Real-world effectiveness and safety of vedolizumab induction therapy for ulcerative colitis: A prospective nationwide Polish observational study.

BACKGROUND: Vedolizumab is recommended as a first-line biological treatment, along with other biological drugs, in ulcerative colitis (UC) patients in whom conventional therapy failed and as a second-line biological treatment following a failure of a tumor necrosis factor alpha (TNF-α) antagonist. OBJECTIVES: We aimed to assess the real-world effectiveness and safety of vedolizumab induction therapy in UC patients treated in the scope of the National Drug Program (NDP) in Poland. MATERIAL AND METHODS: The endpoints were the proportions of patients who reached clinical response, clinical remission and mucosal healing at week 14. Partial Mayo scores, Mayo subscores and C-reactive protein (CRP) levels were also evaluated. RESULTS: Our study population consisted of 100 patients (55 biologic-naïve and 45 biologic-exposed). The median total Mayo score at baseline was 10 (interquartile range (IQR): 9-11), and 52 patients (52%) had extensive colitis. The clinical response at week 14 was achieved in 83 (83%) and clinical remission in 24 (24%) cases. Mucosal healing was observed in 56 (62%) patients at week 14. In patients with prior failure of biologic treatment (n = 25), 17 (68%) responded to vedolizumab treatment. A decrease in the median CRP level (from 3.7 mg/L to 2.6 mg/L) and the median total Mayo score (from 10 to 4) was observed. No new safety concerns were recorded and no patients discontinued the treatment due to adverse events (AEs). CONCLUSIONS: Vedolizumab was effective and safe as induction therapy for UC in a Polish real-world population including patients with severely active UC and a low number of patients with prior biological treatment failures.

Autoimmune Pancreatitis in Patients with Inflammatory Bowel Disease: A Real-World Multicentre Collaborative ECCO CONFER Study.

BACKGROUND: Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP-IBD and predictors of complicated AIP course have rarely been reported. METHODS: An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collected cases of AIP diagnosed in patients with IBD. Complicated AIP was defined as a composite of endocrine and/or exocrine pancreatic insufficiency, and/or pancreatic cancer. We explored factors associated with complicated AIP in IBD. RESULTS: We included 96 patients [53% males, 79% ulcerative colitis, 72% type 2 AIP, age at AIP diagnosis 35 ±â€…16 years]. The majority of Crohn's disease [CD] cases [78%] had colonic/ileocolonic involvement. In 59%, IBD preceded AIP diagnosis, whereas 18% were diagnosed simultaneously. Advanced therapy to control IBD was used in 61% and 17% underwent IBD-related surgery. In total, 82% of patients were treated with steroids for AIP, the majority of whom [91%] responded to a single course of treatment. During a mean follow-up of 7 years, AIP complications occurred in 25/96 [26%] individuals. In a multivariate model, older age at AIP diagnosis was associated with a complicated AIP course (odds ratio [OR] = 1.05, p = 0.008), whereas family history of IBD [OR = 0.1, p = 0.03], and CD diagnosis [OR = 0.2, p = 0.04] decreased the risk of AIP complications. No IBD- or AIP-related deaths occurred. CONCLUSIONS: In this large international cohort of patients with concomitant AIP-IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign and long-term outcomes are favourable, but one-quarter develop pancreatic complications. Age, familial history of IBD, and CD may predict uncomplicated AIP course.

Real-world outcomes of 54-week vedolizumab therapy and response durability after treatment discontinuation in ulcerative colitis: results from a multicenter prospective POLONEZ study.

Background: Vedolizumab is a gut-selective anti-lymphocyte trafficking agent used to treat ulcerative colitis (UC) and Crohn's disease. Objectives: We aimed to evaluate the effectiveness, safety, and durability of the therapeutic effect of vedolizumab after treatment discontinuation in a real-world cohort of patients with UC treated in Poland. Design: This was a multicenter, prospective study involving patients with moderate to severely active UC from 12 centers in Poland who qualified for reimbursed treatment with vedolizumab between February and November 2019. Methods: The primary endpoints were clinical response (⩾2-point improvement from baseline on partial Mayo score) and clinical remission (partial Mayo score 0-1), including steroid-free remission, at week 54. Other outcomes included response durability at 26 weeks after treatment discontinuation, identification of predictors of response and remission, and safety assessment. Results: In all, 100 patients with UC were enrolled (55 biologic naïve and 45 biologic exposed). At baseline, 68% of patients were on corticosteroids and 45% on immunomodulators. Clinical response was observed in 62% of patients, clinical remission in 50%, and steroid-free remission in 42.6% at week 54. Within 26 weeks after treatment discontinuation, 37% of patients who maintained response by week 54 relapsed. The decreased number of liquid stools and rectal bleeding and endoscopic response at week 14 were predictive factors for response at week 54. Time from diagnosis ranging 2-5 years, decreased stool frequency, and non-concomitant use of corticosteroids at baseline and at week 14 were predictive factors for remission at week 54. Partial Mayo score < 3 with no subscale score > 1 at week 54 was a predictive factor for durable response after treatment discontinuation. The rate of serious adverse events related to treatment was 3.63 per 100 patient-years. Conclusion: Vedolizumab is effective and safe in UC treatment in Polish patients. However, the relapse rate after the treatment cessation was high. Registration: ENCePP (EUPAS34119).

The usefulness of selected sequences of magnetic resonance imaging in a diagnostic model for Crohn's disease.

Introduction: We hypothesized that, based on magnetic resonance enterography (MRE) and the apparent diffusion coefficient (ADC), measured in the affected parts of the intestine, it is possible to effectively differentiate active and chronic phases of Crohn's disease. Aim: To create a multidimensional diagnostic model for differentiating between the phases of Crohn's disease. Material and methods: This study included 125 patients - 55 women (aged 19 to 66 years) and 70 men (aged 12 to 67 years) - who underwent MRE and ADC measurement for the first time. Results: The group of potential explanatory variables comprised 11 variables, including the thickness and length of the occupied section, number of lymph nodes, layered bowel wall enhancement, total transitions on fat tissue, and features of restricted diffusion. The final discrimination model was based on 2 variables: ADC (A) and layered bowel wall enhancement (W). Active Crohn's disease was defined as -6.339 + 4.747 × W + 0.008 × A, while chronic Crohn's disease was defined as -11.365 + 2.812 × W + 0.012 × A. Definitive diagnosis was based on histological examination of material collected during ileocolonoscopy in 96 patients, surgery with subsequent histopathological examination in 17 patients, and capsule endoscopy in 12 patients. Conclusions: The predictive model described here could identify the active form of Crohn's disease with a probability of 93.06% and the chronic form with a probability of 75.57%. The use of classic MRE layered bowel wall enhancement and a DWI-based ADC metric eliminates the main shortcomings of both approaches.

Diagnostic and therapeutic management in gastroesophageal reflux disease: consensus of the Polish Society of Gastroenterology.

The paper was prepared by an expert group appointed by the Polish Society of Gastroenterology with an aim to update and systematize the knowledge about diagnosis and treatment of gastroesophageal reflux disease (GERD). Based on the previously published guidelines of international societies, expert consensuses, and recently published good quality data, we formulated 74 statements regarding the definition, diagnosis and treatment of GERD and assessed the level of acceptance of these statements and the reliability of the data. We discussed in details the possibilities and limitations of the available diagnostic methods and therapies, with particular emphasis on the diversity of gastroesophageal reflux symptoms and complications including Barrett's esophagus. Practical principles regarding interpretation of the diagnostic tests are presented. In addition, we discussed the indications for surgical treatment as well as the situations in which surgical treatment is not indicated with emphasis on the importance of preoperative diagnostics. The role of add-on therapy and indications for maintenance treatment are defined.

Characteristics of patients with moderate-to-severe ulcerative colitis treated with vedolizumab: results from a Polish multicenter, prospective, observational real-life study (the POLONEZ study).

BACKGROUND: Vedolizumab, a humanized antibody targeting the α4ß7 integrin, was proven to be effective in the treatment of moderate-to-severe ulcerative colitis (UC) in randomized clinical trials. The aim of the POLONEZ study is to determine the demographic and clinical characteristics of the patients with UC treated with vedolizumab within the scope of the National Drug Program in Poland and to assess the real-world effectiveness and safety of vedolizumab in the study population. Here we report the demographic and clinical characteristics of these patients. METHODS: This prospective study included adult patients eligible for UC treatment with vedolizumab who were recruited from 12 centers in Poland between February and November 2019. Collected data included sex, age, disease duration, presence of extraintestinal manifestations or comorbidities, status of previous biologic treatment, and current concomitant treatment. Disease extent was determined according to the Montreal classification, and disease activity was measured with the Mayo Score. RESULTS: A total of 100 (55 biologic-naïve and 45 biologic-exposed) patients were enrolled in the study (51% female, median age 35 years). Among biologic-exposed patients (mostly infliximab-treated), 57% had failed to respond to the therapy. The disease duration was significantly shorter in biologic-naïve (median 5 years) than in biologic-exposed (8 years, p = 0.004) or biofailure patients (7 years, p = 0.04). In the overall population the median Total Mayo Score was 10. Disease extent and activity were similar between the subgroups. CONCLUSIONS: Our study indicates that patients treated with vedolizumab in Poland receive the drug relatively early after UC diagnosis, but their disease is advanced. More than half of the patients had not been treated with biologic drugs before initiating vedolizumab. The study was registered in ENCePP database (EUPAS34119). LAY SUMMARY: Characteristics of patients treated for ulcerative colitis with vedolizumab in Poland Treatment of moderate-to-severe ulcerative colitis (UC) with the integrin antagonist vedolizumab became available within the Polish National Drug Program (NDP) in 2018. In this study, for the first time, we provide detailed demographic and clinical characteristics of 100 patients (median age 35 years, 51% female) treated with vedolizumab in Poland, of whom 55 were biologic-naïve and 45 biologic-exposed. The median duration of disease was 6 years. The disease duration was shorter in biologic-naïve than in biologic-exposed patients. Most patients were affected by extensive colitis (52%) or left-sided colitis (42%). Median disease activity was 10 according to the Total Mayo Score. Sixty-eight patients received concomitant systemic corticosteroids and 45 patients received immunomodulators. Our findings indicate that Polish patients receiving vedolizumab have a high disease activity and are treated relatively early after UC diagnosis. This might be due to the criteria for inclusion of a patient in the NDP.

Itopride in treatment of laryngopharyngeal symptoms of gastroesophageal reflux disease.

In everyday otolaryngological and gastroenterological practice, the diagnosis and treatment of extraesophageal forms of gastroesophageal reflux disease are often challenging. It is sometimes the case that treatment ordered by other specialists proves ineffective or even worsens the symptoms. There is no golden standard of diagnosis for otolaryngological forms of GERD, and currently used tools (gastroscopy, laryngoscopy, impedance and pH testing) have low sensitivity and specificity. After finishing a course of successful treatment, the patients often come back to our offices with the very same symptoms. In order to improve the efficacy of treatment, a prokinetic agent can be added to the standard proton pump inhibitor therapy.

A novel approach to genome-wide association analysis identifies genetic associations with primary biliary cholangitis and primary sclerosing cholangitis in Polish patients.

BACKGROUND: Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are forms of hepatic autoimmunity, and risk for both diseases has a strong genetic component. This study aimed to define the genetic architecture of PBC and PSC within the Polish population. METHODS: Subjects were 443 women with PBC, 120 patients with PSC, and 934 healthy controls recruited from Gastroenterology Departments in various Polish hospitals. Allelotyping employed a pooled-DNA sample-based genome-wide association study (GWAS) approach, using Illumina Human Omni2.5-Exome BeadChips and the following novel selection criteria for risk loci: blocks of at least 10 single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium, where the distance between each adjacent SNP pair in the block was less than 30 kb, and each SNP was associated with disease at a significance level of P < 0.005. A selected index SNP from each block was validated using TaqMan SNP genotyping assays. RESULTS: Nineteen and twenty-one SNPs were verified as associated with PBC and PSC, respectively, by individual genotyping; 19 (10/9, PBC/PSC) SNPs reached a stringent (corrected) significance threshold and a further 21 (9/12, PBC/PSC) reached a nominal level of significance (P < 0.05 with odds ratio (OR) > 1.2 or < 0.83), providing suggestive evidence of association. The SNPs mapped to seven (1p31.3, 3q13, 6p21, 7q32.1, 11q23.3, 17q12, 19q13.33) and one (6p21) chromosome region previously associated with PBC and PSC, respectively. The SNP, rs35730843, mapping to the POLR2G gene promoter (P = 1.2 × 10-5, OR = 0.39) demonstrated the highest effect size, and was protective for PBC, whereas for PSC respective SNPs were: rs13191240 in the intron of ADGRB3 gene (P = 0.0095, OR = 0.2) and rs3822659 (P = 0.0051, OR = 0.236) along with rs9686714 (P = 0.00077, OR = 0.2), both located in the WWC1 gene. CONCLUSIONS: Our cost-effective GWAS approach followed by individual genotyping confirmed several previously identified associations and discovered new susceptibility loci associated with PBC and/or PSC in Polish patients. However, further functional studies are warranted to understand the roles of these newly identified variants in the development of the two disorders.

The HLA-DQß1 insertion is a strong achalasia risk factor and displays a geospatial north-south gradient among Europeans.

Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQß1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQß1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10(-04), Sweden P=7.44 × 10(-05)). Combining all five European data sets - Central Europe, Italy, Spain, Poland and Sweden - the insertion is achalasia associated with Pcombined=1.67 × 10(-35). In addition, we observe that the frequency of the insertion shows a geospatial north-south gradient. The insertion is less common in northern (around 6-7% in patients and 2% in controls from Sweden and Poland) compared with southern Europeans (~16% in patients and 8% in controls from Italy) and shows a stronger attributable risk in the southern European population. Our study provides evidence that the prevalence of achalasia may differ between populations.

Dynamics of quality of life improvement after floppy Nissen fundoplication for gastroesophageal reflux disease.

INTRODUCTION: Gastroesophageal reflux disease (GERD) has a negative impact on global quality of life (QOL) of patients. In patients affected by GERD, laparoscopic Nissen fundoplication is one of the most commonly performed laparoscopic procedures worldwide. AIM: To prospectively analyze the dynamics of QOL as well as severity of pain in patients with GERD, before and after laparoscopic floppy Nissen fundoplication. MATERIAL AND METHODS: The study involved 104 consecutive patients operated on for GERD in whom laparoscopic floppy Nissen fundoplication was performed. QOL was assessed before surgery and 1, 3, 6, 12 and 24 months after. The following instruments were used: FACIT-G, FACIT-TS-G, GIQLI, GERD symptom scale. RESULTS: It was found that symptom relief and quality of life improvement presented different dynamics in the postoperative course. Observations revealed relief of symptoms 1 month after surgery and improvement in QOL related to the gastrointestinal tract and pain 3 months after surgery. Global QOL increased significantly as late as 12 months after surgery. CONCLUSIONS: Gastroesophageal reflux disease is a chronic disease of long duration, leading to impairment of quality of life. Patients, apart from typical symptoms of GERD, suffer from pain of significant severity. QOL improves significantly after surgery. Surgical treatment results in relief of GERD symptoms, which leads to gradual improvement of QOL.

[Parvovirus B19 DNA testing in Polish blood donors, 2004-2010]. / Badanie DNA parvowirusa B19 (B19V) u Polskich dawcoów krwi, 2004-2010.

UNLABELLED: Since 2004 Polish blood donors have been tested for parvovirus B19 (B19V) DNA. The screening testing has been performed in donors of plasma for fractionation and anti-D and anti-HBs production and donors of erythrocytes used for immunization. AIM is to present methods of the testing, quality control and results in period 2004-2010. MATERIAL AND METHODS: Testing was performed in individual donation testing (IDT) in Regional Blood Transfusion Center (RBTC) in Lublin or in pools of 24 in Institute of Haematology and Transfusion Medicine in Warsaw (IHTM). Quantitative testing with real-time PCR was preceded with nucleic acid isolation on silica based methods (Prepito Viral DNA/RNA, Chemagen and QIAamp DNA Mini Kit, QIAGEN). Amplification was performed initially with home made method and later with commercial assay (Artus Parvo B19 RG PCR Kit on Rotor Gene 6 000). In total 17 625 donations were tested: 8 539 in pools and 9 090 individually. Beside routine external quality control programmes in which both laboratories participated (Proficiency Study VQC,Amsterdam, Holand; EQA Programe, Glasgow, Scotland), panel containing negative samples, positive with very high DNA B 19V level and plasma infected with genotype 2 was prepared for RBTC in Lublin. RESULTS: B19V infection frequency was 1:980 donations, low viraemic donations were detected most frequently (1:1 037). It was identified only one donation with DNA load that could cause potential health risk for plasma product recipients (1:17 625). In one of the donors B 19V DNA was observed for 3 years and 3 months. In acute or persistent phase of infection no clinical or laboratory symptoms (morphology of peripheral blood, ALT) were observed. Due to risk of underestimation of viral load connected with viral genome polymorphism all donations with B19V positive result were not allowed to be clinically used.

Platelet 12-lipoxygenase and stem cells in Barrett's esophagus.

Esophageal adenocarcinoma has shown a significant increase in incidence in recent years. It is thought that the development of gastroesophageal reflux disease (GERD), followed by columnar-lined esophagus and the development of dysplasia, leads to invasive adenocarcinoma. The exact pathogenesis of this process, the diagnosis and differentiation of the metaplastic and dysplastic esophageal lesions have yet to be determined. The purpose of this immunohistochemical study was to investigate the expression of pro-tumorigenic enzyme platelet 12-lipoxygenase (p12LOX) using two new available antibodies in non-dysplastic and dysplastic Barrett's esophagus. The stem cell markers nestin, CD117 and CD44, were then evaluated. The comparative group included GERD carditis, gastric intestinal metaplasia and colorectal adenoma. The overexpression of p12LOX detected by two specific antibodies in the non-dysplastic and dysplastic Barrett's mucosa clearly demonstrated that this enzyme plays an important role in the development of esophageal adenocarcinoma.