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1.
J Clin Med ; 13(10)2024 May 08.
Article En | MEDLINE | ID: mdl-38792308

Background: The incidence of inflammatory bowel diseases (IBDs) in elderly patients is constantly increasing. It results from the combination of an aging population with compounding prevalence of IBD, as well as the growing burden of elderly-onset IBD. The clinical characteristics of elderly patients differ from young subjects with IBD due to the multimorbidity or polypharmacy, affecting the choice of adequate therapeutic options. The aim of this study was to determine the clinical aspects and biological therapy safety in elderly Polish IBD patients. Methods: We conducted a retrospective study aimed at describing the demographic, clinical, and management characteristics of IBD patients treated with a biological therapy in two referral centers within the National Drug Program in Poland. Results: Out of the entire group of 366 studied patients, 51 (13.9%) were aged over 60-32 with ulcerative colitis (UC) and 19 with Crohn's disease (CD). The disease location was predominantly ileocolonic (57.89%) in patients with CD and pancolitis for patients with UC (56.25%). Most of the elderly IBD subjects were characterized by significant comorbidities, with Charlson Comorbidity Index (CCI) ≥ 1 in 66.67% patients. The probability of stopping biological therapy due to adverse events had the tendency to be higher in the CCI ≥ 1 group (20.58% vs. 5.88% in CCI = 0; p = 0.087). The main reasons for the therapy discontinuation included hypersensitivity reactions and liver enzyme abnormalities. Conclusions: In conclusion, our results underline the importance of assessing the comorbidity status instead of the age prior to initiating biological therapy, analyzing additional safety risks, and close monitoring in IBD patients with multiple comorbidities.

2.
Nutrients ; 16(6)2024 Mar 12.
Article En | MEDLINE | ID: mdl-38542721

The prevalence of sarcopenia in inflammatory bowel disease patients has received increasing attention. The aim of this study is to assess the usefulness of determining levels of myostatin (MSTN) and activin A (Act A) as potential markers of disease activity and occurrence of sarcopenia in Crohn's disease and ulcerative colitis patients. The case-control study included 82 patients with Inflammatory Bowel Disease. The control group consisted of 25 healthy volunteers. The serum levels of myostatin and activin A were determined by the quantitative sandwich enzyme-linked immunosorbent assay. Sarcopenia was diagnosed based on the EWGSOP2 criteria. The study found lower levels of myostatin and activin A in the IBD patients. There were significantly lower levels of myostatin (80.6 pg/mL vs. 186.2 pg/mL; p = 0.0364) as well as activin A (32.1 pg/mL vs. 35.2 pg/mL; p = 0.0132) in the IBD patients with sarcopenia compared to those without sarcopenia. Positive correlations were found between MSTN levels and Muscle Mass Index (rho = 0.31; p < 0.005) and hand grip strength (rho = 0.34, p < 0.05) in the IBD patients. The determination of serum levels of MSTN and Act A may be useful in the early diagnosis of sarcopenia in IBD patients.


Activins , Colitis, Ulcerative , Inflammatory Bowel Diseases , Sarcopenia , Humans , Sarcopenia/diagnosis , Sarcopenia/etiology , Myostatin , Case-Control Studies , Hand Strength , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/epidemiology , Colitis, Ulcerative/complications , Biomarkers
3.
Nutrients ; 16(6)2024 Mar 13.
Article En | MEDLINE | ID: mdl-38542725

The aim of this study was to assess the prevalence of malnutrition risk in patients with IBD using different scales to evaluate their usefulness as first-step screening tools for the diagnosis of malnutrition using the GLIM criteria in patients with inflammatory bowel disease. This study included 82 patients with IBD. The Mini Nutritional Assessment, Malnutrition Universal Screening Tool, Saskatchewan IBD-Nutrition Risk and Malnutrition Screening Tool were used to assess malnutrition risk in the study group. In order to diagnose malnutrition, the GLIM criteria were used. According to the GLIM recommendations, malnutrition was diagnosed in 60 patients with IBD (73.17%). Depending on the applied screening tools, the prevalence of moderate and/or high-risk malnutrition in patients with IBD ranged from 20.25% to 43.59%. The highest level of accuracy (ACC) was noted for the MST and MUST questionnaires (92.50% and 90%, respectively), followed by the SASKIBD-NR test (89.97%) and the MNA questionnaire (83.33%). The results of our study indicate a high prevalence of malnutrition in patients with IBD. Thus, there is a need to conduct routine assessments of malnutrition risk using validated scales. The MUST scale seems promising in the assessment of malnutrition risk in patients with IBD as a first step in the assessment of malnutrition using the GLIM criteria.


Inflammatory Bowel Diseases , Malnutrition , Humans , Malnutrition/diagnosis , Malnutrition/epidemiology , Malnutrition/etiology , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/epidemiology , Inflammatory Bowel Diseases/diagnosis , Nutritional Status , Nutrition Assessment , Mass Screening/methods
4.
Hum Genomics ; 18(1): 12, 2024 Feb 02.
Article En | MEDLINE | ID: mdl-38308339

Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10-8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10-7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10-6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10-5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.


Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Genome-Wide Association Study , Genetic Predisposition to Disease , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Regulatory Sequences, Nucleic Acid , Polymorphism, Single Nucleotide/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Binding Sites/genetics
5.
Cancers (Basel) ; 15(23)2023 Nov 25.
Article En | MEDLINE | ID: mdl-38067280

Pancreatic cancer is one of the leading causes off cancer-related deaths globally. In Europe, this type of cancer has the lowest survival rate of all cancers. A majority of patients have unresectable or even metastatic disease. In addition, actual therapeutic options are not curative, and surgical treatment is associated with high post-operative morbidity and a lack of uniform translation of surgical success into long-term survival. Moreover, there is no screening for the general population which is recommended, and the overall poor prognosis in pancreatic cancer is related to late clinical detection. Therefore, early diagnosis and early treatment of pancreatic cancer are particularly critical. In this review, we summarize the most significant gaps and opportunities in the diagnosis and treatment of pancreatic cancer to emphasize need for improvement of early detection and the therapeutic efficacy of the available treatment for this cancer. Novel, inclusive, and intentional research is needed to produce improvements in pancreatic cancer in mm the world.

6.
Prz Gastroenterol ; 18(3): 225-248, 2023.
Article En | MEDLINE | ID: mdl-37937106

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.

7.
J Clin Med ; 12(19)2023 Oct 04.
Article En | MEDLINE | ID: mdl-37834999

The serotonergic pathway may impact the pathogenesis and the course of inflammatory bowel diseases (IBDs). The aim of this study was to investigate the relationship between 5-HT, the serotonin transporter (SERT), and the clinical course of the disease with the occurrence of sleep and mood disorders. Participants completed sleep questionnaires and the Beck Depression Inventory (BDI). Serum 5-HT, SERT protein expression, and mRNA levels were quantified. Additionally, patients treated with anti-TNF therapy were examined before and after treatment. In this study, 77 patients with IBD and 41 healthy controls (HCs) were enrolled and 24 of them were treated with anti-TNF therapy. Patients with IBD had higher 5-HT levels and SERT protein expression than the HCs, but not mRNA SERT levels (p = 0.015, p = 0.001, p = 0.069, respectively). Similar results were obtained for patients in the active state of the disease compared to the non-active state. There was a positive relationship between insomnia severity and SERT protein expression. BDI did not correlate with serotonin or SERT. After anti-TNF therapy, only 5-HT levels were decreased. 5-HT and SERT protein are overexpressed in active IBD and may represent a candidate for novel disease activity biomarkers. The correlation between the SERT protein level and the severity of insomnia symptoms might be among the underlying biochemical factors of sleep disturbances. Anti-TNF treatment might contribute to the reduction in 5-HT levels.

8.
Carcinogenesis ; 44(8-9): 642-649, 2023 12 02.
Article En | MEDLINE | ID: mdl-37670727

Coding sequence variants comprise a small fraction of the germline genetic variability of the human genome. However, they often cause deleterious change in protein function and are therefore associated with pathogenic phenotypes. To identify novel pancreatic ductal adenocarcinoma (PDAC) risk loci, we carried out a complete scan of all common missense and synonymous SNPs and analysed them in a case-control study comprising four different populations, for a total of 14 538 PDAC cases and 190 657 controls. We observed a statistically significant association between 13q12.2-rs9581957-T and PDAC risk (P = 2.46 × 10-9), that is in linkage disequilibrium (LD) with a deleterious missense variant (rs9579139) of the URAD gene. Recent findings suggest that this gene is active in peroxisomes. Considering that peroxisomes have a key role as molecular scavengers, especially in eliminating reactive oxygen species, a malfunctioning URAD protein might expose the cell to a higher load of potentially DNA damaging molecules and therefore increase PDAC risk. The association was observed in individuals of European and Asian ethnicity. We also observed the association of the missense variant 15q24.1-rs2277598-T, that belongs to BBS4 gene, with increased PDAC risk (P = 1.53 × 10-6). rs2277598 is associated with body mass index and is in LD with diabetes susceptibility loci. In conclusion, we identified two missense variants associated with the risk of developing PDAC independently from the ethnicity highlighting the importance of conducting reanalysis of genome-wide association studies (GWASs) in light of functional data.


Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Case-Control Studies , Genome, Human , Genome-Wide Association Study , Genetic Predisposition to Disease , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/genetics , DNA , Polymorphism, Single Nucleotide/genetics
9.
J Clin Med ; 12(18)2023 Sep 13.
Article En | MEDLINE | ID: mdl-37762896

Inflammatory bowel diseases (IBD) are characterised by multifactorial and chronic inflammation. Much attention has been paid to immune dysfunction in inflammatory bowel diseases. The aim of this study was to assess the usefulness of serum IL-6, IL-1ß and IL-10 in determining the activity and nutritional status in IBD patients. The case-control study was carried out on 82 patients with IBD; the control group consisted of 25 clinically healthy subjects. The serum concentrations of IL-6, IL-1 ß and IL-10 were determined by the quantitative sandwich enzyme-linked immunosorbent assay. There were no significant differences in IL-6 and IL-1ß levels in UC and CD patients according to disease activity as assessed by the Montreal classification, Partial Mayo Score and CDAI. Significantly higher IL-6 levels were found in patients with low body fat in comparison to patients with normal body fat. Furthermore, significantly higher mean IL-6 levels were observed in patients with excess body fat in comparison to patients with normal body fat, and also in comparison to patients with deficient body fat. IL-6 and IL-1ß may provide extra information regarding the nutritional status of IBD patients. IL-10 can be considered a non-invasive biomarker of IBD activity.

10.
Metabolites ; 13(9)2023 Sep 12.
Article En | MEDLINE | ID: mdl-37755286

In recent years, a steady increase in the incidence of inflammatory bowel diseases (IBD) has been observed with anemia as their most common extraintestinal symptom. Erythroferrone and Bone Morphogenetic Protein 6 (BMP-6) are recently identified cytokines involved in the process of increased erythropoiesis in anemia of various pathomechanisms. The aim of this study was to analyze the concentration of erythroferrone and BMP-6 in IBD patients in relation to clinical and laboratory data. The study comprised 148 patients: 118 with IBD, including 73 (61.85%) diagnosed with anemia (42 with Crohn's disease (CD) (66.7%) and 31 (56.4%) with ulcerative colitis (UC)) and 30 as a control group. The erythroferrone concentration was significantly higher in IBD patients with anemia (p = 0.009) and higher in UC patients both with and without anemia (p = 0.018), compared to the control group. In CD, no similar difference was observed between patients with and without anemia. Regarding BMP-6, higher levels were found in CD patients with anemia compared to the control group (p = 0.021). The positive correlation between BMP-6 and iron concentration in UC was also noticed. In conclusion, we confirm an increase in erythroferrone concentration in the entire group of IBD patients with anemia, while BMP-6 levels were higher only in anemic CD patients. Due to the clinical importance of anemia in IBD, this problem is worth further analysis and research projects.

12.
Nutrients ; 15(15)2023 Aug 07.
Article En | MEDLINE | ID: mdl-37571416

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is often accompanied by malnutrition that manifests itself as nutrient deficiencies and body mass loss or deficit. The purpose of this study is to evaluate the utility of albumin, transferrin and transthyretin levels in the assessment of nutritional status and IBD activity. The case-control study included 82 IBD patients. The serum concentrations of albumin, transferrin and transthyretine were determined by a quantitative sandwich enzyme-linked immunosorbent assay (ELISA). Significantly lower median concentrations of albumin were found in the IBD patients vs. controls and in CD patients compared to the UC patients. Significantly higher median transthyretin concentrations were found in the IBD patients compared to the healthy subjects. There were no significant differences in median transferrin concentrations between the IBD patients and the healthy subjects. Significantly higher albumin levels were found in IBD patients in remission compared to patients with moderate and severe exacerbation of IBD symptoms. There were no significant differences in the median transferrin or transthyretin levels in patients with IBD depending on disease activity. No differences were identified in the median transferrin or transthyretin levels in the IBD patients according to nutritional status. The median albumin concentrations in the IBD subjects were significantly higher in patients with normal body fat, normal BMI and normal waist circumferences compared to those with an abnormal nutritional status. The albumin levels reflect both nutritional status and disease activity and therefore cannot be considered a prognostic marker of malnutrition in IBD. As regards the utility of transferrin and transthyretin as markers of activity and nutritional status in IBD patients, further studies are required.


Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Malnutrition , Humans , Nutritional Status , Prealbumin , Transferrin/analysis , Case-Control Studies , Inflammatory Bowel Diseases/complications , Colitis, Ulcerative/complications , Colitis, Ulcerative/diagnosis , Crohn Disease/complications , Crohn Disease/diagnosis , Biomarkers , Albumins , Malnutrition/etiology , Malnutrition/complications
14.
J Clin Med ; 12(14)2023 Jul 12.
Article En | MEDLINE | ID: mdl-37510744

Endosonography, a minimally invasive imaging technique, has revolutionized the diagnosis and management of pancreatic diseases. This comprehensive review highlights the latest advancements in endosonography of the pancreas, focusing on key technological developments, procedural techniques, clinical applications and additional techniques, which include real-time elastography endoscopic ultrasound, contrast-enhanced-EUS, EUS-guided fine-needle aspiration or EUS-guided fine-needle biopsy. EUS is well established for T-staging and N-staging of pancreaticobiliary malignancies, for pancreatic cyst discovery, for identifying subepithelial lesions (SEL), for differentiation of benign pancreaticobiliary disorders or for acquisition of tissue by EUS-guided fine-needle aspiration or EUS-guided fine-needle biopsy. This review briefly describes principles and application of EUS and its related techniques.

15.
J Clin Med ; 12(13)2023 Jun 27.
Article En | MEDLINE | ID: mdl-37445352

This study aims to summarize the modifiable risk factors for pancreatic ductal adenocarcinoma (PDAC) that have been known for a long time, as well as information from the most recent reports. As a cancer with a late diagnosis and poor prognosis, accurate analysis of PDAC risk factors is warranted. The incidence of this cancer continues to rise, and the five-year survival rate is the lowest with respect to other tumors. The influence of cigarette smoking, alcohol consumption, and chronic pancreatitis in increasing the risk of pancreatic ductal adenocarcinoma is continually being confirmed. There are also newly emerging reports relating to the impact of lifestyle, including physical activity, the gut and oral microbiome, and hepatotropic viruses. A precise understanding of PDAC risk factors can help to identify groups of high-risk patients, and this may contribute to population awareness and education as well as earlier diagnoses with possible better treatment outcomes.

16.
J Clin Med ; 12(12)2023 Jun 14.
Article En | MEDLINE | ID: mdl-37373743

INTRODUCTION: There are still no effective diagnostic and prognostic biomarkers in pancreatic ductal adenocarcinoma (PDAC). The differentiation between PDAC and chronic pancreatitis (CP) is often challenging. The inflammatory mass in the course of CP causes diagnostic difficulties in differentiating them from neoplastic lesions and, thus, delays the initiation of radical treatment. Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 2 (IGFBP-2) form a network involved in PDAC development. The role of IGFs in promoting pancreatic cancer cell proliferation, survival, and migration is well established, and their ability to stimulate tumor growth and metastasis is well documented. The aim of the study was to evaluate the usability of IGF-1, IGFBP-2, and IGF-1/IGFBP-2 ratio in PDAC and CP differentiation. MATERIAL AND METHODS: The study included 137 patients: 89 patients with PDAC and 48 patients with CP. All subjects were tested for the levels of IGF-1 and IGFBP-2 using the ELISA method (Corgenix UK Ltd. R&D Systems), along with the level of CA 19-9 in serum. Additionally, the IGF-1/IGFBP-2 ratio was calculated. Further analyses used logit and probit models with varying determinants in order to discern between PDAC and CP patients. The models served as a basis for AUROC calculation. RESULTS: The mean IGF-1 serum level was equal to 52.12 ± 33.13 ng/mL in PDAC vs. 74.23 ± 48.98 ng/mL in CP (p = 0.0053). The mean level of IGFBP-2 was equal to 305.95 ± 194.58 ng/mL in PDAC vs. 485.43 ± 299 ng/mL in CP (p = 0.0002). The mean CA 19-9 serum concentration was 434.95 ± 419.98 U/mL in PDAC vs. 78.07 ± 182.36 U/mL in CP (p = 0.0000). The mean IGF-1/IGFBP-2 ratio was 0.213 ± 0.14 in PDAC vs. 0.277 ± 0.33 in CP (p = 0.1914). The diagnostic usefulness of indicators for the purpose of PDAC and CP differentiation was assessed by means of AUROC comparison. The AUROCs of IGF-1, IGFBP-2, and IGF-1/IGFBP-2 ratio ranged below 0.7, being lower than the AUROC of CA 19-9 (0.7953; 0.719 within 95% CI). Together, the CA 19-9 and IGFBP-2 AUROCs also ranged below 0.8. When age was included, the AUROC increased to 0.8632, and its 95% confidence interval held above the 0.8 limit. The sensitivity of the used markers was not correlated to the stage of pancreatic PDAC. CONCLUSIONS: The presented results indicate that CA 19-9 is a marker demonstrating high potential for PDAC and CP differentiation. The inclusion of additional variables into the model, such as the serum level of IGF-1 or IGFBP-2, slightly increased the sensitivity in differentiating CP from PDAC. The IGF-1/IGFBP-2 ratio turned out to be a good marker of pancreatic diseases, but insufficient for the purpose of CP and PDAC differentiation.

17.
J Clin Med ; 12(10)2023 May 14.
Article En | MEDLINE | ID: mdl-37240560

INTRODUCTION: Due to a lack of clear dietary guidelines, patients with inflammatory bowel disease (IBD) self-impose dietary restrictions based on their own nutritional experiences. The aim of this study was to investigate dietary perceptions and behavior in IBD patients. MATERIALS AND METHODS: A total of 82 patients (48 with Crohn's disease and 34 with ulcerative colitis) participated in this prospective, questionnaire-based study. Based on a literature review, the questionnaire was developed to investigate dietary beliefs, behaviors and food exclusions during IBD relapses and remission. RESULTS: The majority of patients (85.4%) believed that diet can be a trigger factor for IBD relapses, and 32.9% believed that diet initiates the disease. The majority of patients (81.7%) believed that they should eliminate some products from their diets. The most often-pointed-out products were spicy and fatty foods, raw fruits and vegetables, alcohol, leguminous foods, cruciferous vegetables, dairy products and milk. Most patients (75%) modified their diets after diagnosis, and 81.7% imposed food restrictions to prevent IBD relapses. CONCLUSIONS: The majority of patients avoided certain foods during relapses as well as to maintain remission of IBD, basing this on their own beliefs, inconsistently with current scientific knowledge. Patient education should be a key determinant in IBD control.

18.
EBioMedicine ; 92: 104616, 2023 Jun.
Article En | MEDLINE | ID: mdl-37209533

BACKGROUND: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture. METHODS: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO. FINDINGS: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level. INTERPRETATION: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO. FUNDING: German Research Foundation (DFG).


Adenocarcinoma , Barrett Esophagus , Esophageal Neoplasms , Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Genome-Wide Association Study , Genetic Heterogeneity , Barrett Esophagus/genetics , Adenocarcinoma/pathology , Esophageal Neoplasms/genetics , Risk Factors
19.
Pol Arch Intern Med ; 133(10)2023 10 26.
Article En | MEDLINE | ID: mdl-37154720

INTRODUCTION: Inflammatory bowel disease (IBD) might be accompanied by emotional disturbances. Circadian rhythm genes, such as brain and muscle ARNT­Like 1 (BMAL1), circadian locomotor output cycles kaput (CLOCK), neuronal PAS domain protein 2 (NPAS2), or nuclear receptor subfamily 1 group D member 1 (NR1D1) are related to inflammation and psychiatric symptoms that might modulate their expression. OBJECTIVES: The study aimed to compare the expression of the BMAL1, CLOCK, NPAS2, NR1D1 mRNA in IBD patients and healthy controls (HCs). We evaluated the association between the gene expression and the disease severity, antitumor necrosis factor (TNF) therapy, sleep quality, insomnia, and depression. PATIENTS AND METHODS: A total of 81 IBD patients and 44 HCs were recruited and classified according to the disease activity and IBD type (ulcerative colitis [UC] or Crohn disease [CD]). The participants filled out questionnaires assessing their sleep quality, daytime sleepiness, insomnia, and depression. Venous blood samples were collected, and the IBD patients on the anti­TNF therapy had their blood drawn before and after 14 weeks of the treatment. RESULTS: In comparison with HCs, the IBD group had decreased expression of all studied genes apart from the BMAL1 gene. UC individuals with exacerbation had decreased expression of the CLOCK and the NPAS2 genes, as compared with the remission group. UC severity negatively correlated with the CLOCK, NPAS2, and NR1D1 mRNA levels. The IBD participants with depression symptoms had a decreased expression of the CLOCK and the NR1D1 genes, as compared with those without mood disturbances. Poor sleep quality was associated with a decreased expression of the NR1D1 gene. Biologic treatment decreased the expression of the BMAL1 gene. CONCLUSIONS: Disruption of the clock gene expression might constitute a molecular background of sleep disorders and depression in IBD and might contribute to UC exacerbation.


Circadian Clocks , Colitis, Ulcerative , Inflammatory Bowel Diseases , Sleep Initiation and Maintenance Disorders , Humans , Circadian Clocks/genetics , Sleep Quality , Sleep Initiation and Maintenance Disorders/genetics , Depression/drug therapy , Depression/genetics , ARNTL Transcription Factors/genetics , Tumor Necrosis Factor Inhibitors , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/genetics , Gene Expression , Necrosis , RNA, Messenger/metabolism
20.
J Clin Med ; 12(7)2023 Mar 23.
Article En | MEDLINE | ID: mdl-37048531

Anaemia is the most common extraintestinal manifestation of inflammatory bowel disease (IBD). Due to its multifactorial etiopathogenesis, the differential diagnosis and treatment of anaemia in IBD is a significant clinical problem. The main aim of our study was to assess the usefulness of laboratory parameters, including hepcidin, in differential diagnoses of anaemia in hospitalized IBD patients. This study also estimated the impact of anaemia on the length of hospitalization and its relationship with clinical data of analyzed patients. The study included 118 adult patients diagnosed with IBD-55 with ulcerative colitis (UC) and 63 with Crohn's disease (CD). Anaemia was significantly more frequent in patients with CD-42 (66.7%)-compared to 31 (56.4%) patients with UC (p = 0.033). The prevalence of anaemia increased significantly with the severity of IBD and the extent of inflammatory changes in the endoscopic examination. Hospitalization time was significantly longer in patients with anaemia, especially in the group with UC. Ferritin concentrations < 30 ng/mL were found only in 15 (20.55%) IBD patients (9 with UC and 6 with CD), and ferritin < 100 ng/mL was observed in 22 (30.14%) patients, equally frequent with UC and CD (p > 0.05). Significantly higher concentrations of transferrin were observed in patients with anaemia in the course of UC compared to CD (2.58 ± 0.90 g/L vs. 2.15 ± 0.82 g/L; p = 0.037). On the other hand, saturation of transferrin < 16% was equally common in UC and CD patients. In our study, hepcidin levels in anaemic UC patients were significantly lower compared to UC without anaemia (p = 0.042), with no similar differences in CD independently of anaemia presence (p = 0.565). To conclude, we observed a high incidence of anaemia in patients with IBD and its significant impact on the length of hospitalization in UC. Routinely determined single laboratory parameters are not sufficient for the differential diagnosis of anaemia, and a complex laboratory assessment, including of hepcidin levels, is necessary for the full picture of anaemia in the course of IBD.

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