Successful pregnancies in a patient with Takayasu arteritis and antiphospholipid syndrome, maintained on infliximab corticosteroid-free regimen: case-based review.

Takayasu arteritis (TA) is a large vessel vasculitis affecting predominantly females below the age of 40. Patients with TA seem to be at increased risk for adverse pregnancy outcomes, resulting in mother or child complications. Although few studies analyzed the presence of antiphospholipid antibodies (APLA) in TA patients, an association between antiphospholipid syndrome (APS) and TA is rarely reported in the literature, mainly in the form of case reports. In fact, very few data regarding pregnancy outcomes in patients with TA and APS are available. An active form of Crohn's disease (CD) might be another risk factor strongly affecting the fertility rate. Here, we would like to present a 33-year-old woman with TA, double-positive APS and Crohn's disease (CD). The report is followed by the literature review of the association of APLA and/or APS with TA, focusing on analyzing the pregnancy outcomes. To our knowledge, this is the first case describing two successful, naturally occurring pregnancies, in a patient suffering from TA, APS and CD, and maintained on infliximab, azathioprine, and a corticosteroid-free regimen.

Anemia as a Problem: GP Approach.

BACKGROUND: Anemia is a presentation of an underlying disease or deficiency. As stated by the WHO, anemia is defined as hemoglobin (Hb) levels <12.0 g/dL in women and <13.0 g/dL in men. This review of clinical practice aimed to determine the diagnostic approach to anemia in primary care patients. SUMMARY: Nutritional deficiencies, medications, chronic inflammatory conditions, malignancy, renal dysfunction, and bone marrow and inherent disorders contribute to anemia development. Anemia is classified and diagnosed by the values of hematological parameters, underlying pathological mechanism, and patient history. The diagnostic approach of anemia in primary care settings is focused on history, physical examination, laboratory findings including complete blood cell count, reticulocyte count, and peripheral smear examination, fecal occult blood test, and ultrasound findings. KEY MESSAGES: Anemia is the most common hematological disorder that represents a major health burden worldwide. Hb levels alter with gender, ethnicity, and physiological status. Anemia is often multifactorial. The evaluation of a patient with anemia in primary care includes clinical history, physical examination, and laboratory findings with fecal occult blood test and abdominal ultrasound. The wide variations in general practice in European countries are based on different health care systems but also knowledge of GPs that reflect educational and research policy.

Jaundice as a Diagnostic and Therapeutic Problem: A General Practitioner's Approach.

BACKGROUND: Jaundice is a common clinical finding in clinical practice of hepatologists and general practitioners. It occurs when serum bilirubin levels exceed 3 mg/dL. SUMMARY: In this review, we summarize the pathophysiological mechanism of jaundice, clinical approach to the patient with jaundice, and laboratory and imaging techniques. Clinical presentation of jaundice manifests through yellow skin and sclera coloration. Evaluation of every patient includes detailed medical history and examination. In the laboratory, evaluation of enzymes of hepatic inflammation as well as cholestatic enzymes with serum bilirubin must be included. Additional laboratory analysis and imaging modalities are needed in order to differentiate jaundice etiology. Moreover, imaging is available and needed in further evaluation, and treatment is dependent on the underlying cause. KEY MESSAGES: In this review, we will outline the pathophysiological mechanism of jaundice, clinical approach to the patient with jaundice, and diagnostic and treatment approach to these patients.

Intestinal Ultrasonography as a Tool for Monitoring Disease Activity in Patients with Ulcerative Colitis.

Background: Ultrasonography is a noninvasive, inexpensive, and widely available diagnostic tool. In the last two decades, the development of ultrasound techniques and equipment has significantly increased the usage of intestine ultrasound (US) in the assessment of the gastrointestinal tract in patients with inflammatory bowel disease (IBD). Although current guidelines suggest routine utilization of US in patients with Crohn's disease, data regarding US usage in ulcerative colitis are still scarce. We aimed to assess the reliability of intestinal ultrasonography in the assessment of disease activity and extension of patients with ulcerative colitis. Methods: Fifty-five patients with a histologically confirmed diagnosis of ulcerative colitis, treated at University Clinical Center of Serbia in the period from 2019 to 2022 were included in this retrospective observational study. The data were obtained from the patient's medical records including history, laboratory, US, and endoscopy findings. US examined parameters were as following: bowel wall thickness (BWT), presence of fat wrapping, wall layer stratification, mesenteric hypertrophy, presence of enlarged mesenteric lymph nodes, and absence or presence of ascites. Results: Our results suggest that there is a strong correlation of BWT and colonoscopy findings regarding disease extension (r = 0.524, p=0.01, p < 0.05). Furthermore, our results have shown a statistically significant correlation of BWT with the Mayo endoscopic score (r = 0.434, p=0.01, p < 0.05), disease activity score (r = 0.369,p=0.01, p < 0.05), degree of ulcerative colitis burden of luminal inflammation (r = 0.366, p=0.01, p < 0.05), and Geboes index (r = 0.298, p=0.027, p < 0.05). Overall accuracy of US for disease extension and activity was statistically significant (p < 0.05). Conclusions: Our results suggest that US is a moderately accurate method for the assessment of disease activity and localization in patients with UC.

Quality of Life in Patients with Primary Biliary Cholangitis: A Single-Center Experience in Serbia.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease, predominantly affecting middle-aged women, which may progress to end-stage liver disease. We aimed to assess the quality of life (QoL) in patients with PBC given that social, economic, and geographical factor also influence QoL. METHODS: This study included patients with diagnosed PBC according to the European Association for the Study of the Liver guidelines, who were treated for at least 6 months in order to allow adequate time for the initial burden of symptoms to subside. We used the PBC-40 questionnaire validated in the Serbian language. RESULTS: The mean total PBC-40 score was 89.4 ± 29.3. The overall frequency of moderate and severe involvement in each domain was as follows: 84.9% (n = 107) in "Symptoms," 29.3% (n = 36) in "Itch," 76.4% (n = 97) in "Fatigue," 58.1% (n = 72) in "Cognitive," 77.2% (n = 98) in "Social," and 70.9% (n = 90) in "Emotional." There was a statistically significant negative correlation of disease duration and albumin score with the Emotional domain score. Furthermore, this domain showed a significant positive correlation with the Mayo score. CONCLUSION: The present study demonstrates that patients with PBC have significant impairment in QoL with fatigue being the most prevalent symptom. The Social and Emotional domains were also significantly affected in these individuals, particularly in patients with peripheral edema who exhibited worse QoL that those who were euvolemic.

Assessment of Duodenal Adenomas and Strategies for Curative Therapy.

BACKGROUND: The increasing incidence of duodenal neoplasm has underlined different methods of resection depending on the clinical presentation, endoscopic features and histopathology. In this comprehensive review, we systematically describe the current knowledge concerning the diagnosis and management of duodenal adenomas (DAs) and discuss data considering all possible therapeutic approaches. SUMMARY: Among a variety of duodenal lesions, including neuroendocrine tumors and gastrointestinal stromal tumors, DAs present precancerous lesions of the duodenal papilla or non-ampullary region necessitating removal. DAs can occur sporadically (SDA) as rare lesions or relatively common in polyposis syndromes. The endoscopic resections of DA are associated with an increased degree of complexity due to distinctive anatomical properties of the duodenal wall, luminal diameter and the presence of ampulla with pancreatic and biliary drainage. The endoscopic techniques including cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), and argon plasma coagulation ablation are suggested to be less invasive than surgical treatment, associated with shorter hospital stay and lower cost. According to the current clinical practice, surgery has been accepted as standard therapeutic approach in familial adenomatous polyposis patients with severe polyposis or DA not amenable to endoscopic resection. Key Messages: The strategy for endoscopic resection of DAs depends on the lesion size, morphology, location, and histopathology findings. Small adenomas are most frequently diagnosed and removed by standard CSP techniques, while large laterally spreading lesions and ampullary adenoma are referred for EMR or endoscopic papillectomy respectively. Screening colonoscopy is indicated in patients with SDA. Additional studies for new endoscopic strategies and techniques for curative therapy of DAs are needed to refine future management decisions. Complete resection of DA is considered curative, but nevertheless, long-term endoscopic follow-up is still required to detect and treat any recurrent arising lesions.

Ultrasonographic Evaluation of Fatty Pancreas in Serbian Patients with Non Alcoholic Fatty Liver Disease-A Cross Sectional Study.

Background and Objectives: The aim of the study was to determine the association between presences of fatty pancreas (FP) with the features of metabolic syndrome (MeS) in patients with non-alcoholic fatty liver disease (NAFLD) and to establish a new noninvasive scoring system for the prediction of FP in patients with NAFLD. Material and Methods: 143 patients with NAFLD were classified according to FP severity grade into the two groups and evaluated for diagnostic criteria of MeS. All patients underwent sonographic examination with adiposity measurements and the liver biopsy. Liver fibrosis was evaluated semi-quantitatively according to the METAVIR scoring system and using non-invasive markers of hepatic fibrosis. Results: Waist circumference (WC) was predictive for increased risk of FP in NAFLD patients. Elevated fasting plasma glucose, total cholesterol, serum amylase and lipase levels were associated with presence of severe FP (p value = 0.052, p value = 0.007, p value = 0.014; p value = 0.024, respectively). Presence of increased amounts of mesenteric fat was associated with severe FP (p value = 0.013). The results of this study demonstrated highly significant association between NAFLD and presence of FP. The model for predicting the presence of FP was designed with probability value above 6.5. Conclusion: Pancreatic fat accumulation leads to worsening of pancreatic function which in turns exacerbates severity of metabolic syndrome associated with both, NAFLD and NAFPD.

Importance of TLR9-IL23-IL17 axis in inflammatory bowel disease development: Gene expression profiling study.

BACKGROUND AND AIMS: Mucosal gene expression have not been fully enlightened in inflammatory bowel disease (IBD). Aim of this study was to define IL23A, IL17A, IL17F and TLR9 expression in different IBD phenotypes. METHODS: Evaluation of mRNA levels was performed in paired non-inflamed and inflamed mucosal biopsies of newly diagnosed 50 Crohn's disease (CD) and 54 ulcerative colitis (UC) patients by quantitative real-time PCR analysis. RESULTS: IL17A and IL17F expression levels were significantly increased in inflamed IBD mucosa. Inflamed CD ileal and UC mucosa showed increased IL23A, while only inflamed CD ileal samples showed increased TLR9 mRNA level. Correlation between analysed mRNAs levels and endoscopic and clinical disease activity were found in UC, but only with clinical activity in CD. CONCLUSION: Both CD and UC presented expression of Th17-associated genes. Nevertheless, expression profiles between different disease forms varies which should be taken into account for future research and therapeutics strategies.

Non-alcoholic fatty pancreas disease.

Obesity is a growing problem worldwide and disorders associated with excess body fat including the metabolic syndrome, type 2 diabetes mellitus (T2DM), cardiovascular disease and malignant neoplasms are becoming a major cause of morbidity and mortality. Over the past decade, a vast amount of research has furthered our understanding of non-alcoholic fatty liver disease; however, only recently pancreatic fat infiltration is coming to the forefront of investigation. Termed non-alcoholic fatty pancreas disease (NAFPD), it is becoming evident that it has important associations with other diseases of obesity. It appears to arise as obesity progresses and after an initial phase of pancreatic hypertrophy and hyperplasia, fatty infiltration becomes apparent. Various studies have demonstrated that NAFPD may exacerbate the severity of acute pancreatitis, promote pancreatic dysfunction associated with insulin resistance and T2DM, and even have links to the development of pancreatic carcinoma, and therefore, it must be investigated in further detail.

The Importance of Artificial Intelligence in Upper Gastrointestinal Endoscopy.

Recently, there has been a growing interest in the application of artificial intelligence (AI) in medicine, especially in specialties where visualization methods are applied. AI is defined as a computer's ability to achieve human cognitive performance, which is accomplished through enabling computer "learning". This can be conducted in two ways, as machine learning and deep learning. Deep learning is a complex learning system involving the application of artificial neural networks, whose algorithms imitate the human form of learning. Upper gastrointestinal endoscopy allows examination of the esophagus, stomach and duodenum. In addition to the quality of endoscopic equipment and patient preparation, the performance of upper endoscopy depends on the experience and knowledge of the endoscopist. The application of artificial intelligence in endoscopy refers to computer-aided detection and the more complex computer-aided diagnosis. The application of AI in upper endoscopy is aimed at improving the detection of premalignant and malignant lesions, with special attention on the early detection of dysplasia in Barrett's esophagus, the early detection of esophageal and stomach cancer and the detection of H. pylori infection. Artificial intelligence reduces the workload of endoscopists, is not influenced by human factors and increases the diagnostic accuracy and quality of endoscopic methods.

Large-Vessel Giant Cell Arteritis following COVID-19-What Can HLA Typing Reveal?

Giant cell arteritis (GCA) is an immune-mediated vasculitis that affects large arteries. It has been hypothesized that viruses may trigger inflammation within the vessel walls. Genetic studies on human leukocyte antigens (HLAs) have previously reported HLA-DRB1*04 as a susceptible allele for GCA and HLA-DRB1*15 as a protective allele for GCA. Here, we discuss the clinical presentation, laboratory findings, HLA class I and class II analysis results, and management of patients with extracranial large-vessel (LV) GCA, detected at least six weeks after recovery from COVID-19. This case series encompassed three patients with LV-GCA (two males and a female with an age range of 63-69 years) whose leading clinical presentation included the presence of constitutional symptoms and significantly elevated inflammatory markers. The diagnosis of LV-GCA was confirmed by CT angiography and FDG-PET/CT, revealing inflammation in the large vessels. All were treated with corticosteroids, while two received adjunctive therapy. By analyzing HLA profiles, we found no presence of the susceptible HLA-DRB1*04 allele, while the HLA-DRB1*15 allele was detected in two patients. In conclusion, LV-GCA may be triggered by COVID-19. We highlight the importance of the early identification of LV-GCA following SARS-CoV-2 infection, which may be delayed due to the overlapping clinical features of GCA and COVID-19. The prompt initiation of therapy is necessary in order to avoid severe vascular complications. Future studies will better define the role of specific HLA alleles in patients who developed GCA following COVID-19.

Hematological Indices Are Useful in Predicting Complications of Liver Cirrhosis.

BACKGROUND: Liver cirrhosis is the final stage of chronic liver disease. We aimed to evaluate non-invasive scores as predictors of complications and outcome in cirrhotic patients. METHODS: A total of 150 cirrhotic patients were included. Models for end-stage liver disease (MELD), albumin-bilirubin (ALBI) score, neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MoLR), and neutrophil-lymphocyte-albumin ratio (NLA) scores were tested in relation to the development of complications and mortality using receiver operating characteristic (ROC) curves. RESULTS: The ROC curve analysis showed (area under the curve) AUC values of NLR, NLA, ALBI, and MELD of 0.711, 0.730, 0.627, and 0.684, respectively, for short-term mortality. MELD, ALBI, and NLA scores showed a statistically significant correlation with hepatic encephalopathy (p = 0.000 vs. 0.014 vs. 0.040, respectively), and the MELD cut-off value of 16 had a sensitivity of 70% and a specificity of 52% (AUC: 0.671, 95% CI (0.577-0.765)). For the assessment of the presence of ascites, the AUC values for NLA and MoLR were 0.583 and 0.658, respectively, with cut-offs of 11.38 and 0.44. CONCLUSIONS: MELD, ALBI, and NLA are reliable predictors of hepatic encephalopathy. NLA and MoLR showed a significant correlation with the presence of ascites, and MELD, ALBI, NLR, and NLA have prognostic value to predict 30-day mortality in cirrhotic patients.

The Quality of Life After Liver Transplantation-The First Experience from Serbia.

Background: Liver transplantation (LT) is the most effective treatment for patients with end-stage liver disease, which dramatically effects patient's quality of life (QoL). The aim of this study was to evaluate the impact of socio-demographic and clinical factors on different QoL domains of patients who underwent orthotopic LT. Methods: A cross-sectional study included a total of 43 patients who underwent a LT from 2013 to 2018. Socio-demographic and clinical data were recorded in each patient. The QoL was estimated using two validated questionnaires: 36-Item Short Form Health Survey (SF-36) and Chronic Liver Disease Questionnaire (CLDQ). Results: Male patients obtained significantly higher scores than women, in the domains of general health perception (83.2 ± 16.3 vs. 71.0 ± 18.4; t = 2.229, p = .031) and physical component summary (69.0 ± 7.2 vs. 62.0 ± 11.4; t = 2.451, p = .019). There were no significant differences in other domains of SF-36 and CLDQ. Etiology of the underlying liver disease and the presence of post-transplant complications showed no effect on score values of SF-36 and CDLQ domains (p < .05). Time from LT showed negative medium correlation with role limitations due to physical health problems (S = -0.417, p = .005), while no other significant correlations were noted in other items of SF-36 and CLDQ. Conclusions: Men had higher scores in the domain of general health perception and physical component summary following LT than women. With the increase in time from LT, patients experience a decrease in limitations due to physical health problems. The audit and improvement of QoL is an essential part of the individualized long-term health-care approach to LT patients.

Genetic Aspects of Micronutrients Important for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC) are complex diseases whose etiology is associated with genetic and environmental risk factors, among which are diet and gut microbiota. To date, IBD is an incurable disease and the main goal of its treatment is to reduce symptoms, prevent complications, and improve nutritional status and the quality of life. Patients with IBD usually suffer from nutritional deficiency with imbalances of specific micronutrient levels that contribute to the further deterioration of the disease. Therefore, along with medications usually used for IBD treatment, therapeutic strategies also include the supplementation of micronutrients such as vitamin D, folic acid, iron, and zinc. Micronutrient supplementation tailored according to individual needs could help patients to maintain overall health, avoid the triggering of symptoms, and support remission. The identification of individuals' genotypes associated with the absorption, transport and metabolism of micronutrients can modify future clinical practice in IBD and enable individualized treatment. This review discusses the personalized approach with respect to genetics related to micronutrients commonly used in inflammatory bowel disease treatment.

The Interrelationship Among Non-Alcoholic Fatty Liver Disease, Colonic Diverticulosis and Metabolic Syndrome.

Non-alcoholic fatty liver disease and colonic diverticulosis are widespread, obesity-related diseases. It has recently become clear that non-alcoholic fatty liver disease is a systemic disease and may play a key role in metabolic syndrome; therefore, the term metabolic-dysfunction-associated fatty liver disease has been introduced in the literature. Excess visceral adipose tissue is an important predictor of complications in both non-alcoholic fatty liver disease and colonic diverticulosis. Current evidence suggests that intestinal dysbiosis may be involved in the development of both non-alcoholic fatty liver disease and colonic diverticulosis, and that metabolic syndrome is a consequence rather than a cause of this complex relationship. In this review, our aim was to assess the current knowledge of the complex interplay between metabolic syndrome, non-alcoholic fatty liver disease, and colonic diverticulosis.

Bacteremia in patients with liver cirrhosis in the era of increasing antimicrobial resistance: single-center epidemiology.

INTRODUCTION: Liver cirrhosis is commonly associated with bacterial infections, which contribute to unfavorable outcome. This study aimed to investigate the epidemiology of bacteremia and patterns of antibiotic resistance in patients with cirrhosis, factors associated with multidrug-resistant infection, and predictors of mortality. METHODOLOGY: This retrospective single-center study included patients with cirrhosis treated between January 2016 and December 2018. Data were collected from the patients' medical records. The severity of liver disease was determined using the Child-Pugh, Model for End-Stage Liver Disease-Na, Chronic Liver Failure-Consortium Acute-on-Chronic Liver Failure, and Chronic Liver Failure-Consortium Acute Decompensation scores. RESULTS: A total of 85 patients with cirrhosis and bacteremia were included (male: 82.4%, mean age 60.3 ± 9.4 years). The etiology of cirrhosis was mainly alcoholism (87.1%). After 30 days, lethal outcome occurred in 44.7% of the patients. The most commonly isolated pathogens were Enterococcus spp. (31.8%), methicillin-sensitive Staphylococcus aureus (15.3%), and Escherichia coli (14.1%), while 37.3% of all isolated microorganisms were multi-drug resistant. Multi-drug resistant infection [odds ratio (OR): 6.198, 95% confidence interval (CI): 2.326-17.540, p = 0.006] and neutrophil-to-lymphocyte ratio (OR = 1.181, 95% CI = 1.043-1.337, p = 0.009) are independent predictors of mortality. The aforementioned scores, which represent the extent of hepatic insufficiency, are significantly higher in patients with multi-drug resistant isolates, while multi-drug resistant bacteremia was more common in patients with more advanced liver disease. CONCLUSIONS: Multi-drug resistant bacteremia is more common in patients in whom liver disease is more severe and is a major independent predictor of mortality.

Enhanced Liver Fibrosis Score as a Biomarker for Vascular Damage Assessment in Patients with Takayasu Arteritis-A Pilot Study.

Takayasu Arteritis (TA) is characterized by granulomatous panarteritis, vessel wall fibrosis, and irreversible vascular impairment. The aim of this study is to explore the usefulness of the Enhanced Liver Fibrosis score (ELF), procollagen-III aminoterminal propeptide (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and hyaluronic acid (HA) in assessing vascular damage in TA patients. ELF, PIIINP, TIMP-1, and HA were measured in 24 TA patients, and the results were correlated with the clinical damage indexes (VDI and TADS), an imaging damage score (CARDS), and disease activity scores (NIH and ITAS2010). A mean ELF score 8.42 (±1.12) and values higher than 7.7 (cut-off for liver fibrosis) in 21/24 (87.5%) of patients were detected. The VDI and TADS correlated significantly to ELF (p < 0.01). Additionally, a strong association across ELF and CARDS (p < 0.0001), PIIINP and CARDS (p < 0.001), and HA and CARDS (p < 0.001) was observed. No correlations of the tested biomarkers with inflammatory parameters, NIH, and ITAS2010 scores were found. To our knowledge, this is the first study that suggests the association of the serum biomarkers PIIINP, HA, and ELF score with damage but not with disease activity in TA patients. The ELF score and PIIINP may be useful biomarkers reflecting an ongoing fibrotic process and quantifying vascular damage.

Perineural invasion as a prognostic factor in patients with stage I-III rectal cancer - 5-year follow up.

BACKGROUND: Rectal cancer (RC) is one of the most common diagnosed cancers, and one of the major causes of cancer-related death nowadays. Majority of the current guidelines rely on TNM classification regarding therapy regiments, however recent studies suggest that additional histopathological findings could affect the disease course. AIM: To determine whether perineural invasion alone or in combination with lymphovascular invasion have an effect on 5-years overall survival (OS) of RC patients. METHODS: A prospective study included newly diagnosed stage I-III RC patients treated and followed at the Digestive Surgery Clinic, Clinical Center of Serbia, between the years of 2014-2016. All patients had their diagnosis histologically confirmed in accordance with both TMN and Dukes classification. In addition, the patient's demographics, surgical details, postoperative pathological details, differentiation degree and their correlation with OS was investigated. RESULTS: Of 245 included patients with stage I-III RC, lymphovascular invasion (LVI) was identified in 92 patients (38%), whereas perineural invasion (PNI) was present in 46 patients (19%). Using Kaplan-Meier analysis for overall survival rate, we have found that both LVI and PNI were associated with lower survival rates (P < 0.01). Moreover when Cox multiple regression model was used, LVI, PNI, older age, male gender were predictors of poor prognosis (HR = 5.49; 95%CI: 2.889-10.429; P < 0.05). CONCLUSION: LVI and PNI were significant factors predicting worse prognosis in early and intermediate RC patients, hence more aggressive therapy should be reserved for these patients after curative resection.

Correlation of Patient-Reported Outcome (PRO-2) with Endoscopic and Histological Features in Ulcerative Colitis and Crohn's Disease Patients.

METHODS: A cross-sectional study was conducted in consecutive newly diagnosed patients with inflammatory bowel disease in a tertiary care referral center. The initial evaluation included patient-reported outcome for stool frequency subscore and rectal bleeding. Endoscopic activity was determined using the Mayo scoring system for ulcerative colitis and the Simple Endoscopic Score for Crohn's disease. Histopathological activity was assessed using a validated numeric scoring system. RESULTS: We included 159 patients (63 Crohn's disease with colonic involvement and 96 with ulcerative colitis). We found significant correlation between the Mayo endoscopic subscoring system and histology activity in ulcerative colitis, while no correlation was found in patients with Crohn's disease. Patient-reported outcome showed inverse correlation with endoscopic and histological activity in Crohn's disease (r s = -0.67; r s = -0.72), while positive correlation was found in ulcerative colitis (r s = 0.84; r s = 0.75). Interpretation and Conclusions. Patient-reported outcome is a practical and noninvasive tool for assessment of disease activity in ulcerative colitis patients but not in Crohn's disease.

Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy.

BACKGROUND: Crohn's disease (CD) is chronic inflammatory bowel disease with different phenotypic characteristics influencing disease prognosis and therapeutic strategies. The aim of this pilot study was to analyze selected inflammatory and apoptotic markers in non-inflamed and inflamed samples of ileal mucosa of non-stricturing/non-penetrating (NS/NP) and stricturing (S) CD mucosal phenotypes in order to characterize their distinct profiles. METHODS: From twenty CD patients (9 NS/NP, 11 S) paired non-inflamed and inflamed ileal biopsies were collected and used for analysis of cytokine (TNF and IL6) and apoptotic (Bcl2, Bax, Fas and FasL) genes' expression levels by real-time PCR, while NFκB transcriptional potency was assessed by electromobility gel shift assay. RESULTS: Our results demonstrated significant upregulation of TNF and IL6 in inflamed area of both NS/NP (p = 0.03, p = 0.01) and S phenotypes (p = 0.04, p = 0.04), respectively. However, TNF increase was more prominent in NS/NP compared to S inflamed mucosa (p = 0.02). Also, level of proapoptotic Bax was significantly higher in NS/NP compared to S inflamed mucosa (p = 0.01). Opposing transcription potency of NFκB has been detected between two phenotypes: being decreased in NS/NP (p = 0.07) and increased in S (p = 0.1) inflamed compared to non-inflamed mucosa, demonstrating trend towards statistical significance. CONCLUSIONS: We found that two distinct CD phenotypes have specific molecular signatures. Obtained results could direct improvement of current and development of new therapeutic strategies based on more specific molecular stratification of CD patients.