Multidisciplinary educational programme for caregivers of children with atopic dermatitis- in South East Norway - an observational study.

BACKGROUND: Educational programmes for caregivers of children with atopic dermatitis (AD) are reported to reduce the severity of AD and improve quality of life (QOL). Oslo University Hospital (OUH) in Norway offers a multidisciplinary educational programme for caregivers of children with AD. We aimed to evaluate the AD educational programme by assessing QOL of the family, the severity of the disease and caregiver's fear of topical corticosteroid (TCS) before and after attending the programme. METHODS: This was a small observational prospective cohort study including 41 caregiver-child pairs. The children (mean age 3.4 years) had doctors' diagnosed AD with a difficult to treat eczema. The children's caregivers were referred from physicians to attend the AD educational programme at our hospital. At inclusion and at a 3 months follow-up QOL was assessed by Dermatitis Family Impact (DFI), the eczema severity by Patient-Orientated - SCORing Atopic Dermatitis (PO-SCORAD) and caregivers fear of TCS was recorded by asking a dichotomous "yes" or "no" question: "Are you worried about using TCS on your child?" RESULTS: Three months after caregivers attending the educational programme there was an improvement in QOL by reduced mean DFI from 9.6 (SD 6.3) to 6.8 (SD 5.4), the mean PO-SCORAD was reduced from 38.5 (SD 15.1) to 24.6 (SD13.6), the number of caregivers reporting fear of TCS use was reduced from 33/46 (72%) to 12/41 (29%). All results p < 0.001. CONCLUSION: Our study suggests beneficial effects by improving QOL of the family, the severity of the eczema and in reducing the fear of TCS when caregivers of children with difficult to treat AD attend an AD multidisciplinary educational programme. Lack of control group makes it difficult to draw definite conclusions.

Skin bioengineering in the diagnosis of occupational protein contact dermatitis.

Protein contact dermatitis (PCD) often presents as chronic hand eczema (CHE) with an immediate hypersensitivity to protein proved by a positive skin prick test or by the presence of specific immunoglobulin E. This is frequently induced by occupational exposure to proteins in food workers, farmers, animal breeders, veterinarians and healthcare professionals. While skin barrier impairment is crucial in the pathogenesis of PCD, methods to assess skin barrier function such as trans-epidermal water loss and stratum corneum hydration are not widely used in clinical settings. We describe the diagnostic workup of occupational PCD due to Argentinean shrimps and discuss how the use of skin bioengineering methods including assessment of corneocytes morphology by Scanning Electron Microscopy provides with insightful information on skin barrier function. Diagnosis of PCD is time-consuming and a multidisciplinary team contributes to early diagnosis and proper occupational rehabilitation.

Treatment of atopic dermatitis with dupilumab: experience from a tertiary referral centre.

BACKGROUND: Management of moderate-to-severe atopic dermatitis (AD) frequently requires treatment with systemic therapies. Dupilumab is the first biological agent approved for treatment of moderate-to-severe AD. Although promising results have appeared in clinical trials, real-life data on efficacy and safety are lacking. OBJECTIVES: To assess effectiveness and safety of treatment with dupilumab in the real-life clinical setting at a Danish tertiary referral centre. METHODS: All patients with AD treated with dupilumab from October 2017 to October 2018 at Bispebjerg Hospital, Denmark, were included in the study. Patients were evaluated three times: at treatment initiation and at 1 and 3 months after first dupilumab injection. At each visit, disease activity was assessed by severity score (Eczema Area and Severity Index, EASI), patient-reported outcomes (Dermatology Life Quality Index, DLQI, pruritus and sleep score) and serological markers [immunoglobulin (Ig)E, eosinophil count and lactate dehydrogenase (LDH)]. RESULTS: A total of 43 patients were included in the study. The mean reduction in EASI score from baseline was 19.6 points (72.4%) at 1-month and 22.6 points (76.7%) at 3-month follow-up. EASI, DLQI, pruritus score, sleep score, IgE and LDH were all statistically significantly reduced between baseline and 1- and 3-month follow-up. Mean reductions in EASI score and LDH at 3-month follow-up were significantly correlated (P = 0.003). One patient (2.3%) discontinued treatment due to side-effects, and seven patients (18.4%) developed conjunctivitis during the study period. CONCLUSION: The effectiveness and safety of dupilumab treatment in a real-life clinical setting are comparable to that of phase 3 clinical trials. LDH is suggested as a potential serological marker predictive of treatment response.

Higher chlorzoxazone clearance in obese children compared with nonobese peers.

AIMS: To test the in vivo activity of Cytochrome P450 (CYP) 2E1 in obese children vs. nonobese children, aged 11-18 years. Secondly, whether the activity of CYP2E1 in these patients is associated with NALFD, diabetes or hyperlipidaemia. METHODS: Seventy children were divided into groups by body mass index (BMI) standard deviation score (SDS). All children received 250 mg oral chlorzoxazone (CLZ) as probe for CYP2E1 activity. Thirteen blood samples and 20-h urine samples were collected per participant. RESULTS: Obese children had an increased oral clearance and distribution of CLZ, indicating increased CYP2E1 activity, similar to obese adults. The mean AUC0-∞ value of CLZ was decreased by 46% in obese children compared to nonobese children. The F was was increased twofold in obese children compared to nonobese children, P < 0.0001. Diabetic biomarkers were significantly increased in obese children, while fasting blood glucose and Hba1c levels were nonsignificant between groups. Liver fat content was not associated with CLZ Cl. CONCLUSION: Oral clearance of CLZ was increased two-fold in obese children vs. nonobese children aged 11-18 years. This indicates an increased CYP2E1 activity of clinical importance, and dose adjustment should be considered for CLZ.

Effectiveness of omalizumab in chronic spontaneous urticaria assessed with patient-reported outcomes: a prospective study.

AIM: To examine the effectiveness of omalizumab (anti-IgE) on symptoms and disease-related quality of life in chronic spontaneous urticaria (CSU) and to identify possible patient-specific factors associated with response to omalizumab in patients with antihistamine refractory CSU. METHODS: Six months prospective trial of omalizumab 300 mg every 4 weeks among patients with CSU from a dermatological university department. The primary outcome was the urticaria activity score in the past week (UAS7) at 3 months. RESULTS: A total of 117 patients (39 men and 78 women) with a mean age of 42 years were included. The mean baseline UAS7 score was 29.3 points (SD = 10.8), which improved to 11.9 points (SD = 12.9) at 3 months follow-up, difference = 17.4 points (95% CI: 14.8-19.9), P < 0.0001. Other patient-reported outcomes (PROs) also improved significantly during 3 months of treatment. No significant further improvement was seen between three and 6 months follow-up. None of the following patient-specific factors: sex, age, age of onset of CSU, symptom duration, presence of chronic inducible urticaria (CINDU), comorbidities, positive urticaria HR test, smoking, ethnicity, angio-oedema, serum total IgE level, CRP, leucocytes, absolute neutrophil count or previous treatment with prednisolone or montelukast were significantly associated with response to omalizumab at 3 months, P > 0.05 for all comparisons. Previous treatment with traditional immunosuppressant drugs (azathioprine, cyclosporine or methotrexate) was associated with poorer treatment response to omalizumab at 3 months, P < 0.001. A strong correlation was seen between different patient-reported outcomes (PROs) at baseline and 3 months follow-up. Fifteen patients (12.8%) reported side-effects of the treatment. CONCLUSION: Omalizumab is a highly effective therapy for antihistamine refractory CSU with treatment effects similar to those observed in randomized controlled trials. Validated PROs to assess disease activity, disease control and impairment of quality of life are valuable tools in the clinical management of CSU. Identification of patient-specific predictors of effect and safety of omalizumab in CSU is still warranted.

Hyponatremia, a risk factor for osteoporosis and fractures in women.

SUMMARY: Hyponatremia has been linked to an increased risk of osteoporosis and fractures. We found an increased hazard ratio of major osteoporotic fractures adjusted for potential confounders, including osteoporosis and medication. A reduced BMD was not sufficiently explaining the association. Our data indicate that hyponatremia should be considered a risk factor for osteoporosis and fractures. INTRODUCTION: Hyponatremia is the most common electrolyte disorder in clinical practice and could be a risk factor for both osteoporosis and fractures. Mild hyponatremia has traditionally been regarded as a benign and asymptomatic condition; however, data from large population and animal studies have led to a reappraisal of this view. The purpose of this study was to evaluate the association of hyponatremia with osteoporosis and major osteoporotic fractures (MOF) in women. METHODS: This is a historical cohort study with fracture follow-up. The study consisted of 5610 patients with available serum sodium and a bone density measurement. Information on potential risk factor was obtained through a questionnaire. Additional information on medication, comorbidities, and fractures was obtained through national registries. RESULTS: Hyponatremia was associated with significant lower T-scores at total hip and a borderline significant lower T-score at femoral neck in the multivariate analysis. No association was found between hyponatremia and the lumbar spine T-score. Hyponatremia was associated with an increased hazard ratio of sustaining a MOF in the period from 6 months prior to 12 months after serum sodium measurement. Finally, data showed a relationship with increasing serum sodium and an increasing T-score estimate and a decreasing hazard ratio of MOF. CONCLUSIONS: Our data suggest that hyponatremia in women increases the risk of osteoporosis and MOF. The increased risk of MOF was independent of osteoporosis.

A randomised, controlled, double-blind trial of ultrasound-guided phrenic nerve block to prevent shoulder pain after thoracic surgery.

Moderate to severe ipsilateral shoulder pain is a common complaint following thoracic surgery. In this prospective, parallel-group study at Odense University Hospital, 76 patients (aged > 18 years) scheduled for lobectomy or pneumonectomy were randomised 1:1 using a computer-generated list to receive an ultrasound-guided supraclavicular phrenic nerve block with 10 ml ropivacaine or 10 ml saline (placebo) immediately following surgery. A nerve catheter was subsequently inserted and treatment continued for 3 days. The study drug was pharmaceutically pre-packed in sequentially numbered identical vials assuring that all participants, healthcare providers and data collectors were blinded. The primary outcome was the incidence of unilateral shoulder pain within the first 6 h after surgery. Pain was evaluated using a numeric rating scale. Nine of 38 patients in the ropivacaine group and 26 of 38 patients in the placebo group experienced shoulder pain during the first 6 h after surgery (absolute risk reduction 44% (95% CI 22-67%), relative risk reduction 65% (95% CI 41-80%); p = 0.00009). No major complications, including respiratory compromise or nerve injury, were observed. We conclude that ultrasound-guided supraclavicular phrenic nerve block is an effective technique for reducing the incidence of ipsilateral shoulder pain after thoracic surgery.

Quality of life and disease severity in patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) affects quality of life (QoL) negatively in patients and their families. We examined the relationship between disease severity and QoL in patients with AD. METHODS: Consecutive, newly referred outpatients with AD, 4 years of age or older, were assessed from January 2012 onwards by means of the dermatology life quality index (DLQI, range 0-30), the Scoring of AD (SCORAD) disease severity score (range 0-103), filaggrin gene (FLG) mutation status and paraclinical tests related to allergy. RESULTS: A total of 250 patients with a mean age of 26.0 years were identified with complete data on DLQI; 148 (59.2%) females and 102 (40.8%) males. Of these 45.6% had asthma, 46.8% had hay fever, 22.7% had a loss-of-function mutation in FLG, and 61.9% had one or more inhalant allergic sensitizations. The correlation between SCORAD and DLQI was 0.42 (P < 0.001). After multivariate adjustment there was an increasing mean DLQI score with increasing disease severity measured by SCORAD (DLQI in mild = 5.30, moderate = 8.59 and severe = 11.94 AD), P-value for difference between groups <0.001; a higher mean DLQI among females than males (9.73 vs. 8.34), P = 0.028; and among patients reporting facial eczema (9.88 vs. 6.24), P = 0.012. No statistically significant influence on DLQI was found for hand or foot eczema, age, blood eosinophil count, allergic sensitization, asthma, hay fever, FLG mutation status and smoking. FLG null mutation status was not significantly associated with SCORAD. CONCLUSION: AD impacts negatively on the QoL, proportional to the severity of the disease. Furthermore, female sex and facial eczema are associated with low QoL. Positive FLG null mutation status is not associated with QoL or disease severity.

Breast cancer genetic risk profile is differentially associated with interval and screen-detected breast cancers.

BACKGROUND: Polygenic risk profiles computed from multiple common susceptibility alleles for breast cancer have been shown to identify women at different levels of breast cancer risk. We evaluated whether this genetic risk stratification can also be applied to discriminate between screen-detected and interval cancers, which are usually associated with clinicopathological and survival differences. PATIENTS AND METHODS: A 77 single-nucleotide polymorphism polygenic risk score (PRS) was constructed for breast cancer overall and by estrogen receptor (ER) status. PRS was inspected as a continuous (per standard deviation increment) variable in a case-only design. Modification of the PRS by mammographic density was evaluated by fitting an additional interaction term. RESULTS: PRS weighted by breast cancer overall estimates was found to be differentially associated with 1865 screen-detected and 782 interval cancers in the LIBRO-1 study {age-adjusted odds ratio (OR)perSD [95% confidence interval (CI)] 0.91 [0.83-0.99], P = 0.023}. The association was found to be more significant for PRS weighted by ER-positive breast cancer estimates [ORperSD = 0.90 (0.82-0.98), P = 0.011]. This result was corroborated by two independent studies [combined ORperSD = 0.87 (0.76-1.00), P = 0.058] with no evidence of heterogeneity. When enriched for 'true' interval cancers among nondense breasts, the difference in the association with PRS in screen-detected and interval cancers became more pronounced [ORperSD = 0.74 (0.62-0.89), P = 0.001], with a significant interaction effect between PRS and mammographic density (Pinteraction = 0.017). CONCLUSION: To our knowledge, this is the first report looking into the genetic differences between screen-detected and interval cancers. It is an affirmation that the two types of breast cancer may have unique underlying biology.

Immunological comparison of allergen immunotherapy tablet treatment and subcutaneous immunotherapy against grass allergy.

BACKGROUND: IgE-mediated allergic rhinitis to grass pollen can successfully be treated with either allergen immunotherapy tablets (SLIT tablet) or SQ-standardized subcutaneous immunotherapy (SCIT). The efficacy of these two treatment modalities for grass allergy is comparable, but the immunological mechanisms may differ. ClinicalTrials.gov ID: NCT01889875. OBJECTIVES: To compare the immunological changes induced by SQ-standardized SCIT and SLIT tablet. METHODS: We randomized 40 individuals with grass pollen rhinitis into groups receiving SCIT, SLIT tablet, or neither and followed them for 15 months with regular serum measurements of specific IgE, IgG4, IgE-blocking factor, facilitated antigen presentation (FAP), and basophil activation test (BAT). Nasal challenges were used to assess changes in nasal sensitivity. RESULTS: After 15 months of treatment IgG4, IgE-blocking factor, FAP, and BAT values differed significantly in both SCIT and SLIT-tablet treatment groups when compared to the control group. Both SCIT and SLIT-tablet groups were significantly different from the control group after 1­3 months of treatment. In general, the changes induced by SCIT reached twice that of SLIT tablet, with the exception of specific IgE where SLIT tablet induced initial threefold increase compared with SCIT. A slight but significant increase in IgE and BAT after season was seen only in the control group. Significant differences between SCIT and SLIT tablet were observed early, but the differences diminished with the length of treatment, especially for FAP inhibition. CONCLUSIONS: Both SCIT and SLIT tablet induce significant changes in specific antibodies (IgE and IgG4) and competition assays (IgE-blocking factor, FAP, and BAT). Overall, SCIT induced larger (two- to threefold) changes than SLIT tablet, with the exception of FAP, where SLIT tablet showed a gradual increase ending at the same level as SCIT. Maximal change was generally reached after 3 months' treatment.

EuroSCORE II and N-terminal pro-B-type natriuretic peptide for risk evaluation: an observational longitudinal study in patients undergoing coronary artery bypass graft surgery.

BACKGROUND: Postoperative heart failure remains the major cause of death after cardiac surgery. As N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a predictor for postoperative heart failure, the aim was to evaluate if preoperative NT-proBNP could provide additional prognostic information to the recently launched EuroSCORE II. METHODS: A total of 365 patients with acute coronary syndrome (ACS) undergoing isolated coronary artery bypass graft (CABG) surgery were studied prospectively. Preoperative NT-proBNP and EuroSCORE II were evaluated with regard to severe circulatory failure after operation according to prespecified criteria. To assess what clinical outcomes are indicated by NT-proBNP levels in different risk categories, the patients were stratified according to EuroSCORE II. Based on receiver operating characteristics analysis, these cohorts were assessed with regard to preoperative NT-proBNP below or above 1028 ng litre(-1). The follow-up time averaged 4.4 (0.7) yr. RESULTS: Preoperative NT-proBNP≥1028 ng litre(-1) [odds ratio (OR) 9.9, 95% confidence interval (CI) 1.01-98.9; P=0.049] and EuroSCORE II (OR 1.24, 95% CI 1.06-1.46; P=0.008) independently predicted severe circulatory failure after operation. In intermediate-risk patients (EuroSCORE II 2.0-10.0), NT-proBNP≥1028 ng litre(-1) was associated with a higher incidence of severe circulatory failure (6.6% vs 0%; P=0.007), renal failure (14.8% vs 5.4%; P=0.03), stroke (6.6% vs 0.7%; P=0.03), longer intensive care unit stay [37 (35) vs 27 (38) h; P=0.002], and worse long-term survival. CONCLUSIONS: Combining EuroSCORE II and preoperative NT-proBNP appears to improve risk prediction with regard to severe circulatory failure after isolated CABG for ACS. NT-proBNP may be particularly useful in patients at intermediate risk according to EuroSCORE II. CLINICAL TRIAL REGISTRATION: NCT00489827.

Circulating C-reactive protein levels as a prognostic biomarker in breast cancer across body mass index groups.

Obesity and systemic inflammation are associated with breast cancer (BC) outcomes. Systemic inflammation is increased in obesity. We examined the association between C-reactive protein (CRP) and disease-free survival (DFS) and overall survival (OS) overall, and according to body mass index (BMI). We assembled a cohort of women with BC (stage I-III) seen at Aarhus University Hospital between 2010 and 2020 who donated blood at BC diagnosis (N = 2673). CRP levels were measured and divided into quartiles. We followed patients from surgery to recurrence, contralateral BC, other malignancy, death, emigration, or end-of-follow-up. We used Cox regression to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) to compare outcomes across CRP quartiles, overall and stratified by BMI (normal-weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and obesity (BMI ≥ 30 kg/m2)). During follow-up, 368 events (212 recurrences, 38 contralateral BCs, and 118 deaths) occurred (median follow-up 5.55 years). For DFS, high CRP (CRP ≥ 3.19 mg/L) was associated with an increased risk of events (HRadj:1.62 [95% CI = 1.14-2.28]). In BMI-stratified analyses, high CRP was associated with elevated risk of events in normal-weight and overweight (HRadj:1.70 [95% CI = 1.09-2.66]; HRadj:1.75 [95% CI = 1.08-2.86]), but in obesity, the estimate was less precise (HRadj:1.73 [95% CI = 0.78-3.83]). For OS, high CRP was associated with increased risk of death (HRadj:2.47 [95% CI = 1.62-3.76]). The association was strong in normal-weight and overweight (HRadj:3.66 [95% CI = 1.95-6.87]; HRadj:1.92 [95% CI = 1.06-3.46]), but less clear in obesity (HRadj:1.40 [95% CI = 0.64-3.09]). To sum up, high CRP levels at BC diagnosis were associated with inferior prognosis in early BC irrespective of BMI, although less clear in patients with obesity.

The complexity of allergic patients' IgE repertoire correlates with serum concentration of allergen-specific IgE.

BACKGROUND: The governing factor of both effector-cell activation and facilitated antigen presentation is IgE-repertoire complexity (IgE-clonality, -affinity and -concentration). Yet, the compositions of individual IgE repertoires and correlation between IgE-repertoire complexity and establishment of allergic sensitization remain to be determined. OBJECTIVE: In complex formation assays with recombinant IgE, allergen and CD23(+) B cells, we assess the composition of serum IgE repertoires and examine the correlation between IgE-titre and IgE-repertoire complexity. METHODS: The capacity of sera, from house dust mite-sensitized individuals, to mediate IgE-Der p 2-CD23 complex formation on CD23(+) B cells was measured. In parallel experiments, the effect of supplementing each serum with one or more Der p 2-specific monoclonal recombinant IgE antibodies on complex formation was determined. RESULTS: Only sera with the highest concentration of Der p 2-specific IgE resulted in complex formation without supplementary recombinant IgE. Intermediately titred sera supported complex formation to various degrees when supplemented with individual recombinant IgE. The degree of complex formation depended on the affinity and epitope specificity of the recombinant IgE. Complex formation by combining serum and recombinant IgEs could not be obtained with sera of relatively low titres of specific IgE. However, these sera had the capacity to dramatically enhance the low complex formation achieved with pairs of affinity-engineered recombinant IgEs. CONCLUSION AND CLINICAL RELEVANCE: Serum IgE complexity can be indirectly assessed by combining sera with defined monoclonal IgEs in IgE-allergen-CD23 complex assays. The observed differences in epitope-coverage of Der p 2-specific serum-IgE in sera of different specific IgE titres indicate that increased IgE titres correlate with increased complexity of the IgE-repertoire. A detailed knowledge of the composition and complexity of allergen-specific IgE repertoires (and the relation to IgE titre), particularly in the early phase of sensitization, may be used to improve the prediction of the persistence and severity of allergic symptoms, as well as the progression of the Allergic March.

Fetal loss in women with hereditary thrombophilic defects and concomitance of other thrombophilic defects: a retrospective family study.

OBJECTIVE: To assess the absolute risk of fetal loss associated with hereditary deficiencies of antithrombin (AT), protein C (PC) and protein S (PS), and the contribution of additional thrombophilic defects to this risk. DESIGN: A retrospective family cohort study. SETTING: A tertiary referral teaching hospital. POPULATION: Women from families with hereditary deficiencies of AT, PC and PS, and their non-deficient relatives. METHODS: We assessed the absolute risk of fetal loss, comparing deficient women with non-deficient female relatives. MAIN OUTCOME MEASURES: Early, late and total fetal loss rates; odds ratios of fetal loss. RESULTS: We evaluated 289 women, who had 860 pregnancies. The total fetal loss rates were 23% (AT deficient), 26% (PC deficient), 11% (type-I PS deficient) and 15% (type-III PS deficient), compared with 11, 18, 12 and 13% in non-deficient women, respectively. Odds ratios were 2.3 (95% CI 0.9-6.1), 2.1 (95% CI 0.9-4.7), 0.7 (95% CI 0.2-1.8) and 1.1 (95% CI 0.6-2.0), none of which reached statistical significance. Differences were mainly the result of higher late fetal loss rates in women deficient in AT (OR 11.3, 95% CI 3.0-42.0) and PC (OR 4.7, 95% CI 1.3-17.4). The concomitance of factor-V Leiden and prothrombin G20210A was observed in 19% of women, and did not increase the risk of fetal loss. CONCLUSIONS: Although absolute risks of fetal loss were high, odds ratios of total fetal loss were not statistically significant in deficient versus non-deficient women. However the higher absolute risks appeared to reflect higher late fetal loss rates as opposed to early fetal loss rates. An additional effect of concomitance of factor-V Leiden and prothrombin G20210A was not demonstrated, which may result from the exclusion of women at highest risk of venous thromboembolism, or from the small numbers sampled in the study.

Mixed venous oxygen saturation predicts short- and long-term outcome after coronary artery bypass grafting surgery: a retrospective cohort analysis.

BACKGROUND: Complications of an inadequate haemodynamic state are a leading cause of morbidity and mortality after cardiac surgery. Unfortunately, commonly used methods to assess haemodynamic status are not well documented with respect to outcome. The aim of this study was to investigate Sv(O2) as a prognostic marker for short- and long-term outcome in a large unselected coronary artery bypass grafting (CABG) cohort and in subgroups with or without treatment for intraoperative heart failure. METHODS: Two thousand seven hundred and fifty-five consecutive CABG patients and subgroups comprising 344 patients with and 2411 patients without intraoperative heart failure, respectively, were investigated. Sv(O2) was routinely measured on admission to the intensive care unit (ICU). The mean (sd) follow-up was 10.2 (1.5) yr. RESULTS: The best cut-off for 30 day mortality related to heart failure based on receiver-operating characteristic analysis was Sv(O2) 60.1%. Patients with Sv(O2) <60% had higher 30 day mortality (5.4% vs 1.0%; P<0.0001) and lower 5 yr survival (81.4% vs 90.5%; P<0.0001). The incidences of perioperative myocardial infarction, renal failure, and stroke were also significantly higher, leading to a longer ICU stay. Similar prognostic information was obtained in the subgroups that were admitted to ICU with or without treatment for intraoperative heart failure. In patients admitted to ICU without treatment for intraoperative heart failure and Sv(O2) ≥60%, 30 day mortality was 0.5% and 5 yr survival 92.1%. CONCLUSIONS: Sv(O2) <60% on admission to ICU was related to worse short- and long-term outcome after CABG, regardless of whether the patients were admitted to ICU with or without treatment for intraoperative heart failure.

Arterial smooth muscle cells express nitric oxide synthase in response to endothelial injury.

Endothelial cells regulate vascular tone by secreting paracrine mediators that control the contractility of arterial smooth muscle cells. Nitric oxide (NO) is an important vasodilating agent that is generated from L-arginine by the enzyme nitric oxide synthase (NOS), which is expressed constitutively by the endothelium. NO also inhibits platelet aggregation, contributing to the antithrombotic properties of the endothelial surface. It would therefore be expected that loss of the endothelium during arterial injury would lead to vasospasm and thrombosis but instead, the neointima formed after injury has a nonthrombogenic surface and a maintained vascular patency. We report here that arterial smooth muscle cells in the neointima formed after a deendothelializing balloon injury to the rat carotid artery express the cytokine-inducible isoform of NOS. Expression was detectable by reverse transcription-polymerase chain reaction from day 1-14 after injury and in situ hybridization showed expression of NOS mRNA by neointimal smooth muscle cells, particularly at the surface of the lesion. This was associated with systemically detectable NO production as revealed by electron paramagnetic resonance spectroscopic analysis of nitrosylated red cell hemoglobin. Local NO production by intimal smooth muscle cells after endothelial injury could represent an important mechanism for the maintenance of arterial patency and nonthrombogenicity in the injured artery.

Association studies on 11 published colorectal cancer risk loci.

BACKGROUND: Recently, several genome-wide association studies (GWAS) have independently found numerous loci at which common single-nucleotide polymorphisms (SNPs) modestly influence the risk of developing colorectal cancer. The aim of this study was to test 11 loci, reported to be associated with an increased or decreased risk of colorectal cancer: 8q23.3 (rs16892766), 8q24.21 (rs6983267), 9p24 (rs719725), 10p14 (rs10795668), 11q23.1 (rs3802842), 14q22.2 (rs4444235), 15q13.3 (rs4779584), 16q22.1 (rs9929218), 18q21.1 (rs4939827), 19q13.1 (rs10411210) and 20p12.3 (rs961253), in a Swedish-based cohort. METHODS: The cohort was composed of 1786 cases and 1749 controls that were genotyped and analysed statistically. Genotype-phenotype analysis, for all 11 SNPs and sex, age of onset, family history of CRC and tumour location, was performed. RESULTS: Of eleven loci, 5 showed statistically significant odds ratios similar to previously published findings: 8q23.3, 8q24.21, 10p14, 15q13.3 and 18q21.1. The remaining loci 11q23.1, 16q22.1, 19q13.1 and 20p12.3 showed weak trends but somehow similar to what was previously published. The loci 9p24 and 14q22.2 could not be confirmed. We show a higher number of risk alleles in affected individuals compared to controls. Four statistically significant genotype-phenotype associations were found; the G allele of rs6983267 was associated to older age, the G allele of rs1075668 was associated with a younger age and sporadic cases, and the T allele of rs10411210 was associated with younger age. CONCLUSIONS: Our study, using a Swedish population, supports most genetic variants published in GWAS. More studies are needed to validate the genotype-phenotype correlations.

Mixed venous oxygen saturation is a prognostic marker after surgery for aortic stenosis.

BACKGROUND: Adequate monitoring of the hemodynamic state is essential after cardiac surgery and is vital for medical decision making, particularly concerning hemodynamic management. Unfortunately, commonly used methods to assess the hemodynamic state are not well documented with regard to outcome. Mixed venous oxygen saturation (SvO(2)) was therefore investigated after cardiac surgery. METHODS: Detailed data regarding mortality were available on all patients undergoing aortic valve replacement for isolated aortic stenosis during a 5-year period in the southeast region of Sweden (n=396). SvO(2) was routinely measured on admission to the intensive care unit (ICU) and registered in a database. A receiver operating characteristics (ROC) analysis of SvO(2) in relation to post-operative mortality related to cardiac failure and all-cause mortality within 30 days was performed. RESULTS: The area under the curve (AUC) was 0.97 (95% CI 0.96-1.00) for mortality related to cardiac failure (P=0.001) and 0.76 (95% CI 0.53-0.99) for all-cause mortality (P=0.011). The best cutoff for mortality related to cardiac failure was SvO(2) 53.7%, with a sensitivity of 1.00 and a specificity of 0.94. The negative predictive value was 100%. The best cutoff for all-cause mortality was SvO(2) 58.1%, with a sensitivity of 0.75 and a specificity of 0.84. The negative predictive value was 99.4%. Post-operative morbidity was also markedly increased in patients with a low SvO(2). CONCLUSION: SvO(2), on admission to the ICU after surgery for aortic stenosis, demonstrated excellent sensitivity and specificity for post-operative mortality related to cardiac failure and a fairly good AUC for all-cause mortality, with an excellent negative predictive value.