Circadian rhythm abnormalities in patients with inflammatory bowel disease - association with adipokine profile.

Background: The role of sleep disturbances in patients with inflammatory bowel disease (IBD) remained relatively unknown. The aim of this study was to identify the adipokine profile in the patients with IBD and its relationship with the circadian rhythm disorders.Methods: Prospective, observational cohort study was performed. In all the enrolled adult IBD patients, the disease activity was assessed by using Crohn's Disease Activity Index (CDAI) for Crohn's disease (CD) and Partial Mayo Score for ulcerative colitis (UC), respectively. All patients were also asked to respond to a questionnaire to define Pittsburgh Quality Sleep Index (PSQI). From all the enrolled patients, 15 mL venous blood was taken to determine adipokine levels and perform standard laboratory tests.Results: Sixty-five IBD patients were enrolled in our study: 30 with CD and 35 with UC. Poor sleep was noted in 69.2% patients with clinically active and in 7.7% patients with inactive disease (p = .0023). In the group of IBD patients with poor sleep, the significantly higher level of serum resistin (p = .0458), and lower level of serum adiponectin and leptin (p = .0215, p = .0201; respectively) were observed. In the IBD patients with exacerbation, the significantly higher level of serum resistin (p = .0396), significantly lower serum level of leptin (p = .0453) and tendency to lower serum level of adiponectin (p = .1214) were recorded.Conclusions: The relationship between circadian rhythm abnormalities and specific adipokine profile may show us a risk factor of developing inflammatory intestinal lesions in IBD patients. This knowledge may allow the treatment of sleep disturbances, body weight-control and dietary habits become new targets in IBD therapy.

The incidence rate of surgical interventions in patients with Crohn's disease treated with anti-tumour necrosis factor biologics.

BACKGROUND: Anti-tumour necrosis factor alpha drugs (anti-TNF-α) effectively reduce the risk of surgery in Crohn's disease (CD). Unsatisfactory response to anti-TNF-α agents leads to the development of disease complications in a great percentage of patients. Simultaneously, possible predictive factors for ares during biological treatment remain uncertain. AIMS: To investigate the incidence rate of intestinal resection during biological treatment and search for predicting factors for ares demanding a surgical intervention. METHODS: A retrospective study of 68 patients qualified for anti-TNF-alpha therapy. The data consisting of demographic details, disease duration and laboratory results before the first drug administration and at the post induction period were collected. The association between these parameters and loss of response (LOR) demanding a surgical intervention was evaluated. RESULTS: LOR to the anti-TNF-alpha therapy was observed in 10/68 patients (14.7%). Mean disease duration at initiation of therapy was statistically longer in operated patients (8.8 ± 2.04 y vs. 4.93 ± 4.29 y; p < 0.02). That group revealed higher CRP values in post induction period compared to group with sustained response (48.24 ± 61.99 mg/l vs. 7.29 ± 13.43 mg/l; p < 0.05), contrary to hematocrit levels, which were lower in this group at each point of the study (30.58 ± 6.19% vs. 36.69 ± 16.0%; p = 0.04) (18.62 ± 18.19% vs. 40.27 ± 4.72%; p < 0.05) (4.01 ± 0.9 x106/µl; p = 0.009) (40.27 ± 4.72 g/dl vs. 18.62 ± 18.19 g/dl; p < 0.05). CDAI was significantly higher at post induction evaluation in the group with LOR (260.75 ± 98.1 vs. 118.12 ± 4.59; p < 0.05). CONCLUSION: CRP and CDAI, expressing in ammation severity, RBC, Hgb, Hct and the disease duration may serve as predictive factors for LOR to biological therapy.

Risk factors and clinical characteristics of rectal cancer recurrence after radical surgical treatment.

<b><br>Introduction:</b> Recurrence of rectal cancer affects from 4% to even 50% of patients after surgical treatment. The incidence may be influenced by numerous factors depending on the patient, the characteristics of the tumor and the type and quality of the surgical technique used.</br> <b><br>Aim:</b> The aim of this study was to assess the clinical characteristics of rectal cancer recurrence, identify potential risk factors and role of patient surveillance after primary resection of rectal cancer.</br> <b><br>Materials and methods:</b> The study comprised patients operated on due to recurrence of rectal cancer at the Department of General and Colorectal Surgery of Medical University of Lodz between 2014 and 2020, who were in the follow-up program at the hospital's outpatient clinic after the primary surgery. Risk factors for disease recurrence were sought by analyzing the characteristics of the primary tumor, treatment history and postoperative care.</br> <b><br>Results:</b> Twenty-nine patients were included in the study, the majority (51.7%) of the patients were men. The largest group was represented by patients with stage II and III disease. The most frequently performed primary surgery was low anterior resection (LAR) (62.8%). 35% of patients received neoadjuvant treatment prior to primary surgery. We demonstrated that the lack of neoadjuvant treatment before primary surgery increases the risk of cancer recurrence nine times. Higher stage of disease at the point of primary surgery is associated with nearly seven times the risk of recurrence compared to stage I disease.</br> <b><br>Conclusions:</b> Optimal preoperative staging, reasonable neoadjuvant treatment, proper surgical technique and precise follow-up regimen are essential for further improvement of rectal cancer outcomes.</br>.

Oxidative Stress Does Not Influence Subjective Pain Sensation in Inflammatory Bowel Disease Patients.

Oxidative stress (OS) has been proposed as a significant causative and propagating factor in inflammatory bowel diseases (IBDs). Modulation of OS is possible through antioxidants and inhibition of oxidizing enzymes. Thirty-one IBD patients and thirty-two controls were included in the study. The aim was to examine the levels of OS in colonic tissue of IBD requiring surgical intervention and control group, and their association with pain intensity. Total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase (CAT) activity, glutathione (GSH) and oxidized glutathione (GSSG) levels, and glutathione peroxidase (GPX) activity as markers of antioxidant defense were determined. Cyclooxygenases activities (Total COX, COX-1 and COX-2) were measured as prooxidant enzymes. Thiobarbituric acid reactive substances (TBARS) concentrations were measured to evaluate lipid peroxidation. Disease activity was assessed, and each subject filled out VAS and Laitinen's pain assessment scales. Correlation between the OS, pain intensity, disease activity parameters, C-reactive protein (CRP), number of stools passed daily, disease duration, and dietary habits was investigated. No TAC differences were found between the groups. A significant decrease of SOD activity and GSH and GSSG levels was seen in IBD patients vs. controls, while GPX activity was diminished significantly only in CD patients. CAT and COX-1 activity was increased, and COX-2 significantly decreased in IBD. TBARS were significantly higher in CD patients compared to control group. No correlation was found between pain scores, inflammatory status, disease activity, disease duration, or dietary habits and OS markers. In our study, OS did not influence pain sensation reported by IBD patients.

The role of adipose tissue in the pathogenesis of Crohn's disease.

Crohn's disease (CD) is a chronic, immune system-mediated inflammatory disease affecting gastrointestinal (GI) tract. The pathogenesis of the intestinal lesions is not entirely explained and understood: excessive activation of the immune system may come as a result of the interaction of environmental, genetic and infectious factors and the mediation of abnormal intestinal flora. The main objective of the current study is to further identify the role of adipose tissue in the pathogenesis of CD. Alterations in body fat distribution, accumulation of intra-abdominal white adipose tissue (WAT) and mesenteric obesity are well-known features of CD. Up to date, data concerning the role of WAT in the pathogenesis of CD is limited with only a few studies on the relationship between WAT and the course of the disease, as well as pro- and anti-inflammatory cytokine profile and general immune system functioning. In this review, we focus on the importance of physiological and pathophysiological WAT functions and secreted adipokines, which seem to have a vital role in the inflammatory and fibrotic processes in CD sufferers.

Genetic Molecular Subtypes in Optimizing Personalized Therapy for Metastatic Colorectal Cancer.

Colorectal cancer (CRC) is a heterogeneous disease entity in terms of both molecular carcinogenesis and morphologic carcinogenesis multistep pathways. Considerable heterogeneity exists within CRC due to the varied genetic and epigenetic mechanisms involved in different carcinogenesis pathways. A better understanding of pathophysiology of tumors is necessary to develop modern and successful means of treatment in metastatic CRC. Over the last 5 years, there has been a surge in interest in the molecular classification of colorectal cancer, as its clinical importance both for predicting prognosis and in guiding personalized treatment had been acknowledged. Recently, the Colorectal Cancer Subtyping Consortium identified four consensus molecular subtypes, CMS 1-4 in CRC; however, attempts to stratify CRC using molecular features for prognostic and predictive purposes in clinical conditions had limited success. In this review, we focused on molecularly defined subtypes of CRC including specific mutations and discuss implications for current and future patient management in metastatic CRC to achieve the maximal therapeutic response for each patient, while reducing adverse side effects of therapy.