Scoring magnetic resonance imaging (MRI) inflammation and structural lesions in sacroiliac joints of patients with axial spondyloarthritis: assessment of all MRI slices of the cartilaginous compartment versus standardized six or five slices.

Objectives: The Spondyloarthritis Research Consortium of Canada (SPARCC) sacroiliac joint (SIJ) scoring system assesses six or five (6/5) semicoronal magnetic resonance imaging (MRI) slices for inflammation/structural lesions in patients with axial spondyloarthritis (axSpA). However, the cartilaginous SIJ compartment may be visible in a few additional slices. The objective was to investigate interreader reliability, sensitivity to change, and classification of MRI scans as positive or negative for various lesion types using an 'all slices' approach versus standard SPARCC scoring of 6/5 slices.Method: Fifty-three axSpA patients were treated with the tumour necrosis factor inhibitor golimumab and followed with serial MRI scans at weeks 0, 4, 16, and 52. The most anterior and posterior slices covering the cartilaginous compartment and the transitional slice were identified. Scores for inflammation, fat metaplasia, erosion, backfill, and ankylosis in the cartilaginous SIJ compartment were calculated for the 'all slices' approach and the 6/5 slices standard.Results: By the 'all slices' approach, three readers scored mean 7.2, 7.7, and 7.0 slices per MRI scan. Baseline and change scores for the various lesion types closely correlated between the two approaches (Pearson's rho ≥ 0.95). Inflammation score was median 13 (interquartile range 6-21, range 0-49) for 6/5 slices versus 14 (interquartile range 6-23, range 0-69) for all slices at baseline. Interreader reliability, sensitivity to change, and classification of MRI scans as positive or negative for various lesion types were similar.Conclusion: The standardized 6/5 slices approach showed no relevant differences from the 'all slices' approach and, therefore, is equally suited for monitoring purposes.

Extremely poor patient-reported outcomes are associated with lack of clinical response and decreased retention rate of tumour necrosis factor inhibitor treatment in patients with axial spondyloarthritis.

OBJECTIVE: To investigate whether axial spondyloarthritis (axSpA) patients with extremely poor patient-reported outcomes (PROs) at start of first tumour necrosis factor inhibitor (TNFi) treatment have poorer treatment response and shorter treatment retention than other patients. METHOD: This observational cohort study was based on the nationwide DANBIO registry. Patients with axSpA who started first TNFi during 2011-2016 were stratified according to baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI ≥ 0.0 to ≤ 4.0, > 4.0 to ≤ 5.0, > 5.0 to ≤ 6.0, > 6.0 to ≤ 7.0, > 7.0 to ≤ 8.0, > 8.0 to ≤ 9.0, and > 9.0 to ≤ 10.0). An extremely poor BASDAI was defined as BASDAI > 9.0 to ≤ 10.0. Treatment responses after 6 months [≥ 50% improvement from baseline BASDAI (BASDAI50), ≥ 40% improvement in Assessment of SpondyloArthritis international Society (ASAS40) response, and ASAS partial remission] in patients with extremely poor PROs were compared with other patients by chi-squared tests, and retention rates by log-rank tests. Similar analyses were done for Bath Ankylosing Spondylitis Functional Index (BASFI), pain score, and patient global score. RESULTS: The study included 1396 patients (median age 39 years, 60% men). Patients with extremely poor baseline BASDAI [63 patients (5%)] were more often women, ever smokers, and human leucocyte antigen-B27 negative, and had higher body mass index. Response rates were poorer in patients with extremely poor BASDAI vs remaining patients (BASDAI50 19% and 41%, respectively, p < 0.001; ASAS40 16% and 35%, p = 0.002; ASAS partial remission 6% and 22%, p < 0.001). Patients with extremely poor BASDAI had lower 1 year treatment retention (51% and 68%, p < 0.001). Largely similar results were found for patients with extremely poor BASFI, pain score, and patient global score. CONCLUSION: Patients who reported an unusually large symptom burden at baseline had poor response rates and low retention rate. In such cases, competing causes of pain should carefully be taken into account when considering treatment with TNFi.

Investigation of a multi-biomarker disease activity score in rheumatoid arthritis by comparison with magnetic resonance imaging, computed tomography, ultrasonography, and radiography parameters of inflammation and damage.

OBJECTIVES: To investigate the multi-biomarker disease activity (MBDA) score by comparison with imaging findings in an investigator-initiated rheumatoid arthritis (RA) trial (HURRAH trial, NCT00696059). METHOD: Fifty-two patients with established RA initiated adalimumab treatment and had magnetic resonance imaging (MRI), ultrasonography (US), computed tomography (CT), and radiography performed at weeks 0, 26, and 52. Serum samples were analysed using MBDA score assays and associations between clinical measures, MBDA score, and imaging findings were investigated. RESULTS: The MBDA score correlated significantly with MRI synovitis (rho = 0.65, p < 0.001), MRI bone marrow oedema (rho = 0.36, p = 0.044), and US power Doppler (PD) score at week 26 (rho = 0.35, p = 0.039) but not at week 0 or week 52. In the 15 patients who had achieved a Disease Activity Score based on C-reactive protein (DAS28-CRP) < 2.6 at week 26, MRI and/or US detected subclinical inflammation and 13 (87%) had a moderate/high MBDA score. For the cohort with available data, none of the four patients in MBDA remission (score ≤ 25) at week 26 had progression of imaging damage from baseline to week 52 whereas progression was observed in three out of nine (33%) and seven out of 21 (33%) patients with moderate (30-44) and high (> 44) MBDA scores, respectively. CONCLUSIONS: In this cohort, the MBDA score correlated poorly with MRI/US inflammation. However, the MBDA score and MRI/US were generally concordant in showing signs of inflammation in most patients in clinical remission during anti-tumour necrosis factor (anti-TNF) therapy. MBDA scores were elevated in all patients with structural damage progression.

Health-related quality of life improves during one year of medical and surgical treatment in a European population-based inception cohort of patients with inflammatory bowel disease--an ECCO-EpiCom study.

BACKGROUND & AIMS: Health-related quality of life (HRQoL) is impaired in patients with Inflammatory Bowel Disease (IBD). The aim was prospectively to assess and validate the pattern of HRQoL in an unselected, population-based inception cohort of IBD patients from Eastern and Western Europe. METHODS: The EpiCom inception cohort consists of 1560 IBD patients from 31 European centres covering a background population of approximately 10.1 million. Patients answered the disease specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and generic Short Form 12 (SF-12) questionnaire at diagnosis and after one year of follow-up. RESULTS: In total, 1079 patients were included in this study. Crohn's disease (CD) patients mean SIBDQ scores improved from 45.3 to 55.3 in Eastern Europe and from 44.9 to 53.6 in Western Europe. SIBDQ scores for ulcerative colitis (UC) patients improved from 44.9 to 57.4 and from 48.8 to 55.7, respectively. UC patients needing surgery or biologicals had lower SIBDQ scores before and after compared to the rest, while biological therapy improved SIBDQ scores in CD. CD and UC patients in both regions improved all SF-12 scores. Only Eastern European UC patients achieved SF-12 summary scores equal to or above the normal population. CONCLUSION: Medical and surgical treatment improved HRQoL during the first year of disease. The majority of IBD patients in both Eastern and Western Europe reported a positive perception of disease-specific but not generic HRQoL. Biological therapy improved HRQoL in CD patients, while UC patients in need of surgery or biological therapy experienced lower perceptions of HRQoL than the rest.

Health care and patients' education in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom study.

BACKGROUND AND AIMS: The EpiCom study and inception cohort was initiated in 2010 in 31 centers from 14 Western and 8 Eastern European countries, covering a 10.1million person background population. Our aim was to investigate whether there is a difference between Eastern and Western Europe in health care and education of patients with inflammatory bowel disease (IBD). METHODS: A quality of care (QoC) questionnaire was developed in the EpiCom group consisting of 16 questions covering 5 items: time interval between the onset of symptoms and diagnosis, information, education, empathy and access to health care providers. RESULTS: Of 1,515 patients, 947 (217 east/730 west) answered the QoC questionnaire. Only 23% of all patients had knowledge about IBD before diagnosis. In Eastern Europe, significantly more patients searched out information about IBD themselves (77% vs. 68%, p<0.05), the main source was the Internet (92% vs. 88% p=0.23). In Western Europe, significantly more patients were educated by nurses (19% vs. 1%, p<0.05), while in Eastern Europe, gastroenterologists were easier to contact (80% vs. 68%, p<0.05). CONCLUSION: Health care differed significantly between Eastern and Western Europe in all items, but satisfaction rates were high in both geographic regions. Because of the low awareness and the rising incidence of IBD, general information should be the focus of patient organizations and medical societies. In Western Europe IBD nurses play a very important role in reducing the burden of patient management.

Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe--an ECCO-EpiCom study.

BACKGROUND AND AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients. METHODS: The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1 million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors. RESULTS: A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p<0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p<0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p<0.01). CONCLUSIONS: In this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle.

East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort.

OBJECTIVE: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East-West gradient in the incidence of IBD in Europe exists. DESIGN: A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience. RESULTS: 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100,000 in 2010 for CD were 6.5 (range 0-10.7) in Western European centres and 3.1 (range 0.4-11.5) in Eastern European centres, for UC 10.8 (range 2.9-31.5) and 4.1 (range 2.4-10.3), respectively, and for IBDU 1.9 (range 0-39.4) and 0 (range 0-1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy. CONCLUSIONS: An East-West gradient in IBD incidence exists in Europe. Among this inception cohort--including indolent and aggressive cases--international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.

[Cataract--an initial symptom of diabetes mellitus in a 14-year old girl]. / Katarakt--debutsymptom på diabetes mellitus hos 14-årig pige.

A 14-year-old girl presented with cataract as an initial sign of IDDM. Before the diagnosis of DM, she showed no acute symptoms, including ketoacidosis. Retrospectively, there had been faint signs of polyuria, polydipsia, and nycturia. Diabetic cataract is a rare complication in young diabetics and is usually associated with long-standing DM and poor metabolic control. Previous cases have a striking resemblance to our patient, thus suggesting that a small group of young diabetics have weak symptoms, but are nevertheless at great risk of developing diabetic complications.

[Iodine therapy for iodine deficiency goiter and autoimmune thyroiditis. A prospective study]. / Jodtherapie der Jodmangelstruma und Autoimmunthyreoiditis. Eine prospektive Studie.

PROBLEM: There is epidemiological and clinical evidence that iodine may induce or promote the manifestation of autoimmune thyroiditis. For this reason it is important to know if substitution of alimentary iodine deficiency or iodine treatment of endemic goitre can cause formation of thyroid antibodies. On the other hand the practical importance of this phenomenon should be evaluated. PATIENTS AND METHODS: During a prospective study we examined 209 patients with endemic non-toxic goitre and 53 healthy people. For treatment were used 200 micrograms iodine/d (n = 119), 500 micrograms iodine/d (n = 27), 1.5 mg iodine/week (n = 41), 150 micrograms iodine/d plus 75 to 100 micrograms T4/d (n = 26), 100 micrograms iodine plus 100 micrograms T4/d (n = 24). The observation took 1 year with a 3-month interval for check ups including clinical examination, ultrasound, TSH, T3, fT4, TPO- and thyreoglobuline antibodies and urinary iodine. RESULTS: After 12 months 7.5% of iodine treated persons had produced antibodies, most of them at low levels. In healthy people we found increased antibody-levels in 3.8%, in patients with goitre in 9.0%, in patients with nodular goitres in 11.1%. 500 micrograms iodine caused the most antibody reaction in 14.8%. People treated with 200 micrograms iodine/d showed positive antibody levels in 5%. T4 seems to reduce antibody-reactions. Pathological antibody-levels were not found in patients with combined iodine/T4- and single-T4 therapy. Among the 22 primary pathological antibody levels only 4 increased further (18.2%). Three of them belonged to the group of 5 persons treated with 500 micrograms iodine/d. Primary high antibody values were normalized in 5 patients (22.7%). Hypothyroid disturbances were not found. Ultrasound did not show any alterations, and the reduction of thyroid volumes in antibody-positive patients was not affected. Median urinary iodine excretion during the observation-interval was 5.2 to 7.2 micrograms/dl. CONCLUSIONS: Possible antibody reactions have no clinical importance at all. Individual cases must be observed. Low iodine doses should be preferred. Combined iodine/T4 treatment seems to have an advantage regarding immunological thyroidal reactions.

[Cryptorchism. Outcome of treatment and referral patterns in an unselected group of patients in a 3-year period]. / Kryptorkisme. Behandlingsresultat og henvisningsmønster hos en uselekteret patientpopulation i en 3-årig periode.

The age of diagnosis and referral together with the efficacy of HCG treatment were studied retrospectively in 196 unselected cryptorchid patients seen over a period of three years. The median age of diagnosis was 2 years and 7 months, whereas the median age of referral was three years later. During the period of study, guidelines for referral and therapy were published in a nationwide journal and in the local region, and a slight but significant fall in age of referral was seen thereafter. The median age of treatment with HCG, 92 patients, was 6 years and 11 months, and median age of surgery, was 7 years and 7 months. The rate of success with HCG was for bilateral testes 41% and for unilateral testes 21%, giving an overall success rate of 30%. This result is lower than previously reported, which is most likely explained by a higher suprascrotal position of testes before treatment. Guidelines and recommendations for referral and therapy seem to influence the time of referral, which is, however, in this study not in accordance with the consensus of definitive treatment before the age of two years. Early diagnosis is recommended and should be followed by referral to a paediatric department with particular interest and knowledge about cryptorchidism.

[The effect of giving a copy of the discharge letter to parents]. / Effekten af kopi af epikrise til foraeldre.

The purpose of this study was to evaluate the effect of giving parents a copy of the discharge letter (DL) concerning the hospitalization of their child. Questionnaires were sent to parents, general practitioners (GP) and health visitors (HV). Sixty-one per cent of the parents and 64% of the GPs and HVs returned the questionnaires. Seventy-seven per cent of the responding parents had received the discharge letter within a week after the discharge, and 64% of the parents understood the DL without difficulties. The majority regarded it as an improvement of the service to the families.

Growth, growth hormone and final height after BMT. Possible recovery of irradiation-induced growth hormone insufficiency.

The aim of the present study was to assess growth, final height, growth hormone (GH) secretion and growth factors after BMT including TBI in childhood. The median age of the 25 participants was 11.3 years at BMT, and a median of 7.5 years had elapsed since BMT. The median height standard deviation score (SDS) declined significantly from diagnosis until 4 years after BMT (n = 25, P = 0.015), and decreased 1.08 SDS from diagnosis until final height (n = 14, P = 0.030). Sitting height to standing height ratio was impaired, -0.64 SDS, P < 0.05. GH insufficiency was found in 32% at follow-up. Repeated assessments of GH production over the years indicated improvement in GH secretion in nine individuals. Evaluation of spontaneous 24-h GH secretion indicated a secretory pattern similar to controls, although the total amount of GH secreted was lower. Neither insulin-like growth factor-1 (IGF-1) nor IGF binding protein-3 (IGFBP-3) alone could be used as a marker of GH insufficiency. IGF-1 was low: -1.18 SDS; (P < 0.001). In conclusion, our study demonstrated the impact on growth, final height, body proportions, GH secretion and growth factors after BMT including TBI. We hypothesize that children who receive BMT at a younger age are more at risk of loss of final height and abnormal body proportions. Our data indicate that some improvement in GH production may occur over the years.

Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 levels are increased in central precocious puberty: effects of two different treatment regimens with gonadotropin-releasing hormone agonists, without or in combination with an antiandrogen (cyproterone acetate).

Central precocious puberty (CPP) is characterized by early activation of the pituitary-gonadal axis, which leads to increased growth velocity and development of secondary sexual characteristics. It is generally believed that gonadal sex steroids stimulate pulsatile GH secretion, which, in turn, stimulates insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) production. However, little is known about GH, IGF-I, and IGFBP-3 serum levels in children with precocious puberty. Treatment of CPP by GnRH agonists has become the treatment of choice. However, the effect of long term treatment with GnRH in combination with an antiandrogen (cyproterone acetate) to block the possible effect of adrenal androgens has not previously been evaluated. We, therefore, studied 40 patients with idiopathic CPP that were treated for 24 months with either GnRH analog (Buserelin) in combination with cyproterone acetate (Androcur; n = 23) or with long acting GnRH analog (Decapeptyl Depot; n = 17). We found that serum IGF-I levels were increased before treatment in both groups (mean +/- SE, 446 +/- 35 and 391 +/- 35 micrograms/L; P < 0.0001, respectively) compared to those in normal age-matched prepubertal children. Similarly, IGFBP-3 levels were significantly elevated (4675 +/- 209 and 4305 +/- 162 micrograms/L, respectively; P < 0.0001) in the two groups. Treatment with GnRH analog in combination with cyproterone acetate significantly decreased height velocity and serum IGF-I and IGFBP-3 levels to normal levels after 2 yr of treatment (P < 0.0001). Serum IGF-I levels remained unchanged during monthly im treatment with long acting GnRH analog, whereas IGFBP-3 levels significantly increased during the first year of this treatment despite unmeasurable estradiol levels. Thus, in both groups, the molar ratio between IGF-I and IGFBP-3 (i.e. free biologically active IGF-I) declined concomitantly with a decrease in growth velocity. Serum levels of IGF-I and IGFBP-3 (expressed as the SD score for bone age), but not those of estradiol, correlated with height velocity before and during treatment (r = 0.34; P < 0.0001 and r = 0.24; P = 0.003, respectively). Six of the patients with a subnormal GH response to clonidine had similar IGF-I and IGFBP-3 serum levels and growth velocity compared to the other 34 girls with CPP and a normal GH response.(ABSTRACT TRUNCATED AT 400 WORDS)

Immunohistochemical characterization of monoclonal antibodies directed against the TSH receptor.

Monoclonal antibodies have been obtained by fusing mouse myeloma cells with spleen cells of mice immunized with crude thyroid membranes. Among the antibodies reactive with different thyroid antigenic components, three were found to specifically react with TSH receptor molecules. These antibodies displayed characteristic staining patterns on frozen sections of thyroid tissue from patients with various thyroid diseases upon identification of antibody binding by indirect peroxidase staining. No specific reactivity was detected with tissue from other human organs, such as pancreas, liver, fat, and muscle. The results demonstrate that the immunoperoxidase technique and the specificity of the monoclonal antibodies produced permitted the identification of cellular constituents that might be important antigens in autoimmune thyroid disease.

Concurrent uveoretinitis and pineocytoma in a child suggests a causal relationship.

Uveoretinitis was observed in a 9-year-old girl 6 months prior to the clinical appearance of a pineal tumour. Surgical removal was not successful but biopsy revealed a parenchymal neoplasm with differentiated pinealocytes and absent mitotic activity. Some of the tumour cells contained S-antigen, rhodopsin, and serotonin. Systemic glucocorticoid therapy followed by radiation therapy caused considerable reduction in size of the tumour and a complete normalisation of all eye symptoms. This report demonstrates for the first time that a pineocytoma can occur together with uveoretinitis in humans. The latter resembles the experimentally induced autoimmune uveoretinitis described in animals. It is speculated that the retinitis might reflect an autoimmune response to S-antigen present in some tumour cells of the pineocytoma.

[Induction of spermatogenesis by pulsatile gonadotropin-releasing hormone treatment in hypogonadotropic hypogonadism]. / Induktion af spermatogenese ved pulsatil gonadotropinfrigørende hormonbehandling af hypogonadotrop hypogonadisme.

A successful case of pulsatile GnRH treatment of a 31 years old male with hypogonadotropic hypogonadism is described. During therapy for six months the secretions of LH, FSH and testosterone were normalised and the testicular volume increased to normal adult size. The sperm count increased from 0.0 to 0.9 mill/ml. Subsequently the sexual partner became pregnant and delivered a normal female infant.