Survival after antireflux surgery versus medication in patients with reflux oesophagitis or Barrett's oesophagus: multinational cohort study.

BACKGROUND: The aim was to examine the hypothesis that antireflux surgery with fundoplication improves long-term survival compared with antireflux medication in patients with reflux oesophagitis or Barrett's oesophagus. METHOD: Individuals aged between 18 and 70 years with reflux oesophagitis or Barrett's oesophagus (intestinal metaplasia) documented from in-hospital and specialized outpatient care were selected from national patient registries in Denmark, Finland, Iceland, and Sweden from 1980 to 2014. The study investigated all-cause mortality and disease-specific mortality, comparing patients who had undergone open or laparoscopic antireflux surgery with fundoplication versus those using antireflux medication. Multivariable Cox regression analysis was used to estimate hazard ratios (HRs) with 95 per cent confidence intervals for all-cause mortality and disease-specific mortality, adjusted for sex, age, calendar period, country, and co-morbidity. RESULTS: Some 240 226 patients with reflux oesophagitis or Barrett's oesophagus were included, of whom 33 904 (14.1 per cent) underwent antireflux surgery. The risk of all-cause mortality was lower after antireflux surgery than with use of medication (HR 0.61, 95 per cent c.i. 0.58 to 0.63), and lower after laparoscopic (HR 0.56, 0.52 to 0.60) than open (HR 0.80, 0.70 to 0.91) surgery. After antireflux surgery, mortality was decreased from cardiovascular disease (HR 0.58, 0.55 to 0.61), respiratory disease (HR 0.62, 0.57 to 0.66), laryngeal or pharyngeal cancer (HR 0.35, 0.19 to 0.65), and lung cancer (HR 0.67, 0.58 to 0.80), but not from oesophageal cancer (HR 1.05, 0.87 to 1.28), compared with medication, The decreased mortality rates generally remained over time. CONCLUSION: In patients with reflux oesophagitis or Barrett's oesophagus, antireflux surgery is associated with lower mortality from all causes, cardiovascular disease, respiratory disease, laryngeal or pharyngeal cancer, and lung cancer, but not from oesophageal cancer, compared with antireflux medication.

Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab.

OBJECTIVE: Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. DESIGN: Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. RESULTS: After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. CONCLUSIONS: In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. TRIAL REGISTRATION NUMBER: EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.

Human leucocyte antigens B*08, DRB1*03 and DRB1*13 are significantly associated with autoimmune liver and biliary diseases in Finnish children.

AIM: The human leucocyte antigen (HLA) allele and haplotype frequencies of the Finnish population are unique because of the restricted and homogenous gene population. There are no published data on HLA genotype associations in paediatric autoimmune liver diseases in Scandinavia. This study characterised the HLA genotypes of children with autoimmune liver or biliary disease in Finland. METHODS: The study cohort comprised 19 paediatric patients (13 female) aged three years to 15 years treated for autoimmune liver or biliary disease at the Children's Hospital, Helsinki University Hospital, between 2000 and 2011, and followed up for four years and three months to 14.6 years. We genotyped HLA-B and HLA-DRB1 in the children, and the HLA antigen frequencies were compared with 19 807 records from the Finnish Bone Marrow Donor Registry. RESULTS: All paediatric patients with autoimmune liver or biliary disease had either autoimmune HLA haplotype B*08;DRB1*03 or DRB1*13. These were significantly more common among patients with autoimmune hepatitis, primary sclerosing cholangitis and autoimmune hepatitis/primary sclerosing cholangitis overlap syndrome than the Finnish control population. HLA RB1*04 was not found in the study cohort. CONCLUSION: Our study found that B*08, DRB1*03 and DRB1*13 were significantly associated with autoimmune liver and biliary diseases in Finnish paediatric patients.

A 10-year follow-up of the European multicenter trial of interferon ß-1b in secondary-progressive multiple sclerosis.

OBJECTIVES: To explore long-term effects of treatment and prognostic relevance of variables assessed at baseline and during the European secondary progressive multiple sclerosis (SPMS) trial of interferon beta 1b (IFNB-1b). METHODS: We assessed 362 patients (60% female; median age 41 years; Expanded Disability Status Scale (EDSS): 5.5; 51% randomized to IFNB-1b) for their EDSS and treatment history after 10 years. Non-parametric analysis of covariance (ANCOVA) and multivariate linear regression models were applied. RESULTS: Median EDSS was 6.0 at the end of the randomized controlled trial (RCT), in the IFNB-1b and placebo groups, and 7.0 in long-term follow-up patients (those receiving IFNB-1b in the RCT were 6.5 and those receiving placebo in the RCT were 7.0; p = 0.086). 24 patients (6.6%) were deceased. The EDSS at baseline and the EDSS change during the RCT were the most important predictors of the EDSS 10 years later (partial R(2): 0.47). The ability to predict changes in EDSS 10 years after the RCT was limited (R(2): 0.12). Magnetic resonance imaging (MRI) measures remained in the predictive models, but explained < 5% of the variability. CONCLUSIONS: The results from this analysis did not provide convincing evidence to support a favorable long-term outcome in those patients allocated IFNB-1b during the RCT, in our SPMS cohort. The progressive stage of the disease remains largely unpredictable by clinical and conventional MRI measures, so better prognostic markers are needed.

Minocycline added to subcutaneous interferon ß-1a in multiple sclerosis: randomized RECYCLINE study.

BACKGROUND AND PURPOSE: Combining different therapies may improve disease control in patients with relapsing-remitting multiple sclerosis (RRMS). This study assessed the efficacy and safety of minocycline added to subcutaneous (sc) interferon (IFN) ß-1a therapy. METHODS: This was a double-blind, randomized, placebo-controlled multicentre study. Within 3 months (±1 month) of starting sc IFN ß-1a 44 µg three times weekly, patients with RRMS were randomized to minocycline 100 mg twice daily or placebo, added to sc IFN ß-1a, for 96 weeks. The primary efficacy endpoint was the time to first qualifying relapse. Secondary efficacy endpoints were the annualized relapse rate for qualifying relapses, the number of new/enlarging T2-weighted lesions and change in brain volume [magnetic resonance imaging (MRI) was performed only in a few selected centres]. In addition, a number of tertiary efficacy endpoints were assessed. RESULTS: One hundred and forty-nine patients received minocycline and 155 received placebo; MRI data were available for 23 and 27 patients, respectively. The time to first qualifying relapse did not differ significantly for minocycline versus placebo (hazard ratio 0.85; 95% confidence interval 0.53, 1.35; log-rank = 0.50; P = 0.48). There were no statistically significant differences between the two groups on other efficacy endpoints, although some numerical trends in favour of minocycline were observed. No unexpected adverse events were reported, but more patients discontinued because of adverse events with minocycline versus placebo. CONCLUSION: Minocycline showed no statistically significant beneficial effect when added to sc IFN ß-1a therapy.

Monocyte-derived dendritic cells from Crohn's disease patients exhibit decreased ability to activate T helper type 17 responses in memory cells.

An increased activation of interleukin (IL)-17A-producing immune cells is a well-established feature of Crohn's disease (CD). Mechanisms that contribute to this aberrant immune activation are, however, less clear. Given that an enhanced induction of innate-immunity associated cytokines IL-6 and IL-23, which promote IL-17 immunity, is also clearly implicated in CD, we hypothesized that monocyte-derived dendritic cells (moDCs) of CD patient origin would mount exaggerated IL-17A responses in T cells. However, we found a significantly attenuated up-regulation of the IL-17A response in allogeneic T helper memory cells in the presence of culture media from lipopolysaccharide (LPS)-stimulated moDCs of CD patients when compared with moDCs of control subjects (median fold-increase in IL-17A mRNA expression 1·09 versus 1·44, P = 0·038). This was accompanied by a lower expression of IL-1ß and IL-6 transcripts in the LPS-treated moDCs (median 9·55 versus 13·9 relative units, P = 0·042, and 2·66 versus 9·06 relative units, P = 0·049, respectively). In addition, the up-regulation of autophagy-related LC3 transcripts was decreased in moDCs of CD patients (median fold-increase in mRNA expression 1·22 versus 1·52, P = 0·029). Our findings reveal similar immunological aberrancies in CD in the general population as reported in CD patients with mutated intracellular bacterial sensor NOD2, namely attenuated activation of innate cytokines and impaired autophagy, combined with a reduced capacity to up-regulate the T helper type 17 (Th17) response. The results presented here emphasize a defective anti-microbial response in the pathogenesis of CD. The increased mucosal Th1 and Th17 responses, which may contribute to the pathogenesis, could be the consequences of primary defects in the innate immunity.

Doppler ultrasound examination of multiple sclerosis patients and control participants: inter-observer agreement and association with disease.

OBJECTIVE: Chronic cerebrospinal venous insufficiency (CCSVI) has been proposed as a major risk factor for multiple sclerosis (MS). The aim of this study was to assess inter-observer agreement between two ultrasound examiners and to compare findings in MS patients and control participants. METHODS: A prospective, blinded, controlled study of MS patients diagnosed within 2 years (MS ≤ 2, n = 39), patients diagnosed more than 10 years ago (MS > 10, n = 43) and age- and sex-matched control participants (n = 40). Ultrasound examinations were performed by two independent examiners. CCSVI criteria 1, 3, 4 and 5 as proposed by Zamboni were explored: (1) reflux in the internal jugular (IJV) and vertebral veins (VV), (3) IJV cross-sectional area (CSA) ≤0.3 cm(2), (4) absence of flow in IJV and VV, and (5) reverted postural control of venous outflow. RESULTS: Criteria 1, 4 and 5 were met in less than 10% of the MS patients and control participants as studied by both examiners. The level of inter-observer agreement was poor for all parameters except assessment of the CSA of IJV at the thyroid level. Findings meeting CCSVI criterion 3 (CSA ≤ 0.3 cm(2)) were observed in 18/40 (45%) of the control participants, in 24/37 (65%) of MS ≤ 2 patients (p = 0.09 vs. control participants) and in 30/43 (70%) of the MS > 10 patients (p = 0.022 vs. control participants). CONCLUSIONS: The feasibility of the CCSVI criteria for common use is questionable because of low inter-observer agreement. Small-calibre IJVs meeting the CCSVI criterion 3 appear common in both Finnish control participants and MS patients, but the clinical significance of this finding is questionable.

Association of celiac disease genes with inflammatory bowel disease in Finnish and Swedish patients.

Some genetic loci may affect susceptibility to multiple immune system-related diseases. In the current study, we investigated whether the known susceptibility loci for celiac disease (CelD) also associate with Crohn's disease (CD) and/or ulcerative colitis (UC), the two main forms of inflammatory bowel disease (IBD), in Finnish patients. A total of 45 genetic markers were genotyped in a Finnish data set comprising 699 IBD patients and 2482 controls. Single-marker association with IBD and its subphenotypes was tested. A meta-analysis with a Swedish UC data set was also performed. A total of 12 single-nucleotide polymorphisms associated with CD and/or UC (P<0.05). In the subphenotype analysis, rs6974491-ELMO1 (P=0.0002, odds ratio (OR): 2.20) and rs2298428-UBE2L3 (P=5.44 × 10(-5), OR: 2.59) associated with pediatric UC and CD, respectively. In the meta-analysis, rs4819388-ICOSLG (P=0.00042, OR: 0.79) associated with UC. In the subphenotype meta-analysis, rs1738074-TAGAP (P=7.40 × 10(-5), OR: 0.61), rs6974491-ELMO1 (P=0.00052, OR: 1.73) and rs4819388-ICOSLG (P=0.00019, OR: 0.75) associated with familial UC, pediatric UC and sporadic UC, respectively. Multiple CelD risk loci also confer susceptibility for CD and/or UC in the Finnish and Swedish populations. Certain genetic risk variants may furthermore predispose an individual for developing a particular disease phenotype.

Association study of FUT2 (rs601338) with celiac disease and inflammatory bowel disease in the Finnish population.

Homozygosity for a nonsense mutation in the fucosyltransferase 2 (FUT2) gene (rs601338G>A) leads to the absence of ABH blood groups (FUT2 non-secretor status) in body fluids. As the secretor status has been shown to be a major determinant for the gut microbial spectrum, assumed to be important in the gut immune homeostasis, we studied the association of rs601338-FUT2 with celiac disease (CelD) and inflammatory bowel disease (IBD) in the Finnish population. Rs601338 was genotyped in CelD (n = 909), dermatitis herpetiformis (DH) (n = 116), ulcerative colitis (UC) (n = 496) and Crohn's disease (CD) (n = 280) patients and healthy controls (n = 2738). CelD showed significant genotypic [P = 0.0074, odds ratio (OR): 1.28] and recessive (P = 0.015, OR: 1.28) association with the rs601338-AA genotype. This was also found in the combined CelD+DH dataset (genotype association: P = 0.0060, OR: 1.28; recessive association: P < 0.011, OR: 1.28). The A allele of rs601338 showed nominal association with dominant protection from UC (P = 0.044, OR: 0.82) and UC+CD (P = 0.035, OR: 0.84). The frequency of non-secretors (rs601338-GG) in controls, CelD, DH, UC and CD datasets was 14.7%, 18%, 18.1%, 14.3% and 16.1%, respectively. No association was evident in the DH or CD datasets alone. In conclusion, FUT2 non-secretor status is associated with CelD susceptibility and FUT2 secretor status may also play a role in IBD in the Finnish population.

Risk factors for complications of ERCP in primary sclerosing cholangitis.

BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiographic pancreatography (ERCP) is the most accurate technique for surveillance of patients with primary sclerosing cholangitis (PSC). Our aim was to evaluate risk factors for complications of ERCP in patients with PSC. PATIENTS AND METHODS: In 2007 - 2009 we performed 441 ERCPs in patients with PSC. The primary tools for ERCP were a guide wire and papillotomy knife to gain access into the biliary duct. If the primary cannulation failed, and the wire went only into the pancreatic duct, pancreatic sphincterotomy was performed. If necessary, a further oblique cut with a needle knife was done in order to expose the biliary duct. RESULTS: Primary cannulation was successful in 389 patients (88.2 %). Of these, 147 (37.8 %) had had biliary sphincterotomy performed previously. In the group with failed primary cannulation, access into the biliary duct was achieved after pancreatic sphincterotomy in 52 patients. In 11 of these, a further cut with a needle knife was performed. Post-ERCP pancreatitis (PEP) was diagnosed in 31 patients (7.0 %). Factors predicting PEP were female sex (odds ratio [OR] 2.6, P = 0.015) and a guide wire in the pancreatic duct (OR 8.2, P < 0.01). Previous biliary sphincterotomy was a protective factor (OR 0.28, P = 0.02). The risk of PEP increased with the number of times the wire accidentally passed into the pancreatic duct (P < 0.001). Cholangitis developed in 6 patients (1.4 %). CONCLUSIONS: In patients with PSC the incidence of ERCP complications remained relatively low. The complication risk increased with the complexity of cannulation. In a patient with PSC in whom follow-up ERCP is planned, biliary sphincterotomy should be considered, as it may protect against PEP.

Patient-controlled sedation for ERCP: a randomized double-blind comparison of alfentanil and remifentanil.

BACKGROUND AND STUDY AIMS: Self-administration of a propofol and opioid mixture by patients (patient-controlled sedation, PCS) could offer a practical alternative for individual sedation during endoscopic retrograde cholangiopancreatography (ERCP). However, what would be the most suitable sedative mixture for PCS is unknown. The aim of this study was to compare remifentanil and alfentanil in the PCS during ERCP. PATIENTS AND METHODS: Eighty-one patients undergoing elective ERCP received PCS with propofol and opioid in three different regimens. The concentrations of opioids in the sedative mixture were 0.02 mg/mL in the remifentanil group (R) and 0.04 mg/mL and 0.08 mg/mL in the alfentanil 1 (A1) and alfentanil 2 (A2) groups, respectively. The infusion pump was adjusted to deliver a 1 mL single dose with zero lockout time. We considered PCS as successful if no procedure interruption due to sedation-related complications occurred or if additional propofol was not needed. The consumption of propofol was registered, and sedation levels and vital signs were monitored. Endoscopist and patient satisfaction with sedation were assessed using structured questionnaires. RESULTS: The consumption (SD) of propofol was 177 (105)mg in group R, 197 (88) mg in group A1 and 162 (70)mg in group A2. PCS was successful in 74 /81 (91 %) of sedations, without differences between the groups in terms of propofol consumption, sedation success rate, sedation levels, vital signs, postprocedural pain, and endoscopist and patient satisfaction. Respiratory depression and nausea were observed more frequently with remifentanil than with alfentanil (P < 0.05). CONCLUSIONS: PCS is an acceptable method of sedation for ERCP. The combination of propofol and alfentanil should be recommended because a remifentanil - propofol mixture depresses spontaneous respiration more and produces nausea more frequently.

Intranasal ketorolac tromethamine (SPRIX(R)) containing 6% of lidocaine (ROX-828) for acute treatment of migraine: safety and efficacy data from a phase II clinical trial.

OBJECTIVE: Ketorolac is a non-triptan, non-opioid, mixed cyclooxygenase (COX)1/2-inhibitor for short-term management of moderate-to-severe acute pain. This trial evaluated an intranasal formulation of ketorolac tromethamine (SPRIX®) containing 6% lidocaine (ROX-828) for the acute treatment of migraine with and without aura as defined by the International Headache Society. METHODS: Patients were randomly assigned 1:1 to self-treat with intranasal ROX-828 (31.5 mg ketorolac tromethamine/200 µL, containing 6% of lidocaine) or placebo (with 6% lidocaine) within four hours of a new migraine attack rated ≥ moderate in pain intensity. Assessments included headache intensity and associated migraine symptoms (nausea, vomiting, phonophobia, photophobia) measured at baseline and at regular intervals through 48 hours post-dosing, and global impression of efficacy (seven-point scale) measured at two hours. RESULTS: Randomized patients who had a migraine attack (N = 140) were evaluable (ROX-828, N = 68; placebo, N = 72). Patients receiving ROX-828 showed a significant (p < 0.05) improvement in pain relief at all time points except 0.5 and 24 hours compared with those who received placebo. More patients achieved pain-free status with ROX-828 than with placebo at 1.5, 3, 4, 24 and 48 hours (p < 0.05); significance at the two-hour time point, which was the primary endpoint, was not met. Patients' global impression of efficacy showed statistically significantly better results for patients receiving ROX-828 than for those receiving placebo. Associated migraine symptoms were significantly improved (p < 0.05) with ROX-828 relative to placebo at several time points throughout the observation period. The most frequently reported adverse events in both groups were associated with nasal discomfort. CONCLUSION: Self-administered intranasal ROX-828 was well tolerated. While the primary endpoint was not met, the results provide preliminary evidence that ROX-828 improves migraine pain.

Early quantification of HCV core antigen may help to determine the duration of therapy for chronic genotype 2 or 3 HCV infection.

The aim of the present study was to evaluate the utility of hepatitis C virus (HCV) core antigen (coreAg) assessment for the identification of candidates for short-term therapy. Plasma samples from HCV genotype 2 or 3-infected patients participating in the NORDynamIC trial (n=382) comparing 12 and 24 weeks of combination treatment with pegylated interferon-α2a and a fixed dose of 800 mg ribavirin daily were analyzed for coreAg. Among the 126 patients (33% of the intention-to-treat population) achieving HCV coreAg levels in plasma below 0.2 pg/mL when assayed on treatment day 3, sustained viral response (SVR) rates of 86% and 84% were achieved in the 12- and 24-week arms, respectively. Similarly, among patients having received at least 80% of the target dose of both pegylated interferon α-2a and of ribavirin for at least 80% of the target treatment duration (per-protocol analysis), the SVR rates were 89% and 95%, respectively. Twelve weeks of combination treatment may be sufficient for genotype 2 or 3-infected patients achieving HCV coreAg levels below 0.2 pg/mL by day 3, signaling a rapid clearance of HCV viremia.

Ribavirin plasma concentration is a predictor of sustained virological response in patients treated for chronic hepatitis C virus genotype 2/3 infection.

In hepatitis C virus (HCV) genotype 1 infection, the likelihood of obtaining sustained virological response (SVR) is associated with higher ribavirin exposure. Such an association has not been demonstrated for HCV genotype 2/3 infection, where a fixed 800 mg daily dosing of ribavirin is generally recommended. The primary aim of this study was to investigate the correlation between ribavirin concentration at day 29 and therapeutic response in patients with HCV genotype 2/3 infection. A total of 382 patients were randomized to 12 or 24 weeks of treatment with pegylated interferon-alfa 2a 180 µg weekly and 800 mg ribavirin daily. Trough plasma concentration of ribavirin was measured at day 29 and week 12 and the primary outcome was SVR (HCV-RNA undetectable 24 weeks after treatment). Of the 382 patients, 355 had a ribavirin concentration available at day 29. SVR was 84% among patients with a ribavirin concentration ≥2 mg/L at day 29 compared to 66% in those with concentrations <2 mg/L (P = 0.002). The corresponding figures in the 12-week treatment group were 74% and 57% (P = 0.12), and in the 24-week treatment group 91% and 75% (P = 0.02), respectively. In a multivariate analysis, ribavirin concentration at day 29 was an independent predictor of SVR (P = 0.002). In conclusion, a higher plasma ribavirin concentration is associated with an increased likelihood of achieving SVR in HCV genotype 2/3 infection. Individualization of ribavirin dosing may be helpful in improving outcome, especially in the presence of unfavourable baseline characteristics. This, however, requires evaluation in a prospective trial.

Hepatitis C treatment response kinetics and impact of baseline predictors.

The optimal duration of treatment for hepatitis C virus (HCV) infections is highly variable but critical for achieving cure (sustained virological response, SVR). We prospectively investigated the impact of age, fibrosis, baseline viraemia and genotype on the early viral kinetics and treatment outcome. Patients treated with peginterferon alfa-2a and ribavirin in standard dosing were included: 49 with genotype 1 treated for 48weeks and 139 with genotype 2 or 3 treated for 24weeks. The reduced SVR rates in patients older than 45years, with severe liver fibrosis or pretreatment viraemia above 400,000IU/mL were strongly associated with slower second phase declines of HCV RNA. Genotype 2/3 infections responded more rapidly than genotype 1, reaching week 4 negativity (RVR) in 59%vs 22%. We conclude that baseline response predictors such as age, fibrosis and viral load were well reflected by the early viral kinetics as assessed by repeated HCV RNA quantifications. The kinetic patterns and the high relapse rate in genotype 2/3 patients without RVR suggest that this group might benefit from treatment durations longer than 24weeks.

Restorative Proctocolectomy in Ulcerative Colitis: Effect of Preoperative Immunomodulatory Therapy on Postoperative Complications and Pouch Failure.

BACKGROUND AND AIMS: Patients with ulcerative colitis are often treated with multiple immunomodulative agents to achieve remission. In refractory disease, the next option is frequently proctocolectomy with ileal pouch-anal anastomosis. No consensus exists as to whether immunomodulatory therapy at the time of ileal pouch surgery leads to any increase in postoperative complications. Our aim was to assess, in ulcerative colitis patients with restorative proctocolectomy, the effect of preoperative anti-tumor necrosis factor therapy and corticosteroids on postoperative complications and pouch failure. MATERIALS AND METHODS: A retrospective medical record review of 445 patients with ulcerative colitis who underwent proctocolectomy with ileal pouch-anal anastomosis in Helsinki University Hospital between January 2005 and June 2016. RESULTS: Anti-tumor necrosis factor agents were not associated with postoperative complications. Only high-dose corticosteroids (prednisolone ⩾20 mg or equivalent) were associated with higher incidence of anastomotic leak (12.6% vs 2.5%, P = 0.002) and wound dehiscence (4.2% vs 0%, P = 0.019), but pouch failure rate was no higher (2.1% vs 0%, P = 0.141) than in patients without corticosteroid treatment. A lower dosage of corticosteroids had no effect on early postoperative complications, but pouch failure rate was increased (4.4% vs 0%, P = 0.015). CONCLUSION: Corticosteroids, but not anti-tumor necrosis factor therapy, were associated with postoperative complications. Preoperative use of corticosteroids may increase pouch failure rate, but the risk is still minor in high-volume centers performing ileal pouch surgery.

HHV-6 infection in multiple sclerosis. A clinical and laboratory analysis.

BACKGROUND AND PURPOSE: To elucidate the role of human herpesvirus-6 (HHV-6) in the development of multiple sclerosis (MS). PATIENTS AND METHODS: Nine patients with MS and with acute or chronic HHV-6 infection were evaluated. RESULTS: Intrathecal antibody production to HHV-6 and oligoclonal IgG bands in the cerebrospinal fluid (CSF) was observed in two patients with a clinically definite MS and chronic HHV-6 infection (based on the presence of HHV-6 specific antibodies in the CSF). A temporal association between the symptoms of clinically possible MS and acute primary HHV-6A infection (based on avidity of HHV-6 specific antibodies) was observed in two patients. CONCLUSIONS: Human herpesvirus-6 infection may be an associated agent in some MS cases. Viral studies are needed to identify a possible viral etiology and give specific therapy.

Migraine with aura is a risk factor for cervical artery dissection: a case-control study.

BACKGROUND: Cervical artery dissection (CAD) is the most common single etiology for stroke in young adults. Migraine, especially with aura (MA), is a known risk factor for ischemic stroke. The association between CAD and migraine was suggested based on a few small studies, but there are no large-scale case-control data, and the mechanisms are not yet clear. METHODS: We compared the lifetime prevalence of migraine and migraine characteristics in 313 CAD patients with 313 healthy age- and sex-matched controls. We also analyzed clinical and radiological characteristics of CAD with respect to migraine subtypes to investigate whether clear phenotypical associations can be found that might help in the search for a possible shared genetic background for migraine and CAD. RESULTS: Migraine was clearly more common in CAD patients than in controls (36 vs. 23%; OR 2.15; 95% CI 1.48-3.14), and the association was also highly significant for MA (23 vs. 12%; OR 2.41; 95% CI 1.53-3.80). Percentages of reported migraine history and MA of CAD patients vs. controls compared separately for both sexes were as follows: for women, migraine 54 vs. 35% (OR 2.30; 95% CI 1.28-4.13), MA 35 vs. 18% (OR 2.79; 95% CI 1.40-5.59); for men, migraine 27 vs. 16% (OR 2.02; 95% CI 1.23-3.31), MA 16 vs. 10% (OR 2.21; 95% CI 1.19-4.11). Over 60% of the CAD patients with still active migraine at the time of dissection reported later alleviation of migraine activity. CONCLUSION: Our observations suggest that patients with CAD are a significant link between ischemic stroke and migraine. This connection may represent a common pathophysiological or genetic background, or both. Migraine activity appears to be alleviated by CAD.

Genetic association study of endothelin-1 and its receptors EDNRA and EDNRB in migraine with aura.

The effect of endothelin-1 and its receptors EDNRA and EDNRB in migraine with aura (MA) susceptibility is not established yet. We studied the association between the MA end-diagnosis and three migraine trait components and 32 single nucleotide polymorphisms (SNPs) capturing the variation of endothelin genes in 850 Finnish migraine patients and 890 non-migrainous individuals. The SNPs showing evidence of association were further studied in 648 German migraine patients and 651 non-migrainous individuals. No significant association was detected. However, the homozygous minor genotype (5% in cases) of the EDNRA SNP rs2048894 showed nominal association with MA both in the Finnish sample (P = 0.015) and in the pooled sample [odds ratio (OR) 1.61, 95% confidence interval (CI) 1.12-2.32, P = 0.010] when adjusted for gender and sample origin. The trait age of onset < 20 years was also associated with rs2048894 (OR 1.69, 95% CI 1.13-2.54, P = 0.011) in the pooled sample. To confirm this finding studies on even larger samples are required.

A novel modification of a flow cytometric assay of phosphorylated STAT1 in whole blood monocytes for immunomonitoring of patients on IFN alpha regimen.

We explored whether episodes stimulating leucocytes in vivo could be tracked from whole blood samples by monitoring activation of STAT1 by flow cytometry. The method was tested in hepatitis C patients (n = 9) that were on interferon (IFN)alpha regimen. CD14+ monocytes responded strongly to IFNalpha/gamma being sensitive indicators for recent immune activation. At 45 min after s.c. IFNalpha 91% of monocytes were phosphorylated STAT1+. The frequency of responding cells decreased to a base level within 6 h. Monocytes, however, had a long-term deficient phosphorylated STAT1 response to IFNalphain vitro that in patients on standard IFNalpha regimen lasted for 48 h. In patients on pegylated IFNalpha the phosphorylated STAT1 response was completely absent. We conclude that whole blood analysis of STAT1 activation by flow cytometry is applicable to monitor immune cells in patient material.