of Eye Pathology, University of Copenhagen, Copenhagen, Denmark.

Objective: To characterize the clinicopathologic features of lacrimal gland lymphoma.

Methods: All cases of lacrimal gland lymphoma from January 1, 1975, through December 31, 2009, were retrieved from The Danish Registry of Pathology. Histologic specimens were reevaluated using a panel of monoclonal antibodies. Clinical files from all patients with confirmed lymphoma were collected.

Results: Twenty-seven patients with lacrimal gland lymphoma were identified. Eight of the patients were men and 19 were women; the median (range) age was 69 (43-87) years. The distribution of lymphoma subtypes was as follows: extranodal marginal zone lymphoma, 10 (37%); follicular lymphoma, 5 (19%); diffuse large B-cell lymphoma, 4 (15%); mantle cell lymphoma, 3 (11%); chronic lymphocytic leukemia/small lymphatic lymphoma, 2 (7%); and unclassified B-cell lymphoma, 3 (11%). Twenty-two patients (81%) had stage I or II lymphoma, 1 patient (4%) had stage III lymphoma, and 4 patients (15%) had stage IV lymphoma. Patients with stage I or II lymphoma were treated with radiotherapy (15 [67%]), chemotherapy (3 [14%]), chemotherapy plus radiotherapy (1 [5%]), and surgery (3 [14%]). Patients presenting with stage III or IV lymphoma were treated with chemotherapy alone. Complete remission was observed in 23 of the patients (85%), although 12 (44%) of these had a relapse, independent of subtype, stage, or treatment. The 5-year overall survival was 70%.

Conclusions: Malignant lymphoma of the lacrimal gland is relatively rare and is mostly prevalent in elderly women. The distribution of lacrimal gland lymphoma subtypes resembles that of lymphoma subtypes of the salivary glands. The majority of lacrimal gland lymphomas are low grade, and the prognosis is relatively good.
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http://dx.doi.org/10.1001/archophthalmol.2011.270DOI Listing
October 2011

Similar cardiovascular risk factor profile in screen-detected and known type 2 diabetic subjects.

Scand J Prim Health Care 2011 Jun 28;29(2):85-91. Epub 2011 Mar 28.

Ørum Health Centre, Tjele.

OBJECTIVE. To compare the cardiovascular disease (CVD) risk factor profile in subjects with screen-detected type 2 diabetes (SDM) and subjects with known type 2 diabetes (KDM). DESIGN. Population-based, cross-sectional survey. SETTING AND SUBJECTS. In a single, semi-rural general practice 2082 subjects were between 20 and 69 years. Of those, 1970 subjects were invited, and a total of 1374 (69.7%) subjects were examined by blood tests, anthropometric measures, and self-administered questionnaires. RESULTS. Before the survey 19 persons were known to have type 2 diabetes. The screening revealed another 31 individuals with type 2 diabetes, diagnosed according to the 1999 World Health Organization criteria. Age, levels of blood pressure, BMI, and dyslipidaemia, and markers of haemostasis and inflammation were comparable in the two groups. Median age in the KDM group was 58 vs. 57 years in the SDM group, p = 0.82, 79% were male vs. 61%, p = 0.23. In both groups 74% had blood pressure ≥ 130/85 mmHg, p = 1.00. In both groups 90% had BMI ≥ 25, p = 1.00, and about half in both groups had BMI ≥ 30, p = 0.56. In the KDM group 63% had dyslipidaemia (low HDL cholesterol or elevated triglycerides) vs. 80% in the SDM group, p = 0.32. Median levels of plasminogen-activator-inhibitor (PAI-1), tissue plasminogen activator (t-PA), as well as fibrinogen and C-reactive protein (CRP) were without statistically significant differences in the two groups, p > 0.1. In contrast, in markers of glycaemic regulation statistically significant differences were found between groups. Median HbA1 was 8.0 vs. 6.5, p < 0.001. Median fasting whole blood glucose level was 8.8 mmol/L vs. 6.3 mmol/L, p < 0.001, and glucose at two hours during OGTT was 16.9 mmol/L vs. 11.2 mmol/L, p < 0.001. Median fasting serum insulin level was 52 pmol/L vs. 80 pmol/L, p = 0.039 and at two hours 127 pmol/L vs. 479 pmol/L, p < 0.001. CONCLUSIONS. The CVD risk-factor profile of SDM patients was similar to the expected adverse profile of patients with KDM. This indicates an already increased risk of cardiovascular disease in diabetic patients before the diabetes becomes clinically manifest, supporting the need for early diagnosis.
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http://dx.doi.org/10.3109/02813432.2011.565164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347946PMC
June 2011

Apolipoprotein E genotype and cognitive dysfunction after noncardiac surgery.

Anesthesiology 2004 Oct;101(4):855-61

Department of Anesthesia 4132, Center of Head and Orthopedics, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.

Background: Apolipoprotein E is important in recovery after neuronal damage. The epsilon4 allele of the apolipoprotein E gene has been shown as a risk factor for Alzheimer disease, poor outcome after cerebral injury, and accelerated cognitive decline with normal aging. The authors hypothesized that patients with the epsilon4 allele would have an increased risk of postoperative cognitive dysfunction (POCD) after noncardiac surgery.

Methods: In a multicenter study, a total of 976 patients aged 40 yr and older undergoing noncardiac surgery were tested preoperatively and 1 week and 3 months after surgery with a neuropsychological test battery comprising seven subtests. POCD was defined as a decline in test performance of more than 2 SD from the expected. Apolipoprotein E genotypes were determined by blood sample analysis at a central laboratory. Multivariate logistic regression analysis with POCD as the dependent variable assessed presence of the epsilon4 allele (yes/no) and other possible risk factors.

Results: The epsilon4 allele was found in 272 patients. One week after surgery, the incidence of POCD was 11.7% in patients with the epsilon4 allele and 9.9% in patients without the epsilon4 allele (P = 0.41). Three months later, POCD was found in 10.3% of patients with the epsilon4 allele and in 8.4% of patients without the epsilon4 allele (P = 0.40). Multivariate logistic regression analysis did not identify the epsilon4 allele as a risk factor at 1 week (P = 0.33) or 3 months (P = 0.57).

Conclusions: The authors were unable to show a significant association between apolipoprotein E genotype and POCD, but statistical power was limited because of a lower incidence of POCD than expected.
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http://dx.doi.org/10.1097/00000542-200410000-00009DOI Listing
October 2004

Postoperative cognitive dysfunction in middle-aged patients.

Anesthesiology 2002 Jun;96(6):1351-7

Department of Anaesthesia, Hope Hospital, Salford, United Kingdom.

Background: Postoperative cognitive dysfunction (POCD) after noncardiac surgery is strongly associated with increasing age in elderly patients; middle-aged patients (aged 40-60 yr) may be expected to have a lower incidence, although subjective complaints are frequent.

Methods: The authors compared the changes in neuropsychological test results at 1 week and 3 months in patients aged 40-60 yr, using a battery of neuropsychological tests, with those of age-matched control subjects using Z-score analysis. They assessed risk factors and associations of POCD with measures of subjective cognitive function, depression, and activities of daily living.

Results: At 7 days, cognitive dysfunction as defined was present in 19.2% (confidence interval [CI], 15.7-23.1) of the patients and in 4.0% (CI, 1.6-8.0) of control subjects (P < 0.001). After 3 months, the incidence was 6.2% (CI, 4.1-8.9) in patients and 4.1% (CI, 1.7-8.4) in control subjects (not significant). POCD at 7 days was associated with supplementary epidural analgesia and reported avoidance of alcohol consumption. At 3 months, 29% of patients had subjective symptoms of POCD, and this finding was associated with depression. Early POCD was associated with reports of lower activity scores at 3 months.

Conclusions: Postoperative cognitive dysfunction occurs frequently but resolves by 3 months after surgery. It may be associated with decreased activity during this period. Subjective report overestimates the incidence of POCD. Patients may be helped by recognition that the problem is genuine and reassured that it is likely to be transient.
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http://dx.doi.org/10.1097/00000542-200206000-00014DOI Listing
June 2002
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