Explore the vast range of titles available.

Filgotinib (GLPG0634, GS-6034) is a once-daily, orally administered, Janus kinase 1 (JAK1)-selective inhibitor. The FITZROY study examined the efficacy and safety of filgotinib for the treatment of moderate-to-severe Crohn's disease. We did a randomised, double-blind, placebo-controlled phase 2 study, which recruited patients from 52 centres in nine European countries. We enrolled eligible patients aged 18–75 years with a documented history of ileal, colonic, or ileocolonic Crohn's disease for 3 months or more before screening, as assessed by colonoscopy and supported by histology, and a Crohn's Disease Activity Index (CDAI) score during screening between 220 and 450 inclusive. Patients were randomly assigned (3:1) to receive filgotinib 200 mg once a day or placebo for 10 weeks. Patients were stratified according to previous anti-tumour necrosis factor alpha exposure, C-reactive protein concentration at screening (≤10 mg/L or >10 mg/L), and oral corticosteroid use at baseline, using an interactive web-based response system. The primary endpoint was clinical remission, defined as CDAI less than 150 at week 10. After week 10, patients were assigned based on responder status to filgotinib 100 mg once a day, filgotinib 200 mg once a day, or placebo for an observational period lasting a further 10 weeks. The filgotinib and placebo treatment groups were compared using ANCOVA models and logistic regression models containing baseline values and randomisation stratification factors as fixed effects. Analyses were done on the intention-to-treat non-responder imputation set. The trial was registered at ClinicalTrials.gov, number NCT02048618. Between Feb 3, 2014, and July 10, 2015, we enrolled 174 patients with active Crohn's disease confirmed by centrally read endoscopy (130 in the filgotinib 200 mg group and 44 in the placebo group). In the intention-to-treat population, 60 (47%) of 128 patients treated with filgotinib 200 mg achieved clinical remission at week 10 versus ten (23%) of 44 patients treated with placebo (difference 24 percentage points [95% CI 9–39], p=0·0077). In a pooled analysis of all periods of filgotinib and placebo exposure over 20 weeks, serious treatment-emergent adverse effects were reported in 14 (9%) of 152 patients treated with filgotinib and three (4%) of 67 patients treated with placebo. Filgotinib induced clinical remission in significantly more patients with active Crohn's disease compared with placebo, and had an acceptable safety profile. Galapagos.

PF-00547659 is a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to selectively reduce lymphocyte homing to the intestinal tract. We aimed to assess the efficacy and safety of PF-00547659 in patients with moderate to severe ulcerative colitis. This phase 2, randomised, double-blind, placebo-controlled clinical trial recruited patients aged 18–65 years from 105 centres in 21 countries, with a history (≥3 months) of active ulcerative colitis extending more than 15 cm beyond the anal verge (with a total Mayo score ≥6 and a Mayo endoscopic subscore ≥2) who had failed or were intolerant to at least one conventional therapy. Patients were stratified by previous anti-TNFα treatment, and randomly assigned by a computer-generated randomisation schedule to receive a subcutaneous injection of 7·5 mg, 22·5 mg, 75 mg, or 225 mg PF-00547659 or placebo at baseline, then every 4 weeks. Patients, investigators, and sponsors were blinded to the treatment. The primary endpoint was the proportion of patients achieving remission (total Mayo score ≤2 with no individual subscore >1 and rectal bleeding subscore ≤1) at week 12. The efficacy analysis included all patients who received at least one dose of the randomised treatment; the safety analysis was done according to treatment received. All p values were one-sided and multiplicity-adjusted. This study is registered with ClinicalTrials.gov, number NCT01620255. Between Nov 2, 2012, and Feb 4, 2016, we screened 587 patients; 357 were eligible and randomly assigned to receive placebo (n=73) or PF-00547659 at doses of 7·5 mg (n=71), 22·5 mg (n=72), 75 mg (n=71), or 225 mg (n=70). Remission rates at week 12 were significantly greater in three of four active-treatment groups than in the placebo group (2·7% [two of 73]): 7·5 mg (11·3% [eight of 71]), 22·5 mg (16·7% [12 of 72]), 75 mg (15·5% [11 of 71]), and 225 mg (5·7% [four of 70]). These rates corresponded to a stratum-adjusted (anti-TNFα-naive and anti-TNFα-experienced) risk difference versus placebo of 8·0% for 7·5 mg (90% CI 1·9 to 14, p=0·0425), 12·8% for 22·5 mg (5·6 to 19·9, p=0·0099), 11·8% for 75 mg (4·8 to 18·8, p=0·0119), and 2·6% for 225 mg (−1·2 to 6·4, p=0·1803). Four of 73 (5·5%) patients had a serious adverse event in the placebo group, 11 of 71 (15·5%) in the 7·5 mg group, one of 70 (1·4%) in the 22·5 mg group, three of 73 (4·1%) in the 75 mg group, and three of 70 (4·3%) in the 225 mg group. No safety signal was observed for the study drug. PF-00547659 was safe and well tolerated in this patient population, and better than placebo for induction of remission in patients with moderate to severe ulcerative colitis. The greatest clinical effects were observed with the 22·5 mg and 75 mg doses. Pfizer.

For homeless people, emergency departments (ED) are the place of medical care and satisfying physiological, safety and social needs. The treatment of the homeless in EDs is a common issue in many countries. The aim of study was to analyze selected parameters of health care to homeless people in EDs. The authors examined the frequency and the seasonality of admissions, their causes, stay duration, insurance status, and the type of radiological diagnostics performed. A retrospective analysis of stays of homeless patients in 3 EDs in one of the largest cities in Poland in 2013-2015 was carried out. Patients were qualified to the population of homeless people based of their registering in ED. Data was obtained on the total number of homeless patients' stays in all 3 EDs, which amounted to 3133. During the 3 years of analysis: 1042 homeless individuals were identified staying 3133 times in EDs; 46.3% of the stays concerned uninsured homeless people; 31% were under influence of alcohol. On average, men used ED services 3 times, while women only twice. No significant seasonality of admissions was observed. Homeless people were admitted mainly for mental disorders and head injuries. Radiological tests were performed 1577 times, including 83% being CT scans. On average, women and those >30 stayed in EDs for the shortest time. The hospital wards admitted 9.3% of the patients. Almost half of homeless patients repeatedly use ED services, regardless of the season. A patient's stay typically lasts 6 h. Half of them were uninsured. The main reasons for admission include mental and behavioral disorders, mostly due to alcohol use and head injuries. The primary radiological diagnostics used were CT scans. Int J Occup Med Environ Health. 2022;35(2):157-67.

Background A characteristic feature of malignant cells, such as colorectal cancer cells, is a profound decrease in the level of 5-hydroxymethylcytosine, a product of 5-methylcytosine oxidation by TET enzymes. Recent studies showed that ascorbate may upregulate the activity of TET enzymes in cultured cells and enhance formation of their products in genomic DNA. Methods The study included four groups of subjects: healthy controls (n = 79), patients with inflammatory bowel disease (IBD, n = 51), adenomatous polyps (n = 67) and colorectal cancer (n = 136). The list of analyzed parameters included (i) leukocyte levels of epigenetic DNA modifications and 8-oxo-7,8-dihydro-2′-deoxyguanosine, a marker of oxidatively modified DNA, determined by means of isotope-dilution automated online two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry, (ii) expression of TET mRNA measured with RT-qPCR, and (iii) chromatographically-determined plasma concentrations of retinol, alpha-tocopherol and ascorbate. Results Patients from all groups presented with significantly lower levels of 5-methylcytosine and 5-hydroxymethylcytosine in DNA than the controls. A similar tendency was also observed for 5-hydroxymethyluracil level. Patients with IBD showed the highest levels of 5-formylcytosine and 8-oxo-7,8-dihydro-2′-deoxyguanosine of all study subjects, and individuals with colorectal cancer presented with the lowest concentrations of ascorbate and retinol. A positive correlation was observed between plasma concentration of ascorbate and levels of two epigenetic modifications, 5-hydroxymethylcytosine and 5-hydroxymethyluracil in leukocyte DNA. Moreover, a significant difference was found in the levels of these modifications in patients whose plasma concentrations of ascorbate were below the lower and above the upper quartile for the control group. Conclusions These findings suggest that deficiency of ascorbate in the blood may be a marker of its shortage in other tissues, which in turn may correspond to deterioration of DNA methylation-demethylation. These observations may provide a rationale for further research on blood biomarkers of colorectal cancer development.

Psychiatric disorders are significantly common complications among patients suffering from inflammatory bowel diseases (IBD). Affective temperament is a concept of core personality traits, which can decribe the vulnerability to mood disorders, therefore its evaluation might convey useful information about patients' mental status in autoimmune disorders. The aim of the study was to evaluate the affective temperament in patients with Crohn's disease (CD) and ulcerative colitis (UC) as characteristic features of these diseases, but also in the clinical course and the severity of anxiety and depression.Due to our knowledge this is the first study of this kind. The study enrolled 130 patients with IBD, including 68 with CD and 62 with UC. We used TEMPS-A to evaluate affective temperament and HADS scales to assess the intensity of depressive and anxiety symptoms. Harvey Bradshaw scale, Crohn's Disease Activity Index (CDAI) and Mayo Score were used to evaluate clinical severity of the diseases. We observed significantly higher prevalence of depressive, cyclothymic and anxiety temperaments in CD patients compared to the control group. Harvey Bradshaw scale, CDAI and Mayo Self Report showed statistically significant outcomes, including significant positive correlations with depressive, cyclothymic and anxiety subscales of TEMPS-A, and negative correlation with the hyperthymic temperament in CD subjects. Our findings indicate significant differences between CD and UC due to temperament traits, and suggest distinct pathogenesis of mood disorders in IBD.

The current ERC guidelines are the source of many positive changes, reduction of mortality, length of hospitalization and improvement of prognosis of STEMI patients. However, there is a small group of patients whose slight modification in guidelines would further reduce in-hospital mortality and hospitalization costs. These are patients with concomitant STEMI infarction and gastrointestinal bleeding. Two separate methods of treatment were compared in patients with concomitant gastrointestinal bleeding and ST-segment elevation myocardial infarction. The first - traditional approach, in the line with the ESC guidelines, the second innovative, with priority for endoscopy. Despite the innovative approach, the patient with endoscopy before PCI was discharged without complication. A patient who has undergone coronary intervention and who has been started on typical antiplatelet therapy prior to gastroenterological diagnosis has died due to massive bleeding. For ethical reasons and in connection with the cardiological guidelines of the management of ACS, a study of patients with ASC a high risk of intestinal bleeding, in which endoscopy will have priority, and only later PCI, will probably never be performed. Although, as the described case shows, despite exceeding the 90 minutes time to implement PCI (<120 minutes) in logistic terms such behavior is completely feasible.

Background Active demethylation of 5-methyl-2′-deoxycytidine (5-mdC) in DNA occurs by oxidation to 5-(hydroxymethyl)-2′-deoxycytidine (5-hmdC) and further oxidation to 5-formyl-2′-deoxycytidine (5-fdC) and 5-carboxy-2′-deoxycytidine (5-cadC), and is carried out by enzymes of the ten-eleven translocation family (TETs 1, 2, 3). Decreased level of epigenetic DNA modifications in cancer tissue may be a consequence of reduced activity/expression of TET proteins. To determine the role of epigenetic DNA modifications in colon cancer development, we analyzed their levels in normal colon and various colonic pathologies. Moreover, we determined the expressions of TETs at mRNA and protein level. The study included material from patients with inflammatory bowel disease (IBD), benign polyps (AD), and colorectal cancer (CRC). The levels of epigenetic DNA modifications and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in examined tissues were determined by means of isotope-dilution automated online two-dimensional ultraperformance liquid chromatography with tandem mass spectrometry (2D-UPLC-MS/MS). The expressions of TET mRNA were measured with RT-qPCR, and the expressions of TET proteins were determined immunohistochemically. Results IBD was characterized by the highest level of 8-oxodG among all analyzed tissues, as well as by a decrease in 5-hmdC and 5-mdC levels (at a midrange between normal colon and CRC). AD had the lowest levels of 5-hmdC and 5-mdC of all examined tissues and showed an increase in 8-oxodG and 5-(hydroxymethyl)-2′-deoxyuridine (5-hmdU) levels. CRC was characterized by lower levels of 5-hmdC and 5-mdC, the lowest level of 5-fdC among all analyzed tissues, and relatively high content of 5-cadC. The expression of TET1 mRNA in CRC and AD was significantly weaker than in IBD and normal colon. Furthermore, CRC and AD showed significantly lower levels of TET2 and AID mRNA than normal colonic tissue. Conclusions Our findings suggest that a complex relationship between aberrant pattern of DNA epigenetic modification and cancer development does not depend solely on the transcriptional status of TET proteins, but also on the characteristics of premalignant/malignant cells. This study showed for the first time that the examined colonic pathologies had their unique epigenetic marks, distinguishing them from each other, as well as from normal colonic tissue. A decrease in 5-fdC level may be a characteristic feature of largely undifferentiated cancer cells.

Inflammatory bowel disease (IBD) is a group of chronic gastrointestinal diseases with frequent systemic complications that are incurable according to current knowledge. These diseases adversely affect various areas of life, lowering patients' quality of life. One of the most frequently reported symptoms is fatigue. Translation and validation of the IBD-F patient self-assessment scale with a Polish IBD population. After consent from the author of the questionnaire had been obtained, the questionnaire was translated using the forward- and back-translation method. After arriving at the final Polish version of the questionnaire and ensuring that the questions and statements were comprehensible, the questionnaire was validated with a group of 129 IBD patients. High values of intraclass correlation coefficient (ICC) were achieved for overall results in both parts of the IBD-F questionnaire between test and retest (values exceeding 0.75). A high Cronbach's α consistency coefficient was achieved for the entire IBD-F questionnaire, both in the test and in the retest (0.968 and 0.975, respectively). Broken down into parts, Cronbach's α coefficient for Section I (presence and severity of fatigue) of the IBD-F questionnaire was 0.883, and for Section II (impact of fatigue on the person's life) it was 0.966. All patients evaluating the Polish version of the IBD-F questionnaire deemed the content of the questions comprehensible. The analysis of the results obtained, the Polish version of the IBD-F questionnaire was considered valid, reliable, and clinically useful.

Disturbances in the central signaling of reactive oxygen species (ROS) in response to energy intake are recognized as taking part in appetitive and consummative phases of eating disorders. This study aimed to verify the hypothesis that blood oxidoreductive balance can also affect demand for energy substances, such as alcoholic beverages in alcohol-dependent individuals, as well as the severity of their alcohol dependence and risk of drinking relapse. The following values were determined in the blood of 54 alcohol-dependent male patients after alcohol withdrawal, again after 4 weeks and after 6 months: the aldehyde products of lipid peroxidation (malonyl dialdehyde [MDA] and 4-hydroxynonenal [4-HNE]), nitric oxide (NO) metabolites, total antioxidant status (TAS), the blood activities of glutathione peroxidase (GSHpx), superoxide dismutase (SOD), glutathione reductase (GSHred), blood glucose, and lipids. Alcoholics who relapsed during 6 months of observation (n = 31, 57%) compared with patients who maintained alcohol abstinence for 6 months (n = 23, 43%) differed only in relation to initial and final NO metabolite serum concentrations. The risk of alcohol drinking relapse was lower in patients with an above-median initial blood concentration of NO metabolites and TAS. The oxidative stress parameters correlated with alcohol-dependence severity markers. No significant correlations between the studied antioxidant balance parameters and markers of nutritional status, including blood glucose and lipids, were found. Although the results of our study have some limitations and require further investigation, they suggest the role of oxidoreductive balance in the pathomechanisms of alcohol dependence and drinking relapse. In addition, due to a lack of association found between blood oxidative stress parameters and BMI, blood glucose, and lipid concentrations, they show the presence of disturbances in systemic ROS signaling in response to energy availability in alcoholics after alcohol withdrawal. •Oxidoreductive homeostasis regulates energy, food and alcohol intake.•Alcoholics had disturbances in their oxidoreductive balance.•Inadequate oxidoreductive response to energy intake may affect alcohol craving.•Abnormalities in oxidoreductive homeostasis may promote alcohol relapse.•The availability of energy substances did not affect oxidoreductive balance.

Inflammatory bowel disease (IBD) is a chronic disorder of the gastrointestinal tract, which can significantly deteriorate everyday functioning. We are, however, still lacking simple methods to assess the influence of IBD on patients' disability. IBD Disk is a new graphical tool that allows for a quick assessment of the influence of IBD on different aspects of everyday life. To present the adaptation process of the IBD Disk in Poland. The Polish IBD Working Group together with the Institute of Translational Medicine in Birmingham (United Kingdom) and a professional translational agency performed a translation and re-translation of the Polish version of the IBD Disk. After full agreement was achieved, the final Polish version was accepted. In the next step, its understandability and ease of use was assessed by using a semiquantitative scale (scale from 1 to 10, where \"1\" means very easy to use, \"10\" means - very difficult to use). In the initial translation phase, the concordance between translation agency and experts was very high. In the re-translation phase only some stylistic and grammatical corrections were made. In the final step the general assessment of understandability of all items of the tool was high. Moreover, patients with IBD assessed the ease of use of the IBD Disk as very easy (median: 1.5 points, 95% confidence interval: 1.0-2.0). The Polish adaptation of IBD Disk directly reflects the original English version. Thus, it can be further used in the validation process among Polish IBD patients.