Assessment of the activity of the immune system in patients with inflammatory bowel diseases and asymptomatic COVID-19.

Introduction: Although the phenomenon of cytokine storm is well described in patients with severe COVID-19, little is known about the role of the immune system in asymptomatic patients, especially in the group with autoimmune diseases, such as inflammatory bowel disease (IBD). Aim: To assess the stimulation of the immune system expressed through the production of cytokines in IBD patients with asymptomatic COVID-19. Material and methods: This is a multi-centre, prospective study in which the concentration of many cytokines (IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL- 15, IL-17, IL-23, IFN-γ, TNF-α, TNF-ß) was assessed in patients with IBD and asymptomatic SARS-CoV-2 infection diagnosed by serological tests. Results: In the group of patients with a recent SARS-CoV-2 infection, defined as positive antibodies in the IgA + IgM class, a higher percentage of patients with the presence of interleukin (IL) 2 (IL-2) was found. No association with other cytokines or effects of IBD activity or treatment was found. However, the effect of the applied treatment on the concentration of some cytokines was found: a negative association of infliximab, vedolizumab, and prednisone with IL-2, a positive correlation of steroids, thiopurines with IL-10, and in the case of tumor necrosis factor-α (TNF-α), negative with infliximab, and positive with vedolizumab. Conclusions: The increased concentration of IL-2 may result from its regulatory role in inhibiting excessive activation of the immune system; however, considering the studies of patients with severe COVID-19, its role in the initial phase of SARS-CoV-2 infection requires further research.

A Low FODMAP Diet Supplemented with L-Tryptophan Reduces the Symptoms of Functional Constipation in Elderly Patients.

(1) Background: The elderly suffer from functional constipation (FC), whose causes are not fully known, but nutritional factors may play a role. The aim of the present study was to assess the effect of a low FODMAP diet supplemented with L-tryptophan (TRP) on its metabolism and symptoms of functional constipation in elderly patients. (2) Methods: This study included 40 people without abdominal complaints (Group I, controls) and 60 patients with FC, diagnosed according to the Rome IV Criteria (Group II). Two groups were randomly selected: Group IIA (n = 30) was qualified for administration of the low FODMAP diet, and the diet of patients of Group IIB (n = 30) was supplemented with 1000 mg TRP per day. The severity of abdominal symptoms was assessed with an abdominal pain index ranging from 1 to 7 points (S-score). The concentration of TRP and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and 3-indoxyl sulfate (3-IS) in urine were determined using the LC-MS/MS method. (3) Results: In Group II, 5-HIAA concentration in urine was lower, and KYN and 3-IS concentrations were higher than in the control group. A negative correlation was found between the S-score and urinary concentration of 5-HIAA (p < 0.001), and 3-IS concentration was positively correlated with the S-score. However, the correlation between the S-score and 3-IS concentration was negative (p < 0.01). After a dietary intervention, 5-HIAA concentration increased in both groups, and the severity of symptoms decreased, but the decrease was more pronounced in Group IIB. (4) Conclusion: A low FODMAP diet supplemented with L-tryptophan has beneficial effects in elderly patients suffering from functional constipation.

The Variability of Tryptophan Metabolism in Patients with Mixed Type of Irritable Bowel Syndrome.

Patients with a mixed type of irritable bowel syndrome (IBS-M) experience constipation and diarrhea, which alternate between weeks or months. The pathogenesis of this syndrome is still little understood. The aim of the study was mainly to evaluate the urinary excretion of selected tryptophan (TRP) metabolites during the constipation and diarrhea periods of this syndrome. In 36 patients with IBS-M and 36 healthy people, serum serotonin level was measured by ELISA and urinary levels of 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN) and indican (3-IS) were determined using the LC-MS/MS method. The levels of all above metabolites were higher in the patient group, and increased significantly during the diarrheal period of IBS-M. In particular, the changes concerned 5-HIAA (3.67 ± 0.86 vs. 4.59 ± 0.95 mg/gCr, p < 0.001) and 3-IS (80.2 ± 17.4 vs. 93.7 ± 25.1 mg/g/Cr, p < 0.001). These changes coexisted with gut microbiome changes, assessed using hydrogen-methane and ammonia breath tests. In conclusion, the variability of TRP metabolism and the gut microbiome may cause the alternation of IBS-M symptoms.

Diagnostic and therapeutic recommendations on Helicobacter pylori infection. Recommendations of the Working Group of the Polish Society of Gastroenterology.

Helicobacter pylori remains a major health problem worldwide, causing considerable morbidity and mortality due to peptic ulcer disease and gastric cancer. These guidelines constitute an update of the previous "Recommendations on the diagnosis and management of Helicobacter pylori infection" issued in 2014. They have been developed by a Task Force organized by the Governing Board of the Polish Society of Gastroenterology. They discuss, with particular emphasis on new scientific data covering papers published since 2014: the epidemiology, clinical presentation, diagnostic principles and criteria for the diagnosis, and recommendations for the treatment of H. pylori infection. The guidelines in particular determine which patients need to be tested and treated for infection. The Task Force also discussed recommended treatment algorithms. Accordingly, a combination of available evidence and consensus-based expert opinion were used to develop these best practice advice statements. It is worth noting that guidelines are not mandatory to implement but they offer advice for pragmatic, relevant and achievable diagnostic and treatment pathways based on established key treatment principles and using local knowledge and available resources to guide regional practice.

Reduced Intake of Dietary Tryptophan Improves Beneficial Action of Budesonide in Patients with Lymphocytic Colitis and Mood Disorders.

Lymphocytic colitis (LC) is a gastrointestinal (GI) tract disease with poorly known pathogenesis, but some environmental and lifestyle factors, including certain dietary components, may play a role. Tryptophan is an essential amino acid, which plays important structural and functional roles as a component of many proteins. It is important in the development and maintenance of the body, in which it is metabolized in two main pathways: kynurenine (KYN) and serotonin. In this work, we explored the effect of reducing of TRP in the diet of patients with LC with mood disorders. We enrolled 40 LC patients who had a normal diet, 40 LC patients with the 8-week diet with TRP content reduced by 25% and 40 controls. All LC patients received budesonide at 9 mg per day, and the severity of their GI symptoms was evaluated by the Gastrointestinal Symptoms Rating Scale. Mood disorders were evaluated by the Hamilton Anxiety Rating Scale (HAM-A) and the Hamilton Depression Rating Scale (HAM-D). The concentration of TRP and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA), in urine were determined. Budesonide improved the GI and mental states of LC patients, and the diet with reduced TRP content further amended these symptoms. Dietary intervention decreased the concentration of 5-HIAA by about 50% (3.4 vs. 6.3) and QA by about 45% (3.97 vs. 7.20). These changes were correlated with a significant improvement in the profitable action of budesonide on gastrointestinal and mental health of LC patients as they displayed significantly lower GSRS, HAM-A and HAM-B scores after than before the intervention-10.5 vs. 32, 11.0 vs. 21 and 12 vs. 18, respectively. In conclusion, a reduction in TRP intake in diet may improve GI and mental symptoms in LC patients treated with budesonide and these changes may be mediated by the products of TRP metabolism.

Beneficial Effect of Increased Tryptophan Intake on Its Metabolism and Mental State of the Elderly.

The elderly often suffer from sleep disorders and depression, which contribute to mood disorders. In our previous work, we showed that elderly individuals with mood disorders had a lower intake of TRP and recommended a TRP-based dietary intervention to improve the mental state of such individuals. In this work, we assessed the impact of a TRP-rich diet on the mental state of, and TRP metabolism in, elderly individuals with mood disorders. Forty elderly individuals with depression and sleep disorders and an equal number of elderly subjects without mood disorders were enrolled in this study. TRP intake was evaluated with the nutrition calculator. Patients with mood disorders had a lower TRP intake than their normal counterparts and received a TRP-rich diet with TRP content of 25 mg per kilogram of the body per day for 12 weeks. The mental state was assessed before and after this dietary intervention with the Hamilton Depression Rating Scale (HAM-D) and the Insomnia Severity Index (ISI). At those times, urinary levels of TRP and its metabolites 5-hydroxyindoleacetic acid (5-HIAA), L-kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QA) were determined by liquid chromatography with tandem mass spectrometry and related to creatinine level. After TRP-based dietary intervention, the score of ISI and HAM-D decreased by more than half. A correlation analysis reveals that TRP, 5-HIAA, and KYNA might have anti-depressive action, while KYN and QA-pro-depressive. The levels of TRP, 5-HIAA, and KYNA in urine of mood disorder patients increased, while the levels of KYN and QA decreased. In conclusion, dietary consumption of adequate amount of tryptophan has a beneficial effect on mental health of the elderly with mood disorders and improves metabolism of this amino acid. Therefore, a TRP-enriched diet may be considered as a component of the treatment of elderly individuals with mood disorders.

Nutritional Status Indicators as a Predictor of Achieving Remission at Week 14 during Vedolizumab Therapy in Patients with Ulcerative Colitis: A Pilot Study.

Background: The loss of response or failure to achieve remission to vedolizumab in ulcerative colitis (UC) patients is currently a major clinical problem. Recently, Nutritional Risk Index (NRI), Controlling Nutritional Status (CONUT), and Malnutrition Universal Screening Tool (MUST) have been suggested as a new prognostic factor of UC activity. Here, we aimed at confirmation of hypotezis that NRI, CONUT and MUST may be used as inexpensive and efficient predictive biomarkers of response in UC patients treated with vedolizumab. Methods: This study was conducted in retrospective manner in 32 adult patients with UC of Caucasian origin (21 men and 11 women), who were qualified for 52-week therapy with vedolizumab and finished the 14-weeks from January 2020 to March 2022. Our study analyzed the 45 courses of vedolizumab therapy. Nutritional status indicators, i.e., the NRI, CONUT and MUST of each UC patient, were marked at the time of qualifying for biological treatment. Results: In our study, the MUST score was significantly lower in UC patients who positively achieved clinical remission at week 14 during vedolizumab induction therapy (0.33 ± 0.49 vs. 1.37 ± 0.83; p = 0.002). The analysis showed the lower baseline NRI and CONUT scores in patients with positive clinical remission at week 14 (NRI: 96.42 ± 4.29 vs. 101.41 ± 7.09; p = 0.024; CONUT: 1.00 ± 1.08 vs. 2.16 ± 1.46; p = 0.031). Conclusions: Nutritional status indicators (NRI, MUST and CONUT) may become valuable predictor of achieving remission at week 14 during vedolizumab therapy in UC patients.

Effects of Microencapsulated Sodium Butyrate, Probiotics and Short Chain Fructooligosaccharides in Patients with Irritable Bowel Syndrome: A Study Protocol of a Randomized Double-Blind Placebo-Controlled Trial.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease in the pathogenesis of which gut dysbiosis may play an important role. Thus, probiotics, prebiotics, or microbiota metabolites, such as butyric acid, are considered to be effective therapy for IBS. However, there are still no trials presenting the efficacy of these three biotic components administered simultaneously. This study aims to evaluate the effects of the product comprising sodium butyrate, probiotics, and short-chain fructooligosaccharides (scFOS) on the severity of clinical IBS symptoms and the quality of life (IBS-QOL). This is a randomized double-blind placebo-controlled trial conducted in 120 adults with IBS diagnosed according to Rome IV criteria. The intervention group (n = 60) will receive a mixture of the following components: 300 mg of colon-targeted microencapsulated sodium butyrate combined with probiotic Lactobacillus strains (L. rhamnosus and L. acidophilus) and Bifidobacterium strains (B. longum, B. bifidum, B. lactis), and 64 mg of prebiotic scFOS. The control group (n = 60) will receive a placebo (maltodextrin). The primary outcomes will be changes in IBS symptoms with the use of the IBS-Severity Scoring System (IBS-SSS), IBS-Global Improvement Scale (IBS-GIS), IBS-Adequate Relief (IBS-AR), and IBS-QOL after 12 weeks of intervention. The secondary outcomes will be the type of stools, patient-recorded symptoms, adverse events, anthropometric and nutritional parameters, and inflammatory cytokine levels. The findings will provide the first evidence of the use of a combination of three biotic compounds in IBS. The study was registered in the clinicaltrials.gov registry under the number NCT05013060.

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.

The association of the quality of sleep with proinflammatory cytokine profile in inflammatory bowel disease patients.

BACKGROUND: The role of circadian rhythm abnormalities in patients with inflammatory bowel disease (IBD) remains relatively unknown. The aim of this study was to identify the inflammatory cytokine profile in the IBD patients and its relationship with the quality of sleep. METHODS: Prospective, single-center observational cohort study was performed. In all enrolled adult IBD patients, the disease activity was assessed using Crohn's Disease Activity Index (CDAI) for Crohn's disease (CD) and Partial Mayo Score for ulcerative colitis (UC), respectively. To assess the quality of sleep, all patients were asked to respond to a questionnaire to define Pittsburgh Quality Sleep Index (PSQI). From all enrolled patients, 15 ml venous blood was taken to determine serum inflammatory cytokine levels and perform standard laboratory tests. RESULTS: Fifty-two IBD patients were enrolled in the study: 32 with CD and 20 with UC. The poor sleep was noted in 69.4% of patients with clinically active and in 6.3% of patients with inactive disease. In the group of IBD patients with poor sleep, the significantly higher level of serum IL-6, IL-17, and IL-23 were observed. In IBD patients with exacerbation, the significantly higher level of serum IL-6, IL-17, and IL-23 were recorded. CONCLUSIONS: The relationship between quality of sleep and proinflammatory cytokine profile may show us a predisposition for the development of inflammatory intestinal lesions in IBD patients with sleep disturbances. This knowledge may allow the pharmacological and behavioral therapies of circadian rhythm abnormalities to become new significant targets in IBD patients.

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.

Social Distancing during COVID-19 Pandemic among Inflammatory Bowel Disease Patients.

(1) Background: Social distancing rules have been widely introduced in the fight against the coronavirus disease 2019 (COVID-19) pandemic. So far, the effectiveness of these methods has not been assessed in the group of inflammatory bowel disease (IBD) patients. (2) Methods: The study included 473 patients with IBD who made 1180 hospital visits from 1 May to 30 September 2020. During each visit, the patients completed a five-step, progressive scale that was developed to assess the degree of social isolation. In parallel, other demographic data were collected and the concentrations of anti-severe acute respiratory coronavirus 2 (SARS-CoV-2) IgG and IgM+IgA antibodies were measured using the ELISA method. (3) Results: The study found a significant correlation between the degree of social distancing and the presence of anti-SARS-CoV-2 antibodies in the groups with the lowest degree of isolation (3 to 5). (4) Conclusions: Maintaining social distancing is an effective method for reducing the spread of SARS-CoV-2 virus among IBD patients.

Insulin-like growth factor 1 and insulin-like growth factor binding protein 2 serum levels as potential biomarkers in differential diagnosis between chronic pancreatitis and pancreatic adenocarcinoma in reference to pancreatic diabetes.

INTRODUCTION: Insulin-like growth factor 1 (IGF-1) has been connected with development of pancreatic ductal adenocarcinoma (PDAC). AIM: To evaluate the serum concentration levels of IGF-1 and insulin-like growth factor binding protein 2 (IGFBP-2) in patients with chronic pancreatitis (CP) and PDAC. Their values in diabetes mellitus (DM) were also assessed. MATERIAL AND METHODS: The study included 83 patients with CP, 92 patients with PDAC, and 20 subjects as a control group. The concentrations of IGF-1 and IGFBP-2 were estimated with ELISA (Corgenix UK Ltd, R&D Systems). RESULTS: The IGF-1 was higher in CP compared with PDAC (81.11 ±57.18 ng/ml vs. 53.18 ±36.05 ng/ml, p < 0.001), and both CP and PDAC were different from controls (81.11 ±57.18 ng/ml vs. 70.66 ±16.57 ng/ml, p < 0.001 and 53.18 ±36.05 ng/ml vs. 70.66 ±16.57 ng/ml, p < 0.001). CP without cysts have lower IGF-1 compared to those with CP and cysts (60.35 ±34.68 ng/ml vs. 93.55 ±64.78 ng/ml, p < 0.05). IGF-1 in CP without DM was higher compared to IGF-1 in PDAC without DM (91.13 ±65.48 ng/ml vs. 54.75 ±40.41 ng/ml, p < 0.001). In CP and DM the IGF-1 was elevated in comparison to PDAC and DM (62.20 ±32.38 ng/ml vs. 48.45 ±24.88 ng/ml, p < 0.05). IGFBP-2 was higher in CP compared to PDAC (512.42 ±299.77 ng/ml vs 301.59 ±190.36 ng/ml, p < 0.001). In CP and PDAC the IGFBP-2 level was elevated compared to the control group (512.42 ±299.77 ng/ml vs. 51.92 ±29.40 ng/ml, p < 0.001 and 301.59 ±190.36 ng/ml vs. 51.92 ±29.40 ng/ml, p < 0.001). IGFBP-2 in CP without DM was higher compared to PDAC without DM (559.39 ±281.43 vs. 296.53 ±196.93, p < 0.001). CONCLUSIONS: IGF-1 and IGFBP-2 may be biomarkers of CP and PDAC. IGF-1 may be an indicator that signals whether pancreatic diabetes is from CP or PDAC.

The 25(OH)D3, but Not 1,25(OH)2D3 Levels Are Elevated in IBD Patients Regardless of Vitamin D Supplementation and Do Not Associate with Pain Severity or Frequency.

Due to its immunomodulatory effect, vitamin D has been associated with clinical parameters and outcomes in inflammatory bowel diseases (IBDs) which are chronic conditions of the gastrointestinal tract. Upon synthesis or digestion, vitamin D is metabolized in the liver to form 25(OH)D3, the major circulating metabolite. Further renal hydroxylation generates 1,25(OH)2D3, the most potent metabolite. Our aim was to examine the association between vitamin D levels, and its supplementation and pain intensity in 39 IBD patients and 33 healthy individuals. 25(OH)D3 and 1,25(OH)2D3 serum levels were measured. Each subject filled out visual analog scale (VAS) and Laitinen's pain assessment scales. Laboratory results were obtained, and disease activity was assessed. Linear regression was employed to investigate the correlation between 25(OH)D3, 1,25(OH)2D3 and pain intensity, clinical activity parameters, C-reactive protein, disease duration, and dietary habits. In IBD patients, 25(OH)D3 was increased, whereas 1,25(OH)2D3 was not. Vitamin D3 supplementation did not influence their levels. No correlation was found between pain scores, disease activity, inflammatory status, disease duration or dietary habits and both forms of vitamin D. Elevated 25(OH)D3 and normal 1,25(OH)D3 were found in IBD patients as compared to the controls. We discovered no effect from supplementation and no association between pain severity and vitamin D.

Inflammatory bowel disease is associated with higher seroprevalence rates of antibodies against SARS-CoV-2.

INTRODUCTION: According to the current data, there has been no increase in the incidence of COVID­19 in patients with inflammatory bowel disease (IBD). OBJECTIVES: The available data are based on symptomatic cases and do not include the asymptomatic ones. To measure the exact infection rate, we initiated a study that aimed to assess the seroprevalence of anti-SARS­CoV­2 antibodies in IBD. PATIENTS AND METHODS: A total of 864 individuals were enrolled in the study, including 432 patients with IBD (290 with Crohn disease and 142 with ulcerative colitis) and 432 controls without IBD (healthcare professionals) matched for age and sex. Serum samples were prospectively collected, and the presence of anti-SARS­CoV­2 immunoglobulin (Ig) G and IgM + IgA antibodies were measured using the enzyme­linked immunoassay method (Vircell Microbiologists). RESULTS: A significantly higher percentage of positive results for anti-SARS­CoV­2 antibodies, both in the IgG and IgM + IgA class, was found in patients with IBD (4.6% and 6%, respectively, compared with 1.6% and 1.1%, respectively, in controls; both P values <0.05). No patient had symptomatic COVID­19. There was no association among patients' age, sex, drugs used for IBD, or disease activity and the occurrence of IgG antibodies. CONCLUSION: Patients with IBD may be at higher risk of developing SARS­CoV­2 infection, defined as the presence of elevated levels of anti-SARS­CoV­2 IgG antibodies, but not of having a symptomatic and / or severe course of COVID­19 compared with healthcare professionals without IBD.

Serotonin in the Pathogenesis of Lymphocytic Colitis.

Lymphocytic colitis (LC) is a chronic inflammatory disease associated with watery diarrhea, abdominal pain, and colonic intraepithelial lymphocytosis. Serotonin (5-hydroxytryptamine, 5-HT) is reported to increase in certain colon diseases; however, little is known regarding its metabolism in LC. In the present work, the level of 5-HT in serum and the number of enteroendocrine cells (EECs) as well as the expression of the 5-HT rate-limiting enzyme tryptophan hydroxylase 1 (TPH1) in colonic biopsies and urine 5-hydroxyindoeoacetic acid (5-HIAA) were determined in 36 LC patients that were treated with budesonide and 32 healthy controls. The 5-HT serum and 5-HIAA urine levels were measured using ELISA, the EEC number was determined immunohistochemically, and the colonic TPH1 mRNA expression was determined using RT-PCR. The levels of 5-HT and 5-HIAA and the number of EECs were higher in LC patients than in the controls, and positive correlations were observed between the 5-HT and 5-HIAA levels, 5-HT and EEC number, TPH1 mRNA and EEC number, as well as the severity of disease symptoms and 5-HIAA. Budesonide decreased the levels of 5-HT, 5-HIAA, and TPH1 expression and the number of EECs to values that did not differ from those for controls. In conclusion, the serotonin metabolism may be important for LC pathogenesis, and the urinary level of 5-HIAA may be considered as a non-invasive marker of this disease activity.

Protection and regeneration of esophageal, pharyngeal, and laryngeal mucosa as a major element in therapy of patients with esophageal and extraesophageal reflux symptoms.

Treatment of esophageal and extraesophageal reflux syndromes is mainly focused on inhibiting the secretion of hydrochloric acid. In spite of the high efficacy of proton pump inhibitors, approx. 30-60% of GERD patients experience daily symptoms. Beside acid reflux, other factors such as abnormal esophageal peristalsis, visceral hypersensitivity, ineffective esophageal clearance mechanisms, and impaired mucosal barrier also play an important role in generating GERD symptoms. An additional therapeutic proposition is a procedure aimed at improving the defense mechanisms of esophageal mucosa rather than inhibiting the damage-inducing factors. The preparation consisting of hyaluronic acid (HA), chondroitin sulfate (SC) and poloxamer 407 protects against harmful factors (hydrochloric acid, pepsin) and accelerates mucosal healing and regeneration, constituting a substantial element of monotherapy or add-on therapy in patients with gastroesophageal reflux disease.

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.

Serum Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor-binding Protein 2 as a Novel Biomarker in the Detection of Pancreatic Adenocarcinoma.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 2 (IGFBP-2) are proteins that belong to the IGF axis, which is involved in glucose and lipid metabolism and may as well promote carcinogenesis. GOALS: The aim of this study was to evaluate the serum concentration levels of IGF-1 and IGFBP-2 in patients with newly diagnosed pancreatic adenocarcinoma (PDAC) to verify their possible role in the diagnosis of the disease. STUDY: The study included 69 patients with PDAC and 20 healthy controls. The concentrations of IGF-1 and IGFBP-2 were estimated by means of ELISA. The study protocol was approved by the Bioethics Committee at the Medical University of Lodz in Poland. RESULTS: PDAC patients compared with controls have a significantly lower mean serum IGF-1 level (45.83±30.03 vs. 70.66±60.57 ng/mL; P<0.0001). In contrast, in PDAC patients, the mean IGFBP-2 level was significantly higher compared with the control group (225.06±86.37 vs. 51.92±29.40 ng/mL; P<0.0001). The results show that, at the 0.01 sensitivity level, the IGF-1/IGFBP-2 ratio <0.85 points indicates PDAC presence. At this level of sensitivity, the test has a specificity of 0.097 (α=0.01; ß=0.097; IGF-1/IGFBP-2≤0.85). CONCLUSIONS: Our results show that IGF-1 to IGFBP-2 ratio ≤0.85 may be a powerful PDAC indicator. Further studies in this area in a larger patient group are necessary to confirm our findings.