Search

Purpose: To establish 60Co gamma -ray dose-response curves for dicentrics and translocations visualized by chromosome painting and for dicentrics analysed after conventional solid staining. Materials and methods : Analysis of chromosomal aberrations was performed on peripheral blood lymphocytes obtained from 48 h old cultures of irradiated whole blood. Dicentrics were scored from Giemsa-stained preparations, and bi-coloured dicentrics and translocations after FISH painting of chromosomes 1, 2 and 4. Results : Equal frequencies of complete dicentrics and translocations, where both members of the exchanges were seen, were observed in the chromosome painting analysis at all doses, resulting in similar calibration curves. Due to differences in scoring criteria, dicentrics scored in conventionally Giemsastained slides agreed better with data for total than for complete exchanges. Donor differences for translocations at the control level and at low doses were seen and large uncertainty surrounds the linear component of the dose-response for total translocations. Conclusions : Dose reconstruction of past exposures in cases of low doses is very dependent on the linear coefficient of the curve. Results indicate that total translocations would give less reliable dose estimates and therefore complete translocations are preferred. [ABSTRACT FROM AUTHOR]

Purpose: To assess the validity of translocations for retrospective biodosimetry using FISH chromosome painting of peripheral lymphocytes in repeated samples of people accidentally exposed to radiation. Materials and methods : Blood samples from five people exposed to mainly whole-body irradiation of gamma -rays from a radiation accident in Estonia in 1994 were taken at 2-4 month intervals. A total of eight samplings were carried out, including one directly after the accident. Fluorescence in situ hybridization with probes for chromosomes 1, 2 and 4 was performed on metaphase preparations from 48h whole blood cultures; 1500 cells were scored from each individual per time point. Results: Translocations remained relatively stable during 2 years after exposure in all subjects. A noticeable decrease in complete translocation yields and a significant decrease in incomplete translocations were observed in one person. In addition to wholebody exposure, he had also been exposed to partial-body irradiation. Due to the overall persistence of translocations, dose estimates were very similar throughout the 2 year period. A rapid decline in dicentric frequencies was noted during the first year after exposure. Conclusions: The results suggest that during 2 years the yield of translocations in peripheral lymphocytes remained at a constant level after whole-body exposure. This finding supports the use of translocations for retrospective dosimetry, at least within this relatively short period of follow-up. In the case of partial-body irradiation, however, the elimination of co-existing unstable aberrations reduced the translocation yield over time. Follow-up will be continued in order to determine the stability of translocations over longer times. [ABSTRACT FROM AUTHOR]

Purpose: To analyze treatment persistence and treatment outcomes of vedolizumab as first-line biological treatment in Crohn's disease (CD) and ulcerative colitis (UC) patients in a Finnish real-world setting., Methods: Observational, retrospective, multi-center chart review study that included adult CD and UC patients initiating vedolizumab as first-line biological treatment between 2014 and 2020., Results: The cohort consisted of 54 CD and 69 UC patients. At month 12, treatment persistence was 84.9 % in CD and 64.7 % in UC. Most vedolizumab discontinuations (CD, n = 11; UC, n = 26) were due to inefficacy. Discontinuations due to adverse events were rare (n < 5). Efficacy improvements were observed in treatment persistent patients at 12 months vs. baseline in the Harvey-Bradshaw Index (CD, 1.8 vs. 3.9, p = 0.001), Partial Mayo Score (UC, 1.0 vs. 4.9, p < 0.001), Physician's Global Assessment (CD, 0.9 vs. 1.8, p < 0.001; UC, 0.4 vs. 2.1, p < 0.001), along with positive endoscopic and biochemical outcomes. Clinical remission was 90.9 % vs. 63.0 % for CD, and 81.6 % vs. 12.3 % for UC, while corticosteroid use was 15.9 % vs. 53.7 % for CD, and 14.6 % vs. 92.8 % for UC at 12 months and baseline, respectively., Conclusion: Vedolizumab was associated with improvements in efficacy, endoscopic activity, biochemical parameters, and decreased corticosteroid burden when used as a first-line biological treatment., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Tero Ylisaukko-oja reports financial support was provided by MedEngine Oy. Sarah Smith reports financial support was provided by MedEngine Oy. Jari Jokelainen reports financial support was provided by MedEngine Oy. Paula Haiko reports financial support was provided by Takeda Oy. Anja Eberl reports was provided by Janssen-Cilag SAS. Clas-Göran af Björkesten reports financial support was provided by AbbVie Inc. Clas-Göran af Björkesten reports financial support was provided by Bristol Myers Squibb Co. Clas-Göran af Björkesten reports financial support was provided by Janssen Pharmaceuticals Inc. Clas-Göran af Björkesten reports financial support was provided by Merck Sharp & Dohme Corp. Clas-Göran af Björkesten reports financial support was provided by Pfizer Inc. Clas-Göran af Björkesten reports financial support was provided by Takeda Oy. Clas-Göran af Björkesten reports financial support was provided by Mylan Pharmaceuticals Inc. Clas-Göran af Björkesten reports financial support was provided by Ferring Pharmaceuticals Inc. Clas-Göran af Björkesten reports financial support was provided by Vifor (International) AG. Heikki Nuutinen reports financial support was provided by Takeda Oy. Pauliina Molander reports financial support was provided by AbbVie Oy. Pauliina Molander reports financial support was provided by Bristol Myers Squibb Co. Pauliina Molander reports financial support was provided by Gilead Sciences. Pauliina Molander reports financial support was provided by Janssen-Cilag SAS. Pauliina Molander reports financial support was provided by Orion Corporation. Pauliina Molander reports financial support was provided by Pfizer. Pauliina Molander reports financial support was provided by Sandoz Inc. Pauliina Molander reports financial support was provided by Takeda Oy. Pauliina Molander reports financial support was provided by Tillotts Pharma AG. Pauliina Molander reports financial support was provided by Viatris. Ritva Koskela reports financial support was provided by Pfizer Inc. Ritva Koskela reports financial support was provided by Vifor (International) AG. Ritva Koskela reports financial support was provided by Janssen Pharmaceuticals Inc. Ritva Koskela reports financial support was provided by Takeda Oy. Ritva Koskela reports financial support was provided by Ferring Pharmaceuticals Inc. Taina Sipponen reports financial support was provided by AbbVie Oy. Taina Sipponen reports financial support was provided by Bristol Myers Squibb Co. Taina Sipponen reports financial support was provided by Pfizer. Taina Sipponen reports financial support was provided by Takeda Oy. Taina Sipponen reports financial support was provided by Celltrion, Inc. Taina Sipponen reports financial support was provided by Janssen-Cilag SAS. Tero Ylisaukko-oja reports a relationship with MedEngine Oy that includes: equity or stocks., (© 2024 The Authors.)

Objectives: It has been suggested that celiac disease could be diagnosed non-invasively in adults with transglutaminase antibody (TGA) levels >10x upper limit of normal (ULN). It is, however, unclear if high values signify more advanced disease and higher risk of co-morbidities. We investigated the association between the TGA levels, clinical characteristics and non-celiac endoscopic findings., Methods: Medical data on 450 celiac disease patients at diagnosis were collected. They were further divided into those with high positive (>10x ULN, n  = 164), moderately positive (1-10x ULN, n  = 219), and negative ( n  = 67) TGA., Results: Median age of patients was 50 years and 60% were women. Patients with negative TGA were older (median age 58 vs. 51 vs. 46 years respectively, p  = 0.002) and had more often weight loss (27% vs. 10% vs. 9%, p  < 0.001) and abdominal pain or dyspepsia (40% vs 27% vs. 22%, p  = 0.017) than did those with moderately positive/high TGA. The groups did not differ in sex, BMI, or other symptoms. Major endoscopic findings included one esophageal adenocarcinoma presenting with dysphagia, six esophagitis, three gastric ulcers, and 39 H. Pylori or other active gastritis. High, moderately positive or negative TGA levels were not associated with these findings in crude or age-adjusted analyses., Conclusions: Presentation was similar in patients with moderate or high levels of TGA, whereas patients with negative TGA were different. The level of TGA was not associated with incidental endoscopic findings and the only malignancy presented with an alarm symptom atypical to celiac disease.

Background and Aims: The early outcomes of ulcerative colitis (UC) after rescue therapy with cyclosporine A (CyA) are well known. Published data on the safety of this treatment in perioperative use and data on the long-term prognosis are scarce and are investigated here., Methods: All UC patients treated with CyA in Tampere University Hospital between 2009 and 2018 were reviewed from patient records., Results: A total of 182 patients were included with the median follow-up of 3.8 (range 0-13) years. Of all patients, 139 (76%) responded to CyA. A quarter of the responders achieved long-term remission and used thiopurines as maintenance therapy at the end of follow-up. Altogether 83 (46%) needed further enhancement of treatment with corticosteroids (Cs) and 57 (31%) with biologicals or small molecules. Of the nonresponders 27 (55%) were treated surgically within admission to index flare. Infliximab was used as a third-line rescue therapy for 16 patients of whom four benefitted. The overall colectomy rate in this series was 45%. When compared to Cs alone CyA did not increase the risk for severe postoperative complications in patients treated for severe treatment-refractory UC., Conclusion: In conclusion, despite the good initial response to CyA, a large proportion of patients relapsed during long-term follow-up and the colectomy rates remain high. Other therapy attempts after failure of CyA merely postpone surgery in many. We therefore recommend informing patients about the possibility of surgery prior to the initiation of rescue therapy.

Background and Aims: Therapy with two concomitant biologicals targeting different inflammatory pathways has emerged as a new therapy option for treatment refractory inflammatory bowel disease (IBD). Data on the efficacy and safety of dual biological therapy (DBT) are scarce and are investigated in this study., Materials and Methods: Data on all patients treated with a combination of two biologicals in four Finnish tertiary centres were collected and analysed. Remission was assessed by a physician on the basis of biomarkers, endoscopic evaluation and alleviation of symptoms., Results: A total of 16 patients with 22 trials of DBT were included. Fifteen patients had Crohn's disease. The most common combination of DBT was adalimumab (ADA) and ustekinumab (USTE; 36%) with median follow-up of nine months (range 2-31). Altogether seven (32%) patients were in remission at the end of follow-up and in two trials response to DBT was assessed to be partial with the relief of patient symptoms. In a total of four trials DBT reduced the need for corticosteroids. The majority of patients achieving a response to DBT were treated with the combination of ADA and USTE (56%). At the end of follow-up all nine (41%) patients responding to DBT continued treatment. Infection complications occurred in three patients (19%)., Conclusion: DBT is a promising alternative treatment for refractory IBD, and half of our patients benefitted from it. More data on the efficacy and safety of DBT are needed especially in long-term follow up.

Background: Real-world evidence to support optimal ustekinumab dosing for refractory Crohn's disease (CD) patients remains limited. Data from a retrospective nationwide chart review study was utilized to explore ustekinumab dosing dynamics and optimization, identify possible clinical predictors of dose intensification, and to evaluate ustekinumab trough concentrations (TCs) and concomitant medication use in Finland., Methods: Information gathered from17 Finnish hospitals included clinical chart data from 155 adult CD patients who received intravenous ustekinumab induction during 2017-2018. Data on ustekinumab dosing and TCs, concomitant corticosteroid and immunosuppressant use, and antiustekinumab antibodies were analyzed in a two-year follow-up, subject to availability., Results: Among 140 patients onustekinumab maintenance therapy, dose optimization was required in 55(39%) of the patients, and 41/47 dose-intensified patients (87%) persisted on ustekinumab. At baseline, dose-intensified patient group had significantly higher C-reactive protein (CRP) levels, and at week 16, significantly lower ustekinumab TCs than in patients without dose intensification. Irrespective of dose optimization, a statistically significant reduction in the use of corticosteroids was observed at both 16 weeks and one year, coupled with an increased proportion of patients on ustekinumab monotherapy. Antiustekinumab antibodies were undetectable in all 28 samples from 25 patients collected throughout the study period., Conclusions: Nearly a third of all CD patients on ustekinumab maintenance therapy, with a history of treatment-refractory and long-standing disease, required dose intensification. These patients persisted on ustekinumab and had significant reduction of corticosteroid use. Increased baseline CRP was identified as the sole indicator of dose intensification., Trial Registration: EUPAS30920.

Background and Aims: Every fifth patient with ulcerative colitis (UC) experiences severe acute flare at some point in the course of the disease. Corticosteroids (Cs) remain the treatment of choice in acute flare. Data on the efficacy of first intravenous Cs in the long-term prognosis of UC are scarce and were investigated here., Materials and Methods: All episodes of patients with acute UC admitted to Tampere University Hospital and treated with intravenous Cs between January 2007 and January 2016 were identified from patient records and reviewed. The risks for colectomy and for continuous use of Cs were evaluated. Predictive factors were analysed., Results: The study comprised 217 patients of whom 184 (85%) responded to intravenous Cs at index flare. Of the 33 non-responders, 31 (94%) were treated with intravenous cyclosporine A and 28 responded. Five (2.3%) patients needed emergency colectomy. Twenty-six (12%) patients underwent colectomy within 1 year of index flare. Overall colectomy rate was 56 (26%) during follow-up (median 7.5 years, range 0.1-10.5). Six months after index flare 66 (30%) patients were still on steroids. In this series 149 (69%) required further Cstherapy and 104 (48%) needed rehospitalization for new flare at some point during follow-up. Overall 155 patients were treated with thiopurines, of whom 72% within the first year after admission. A total of 36 patients had infliximab as a first-line biological treatment, nine needed second-line therapy with adalimumab or vedolizumab after infliximab failed., Conclusion: Although intravenous Cs were efficient in inducing clinical response in patients with severe acute UC, only one fifth maintained remission in the long term. Two-thirds of patients required further Cs and the overall colectomy rate remained at 26%. High relapse rate indicates the need for closer monitoring of these patients. Enhancement of maintenance therapy should be considered at early stage after acute flare.

Objective: Long-term evidence on ustekinumab treatment response and persistence in patients with Crohn's disease in a real-world setting is scarce. We performed a retrospective nationwide chart review study of long-term clinical outcomes in Crohn's disease patients treated with ustekinumab., Methods: The study was conducted in 17 Finnish hospitals and included adult Crohn's disease patients who received an initial intravenous dose of ustekinumab during 2017-2018. Disease activity data were collected at baseline, 16 weeks, and 1 year from health records., Results: The study included 155 patients. The disease was stricturing or penetrating in 69 and 59% had prior Crohn's disease-related surgeries, and 97% had a treatment history of at least one biologic agent. Of 93 patients with ≥1 year of follow-up, 77 (83%) were still on ustekinumab at 1 year. In patients with data available, from baseline to the 1-year follow-up the simple endoscopic score for Crohn's disease (SES-CD) decreased from 10 to 3 (P = 0.033), C-reactive protein from 7  to 5 mg/L, (P < 0.001) and faecal calprotectin from 776 to 305 μg/g (P < 0.001)., Conclusions: Ustekinumab treatment in patients with highly refractory Crohn's disease resulted in high long-term treatment persistence and significantly reduced disease activity, assessed with objective markers for intestinal inflammatory activity.

Introduction: We assessed whether celiac disease-associated mortality is increased in Finland among patients diagnosed in the 21st century, given recent improvements in diagnostic and treatment facilities., Methods: Biopsy-proven patients with celiac disease (Marsh III) and dermatitis herpetiformis aged 20-79 years (median 50 years) diagnosed 2005-2014 (n = 12,803) were identified from the national dietary grant registry. Dates and causes of death were obtained from Statistics Finland. Overall mortality and causes of death were compared with reference individuals (n = 38,384) matched for age, sex, and area of residence (at the time of celiac disease diagnosis) selected from the Population Information System., Results: During a mean follow-up of 7.7 years (SD ±3.0 years), 884 (6.9%) and 2,613 (6.8%) deaths occurred among the celiac cohort and reference group, respectively. Overall mortality (hazard ratio [HR] 1.01, 95% confidence intervals [CIs] 0.94-1.09), mortality from all malignancies (HR 1.11, 95% CI 0.96-1.27), gastrointestinal tract malignancies (HR 1.21, 95% CI 0.56-1.71), or cardiovascular diseases (HR 0.91, 95% CI 0.77-1.07) were not increased among patients with celiac disease. Overall, mortality from lymphoproliferative diseases (HR 2.36, 95% CI 1.65-3.39) and nonmalignant digestive diseases (HR 2.19, 95% CI 1.40-3.43) was increased, but HRs decreased after the exclusion of the first 2 years of follow-up (HR 1.71, 95% CI 1.10-2.66 and HR 1.75, 95% CI 1.01-3.05, respectively)., Discussion: The overall mortality in adult celiac disease diagnosed 2005-2014 was not increased. Mortality from lymphoproliferative diseases was increased but lower than previously reported.

Background and aims: A multicentre, retrospective, non-interventional, patient chart review study was conducted to investigate deep (DR) and histological remission rates during maintenance therapy with biological agents in inflammatory bowel disease (IBD). Methods: We reviewed clinical, endoscopic, and histological findings, and laboratory markers such as C-reactive protein (CRP) and faecal calprotectin (FC) on average of nine years after the initiation of anti-TNF-therapy. DR was defined as no clinical symptoms (The physicians' global assessment scores; PGA = 0) with endoscopic remission (the Simple Endoscopic Score for Crohn's Disease [SES-CD] ≤ 2 or Mayo endoscopic subscore ≤1). Histological activity was defined as normal if only architectural alterations without cellularity changes occurred. Results: Of 117 IBD patients on maintenance therapy, 72 (62%; CD n  = 55 [56%], UC n  = 17 [85%]) patients were in DR. Of patients in DR, 76% were also in histological remission. 77% of patients remained on initiated biological treatment. UC patients achieved DR significantly more often than CD patients ( p  = .016). Both median CRP and FC levels were significantly lower in patients with DR. Conclusion: Reassuringly, almost two thirds of the IBD patients on maintenance therapy with biological agents maintained DR in the long-term, and more than two thirds of patients in DR achieved also histological remission. CD patients in DR had fewer surgical operations due to CD than patients not achieving DR.

Dermatitis herpetiformis (DH) is an extraintestinal manifestation of celiac disease causing an itchy, blistering rash. Granular IgA deposits in the skin are pathognomonic for DH, and the treatment of choice is a lifelong gluten-free diet (GFD). Preliminary evidence suggests that there are patients with DH who redevelop gluten tolerance after adherence to a GFD treatment. To evaluate this, we performed a 12-month gluten challenge with skin and small-bowel mucosal biopsy samples in 19 patients with DH who had adhered to a GFD for a mean of 23 years. Prechallenge biopsy was negative for skin IgA and transglutaminase 3 deposits in 16 patients (84%) and indicated normal villous height-to-crypt depth ratios in the small bowel mucosa in all 19 patients. The gluten challenge caused a relapse of the rash in 15 patients (79%) in a mean of 5.6 months; of these 15 patients, 13 had skin IgA and transglutaminase 3 deposits, and 12 had small-bowel villous atrophy. In addition, three patients without rash or immune deposits in the skin developed villous atrophy, whereas one patient persisted without any signs of relapse. In conclusion, 95% of the patients with DH were unable to tolerate gluten even after long-term adherence to a GFD. Therefore, lifelong GFD treatment remains justified in all patients with DH., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Goals: The aim of this study was to investigate the role of dietary factors, distinct small-bowel mucosal immune cell types, and epithelial integrity in the perpetuation of gastrointestinal symptoms in treated celiac disease patients., Background: For unexplained reasons, many celiac disease patients suffer from persistent symptoms, despite a strict gluten-free diet (GFD) and recovered intestinal mucosa., Study: We compared clinical and serological data and mucosal recovery in 22 asymptomatic and 25 symptomatic celiac patients on a long-term GFD. The density of CD3 and γδ intraepithelial lymphocytes (IELs), CD25 and FOXP3 regulatory T cells, and CD117 mast cells, and the expression of tight junction proteins claudin-3 and occludin, heat shock protein 60, interleukin 15, and Toll-like receptor 2 and 4 were evaluated in duodenal biopsies., Results: All subjects kept a strict GFD and had negative celiac autoantibodies and recovered mucosal morphology. The asymptomatic patients had higher mean fiber intake (20.2 vs. 15.2 g/d, P=0.028) and density of CD3 IELs (59.3 vs. 45.0 cell/mm, P=0.045) than those with persistent symptoms. There was a similar but nonsignificant trend in γδ IELs (17.9 vs. 13.5, P=0.149). There were no differences between the groups in other parameters measured., Conclusions: Low fiber intake may predispose patients to persistent symptoms in celiac disease. There were no differences between the groups in the markers of innate immunity, epithelial stress or epithelial integrity. A higher number of IELs in asymptomatic subjects may indicate that the association between symptoms and mucosal inflammation is more complicated than previously thought.

Background: In coeliac disease, ingestion of gluten induces the production of transglutaminase 2 (TG2)-targeted autoantibodies by TG2-specific plasma cells present at high frequency in the small intestinal mucosa in untreated disease. During treatment with a gluten-free diet (GFD), the number of these cells decreases considerably. It has not been previously investigated whether the cells are also present prior to development of villous atrophy, or in non-responsive patients and those with dietary lapses. We aimed to define the frequency of small bowel mucosal TG2-specific plasma cells in coeliac disease patients with varying disease activity, and to investigate whether the frequency correlates with serum and small intestinal TG2-targeting antibodies as well as mucosal morphology and the number of intraepithelial lymphocytes., Results: Mucosal TG2-specific plasma cells were found in 79% of patients prior to development of mucosal damage, in all patients with villous atrophy, and in 63% of the patients after 1 year on GFD. In these disease stages, TG2-specific plasma cells accounted for median of 2.3, 4.3, and 0.7% of all mucosal plasma cells, respectively. After long-term treatment, the cells were present in 20% of the patients in clinical remission (median 0%) and in 60% of the patients with poor dietary adherence (median 5.8%). In patients with non-responsive coeliac disease despite strict GFD, the cells were found in only one (9%) subject; the cells accounted for 2.4% of all plasma cells. A positive correlation between the percentage of TG2-specific plasma cells and serum TG2 antibody levels (r S  = 0.69, P < 0.001) and the intensity of mucosal TG2-targeting IgA deposits (r S  = 0.43, P < 0.001) was observed., Conclusions: Our results show that TG2-specific plasma cells are already detectable prior to villous atrophy, and that generally their frequency increases during overt disease. By contrast, on GFD, the percentage of these cells decreases. Overall, the presence of TG2-specific plasma cells in the small bowel mucosa mirrors the presence of gluten in the diet, but the frequency is not always parallel to the level of serum or intestinal TG2 antibodies. These findings increase the knowledge about the development of the TG2 plasma cell responses especially in the early phases of coeliac disease.

Background and Aims: In nonresponsive celiac disease (NRCD), the symptoms and duodenal damage persist despite a gluten-free diet. Celiac disease patients with persistent symptoms are found to have a dysbiotic microbiota. We thus hypothesized that increased seroreactivity to the serum gluten-sensitive microbial antibodies Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (I2), and Bacteroides caccae TonB-linked outer membrane protein (OmpW) is associated with NRCD., Methods: ASCA, I2 and OmpW were measured in 20 seronegative CD patients with persistent villous damage despite strict dietary treatment (NRCD group). Fifty-eight responsive patients served as CD controls (55 on gluten-free treatment) and 80 blood donors as non-CD controls., Results: At least one microbial marker was positive in 80% of NRCD patients, in 97% of untreated CD and 87% of treated CD patients, and in 44% of controls. NRCD patients had the highest frequency of ASCA positivity (65% vs 52, 20, and 0%, respectively) and also significantly higher ASCA IgA (median 14.5 U/ml) and IgG (32.5 U/ml) titers than treated CD patients (7.0 U/ml, 13.0 U/ml) and non-CD controls (4.5 U/ml, 5.8 U/ml). The frequencies of I2 and OmpW were lower in NRCD than in untreated CD (65% and 45% vs 86% and 59%, respectively), and I2 titers were higher in NRCD (median absorbance 0.76) and untreated (1.0) and treated (0.83) CD than controls (0.32). OmpW was elevated in untreated (1.1) and treated (0.94) CD patients compared with controls (0.79)., Conclusions: Seropositivity and high titers of ASCA are associated with NRCD and might serve as an additional follow-up tool in CD.

Introduction: Guidelines recommend regular follow-up in coeliac disease, but effect of this on long-term outcomes remains unclear., Aims: To evaluate predictors and significance of long-term follow-up., Methods: 677 previously diagnosed coeliac patients were recruited for a nationwide health survey. Medical data were gathered through interviews and patient records. Current symptoms and quality of life were assessed by validated questionnaires and blood samples were drawn for serology. All variables were compared between patients with and without long-term (>2 years) follow-up., Results: 15% had long-term follow-up, median duration 10 years. Predictors (p < 0.05) for the follow-up were immunological (35% vs. 24%) and circulatory (20% vs. 12%) comorbidities, whereas it was less common in subjects with musculoskeletal (23% vs. 34%) comorbidity and those not belonging to any at-risk group (16% vs. 27%). Patients with or without follow-up had comparable age, adherence and ability to manage a gluten-free diet and frequency of seropositivity. Also questionnaire scores paralleled, but those without follow-up reported more overall symptoms (16% vs. 26%). Most patients wished for follow-up., Conclusion: Only a minority of patients had regular follow-up. However, patients with and without the follow-up were comparable in most long-term outcomes, indicating that it might not be always necessary. The results call for more personalized follow-up policies in coeliac disease., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The mammalian nucleus has a distinct substructure that cannot be visualized directly by conventional microscopy. In this study, the organization of the DNA within the nucleus of multiple myeloma (MM) cells, their precursor cells (monoclonal gammopathy of undetermined significance; MGUS) and control lymphocytes of the representative patients is visualized and quantified by superresolution microscopy. Three-dimensional structured illumination microscopy (3D-SIM) increases the spatial resolution beyond the limits of conventional widefield fluorescence microscopy. 3D-SIM reveals new insights into the nuclear architecture of cancer as we show for the first time that it resolves organizational differences in intranuclear DNA organization of myeloma cells in MGUS and in MM patients. In addition, we report a significant increase in nuclear submicron DNA structure and structure of the DNA-free space in myeloma nuclei compared to normal lymphocyte nuclei. Our study provides previously unknown details of the nanoscopic DNA architecture of interphase nuclei of the normal lymphocytes, MGUS and MM cells. This study opens new avenues to understanding the disease progression from MGUS to MM., (© 2014 Wiley Periodicals, Inc.)

Objectives: The association between celiac disease and malignancies is well recognized. In Finland, the prevalence of clinically diagnosed adult celiac disease is 0.6%. In this large, population-based cohort, we aimed at a realistic projection of the cancer risk., Methods: In the period 2002-2011, the register comprised 32,439 adult celiac patients. This was linked with the Finnish Cancer Registry, which covers over 98% of diagnosed malignancies. The standardized incidence ratio (SIR) was calculated for the malignancies, on the basis of incidence figures for the whole population. A time-stratified analysis was made in celiac patients diagnosed after 2004 (n=11,991). Lifestyle factors, including smoking habits and obesity, were not obtainable., Results: The overall incidence ratio of malignant diseases was not increased (SIR 0.94; 95% confidence intervals 0.89-0.98), but it was ≥5 years from the diagnosis of celiac disease (1.31, 1.04-1.63). The SIRs for non-Hodgkin lymphoma (NHL; 1.94; 1.62-2.29), small-intestinal cancer (4.29; 2.83-6.24), colon cancer (1.35; 1.13-1.58), and basal cell carcinoma of the skin (1.13; 1.03-1.22) were increased, whereas those for lung cancer (0.60; 0.48-0.74), pancreatic cancer (0.73; 0.53-0.97), bladder cancer (0.53; 0.35-0.77), renal cancer (0.72; 0.51-0.99), and breast cancer (0.70; 0.62-0.79) were decreased. SIR for NHL immediately after the diagnosis of celiac disease was 2.56 (1.37-4.38)., Conclusions: There was no increased SIR of cancer in the whole series, but SIR was increased after 5 years from the diagnosis of celiac disease. The risk of breast and lung cancers was decreased. The risk of small-intestinal cancer and NHL was increased, but to a lesser extent than previously described.

Multiple myeloma (MM) is preceded by monoclonal gammopathy of undetermined significance (MGUS). Up to date, it is difficult to predict an individual's time to disease progression and the treatment response. To examine whether the nuclear telomeric architecture will unravel some of these questions, we carried out. Three-dimensional (3D) telomere analysis on samples from patients diagnosed with MGUS and MM, as well as from patients who went into relapse. Telomere signal intensity, number of telomere aggregates, nuclear volume, and the overall nuclear telomere distribution (a/c ratio) were analyzed. The telomeric profiles allowed for the differentiation of the disease stages. The telomeric profiles of myeloma cells obtained from blood and bone marrow aspirates were identical. Based on this study, we discuss the use of 3D telomere profiling as a potential future tool for risk stratification and personalized treatment decisions.