Tofacitinib real-world experience in ulcerative colitis in Finland (FinTofUC): a retrospective non-interventional multicenter patient chart data study.

OBJECTIVES: The aim was to define the effectiveness of tofacitinib and to characterize the patient population receiving tofacitinib in a real-world cohort clinical setting for ulcerative colitis (UC) in Finland. METHODS: This is a retrospective non-interventional multicenter patient chart data study conducted in 23 Finnish Inflammatory Bowel Disease (IBD) centers. Baseline demographic and clinical data, clinical remission, steroid-free remission rate and time to tofacitinib discontinuation, colectomy or UC-related hospitalization were studied. RESULTS: The study included 252 UC patients of which 69% were male. Most patients had extensive disease (71%) and were bio-experienced (81%). Tofacitinib demonstrated positive treatment outcomes with clinical response, clinical remission, and steroid-free clinical remission at one year in 33%, 34% and 31% of patients, respectively. Moreover, 64% of patients in pMayo remission at week 16 from the start of tofacitinib were still in remission at one year. Only no or mild disease activity compared to moderate activity at baseline was associated with a higher probability of achieving remission according to pMayo at six months, p = .008. Hospitalizations and/or colectomies during the study period (before treatment discontinuation/end of follow-up) were low (n = 24), with less than 5 colectomies. CONCLUSIONS: In this real-world cohort, including a majority of bio-experienced UC patients, tofacitinib was effective in achieving steroid-free clinical remission in a third of the population at one year. A majority of patients in remission at week 16 were also in remission at one year. Results are in line with earlier published real-world studies. Registration: ClinicalTrials.gov NCT05082428.

Discontinuing low-dose acetylsalicylic acid after gastrointestinal bleeding is associated with increased mortality.

BACKGROUND: Gastrointestinal bleeding is a common clinical problem in patients using low-dose acetylsalicylic acid (ASA). It is uncertain whether aspirin should continue to be used in patients who develop acute gastrointestinal bleeding during low-dose ASA therapy. AIMS: To assess whether ASA should be continued in patients who develop GI bleeding during low-dose ASA. METHODS: All patients admitted to an academic hospital for acute gastrointestinal bleeding between 2009 and 2011 were reviewed retrospectively. Clinical characteristics, comorbidities, medications and treatments were recorded from the patient records. Patients were divided into two groups based on continuing or discontinuing ASA after discharge. RESULTS: A total of 548 patients were included. ASA was continued in 282 (51.5%) (ASAc group) and discontinued in 266 (48.5%) patients (ASAd group). ASAc patients had more often coronary artery disease (57.8% vs. 42.5%, p < .001) and peripheral artery disease (17.4% vs. 9.0%, p = .004) than ASAd patients, whereas no differences were found in other comorbidities. There was no difference in 30-day all-cause mortality between ASAd and ASAc groups. However, after adjustment for age, gender and comorbidities, one-year all-cause mortality was double in the ASAd group (hazard ratio 2.16, 95% confidence interval 1.39-3.35). ASAd and ASAc groups did not differ with respect to cardiovascular mortality (4.9% vs. 5.3%, p = .811, respectively) or re-bleeding (10.2% vs. 9.2%, p = .713, respectively). CONCLUSION: Continuing low-dose ASA after gastrointestinal bleeding was associated with lower all-cause mortality during the first year without increasing the risk of re-bleeding.

A nationwide real-world study on dynamic ustekinumab dosing and concomitant medication use among Crohn's disease patients in Finland.

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.

Ustekinumab for Crohn's disease: a nationwide real-life cohort study from Finland (FINUSTE).

Background: Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, has been approved for treatment of Crohn's Disease (CD) since the end of 2016. This nationwide noninterventional, retrospective chart review explored real-life data in patients receiving UST to provide guidance in UST treatment in the era of increasing prevalence of CD. Methods: The study assessed UST treatment patterns such as dosing frequency, concomitant medication and persistence in 48 CD patients commencing UST therapy in 12 Finnish hospitals during 2017. Clinical remission and response rates were explored using a modified Harvey-Bradshaw index (mHBI) and endoscopic response via the simple endoscopic score for Crohn's disease (SES-CD) as proportions of patients at week 16 and at the end of follow-up. Results: Forty patients (83%) continued UST-treatment at the end of follow-up. At week 16, clinical response and endoscopic healing was observed, where data were available; mHBI decreased from 9 to 3 (p = .0001) and SES-CD from 12 to 3 (p = .009). Clinical benefit was achieved by 83% (19/23) at week 16 and by 76% (16/21) at the end of follow-up. The proportion of patients using corticosteroids decreased from 48% to 25% at week 16 and to 13% at the end of the follow-up. Conclusion: UST showed to be effective and persistent, inducing short-term clinical benefit and endoscopic response in this real-life nationwide study of CD patients. Significant corticosteroid tapering in patients with highly treatment refractory and long-standing CD was observed.

[Esophageal varices and dyspnea. A clinicopathological conference report]. / Ruokatorven laskimolaajentumat ja hengenahdistus.

A young man who had moved from India to Finland was extensively examined for abdominal complaints. The findings included large esophageal varices, open portal vein and enlarged lymph nodes. The large spleen was excised. The diagnosis did not become clear from laboratory investigations. After ten years the patient was repeatedly examined to reveal the cause of esophageal varices and abdominal complaints. Autoimmune pancreatitis and cholangitis were suspected after 23 years from the initial symptoms. In the end, the most plausible explanation for the patient's mixed disease was tuberculosis. Sarcoidosis was another disease that came into question.

[Radio frequency ablation of Barrett's esophagus--can the risk of esophageal adenocarcinoma be reduced?]. / Barrettin ruokatorven radiotaajuusablaatio--voiko ruokatorven adenokarsinooman riskiä vähentää?

Barrett's esophagus occurs in a little less than 2% of the population. Of the patients, very few develop esophageal adenocarcinoma, and on the other hand only a small part of esophageal adenocarcinoma patients are diagnosed with Barrett's lesion. If Barrett's lesion has a separate visible elevated or depressed lesion it should first be treated with endoscopic mucosal resection, and thereafter the remaining Barrett's lesion should be destructed by a new technique called radiofrequency ablation, RFA. After destruction of the aberrant mucosal lesion with RFA it will be replaced with normal esophageal mucosa and the risk for malignant trasformation is dimished near to zero. RFA is considered the first-line treatment treatment option of dysplastic Barrett's esophagus.

Severe gastro-oesophageal reflux necessitating fundoplication after percutaneous endoscopic and open gastrostomy in children.

PURPOSE: The three major techniques for a gastrostomy in children are open gastrostomy (OG), percutaneous endoscopic gastrostomy (PEG) and laparoscopic-assisted gastrostomy. Here, we have evaluated the outcome after OG and PEG in 69 children operated in Kuopio University Hospital. METHODS: The medical records of 69 consecutive children who had either PEG (n = 56) or OG (n = 13) over an 18-year period (1990-2008) were reviewed. RESULTS: There was no difference between the PEG- and OG-groups in the patients' characteristics, indications for tube placement and hospital stay. The mean procedure time was 43 min shorter in the PEG-group (28 ± 38 min) than in the OG-group (71 ± 58 min) (P = 0.003). Four children (8%) in the PEG-group and one (8%) in the OG-group required later surgical interventions related to gastrostomy. Severe gastro-oesophageal reflux (GER) necessitating fundoplication was detected in 15 children (27%) in the PEG-group and in 7 children (54%) in the OG-group (P = 0.06). CONCLUSION: The results of this study indicated a higher incidence for severe GER leading to fundoplication in children with OG, while no difference with complications and clinical outcome between the two techniques, OG and PEG, were observed.

Association between mental distress, gastrointestinal symptoms, and health-care utilization in functional dyspepsia: a prospective 7-year follow-up study.

OBJECTIVE: The association between psychosocial factors and gastrointestinal symptoms is unclear. It has been proposed that they simply drive health-care seeking of patients. We therefore aimed to study whether mental distress would increase health-care utilization in functional dyspepsia (FD). METHODS: 171 primary care FD patients completed questionnaires screening gastrointestinal symptoms, mental distress, and health-care utilization between 1993 and 2000. These included the Bowel Disease Questionnaire and 12-item General Health Questionnaire. The patients' medical records were reviewed in primary care centers, Kuopio University Hospital, local hospitals, and private clinics. RESULTS: The majority of patients revisited their general practitioner (GP), and most of them were prescribed antisecretory medication. Repeated gastroscopy and lower gastrointestinal endoscopy were performed in 26% of the patients. A radiological reinvestigation, usually upper abdominal ultrasound, was performed in one-third. Nine percent were hospitalized due to gastrointestinal reasons. A single additional bowel symptom increased the probability of repeated endoscopy by 19%, a visit to the GP by 19%, and an inpatient period by 51%. Neither an increase in the dyspepsia score nor the presence of mental distress or suspicion of serious illness increased the probability of health-care utilization. CONCLUSION: There is no association between mental distress and health-care utilization for gastrointestinal symptoms.

[Amyloidosis--uncommon etiology for ascites]. / Amyloidoosi--askiteksen harvinainen syy.

Ascites is an accumulation of fluid into the peritoneal cavity. Most often it is an end-complication of chronic liver disease. Other reasons for ascites should be considered sometimes in clinical practice. We present a patient who had primary (AL) amyloidosis as the reason for remarkable amount of ascites. The prognosis of amyloidosis is poor especially if the diagnosis is delayed.

Objectively assessed disease activity and drug persistence during ustekinumab treatment in a nationwide real-world Crohn's disease cohort.

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.

Medication-free colonoscopy--factors related to pain and its assessment.

AIM: This paper is a report of a study conducted to determine the possibility of performing colonoscopy without medication, elucidate the factors related to a painful colonoscopy experience and compare colonoscopy patients' reported pain assessment to nurses' and endoscopists' observations. BACKGROUND: Sedation and pain medication are routinely administered for colonoscopies in many countries. However, medication-free colonoscopies have attracted attention because the use of medication requires a time commitment from patients and increases complications. Earlier studies show that, for instance, gender, age and pelvic operations may increase the risk of painful colonoscopy and those healthcare professionals and patients appear to assess pain differently. METHOD: A cross-sectional descriptive study was conducted in a Finnish university hospital using questionnaires developed for this study and analysed statistically. The sample of 138 colonoscopy patients, 11 nurses and 11 endoscopists was recruited in 2006. RESULTS: Over three-quarters of patients reported mild pain or no pain at all. Patients' nervousness is a risk factor for experiencing pain during colonoscopy. Both nurses and endoscopists slightly underestimated the intensity of pain experienced by patients. CONCLUSION: It is possible to perform colonoscopy without medication with most patients and focus sedation and pain medication on at-risk patients, especially those who are nervous. Before the procedure, nurses must devote time to discovering which patients are nervous and at risk of having a painful colonoscopy to present them for sedation. To improve pain management for patients having colonoscopy, endoscopists and nurses should participate systematically in pain education and use pain scales.

LFRET, a novel rapid assay for anti-tissue transglutaminase antibody detection.

The diagnosis of celiac disease (CD) is currently based on serology and intestinal biopsy, with detection of anti-tissue transglutaminase (tTG) IgA antibodies recommended as the first-line test. Emphasizing the increasing importance of serological testing, new guidelines and evidence suggest basing the diagnosis solely on serology without confirmatory biopsy. Enzyme immunoassays (EIAs) are the established approach for anti-tTG antibody detection, with the existing point-of-care (POC) tests lacking sensitivity and/or specificity. Improved POC methods could help reduce the underdiagnosis and diagnostic delay of CD. We have previously developed rapid homogenous immunoassays based on time-resolved Förster resonance energy transfer (TR-FRET), and demonstrated their suitability in serodiagnostics with hanta- and Zika virus infections as models. In this study, we set out to establish a protein L -based TR-FRET assay (LFRET) for the detection of anti-tTG antibodies. We studied 74 patients with biopsy-confirmed CD and 70 healthy controls, with 1) the new tTG-LFRET assay, and for reference 2) a well-established EIA and 3) an existing commercial POC test. IgG depletion was employed to differentiate between anti-tTG IgA and IgG positivity. The sensitivity and specificity of the first-generation tTG-LFRET POC assay in detection of CD were 87.8% and 94.3%, respectively, in line with those of the reference POC test. The sensitivity and specificity of EIA were 95.9% and 91.9%, respectively. This study demonstrates the applicability of LFRET to serological diagnosis of autoimmune diseases in general and of CD in particular.

Unkilned and large amounts of oats in the coeliac disease diet: a randomized, controlled study.

OBJECTIVE: There is evidence for the long-term safety of oats as part of a gluten-free diet in coeliac disease (CD). Oats is generally processed by kilning, which theoretically may change its antigenic properties and be the reason that it is tolerated by patients with CD. The aim of this study was to investigate the suitability of large amounts of unkilned oats, comparing its use with kilned oats in adult coeliac patients. MATERIAL AND METHODS: The study group included 13 men and 19 women with CD in remission. The goal of daily intake of oats was 100 g during one year. These patients using oats as part of their gluten-free diet were randomized to two treatment groups. One group used regular oats and the other unkilned oats. After 6 months the patients changed the treatment groups. Food intake, symptoms, histology of the small intestine and the levels of endomysial antibodies were noted. RESULTS: No marked changes were found in the duodenal biopsies, in the levels of endomysial antibodies or in the well-being of the patients. Compliance with the diet did not change during the follow-up. CONCLUSIONS: Large amounts of both unkilned and regular kilned oats are well tolerated by adult patients with CD. Oats is therefore not harmful, even in its unkilned form, which indicates that its antigenic nature is not changed by common industrial food processing in such a way that would prevent the provoking of CD.

Removing a biliary T-tube and retained stones by ERCP. A case report.

A time-honored praxis is to insert a T-tube after open choledochotomy. Well-known complications of T-tube removal include bile leakage, peritonitis, sepsis and postoperative biliary stenosis. A retained T-tube fragment after surgical common bile duct exploration is an uncommon complication of T-tube removal. We report the first case of retained bile duct stones with a whole T-tube jammed into the biliary tree. A 31-year-old female with gallstone disease was operated on. The operation was started by laparoscopy but converted to open laparotomy because of perforation of the gallbladder. T-tube was inserted but several stones remained in the bile duct. Afterwards routine T-tube removal was impossible: the T-tube had become trapped in the common bile duct. This combination of complications was successfully treated by ERCP.

Imaging and Treatment Features of Idiopathic Pancreatitis and Pancreas Divisum in a Young Man: A Case Report.

Some patients with pancreas divisum (PD) develop symptoms of recurrent pancreatitis. This is probably caused by insufficient drainage of the pancreatic duct. Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive test reported to be highly accurate in diagnosing PD. Endoscopic minor papilla sphincterotomy is most effective in the treatment of patients with PD and pancreatic stones. We report a case of 17-year-old boy who has suffered from several abdominal pain attacks throughout his childhood without a specific diagnosis. Radiological findings after the first episode of pancreatitis were typical for PD and led to specific treatment and cure.

Characteristics of patients with a retained wireless capsule endoscope (WCE) necessitating laparotomy for removal of the capsule.

AIM: A capsule endoscope is a wireless miniature camera used to take images of the small bowel mucosa. Retention of the wireless capsule endoscope (WCE), defined as at least two weeks' retention or an obstruction demanding removal by laparotomy, is the main and practically only complication of the procedure. The aim of this study was to evaluate the characteristics of patients with a retained WCE necessitating laparotomy for removal of the capsule or capsule fragments. PATIENTS AND METHODS: The medical records of 555 patients who had undergone the WCE procedure over a 7-year period (2002-2008) were reviewed. The indications for the WCE procedure were, obscure gastrointestinal bleeding, Crohn's disease, abdominal pain and suspicion of malignancy. RESULTS: A retained WCE requiring operative treatment was found in 10 cases (in nine patients, twice in one patient). The WCE retention frequency of 1.8% (10/555) equalled that in the literature. CONCLUSION: The retention rate of WCE capsules is low and routine examination of the small bowel with MRI or CT is not necessary before WCE. These examinations were enable to predict WCE retention according to our results.

No observed local immunological response at cell level after five years of oats in adult coeliac disease.

OBJECTIVE: Our earlier 5-year follow-up study produced the first evidence to show the long-term safety of oats as part of a coeliac diet. The objective of the present study was to clarify its applicability by analysing local cellular immunological responses after 5 years' consumption of oats by adult coeliac patients. MATERIAL AND METHODS: Forty-two coeliac patients took part in an earlier oats intervention study for 6-12 months. Twenty-two of these patients originally consumed oats as part of their gluten-free diet. During the 5-year follow-up 10 patients had felt uncertain about the safety of long-term consumption of oats and gave up this part of their diet. Finally, 12 of the 22 patients consumed oats for the whole 5-year period. The control group consisted of the remaining 20 coeliac patients using a strict, conventional, gluten-free diet without oats. Intraepithelial CD3, alphabetaTCR (alphabetaIEL) and gammadeltaTCR (gammadeltaIEL) T cells were counted after specific staining of small intestinal biopsy specimens. RESULTS: There were no differences in the densities of CD3, alphabetaIEL and gammadeltaIEL T cells between the oat and the control groups. CONCLUSIONS: Long-term use of oats included in the gluten-free diets of patients with coeliac disease does not stimulate an immunological response locally in the mucosa of the small intestine.

Analysis of the risk factors and their combinations in acute gastroduodenal ulcer bleeding: a case-control study.

OBJECTIVE: Traditional non-steroidal anti-inflammatory drugs (NSAIDs) including ASA for thrombosis prophylaxis (ASA-TP), for pain medication (ASA-P) or non-ASA NSAIDs (NANSAIDs), Helicobacter pylori infection, CagA strains of H. pylori and smoking are reported risk factors for peptic ulcer bleeding (PUB), but the combined and the dose effects of these factors are controversial. The aim of this study was to estimate the significance of these risk factors and their combinations in PUB. MATERIAL AND METHODS: PUB patients (n = 94) were compared with an age- (+/- 5 years) and gender-matched control group of non-ulcer patients (n = 94) attending elective endoscopy. A questionnaire on the possible risk factors (previous gastric and duodenal ulcer, use of ASA-TP, ASA-P, NANSAIDs, warfarin, alcohol and smoking) was completed. H. pylori infection was determined as positive if histology and/or urease tests were positive. CagA antibodies of IgG class were determined using an immunoblot method. RESULTS: H. pylori infection (odds ratio (OR) 8.8), the use of ASA-P (OR 3.5), ASA-TP (OR 4.07), NANSAIDs with > or =1 defined daily dose (OR 6.56), smoking > or =20 cigarettes daily (OR 6.43) and previous duodenal ulcer (DU) (OR 8.96) were independent risk factors for PUB. At least two risk factors were present in 65% of PUB patients. CagA strains were detected in 97% of the H. pylori-positive cases and in 96% of the respective controls. ASA, ibuprofen, ketoprofen and smoking were dose-dependent risk factors for PUB. CONCLUSIONS: Previous DU, H. pylori, the use of any ASA and smoking explained the majority of the PUB episodes. CagA strains of H. pylori were not associated with PUB. Two-thirds of the PUB patients had at least two risk factors, but their combination did not potentiate the risk.