Næstved Sygehus

Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness. Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated. Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated? Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.

BACKGROUND: Fast and accurate staging is essential for choosing treatment for non-small-cell lung cancer (NSCLC). The purpose of this randomized study was to evaluate the clinical effect of combined positron-emission tomography and computed tomography (PET-CT) on preoperative staging of NSCLC. METHODS: We randomly assigned patients who were referred for preoperative staging of NSCLC to either conventional staging plus PET-CT or conventional staging alone. Patients were followed until death or for at least 12 months. The primary end point was the number of futile thoracotomies, defined as any one of the following: a thoracotomy with the finding of pathologically confirmed mediastinal lymph-node involvement (stage IIIA [N2]), stage IIIB or stage IV disease, or a benign lung lesion; an exploratory thoracotomy; or a thoracotomy in a patient who had recurrent disease or death from any cause within 1 year after randomization. RESULTS: From January 2002 through February 2007, we randomly assigned 98 patients to the PET-CT group and 91 to the conventional-staging group. Mediastinoscopy was performed in 94% of the patients. After PET-CT, 38 patients were classified as having inoperable NSCLC, and after conventional staging, 18 patients were classified thus. Sixty patients in the PET-CT group and 73 in the conventional-staging group underwent thoracotomy (P=0.004). Among these thoracotomies, 21 in the PET-CT group and 38 in the conventional-staging group were futile (P=0.05). The number of justified thoracotomies and survival were similar in the two groups. CONCLUSIONS: The use of PET-CT for preoperative staging of NSCLC reduced both the total number of thoracotomies and the number of futile thoracotomies but did not affect overall mortality. (ClinicalTrials.gov number, NCT00867412.)

OBJECTIVES: Immune diseases such as asthma, allergy, inflammatory bowel disease, and type 1 diabetes have shown a parallel increase in prevalence during recent decades in westernized countries. The rate of cesarean delivery has also increased in this period and has been associated with the development of some of these diseases. METHODS: Mature children born by cesarean delivery were analyzed for risk of hospital contact for chronic immune diseases recorded in the Danish national registries in the 35-year period 1977-2012. Two million term children participated in the primary analysis. We studied childhood diseases with a suspected relation to a deviant immune-maturation and a debut at young age. The effect of cesarean delivery on childhood disease incidences were estimated by means of confounder-adjusted incidence rate ratios with 95% confidence intervals obtained in Poisson regression analyses. RESULTS: Children delivered by cesarean delivery had significantly increased risk of asthma, systemic connective tissue disorders, juvenile arthritis, inflammatory bowel disease, immune deficiencies, and leukemia. No associations were found between cesarean delivery and type 1 diabetes, psoriasis, or celiac disease. CONCLUSIONS: Cesarean delivery exemplifies a shared environmental risk factor in early life associating with several chronic immune diseases. Understanding commonalities in the underlying mechanisms behind chronic diseases may give novel insight into their origin and allow prevention.

BACKGROUND: Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contributing factor to the increasing prevalence of wheezing disorders. We assessed the effect of supplementation with n-3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring. METHODS: ) cohort and were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children's lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization. RESULTS: A total of 695 children were included in the trial, and 95.5% completed the 3-year, double-blind follow-up period. The risk of persistent wheeze or asthma in the treatment group was 16.9%, versus 23.7% in the control group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.97; P=0.035), corresponding to a relative reduction of 30.7%. Prespecified subgroup analyses suggested that the effect was strongest in the children of women whose blood levels of eicosapentaenoic acid and docosahexaenoic acid were in the lowest third of the trial population at randomization: 17.5% versus 34.1% (hazard ratio, 0.46; 95% CI, 0.25 to 0.83; P=0.011). Analyses of secondary end points showed that supplementation with n-3 LCPUFA was associated with a reduced risk of infections of the lower respiratory tract (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.033), but there was no statistically significant association between supplementation and asthma exacerbations, eczema, or allergic sensitization. CONCLUSIONS: Supplementation with n-3 LCPUFA in the third trimester of pregnancy reduced the absolute risk of persistent wheeze or asthma and infections of the lower respiratory tract in offspring by approximately 7 percentage points, or one third. (Funded by the Lundbeck Foundation and others; ClinicalTrials.gov number, NCT00798226 .).

IMPORTANCE: Biomarkers for the early diagnosis of patients with pancreatic cancer are needed to improve prognosis. OBJECTIVES: To describe differences in microRNA expression in whole blood between patients with pancreatic cancer, chronic pancreatitis, and healthy participants and to identify panels of microRNAs for use in diagnosis of pancreatic cancer compared with the cancer antigen 19-9 (CA19-9). DESIGN, SETTING, AND PARTICIPANTS: A case-control study that included 409 patients with pancreatic cancer and 25 with chronic pancreatitis who had been included prospectively in the Danish BIOPAC (Biomarkers in Patients with Pancreatic Cancer) study (July 2008-October 2012) plus 312 blood donors as healthy participants. The microRNA expressions in pretreatment whole blood RNA samples were collected and analyzed in 3 randomly determined subcohorts: discovery cohort (143 patients with pancreatic cancer, 18 patients with chronic pancreatitis, and 69 healthy participants), training cohort (180 patients with pancreatic cancer, 1 patient with chronic pancreatitis, and 199 healthy participants), and validation cohort (86 patients with pancreatic cancer, 7 patients with chronic pancreatitis, and 44 healthy participants); 754 microRNAs were screened in the discovery cohort and 38 microRNAs in the training cohort and 13 microRNAs in the validation cohort. MAIN OUTCOMES AND MEASURES: Identification of microRNA panels (classifiers) for diagnosing pancreatic cancer. RESULTS: The discovery cohort demonstrated that 38 microRNAs in whole blood were significantly dysregulated in patients with pancreatic cancer compared with controls. These microRNAs were tested in the training cohort and 2 diagnostic panels were constructed comprising 4 microRNAs in index I (miR-145, miR-150, miR-223, miR-636) and 10 in index II (miR-26b, miR-34a, miR-122, miR-126*, miR-145, miR-150, miR-223, miR-505, miR-636, miR-885.5p). The test characteristics for the training cohort were index I area under the curve (AUC) of 0.86 (95% CI, 0.82-0.90), sensitivity of 0.85 (95% CI, 0.79-0.90), and specificity of 0.64 (95% CI, 0.57-0.71); index II AUC of 0.93 (95% CI, 0.90-0.96), sensitivity of 0.85 (95% CI, 0.79-0.90), and specificity of 0.85 (95% CI, 0.80-0.85); and CA19-9 AUC of 0.90 (95% CI, 0.87-0.94), sensitivity of 0.86 (95% CI, 0.80-0.90), and specificity of 0.99 (95% CI, 0.96-1.00). Performances were strengthened in the validation cohort by combining panels and CA19-9 (index I AUC of 0.94 [95% CI, 0.90-0.98] and index II AUC of 0.93 [95% CI, 0.89-0.97]). Compared with CA19-9 alone, the AUC for the combination of index I and CA19-9 was significantly higher (P = .01). The performance of the panels in patients with stage IA-IIB pancreatic cancer was index I AUC of 0.80 (95% CI, 0.73-0.87); index I and CA19-9 AUC of 0.83 (95% CI, 0.76-0.90); index II AUC of 0.91 (95% CI, 0.87-0.94); and index II and CA19-9 AUC of 0.91 (95% CI, 0.86-0.95). CONCLUSIONS AND RELEVANCE: This study identified 2 diagnostic panels based on microRNA expression in whole blood with the potential to distinguish patients with pancreatic cancer from healthy controls. Further research is necessary to understand whether these have clinical implications for early detection of pancreatic cancer and how much this information adds to serum CA19-9.

UNLABELLED: The study was conducted to determine age and sex stratified normal values for 24-h ambulatory blood pressure. A sample of 352 healthy subjects (all white) were randomly selected from the community register and stratified by sex and age groups in decades from 20 to 79 years of age. Persons with a history of hypertension, cerebral apoplexy, diabetes, myocardial or renal disease, and who were taking blood pressure-influencing medication were excluded. Ambulatory blood pressure was recorded over 24 h, with measurements taken every 15 min from 07:00 to 22:59, and every 30 min from 23:00 to 6:59. Systolic blood pressure increased only slightly with age and was significantly higher in men than in women. The diastolic blood pressure increased only slightly with age in both sexes until the 50 to 59 years age group and declined thereafter. The diastolic blood pressure was not different for the two sexes. Both systolic and diastolic blood pressure were approximately 15% lower during the night regardless of age or sex. Ambulatory blood pressure during the daytime was on an average of 5 mm Hg lower than office blood pressure, but the mean difference between the two measurements increased with age. The variability of the difference also increased with age. IN CONCLUSION: Normal values for ambulatory blood pressure are presented in a randomly selected age- and gender-stratified population. Differences between office blood pressure and ambulatory blood pressure increased with age suggesting that the previously observed higher blood pressure seen in the elderly partly might be explained by a greater impact of white coat hypertension in older people.

BACKGROUND: Adjuvant chemotherapy is established routine therapy for colon cancer (CC) patients with radically resected stage III and 'high-risk' stage II disease. The decision on recommending adjuvant chemotherapy, however, is based on data from older patient cohorts not reflecting improvements in pre-operative staging, surgery, and pathological examination. The aim is to review the current risk of recurrence in stage II and III patients and second, to estimate the relative importance of routinely assessed clinico-pathological variables. METHODS: The PubMed/MEDLINE and the Cochrane databases were systematically searched for randomized controlled studies and observational studies published after 1 January 2005 with patients included after January 1995 on prognosis in surgically treated stage II and III CC patients. RESULTS: Of 2596 studies identified, 37 met the inclusion criteria and 25 provided data for meta-analysis. The total patient sample size in the 25 studies reporting either disease-free (DFS) or recurrence-free survival was 15 559 in stage II and 18 425 in stage III. Five-year DFS for stage II patients operated without subsequent adjuvant chemotherapy was 81.4% [95% confidence interval (CI) 75.4-87.4; in studies with good/very good quality of reporting 82.7%, (95% CI 80.8-84.6)]. For stage II patients treated with adjuvant chemotherapy, the five-year DFS was 79.3% (95% CI 75.6-83.1). For stage III patients without chemotherapy, five-year DFS was 49.0% (95% CI 23.2-74.8) and for those treated with adjuvant chemotherapy, 63.6% (95% CI 59.3-67.9). The prognostic impact of commonly investigated clinico-pathological parameters, (pT-stage, pN-stage, differentiation, number of lymph nodes studied, MMR-status, and emergency surgery) were confirmed. CONCLUSIONS: In this meta-analysis, studies with good quality of reporting show a five-year DFS of 82.7% for stage II CC without adjuvant chemotherapy, whereas the five-year DFS is 63.8% for stage III CC with adjuvant chemotherapy. Due to insufficient reporting on treatment quality the presented DFS is likely an under-estimation of what is achieved at high-quality centers today.

A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.

Microglia and infiltrating leukocytes are considered major producers of tumor necrosis factor (TNF), which is a crucial player in cerebral ischemia and brain inflammation. We have identified a neuroprotective role for microglial-derived TNF in cerebral ischemia in mice. We show that cortical infarction and behavioral deficit are significantly exacerbated in TNF-knock-out (KO) mice compared with wild-type mice. By using in situ hybridization, immunohistochemistry, and green fluorescent protein bone marrow (BM)-chimeric mice, TNF was shown to be produced by microglia and infiltrating leukocytes. Additional analysis demonstrating that BM-chimeric TNF-KO mice grafted with wild-type BM cells developed larger infarcts than BM-chimeric wild-type mice grafted with TNF-KO BM cells provided evidence that the neuroprotective effect of TNF was attributable to microglial- not leukocyte-derived TNF. In addition, observation of increased infarction in TNF-p55 receptor (TNF-p55R)-KO mice compared with TNF-p75R and wild-type mice suggested that microglial-derived TNF exerts neuroprotective effects through TNF-p55R. We finally report that TNF deficiency is associated with reduced microglial population size and Toll-like receptor 2 expression in unmanipulated brain, which might also influence the neuronal response to injury. Our results identify microglia and microglial-derived TNF as playing a key role in determining the survival of endangered neurons in cerebral ischemia.

<h3>Importance</h3> Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring, but the preventive effect of vitamin D supplementation to pregnant women is unknown. <h3>Objective</h3> To determine whether supplementation of vitamin D₃during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring. <h3>Design, Setting, and Participants</h3> A double-blind, single-center, randomized clinical trial conducted within the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort. Enrollment began March 2009 with a goal of 708 participants, but due to delayed ethical approval, only 623 women were recruited at 24 weeks of pregnancy. Follow-up of the children (N = 581) was completed when the youngest child reached age 3 years in March 2014. <h3>Interventions</h3> Vitamin D₃(2400 IU/d; n = 315) or matching placebo tablets (n = 308) from pregnancy week 24 to 1 week postpartum. All women received 400 IU/d of vitamin D₃as part of usual pregnancy care. <h3>Main Outcomes and Measures</h3> Age at onset of persistent wheeze in the first 3 years of life. Secondary outcomes included number of episodes of troublesome lung symptoms, asthma, respiratory tract infections, and neonatal airway immunology. Adverse events were assessed. <h3>Results</h3> Of the 581 children, persistent wheeze was diagnosed during the first 3 years of life in 47 children (16%) in the vitamin D₃group and 57 children (20%) in the control group . Vitamin D₃supplementation was not associated with the risk of persistent wheeze (hazard ratio [HR], 0.76 [95% CI, 0.52-1.12],<i>P</i> = .16), but the number of episodes of troublesome lung symptoms was reduced (mean episodes [95% CI]: 5.9 [5.2-6.6] for the vitamin D₃group vs 7.2 [6.4-8.1] for the control group; incidence risk ratio [IRR], 0.83 [95% CI, 0.71-0.97],<i>P</i> = .02), and the airway immune profile was up-regulated (principal component analysis,<i>P</i> = .04). There was no effect on additional end points, including asthma (32 children [12%] in the vitamin D₃group vs 47 children [14%] in the control group; odds ratio, 0.82 [95% CI, 0.50-1.36],<i>P</i> = .45), and respiratory tract infections (upper, mean [95% CI]: 5.2 [4.8-5.5] in the vitamin D₃group vs 5.3 [4.9-5.6] in the control group, IRR, 0.99 [95% CI, 0.90-1.09],<i>P</i> = .84; lower: 94 children [32%] in the vitamin D₃group vs 95 children [33%] in the control group, HR, 0.96 [95% CI, 0.72-1.27],<i>P</i> = .76). Intrauterine death was observed in 1 fetus (0%) in the vitamin D₃group vs 3 fetuses (1%) in the control group and congenital malformations in 17 neonates (5%) in the vitamin D₃group vs 23 neonates (8%) in the control group. <h3>Conclusions and Relevance</h3> The use of 2800 IU/d of vitamin D₃during the third trimester of pregnancy compared with 400 IU/d did not result in a statistically significant reduced risk of persistent wheeze in the offspring through age 3 years. However, interpretation of the study is limited by a wide CI that includes a clinically important protective effect. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00856947

TOPIC: We performed a systematic review and meta-analysis to evaluate the benefit and harms associated with implantation of toric intraocular lenses (IOLs) during cataract surgery. Outcomes were postoperative uncorrected distance visual acuity (UCDVA) and distance spectacle independence. Harms were evaluated as surgical complications and residual astigmatism. CLINICAL RELEVANCE: Postoperative astigmatism is an important cause of suboptimal UCDVA and need for distance spectacles. Toric IOLs may correct for preexisting corneal astigmatism at the time of surgery. METHODS: We performed a systematic literature search in the Embase, PubMed, and CENTRAL databases within the Cochrane Library. We included randomized clinical trials (RCTs) if they compared toric with non-toric IOL implantation (± relaxing incision) in patients with regular corneal astigmatism and age-related cataracts. We assessed the risk of bias using the Cochrane Risk of Bias tool. We assessed the quality of evidence across studies using the GRADE profiler software (available at: www.gradeworkinggroup.org). RESULTS: We included 13 RCTs with 707 eyes randomized to toric IOLs and 706 eyes randomized to non-toric IOLs; 225 eyes had a relaxing incision. We found high-quality evidence that UCDVA was better in the toric IOL group (logarithm of the minimum angle of resolution [logMAR] mean difference, -0.07; 95% confidence interval [CI], -0.10 to -0.04) and provided greater spectacle independence (risk ratio [RR], 0.51; 95% CI, 0.36-0.71) and moderate quality evidence that toric IOL implantation was not associated with an increased risk of complications (RR, 1.73; 95% CI, 0.60-5.04). Residual astigmatism was lower in the toric IOL group than in the non-toric IOL plus relaxing incision group (mean difference, 0.37 diopter [D]; 95% CI, -0.55 to -0.19). CONCLUSIONS: We found that toric IOLs provided better UCDVA, greater spectacle independence, and lower amounts of residual astigmatism than non-toric IOLs even when relaxing incisions were used.

Anemia is a major global health problem, especially in developing countries. This fundamental health issue still has not been solved and continues to exist affecting the health, quality of life, and working capacity in billions of people all over the world. This paper gives a review on the prevalence and major causes of anemia seen on a global scale. Most cases of anemia are due to iron deficiency, which often work in symphony with folate deficiency and/or vitamin B12 deficiency as well as with infections. More efforts should be dedicated to tackle this massive problem--we have the tools, and we know the ways. Iron fortification of appropriate food items combined with iron supplements in specific population groups has proven to be efficient. Initially, the efforts should be centered on the specific risk groups for iron deficiency anemia, i.e., young children, adolescent females, women of reproductive age, as well as pregnant women and postpartum lactating mothers.

Electroporation of cells with short, high-voltage pulses causes a transient permeabilization of cell membranes that permits passage of otherwise nonpermeating ions and molecules. In this study, we illustrate how electroporation with isotonic calcium can achieve highly effective cancer cell kill in vivo. Calcium electroporation elicited dramatic antitumor responses in which 89% of treated tumors were eliminated. Histologic analyses indicated complete tumor necrosis. Mechanistically, calcium electroporation caused acute ATP depletion likely due to a combination of increased cellular use of ATP, decreased production of ATP due to effects on the mitochondria, as well as loss of ATP through the permeabilized cell membrane. Taken together, our findings offer a preclinical proof of concept for the use of electroporation to load cancer cells with calcium as an efficient anticancer treatment. Electroporation equipment is already used clinically to enhance the delivery of chemotherapy to superficial tumors, with trials on internal tumors in progress, enabling the introduction of calcium electroporation to clinical use. Moreover, the safety profile, availability, and low cost of calcium facilitate access to this technology for many cancer patients in developed and developing countries.

BACKGROUND: Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs. METHODS: Guidelines for defining the HGPs were established by a large international team. To assess the validity of these guidelines, 12 independent observers scored a set of 159 liver metastases and interobserver variability was measured. In an independent cohort of 374 patients with colorectal liver metastases (CRCLM), the impact of HGPs on overall survival after hepatectomy was determined. RESULTS: Good-to-excellent correlations (intraclass correlation coefficient >0.5) with the gold standard were obtained for the assessment of the replacement HGP and desmoplastic HGP. Overall survival was significantly superior in the desmoplastic HGP subgroup compared with the replacement or pushing HGP subgroup (P=0.006). CONCLUSIONS: The current guidelines allow for reproducible determination of liver metastasis HGPs. As HGPs impact overall survival after surgery for CRCLM, they may serve as a novel biomarker for individualised therapies.

IMPORTANCE An association between the metabolic syndrome (MetS) and chronic inflammatory diseases, such as psoriasis or rheumatoid arthritis, has been suggested.Hidradenitis suppurativa (HS), a more localized chronic inflammation of the skin, has been speculated to have a similar association. Hidradenitis suppurativa is a substantial burden for the individual and a socioeconomic burden globally. Information about the burden of possible comorbidities is scarce.OBJECTIVE To investigate the possibility of an association between HS and MetS.DESIGN, SETTING, AND PARTICIPANTS Cross-sectional population- and hospital-based study of HS and MetS.We identified 32 patients with physician-verified HS from the outpatient clinic at the Department of Dermatology, Roskilde Hospital, and 326 patients with HS and 14 851 individuals without HS from the general population. Individuals with HS were younger,predominantly female, and more often smokers compared with the non-HS group.EXPOSURE Hidradenitis suppurativa.MAIN OUTCOMES AND MEASURES Metabolic syndrome and its components of diabetes mellitus, hypertension, dyslipidemia, and obesity.RESULTS When compared with the non-HS group, the odds ratios (ORs) for the hospital HS and population HS groups were 3.89 (95%CI, 1.90-7.98) and 2.08 (95%CI, 1.61-2.69),respectively, for MetS; 5.74 (95%CI, 1.91-17.24) and 2.44 (95%CI, 1.55-3.83), respectively, for diabetes mellitus; 6.38 (95%CI, 2.99-13.62) and 2.56 (95%CI, 2.00-3.28), respectively, for general obesity; and 3.62 (95%CI, 1.73-7.60) and 2.24 (95%CI, 1.78-2.82), respectively, for abdominal obesity. With regard to dyslipidemia, significant results were found for decreased levels of high-density lipoprotein cholesterol, with ORs of 2.97 (95%CI, 1.45-6.08) and 1.94(95%CI, 1.52-2.48) for the hospital HS and general population HS groups, respectively, when compared with the non-HS group. With regard to increased triglyceride levels, only the result for the population HS group compared with the non-HS group was significant, with an OR of1.49 (95%CI, 1.18-1.87). The OR for hypertension, which was only significant for the hospital HS group compared with the non-HS group, was 2.14 (95%CI, 1.01-4.53). Obesity and inflammation acted as possible confounders. The ORs were higher for the hospital HS group compared with the population HS group. The association between HS and MetS was not influenced by the degree of HS severity.CONCLUSIONS AND RELEVANCE As with more systemic inflammatory diseases, HS appears to be associated with MetS, indicating substantial comorbidities. Because this study is cross-sectional, causality remains to be explored.

UNLABELLED: During the past decade planning of adjuvant radiotherapy (RT) of early breast cancer has changed from two-dimensional (2D) to 3D conformal techniques. In the planning computerised tomography (CT) scan both the targets for RT and the organs at risk (OARs) are visualised, enabling an increased focus on target dose coverage and homogeneity with only minimal dose to the OARs. To ensure uniform RT in the national prospective trials of the Danish Breast Cancer Cooperative Group (DBCG), a national consensus for the delineation of clinical target volumes (CTVs) and OARs was required. MATERIAL AND METHODS: A CT scan of a breast cancer patient after surgical breast conservation and axillary lymph node (LN) dissection was used for delineation. During multiple dummy-runs seven experienced radiation oncologists contoured all CTVs and OARs of interest in adjuvant breast RT. Two meetings were held in the DBCG Radiotherapy Committee to discuss the contouring and to approve a final consensus. The Dice similarity coefficient (DSC) was used to evaluate the delineation agreement before and after the consensus. RESULTS: The consensus delineations of CTVs and OARs are available online and a table is presented with a contouring description of the individual volumes. The consensus provides recommendations for target delineation in a standard patient both in case of breast conservation or mastectomy. Before the consensus, the average value of the DSC was modest for most volumes, but high for the breast CTV and the heart. After the consensus, the DSC increased for all volumes. CONCLUSION: The DBCG has provided the first national guidelines and a contouring atlas of CTVs and OARs definition for RT of early breast cancer. The DSC is a useful tool in quantifying the effect of the introduction of guidelines indicating improved inter-delineator agreement. This consensus will be used by the DBCG in our prospective trials.

OBJECTIVE: Cyanoacrylate (CA) embolization of refluxing great saphenous veins (GSVs) has been previously described. The outcomes from a multicenter study are still lacking. METHODS: A prospective multicenter study was conducted in seven centers in four European countries to abolish GSV reflux by endovenous CA embolization. Neither tumescent anesthesia nor postinterventional compression stockings were used. Varicose tributaries remained untreated until at least 3 months after the index treatment. Clinical examination, quality of life assessment, and duplex ultrasound evaluation were performed at 2 days and after 1, 3, 6, and 12 months. RESULTS: In 70 patients, of whom 68 (97.1%) were available for 12-month follow-up, 70 GSVs were treated. Two-day follow-up showed one proximal and one distal partial recanalization. Three additional proximal recanalizations were observed at 3-month (n = 2) and 6-month (n = 1) follow-up. Cumulative 12-month survival free from recanalization was 92.9% (95% confidence interval, 87.0%-99.1%). Mean (standard deviation) Venous Clinical Severity Score improved from 4.3 ± 2.3 at baseline to 1.1 ± 1.3 at 12 months. Aberdeen Varicose Vein Questionnaire score showed an improvement from 16.3 at baseline to 6.7 at 12 months (P < .0001). Side effects were generally mild; a phlebitic reaction occurred in eight cases (11.4%) with a median duration of 6.5 days (range, 2-12 days). Pain without a phlebitic reaction was observed in five patients (8.6%) for a median duration of 1 day (range, 0 -12 days). No serious adverse event occurred. Paresthesia was not observed. CONCLUSIONS: Endovenous CA embolization of refluxing GSVs is safe and effective without the use of tumescent anesthesia or compression stockings.

Isolated obstruction of the splenic vein leads to segmental portal hypertension, which is a rare form of extrahepatic portal hypertension, but it is important to diagnose, since it can be cured by splenectomy. In a review of the English literature, 209 patients with isolated splenic vein obstruction were found. Pancreatitis caused 65% of the cases and pancreatic neoplasms 18%, whereas the rest was caused by various other diseases. Seventy-two per cent of the patients bled from gastroesophageal varices, and most often the bleeding came from isolated gastric varices. The spleen was enlarged in 71% of the patients. A correct diagnosis in connection with the first episode of bleeding was made in only 49%; 22% were operated on because of gastrointestinal bleeding, but the cause of bleeding was not found. The diagnosis should be suspected in patients with gastroesophageal varices, but without signs of a liver disease, especially if isolated gastric varices are found. The diagnosis is confirmed by portography.

BACKGROUND: Previous twin studies have shown greater concordance rates for psoriasis in MZ than in DZ twins, and heritability estimates between 66% and 90%. This supports a genetic influence on psoriasis, but also highlights the fact that genes are not the only explanation for the disease. OBJECTIVES: To study the concordance of psoriasis in a population-based twin sample. METHODS: Data on psoriasis in 10 725 twin pairs, aged 20-71 years, from the Danish Twin Registry was collected via a questionnaire survey. The concordance and heritability of psoriasis were estimated. RESULTS: In total, 4·1% of the men and 4·2% of the women had a lifetime history of psoriasis. The proband-wise concordance for psoriasis was larger in monozygotic than in dizygotic twins, 0·33 vs. 0·17. Genetic factors explained 68% (60-75%) of the variation in the susceptibility to psoriasis, whereas the rest of the variation was explained by nonshared environmental factors. CONCLUSION: The results confirm that psoriasis is a complex multifactorial disease controlled by both exogenous and endogenous factors.

Abstract: This is a systematic review of cases with Lemierre’s syndrome (LS) in the past 5 years. LS is characterized by sepsis often evolving after a sore throat or tonsillitis and then complicated by various septic emboli and thrombosis of the internal jugular vein. Symptoms include sepsis, pain, and/or swelling in the throat or neck, as well as respiratory symptoms. Laboratory findings show elevated infectious parameters and radiological findings show thrombosis of the internal jugular vein and emboli in the lungs or other organs. The syndrome is often associated with an infection with Fusobacterium necrophorum . We found a total of 137 cases of LS, of which 47 were infected with F. necrophorum and others with Staphylococcus and Streptococcus . Complications of this rare but severe disease included osteomyelitis, meningitis, and acute respiratory distress syndrome. Mortality was extremely high in the pre-antibiotic era but has diminished with the advent of antibiotics. This review showed a mortality rate of only 2% of which none of the cases involved fusobacteria. Duration of treatment varied; a 4–6-week course of carbapenem or piperacillin/tazobactam in combination with metronidazole was optimum. Other treatment options included anticoagulants in 46% of cases, which is unwarrantedly high, as to date, no evidence of the positive effects of anticoagulants in LS exists. Only two cases had ligation of the internal jugular vein performed. This review confirms the rare, but severe aspects of LS. Mortality from LS in this day and age appears to be low, however the syndrome is difficult to recognize, and still requires the full attention of the clinician. Keywords: Lemierre’s syndrome, fusobacteria, postanginal sepsis