Publications by authors named "Ewa Małecka-Panas"

123 Publications

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.

Prz Gastroenterol 2021 9;16(1):36-42. Epub 2020 May 9.

Clinic of Gastroenterology, Medical University of Lodz, Lodz, Poland.

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, < 0.001), and both CP and PDAC were different from controls (81.11 ±57.18 ng/ml vs. 70.66 ±16.57 ng/ml, < 0.001 and 53.18 ±36.05 ng/ml vs. 70.66 ±16.57 ng/ml, < 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, < 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, < 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, < 0.05). IGFBP-2 was higher in CP compared to PDAC (512.42 ±299.77 ng/ml vs 301.59 ±190.36 ng/ml, < 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, < 0.001 and 301.59 ±190.36 ng/ml vs. 51.92 ±29.40 ng/ml, < 0.001). IGFBP-2 in CP without DM was higher compared to PDAC without DM (559.39 ±281.43 vs. 296.53 ±196.93, < 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.
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http://dx.doi.org/10.5114/pg.2020.95091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112262PMC
May 2020

Genome-wide scan of long noncoding RNA single nucleotide polymorphisms and pancreatic cancer susceptibility.

Int J Cancer 2021 Jun 3;148(11):2779-2788. Epub 2021 Feb 3.

Department of General Surgery, University of Heidelberg, Heidelberg, Germany.

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cancer-related cause of death by 2030. Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention strategies. Long noncoding RNAs (lncRNAs) are involved in regulation of key biological processes, and the possible role of their genetic variability has been unexplored so far. Combining genome wide association studies and functional data, we investigated the genetic variability in all lncRNAs. We analyzed 9893 PDAC cases and 9969 controls and identified a genome-wide significant association between the rs7046076 SNP and risk of developing PDAC (P = 9.73 × 10 ). This SNP is located in the NONHSAG053086.2 (lnc-SMC2-1) gene and the risk allele is predicted to disrupt the binding of the lncRNA with the micro-RNA (miRNA) hsa-mir-1256 that regulates several genes involved in cell cycle, such as CDKN2B. The CDKN2B region is pleiotropic and its genetic variants have been associated with several human diseases, possibly though an imperfect interaction between lncRNA and miRNA. We present a novel PDAC risk locus, supported by a genome-wide statistical significance and a plausible biological mechanism.
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http://dx.doi.org/10.1002/ijc.33475DOI Listing
June 2021

Expression of FFAR3 and FFAR4 Is Increased in Gastroesophageal Reflux Disease.

J Clin Med 2020 Dec 20;9(12). Epub 2020 Dec 20.

Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, 92-215 Lodz, Poland.

Background: The negative impact of a high-fat diet on the course of gastroesophageal reflux disease (GERD) has been previously reported. Free fatty acid receptors (FFARs) may be mediators of this phenomenon. The aim of this study was to characterize the role of FFARs in the course of nonerosive (NERD) and erosive (ERD) reflux disease.

Methods: Collectively, 73 patients (62 with GERD and 11 healthy controls (HCs)) were recruited to the study. Esophageal biopsies were drawn from the lower third of the esophagus and kept for further experiments. Quantitative, real-time polymerase chain reaction was used to assess the expression of FFAR1, FFAR2, FFAR3, and FFAR4 in biopsies. Histological evaluation of dilated intracellular spaces (DISs) was also performed.

Results: FFAR3 exhibited the highest expression, and FFAR4 exhibited the lowest expression in all esophageal samples. Higher relative expression of FFAR1 and FFAR2 and significantly higher expression of FFAR3 ( = 0.04) was noted in patients with GERD compared to respective HCs. Patients with nonerosive GERD (NERD) presented higher expression of all FFARs compared to patients with erosive GERD (ERD) and respective HCs. Interestingly, in patients with ERD, the expression of FFAR3 was lower than in HCs. Significant, weak, positive correlation was found for FFAR3 and FFAR4 expression and DIS scores (r = 0.36, < 0.05 for FFAR 3, and r = 0.39, < 0.05 for FFAR4).

Conclusions: In this study, we show that FFARs may play a role in GERD pathogenesis, particularly in the NERD type. It may be assumed that FFARs, in particular FFAR3 and FFAR4, may have diagnostic and therapeutic potential in GERD.
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http://dx.doi.org/10.3390/jcm9124111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766740PMC
December 2020

Procoagulant Disorders in Patients with Newly Diagnosed Pancreatic Adenocarcinoma.

Medicina (Kaunas) 2020 Dec 9;56(12). Epub 2020 Dec 9.

Department of Digestive Tract Diseases, Medical University of Lodz, Kopcinskiego 22, 90-153 Lodz, Poland.

: Cancer coagulopathy is thought to be partially due to the up-regulation of tissue factor (TF), thrombin-antithrombin complex (TAT) and soluble P-selectin (sP-selectin). The purpose of this study was to evaluate the clinical significance of TF, TAT and sP-selectin in patients with pancreatic cancer. The study included 93 subjects: 73 newly diagnosed patients with pancreatic adenocarcinoma (42 with stage I-III and 31 with metastatic cancer (stage IV)) and a control group of 20 healthy subjects. Analyzed patients were hospitalized in the Department of Digestive Tract Diseases, Medical University of Lodz or in the Department of Digestive Tract Surgery, Silesian University, Katowice, Poland. All laboratory parameters were measured using ELISA procedures. TF plasma levels were detectable in all patients and were significantly higher in metastatic cancer compared to stage I-III patients and the control group ( < 0.05). In patients with pancreatic adenocarcinoma, the median levels of TAT were also elevated compared to the control group. Moreover, patients with metastases had significantly higher TAT concentration compared to the I-III cancer group. On the other hand, only the metastatic patients group showed significantly higher plasma sP-selectin levels compared to the controls ( = 0.009), whereas there was no difference between localized and metastatic cancer patients. The coagulation disorders are present in the majority of patients with pancreatic adenocarcinoma already at the diagnosis stage and reflect cancer progression and spread.
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http://dx.doi.org/10.3390/medicina56120677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763230PMC
December 2020

Novel selective agonist of GPR18, PSB-KK-1415 exerts potent anti-inflammatory and anti-nociceptive activities in animal models of intestinal inflammation and inflammatory pain.

Neurogastroenterol Motil 2021 03 14;33(3):e14003. Epub 2020 Oct 14.

Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.

Background: GPR18 is a recently deorphanized receptor which was reported to act with several endogenous cannabinoid ligands. Here, we aimed to describe the role of GPR18 in intestinal inflammation and inflammatory pain.

Methods: The anti-inflammatory activity of selective GPR18 agonist, PSB-KK-1415, and antagonist, PSB-CB5, was characterized in semi-chronic and chronic mouse models of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). The extent of inflammation was evaluated based on the macroscopic and microscopic scores, quantification of myeloperoxidase (MPO) activity, and Western blot analyses of tumor necrosis factor-α (TNF-α) and interleukin-6 in colonic tissue. The expression of GPR18 in colonic samples from patients with Crohn's disease (CD) was quantified using real-time PCR. The anti-nociceptive potential of the agonist in intestinal inflammation was evaluated in the mouse model of inflammatory pain.

Key Results: In semi-chronic colitis, PSB-KK-1415 reduced macroscopic score (1.79 ± 0.22 vs. 2.61 ± 0.48), expression of TNF-α (1.89 ± 0.36 vs. 2.83 ± 0.64), and microscopic score (5.00 ± 0.33 vs. 6.45 ± 0.40), all compared to mice with colitis. In chronic colitis, PSB-KK-1415 decreased macroscopic score (3.33 ± 1.26 vs. 4.00 ± 1.32) and MPO activity (32.23 ± 8.51 vs. 41.33 ± 11.64) compared to inflamed mice. In the mouse model of inflammatory pain, PSB-KK-1415 decreased the number of pain-induced behaviors in both, controls (32.60 ± 2.54 vs. 58.00 ± 6.24) and inflamed mice (60.83 ± 2.85 vs. 85.00 ± 5.77) compared to animals without treatment with PSB-KK-1415 (P < 0.005 for both). Lastly, we showed an increased expression of GPR18 in CD patients compared to healthy controls (3.77 ± 1.46 vs. 2.38 ± 0.66, p = 0.87).

Conclusions & Inferences: We showed that GPR18 is worth considering as a potential treatment target in intestinal inflammation and inflammatory pain.
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http://dx.doi.org/10.1111/nmo.14003DOI Listing
March 2021

Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis - An international cohort study.

Pancreatology 2020 Oct 22;20(7):1323-1331. Epub 2020 Aug 22.

Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.

Background: Acid suppressing drugs (ASD) are generally used in acute pancreatitis (AP); however, large cohorts are not available to understand their efficiency and safety. Therefore, our aims were to evaluate the association between the administration of ASDs, the outcome of AP, the frequency of gastrointestinal (GI) bleeding and GI infection in patients with AP.

Methods: We initiated an international survey and performed retrospective data analysis on AP patients hospitalized between January 2013 and December 2018.

Results: Data of 17,422 adult patients with AP were collected from 59 centers of 23 countries. We found that 23.3% of patients received ASDs before and 86.6% during the course of AP. ASDs were prescribed to 57.6% of patients at discharge. ASD administration was associated with more severe AP and higher mortality. GI bleeding was reported in 4.7% of patients, and it was associated with pancreatitis severity, mortality and ASD therapy. Stool culture test was performed in 6.3% of the patients with 28.4% positive results. Clostridium difficile was the cause of GI infection in 60.5% of cases. Among the patients with GI infections, 28.9% received ASDs, whereas 24.1% were without any acid suppression treatment. GI infection was associated with more severe pancreatitis and higher mortality.

Conclusions: Although ASD therapy is widely used, it is unlikely to have beneficial effects either on the outcome of AP or on the prevention of GI bleeding during AP. Therefore, ASD therapy should be substantially decreased in the therapeutic management of AP.
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http://dx.doi.org/10.1016/j.pan.2020.08.009DOI Listing
October 2020

Determinants of Sleep Quality in Inflammatory Bowel Diseases.

J Clin Med 2020 Sep 10;9(9). Epub 2020 Sep 10.

Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, 92-215 Lodz, Poland.

The causes of disordered sleep, frequently reported by patients with inflammatory bowel diseases (IBD), are poorly understood. The study aimed to evaluate sleep quality in IBD patients and to identify factors affecting their sleep. IBD patients (n = 133) and healthy controls (HC; n = 57) were included in the study and completed sleep questionnaires (Pittsburgh Sleep Quality Index (PSQI), Athens insomnia scale (AIS), and Epworth sleepiness scale (ESS)), Beck Depression Inventory (BDI), and pain scales (Visual Analogue Scale and Laitinen Pain Scale). IBD patients attained higher scores in all sleep questionnaires compared to HC: PSQI, AIS, and ESS (all < 0.001). They also had prolonged sleep latency ( < 0.001) with reduced sleep efficiency ( < 0.001). Patients in exacerbation of IBD had higher scores in PSQI ( = 0.008), ESS ( = 0.009), but not in AIS, compared to those in remission. Participants with comorbid chronic diseases had higher scores in PSQI and AIS, but not in ESS, compared to others. Multiple regression revealed that the sleep questionnaire results were significantly affected by mood level (BDI), but not by the aforementioned pain scales. Sleep impairment in IBD patients is a common problem that deserves attention in everyday clinical practice and mood level seems to be the main factor affecting the quality of sleep in IBD patients.
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http://dx.doi.org/10.3390/jcm9092921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563861PMC
September 2020

Brain-derived neurotrophic factor is elevated in the blood serum of Crohn's disease patients, but is not influenced by anti-TNF-α treatment-A pilot study.

Neurogastroenterol Motil 2020 Aug 31:e13978. Epub 2020 Aug 31.

Department of Sleep Medicine and Metabolic Disorders, Medical University of Lodz, Lodz, Poland.

Background: Brain-derived neurotrophic factor (BDNF) is associated with depression, pain, or sleep disorders, factors that are thought to be involved in the pathogenesis and clinical course of Crohn's disease (CD). Therefore, the study aimed at assessing the BDNF serum level in patients with CD and evaluates the effect of anti-TNF-α therapy on the BDNF level and its impact on sleep, mood, and pain parameters.

Methods: Fifty-eight CD patients and 26 healthy controls (HC) were included in the study. The severity of insomnia symptoms was assessed by the Athens Insomnia Scale (AIS). Subjective pain intensity was estimated by the Visual Analogue Scale (VAS) and Laitinen Pain Scale. Mood level was measured using the Beck Depression Inventory (BDI). Seventeen patients were treated with anti-TNF-α therapy for 14 weeks and were re-examined after treatment.

Key Results: CD patients had a higher serum BDNF level than HC (P = .010). No correlation between clinical severity and BDNF was found. There were positive correlations between the BDNF level and the results of AIS (r = 0.253, P = .020), the severity of pain measured using the VAS (r = 0.251, P = .021) and the Laitinen Pain Scale (r = 0.218, P = .047), but not BDI. No differences were observed in the BDNF level before and after 14 weeks of anti-TNF-α therapy.

Conclusions And Inferences: Increased BDNF level in CD patients suggests that it may be involved in the pathogenesis and clinical course of the disease. Further research into BDNF might contribute to a better understanding of the effects of sleep and pain on the course of CD.
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http://dx.doi.org/10.1111/nmo.13978DOI Listing
August 2020

Analysis of GPRC6A variants in different pancreatitis etiologies.

Pancreatology 2020 Oct 8;20(7):1262-1267. Epub 2020 Aug 8.

Else Kröner-Fresenius-Zentrum für Ernährungsmedizin (EKFZ), Paediatric Nutritional Medicine, Technische Universität München (TUM), Freising, Germany.

Background: The G-protein-coupled receptor Class C Group 6 Member A (GPRC6A) is activated by multiple ligands and is important for the regulation of calcium homeostasis. Extracellular calcium is capable to increase NLRP3 inflammasome activity of the innate immune system and deletion of this proinflammatory pathway mitigated pancreatitis severity in vivo. As such this pathway and the GPRC6A receptor is a reasonable candidate gene for pancreatitis. Here we investigated the prevalence of sequence variants in the GPRC6A locus in different pancreatitis aetiologies.

Methods: We selected 6 tagging SNPs with the SNPinfo LD TAG SNP Selection tool and the functional relevant SNP rs6907580 for genotyping. Cohorts from Germany, further European countries and China with up to 1,124 patients and 1,999 controls were screened for single SNPs with melting curve analysis.

Results: We identified an association of rs1606365(G) with alcoholic chronic pancreatitis in a German (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.65-0.89, p = 8 × 10) and a Chinese cohort (OR 0.78, 95% CI 0.64-0.96, p = 0.02). However, this association was not replicated in a combined cohort of European patients (OR 1.18, 95% CI 0.99-1.41, p = 0.07). Finally, no association was found with acute and non-alcoholic chronic pancreatitis.

Conclusions: Our results support a potential role of calcium sensing receptors and inflammasome activation in alcoholic chronic pancreatitis development. As the functional consequence of the associated variant is unclear, further investigations might elucidate the relevant mechanisms.
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http://dx.doi.org/10.1016/j.pan.2020.08.001DOI Listing
October 2020

A simple index to predict the efficiency of adalimumab treatment in Crohn disease with a limited duration of therapy.

Pol Arch Intern Med 2020 10 9;130(10):910-912. Epub 2020 Jul 9.

Department of Digestive Tract Diseases, Medical University of Lodz, Łódź, Poland

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http://dx.doi.org/10.20452/pamw.15507DOI Listing
October 2020

Polygenic and multifactorial scores for pancreatic ductal adenocarcinoma risk prediction.

J Med Genet 2020 Jun 26. Epub 2020 Jun 26.

Cancer Center Amsterdam, Amsterdam, The Netherlands.

Background: Most cases of pancreatic ductal adenocarcinoma (PDAC) are asymptomatic in early stages, and the disease is typically diagnosed in advanced phases, resulting in very high mortality. Tools to identify individuals at high risk of developing PDAC would be useful to improve chances of early detection.

Objective: We generated a polygenic risk score (PRS) for PDAC risk prediction, combining the effect of known risk SNPs, and carried out an exploratory analysis of a multifactorial score.

Methods: We tested the associations of the individual known risk SNPs on up to 2851 PDAC cases and 4810 controls of European origin from the PANcreatic Disease ReseArch (PANDoRA) consortium. Thirty risk SNPs were included in a PRS, which was computed on the subset of subjects that had 100% call rate, consisting of 839 cases and 2040 controls in PANDoRA and 6420 cases and 4889 controls from the previously published Pancreatic Cancer Cohort Consortium I-III and Pancreatic Cancer Case-Control Consortium genome-wide association studies. Additional exploratory multifactorial scores were constructed by complementing the genetic score with smoking and diabetes.

Results: The scores were associated with increased PDAC risk and reached high statistical significance (OR=2.70, 95% CI 1.99 to 3.68, p=2.54×10 highest vs lowest quintile of the weighted PRS, and OR=14.37, 95% CI 5.57 to 37.09, p=3.64×10, highest vs lowest quintile of the weighted multifactorial score).

Conclusion: We found a highly significant association between a PRS and PDAC risk, which explains more than individual SNPs and is a step forward in the direction of the construction of a tool for risk stratification in the population.
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http://dx.doi.org/10.1136/jmedgenet-2020-106961DOI Listing
June 2020

Efficiency and safety of one-year anti-TNF-α treatment in Crohn's disease: a Polish single-centre experience.

Prz Gastroenterol 2020 1;15(2):156-160. Epub 2019 Dec 1.

Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland.

Introduction: Anti-TNF-α therapy of Crohn's disease (CD) represents considerable progress in inflammatory bowel disease (IBD) treatment; however, many patients still require surgical intervention. The Polish National Insurance Fund currently only covers up to 2 years of infliximab (IFX) therapy in CD patients and 1 year of adalimumab (ADA).

Aim: To estimate the effectiveness and side effects of the anti-TNF-α Polish therapeutic program in CD patients.

Material And Methods: In this retrospective study, medical documentation of 80 CD patients treated with anti-TNF-α (IFX or ADA) was analysed. Fifty-two patients finished 1 year of therapy, and 28 individuals did not complete it due to lack of response to treatment or severe side effects.

Results: After treatment, 27 (67.50%) patients achieved a semi-annual remission and 14 (35%) achieved yearly remission. Twenty percent of patients experienced severe side effects such as anaphylactic shock, pneumonia, shingles, or upper respiratory tract infections. A strong negative correlation between the number of patients in remission and the period since therapy termination ( = -0.996, < 0.001) was found. During the 1-year follow-up, 20 patients were re-enrolled in the biological therapy program (the median time to next therapy was 231 days IQR: 126.5-300.5).

Conclusions: Anti-TNF-α treatment in CD is relatively safe. The restricted time period of the therapy affects the clinical course of the disease and entails the need to resume biological therapy.
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http://dx.doi.org/10.5114/pg.2019.90079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294981PMC
December 2019

Genome-wide association study identifies an early onset pancreatic cancer risk locus.

Int J Cancer 2020 10 1;147(8):2065-2074. Epub 2020 May 1.

Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.

Early onset pancreatic cancer (EOPC) is a rare disease with a very high mortality rate. Almost nothing is known on the genetic susceptibility of EOPC, therefore, we performed a genome-wide association study (GWAS) to identify novel genetic variants specific for patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) at younger ages. In the first phase, conducted on 821 cases with age of onset ≤60 years, of whom 198 with age of onset ≤50, and 3227 controls from PanScan I-II, we observed four SNPs (rs7155613, rs2328991, rs4891017 and rs12610094) showing an association with EOPC risk (P < 1 × 10 ). We replicated these SNPs in the PANcreatic Disease ReseArch (PANDoRA) consortium and used additional in silico data from PanScan III and PanC4. Among these four variants rs2328991 was significant in an independent set of 855 cases with age of onset ≤60 years, of whom 265 with age of onset ≤50, and 4142 controls from the PANDoRA consortium while in the in silico data, we observed no statistically significant association. However, the resulting meta-analysis supported the association (P = 1.15 × 10 ). In conclusion, we propose a novel variant rs2328991 to be involved in EOPC risk. Even though it was not possible to find a mechanistic link between the variant and the function, the association is supported by a solid statistical significance obtained in the largest study on EOPC genetics present so far in the literature.
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http://dx.doi.org/10.1002/ijc.33004DOI Listing
October 2020

[Pulmonary manifestations of crohn's disease or chronic pharmacotherapy complications? - case report].

Wiad Lek 2020 ;73(1):196-200

Klinika Chorób Przewodu Pokarmowego, Uniwersytet Medyczny W Łodzi, Łódź, Polska.

Pareneteral manifestations of Crohn's disease (ChLC), apart from the most common skin and joint symptoms include also complications from the respiratory system. In addition chronic pharmacotherapy of ChLC, especially 5-aminosalicylic acid or anti-TNF- α drugs, is associated with possible pulmonologic side effects, sometimes difficult to differentiate. In this study, we describe a patient with ChLC, with a history of pneumocystic pneumonia, who was diagnosed with exfoliative institial pneumonitis as a result of chronic use of mesalazine. This disease is characterized by accumulation of alveolar macrophages in the lumen of the alveoli and intrabepticular septum. The most common etiologic factor is exposure to tobacco smoke. Our patient, non-smoker, was finally diagnosed after lung biopsy and histopathological evaluation. The gradual clinical improvement after mesalazine was an additional factor confirming the etiology of the disease. This side effect of mesalazine is not common but it should be considered in all patient treated with 5-aminosalicylic acid.
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March 2020

Biosimilar biological drugs in the treatment of inflammatory bowel diseases.

Prz Gastroenterol 2019 20;14(4):223-227. Epub 2019 Dec 20.

Department of Gastroenterology with Inflammatory Bowel Disease Subdivision, Central Clinical Hospital of the Ministry of the Interior and Administration, Warsaw, Poland.

Within the last 20 years, tumour necrosis factor inhibitors have been proven to be effective in achieving and maintaining clinical and endoscopic remission in patients with Crohn's disease and ulcerative colitis. Since 2013, when infliximab originator lost its patent protection, patients with inflammatory bowel diseases (IBDs) in Poland have also been treated with biosimilar drugs. Biosimilars are drugs with high similarity to their reference products in terms of physicochemical properties, including structure, safety, and efficacy. Biosimilars are approved for use on the basis of the same rigorous quality standards as their reference products. In 2018, also biosimilars of adalimumab have become available. Studies published to date have shown that biosimilars do not differ from reference drugs in terms of the efficacy and safety. There are numerous data to confirm that a single switch of biological drugs (mainly from reference to biosimilar drugs) has no effect on therapy efficacy and safety. However, a significantly lower cost of therapy with biosimilars not only allows us to treat a much larger number of patients but may also necessitate multiple switches from reference drugs to biosimilars (including biosimilars produced by different manufacturers). Recently, the first results have been published concerning multiple switches in patients with psoriasis and rheumatoid arthritis. However, no such data are currently available for patients with IBDs.
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http://dx.doi.org/10.5114/pg.2019.90093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983762PMC
December 2019

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.

J Clin Gastroenterol 2020 10;54(9):e83-e88

Clinic of Gastroenterology, Medical University of Lodz.

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; β=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.
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http://dx.doi.org/10.1097/MCG.0000000000001297DOI Listing
October 2020

Mannose-binding lectin (MBL) in adult patients with inflammatory bowel disease.

Immunobiology 2020 01 31;225(1):151859. Epub 2019 Oct 31.

Laboratory of Immunobiology of Infections, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Łódź, Poland. Electronic address:

Inflammatory bowel disease (IBD) refers to disorders associated with progressive inflammatory processes in the gastrointestinal system. IBD consists of two major forms, Crohn's disease (CD), and ulcerative colitis (UC). IBD became a global disease in the 21 century. Its pathogenesis is still not fully understood. Mannose-binding lectin (MBL) is a pattern-recognising molecule, involved in anti-microbial and anti-cancer immunity. It is able to opsonize microorganisms and abnormal host cells, and to initiate complement activation. The aim of this study was to investigate possible involvement of MBL in inflammatory bowel disease in adults. Forty persons diagnosed with CD and 28 with ulcerative colitis were recruited. The control group consisted of 136 healthy persons. Single nucleotide polymorphisms of the MBL2 gene (localised to both promoter and exon 1) were determined as were serum MBL concentrations. The exon 1 variant alleles and MBL deficiency-associated genotypes were more frequent among patients compared with controls, although this difference was not statistically significant. No differences of MBL levels were found between the major groups. However in MBL2 A/A homozygous IBD patients, the median was significantly higher than in corresponding healthy subjects. That was particularly evident in the case of active Crohn's disease (1493 ng/ml vs. 800 ng/ml, p = 0.021). It may suggest that MBL and MBL-dependent complement activation contributes to excessive inflammation and its adverse effects in the course of CD. It cannot also be excluded that high MBL activity constitutes in some cases part of a multifactorial network conducing to development of CD.
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http://dx.doi.org/10.1016/j.imbio.2019.10.008DOI Listing
January 2020

Common variants in glyoxalase I do not increase chronic pancreatitis risk.

PLoS One 2019 29;14(10):e0222927. Epub 2019 Oct 29.

Else Kröner-Fresenius-Zentrum für Ernährungsmedizin (EKFZ), Paediatric Nutritional Medicine, Technische Universität München (TUM), Freising, Germany.

Introduction: Chronic pancreatitis (CP) may be caused by oxidative stress. An important source of reactive oxygen species (ROS) is the methylglyoxal-derived formation of advanced glycation endproducts (AGE). Methylglyoxal is detoxified by Glyoxalase I (GLO1). A reduction in GLO1 activity results in increased ROS. Single nucleotide polymorphisms (SNPs) of GLO1 have been linked to various inflammatory diseases. Here, we analyzed whether common GLO1 variants are associated with alcoholic (ACP) and non-alcoholic CP (NACP).

Methods: Using melting curve analysis, we genotyped a screening cohort of 223 ACP, 218 NACP patients, and 328 controls for 11 tagging SNPs defined by the SNPinfo LD TAG SNP Selection tool and the functionally relevant variant rs4746. For selected variants the cohorts were extended to up to 1,441 patient samples.

Results: In the ACP cohort, comparison of genotypes for rs1937780 between patients and controls displayed an ambiguous result in the screening cohort (p = 0.08). However, in the extended cohort of 1,441 patients no statistically significant association was found for the comparison of genotypes (p = 0.11), nor in logistic regression analysis (p = 0.214, OR 1.072, 95% CI 0.961-1.196). In the NACP screening cohort SNPs rs937662, rs1699012, and rs4746 displayed an ambiguous result when patients were compared to controls in the recessive or dominant model (p = 0.08, 0.08, and 0.07, respectively). Again, these associations were not confirmed in the extended cohorts (rs937662, dominant model: p = 0.07, logistic regression: p = 0.07, OR 1.207, 95% CI 0.985-1.480) or in the replication cohorts for rs4746 (Germany, p = 0.42, OR 1.080, 95% CI 0.673-1.124; France, p = 0.19, OR 0.90, 95% CI 0.76-1.06; China, p = 0.24, OR 1.18, 95% CI 0.90-1.54) and rs1699012 (Germany, Munich; p = 0.279, OR 0.903, 95% CI 0.750-1.087).

Conclusions: Common GLO1 variants do not increase chronic pancreatitis risk.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222927PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818803PMC
March 2020

Sex- and Age-Related Estrogen Signaling Alteration in Inflammatory Bowel Diseases: Modulatory Role of Estrogen Receptors.

Int J Mol Sci 2019 Jun 28;20(13). Epub 2019 Jun 28.

Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska St. 141/143, 90-236 Lodz, Poland.

The pathogenesis of inflammatory bowel diseases (IBD) seems to be associated with alterations of immunoregulation. Several lines of evidence suggest that estrogens play a role in the modulation of immune responses and may be related to the etiology of IBD. The purpose of this work was to examine the involvement of G protein-coupled estrogen receptor (GPER), estrogen receptor α (ERα), estrogen receptor β (ERβ) and ERα spliced variants ERα36 and ERα46 in Crohn's disease (CD) and ulcerative colitis (UC). The studied group included 73 patients with IBD and 31 sex and age-related controls. No differences in serum levels of 17β-estradiol nor of CYP1A1 and SULT1E1 enzymes involved in estrogen catabolism were stated. The expression pattern of estrogen receptors in tissue samples was quantified using real-time PCR and Western blotting. Statistically significant up-regulation of GPER and ERα in both CD and UC as well as down-regulation of ERβ in CD patients was found. However, differences in the expression of estrogen receptors in CD and UC have been identified, depending on the sex and age of patients. In men, up-regulation of GPER, ERα and ERα46 expression was shown in CD and UC patients. In women under 50 years of age, GPER protein level increased in UC whereas ERβ expression tended to decrease in CD and UC patients. In turn, in women over 50 the protein level of ERα increased in UC while ERβ expression decreased in CD patients. Dysregulation of estrogen receptors in the intestinal mucosa of patients with CD and UC indicates that estrogen signaling may play a role in the local immune response and maintain epithelial homeostasis in a gender- and age-dependent manner.
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http://dx.doi.org/10.3390/ijms20133175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651503PMC
June 2019

Antibiotic therapy in acute pancreatitis: From global overuse to evidence based recommendations.

Pancreatology 2019 Jun 19;19(4):488-499. Epub 2019 Apr 19.

First Department of Medicine, Faculty of Medicine, University of Szeged, Szeged, Hungary.

Background: Unwarranted administration of antibiotics in acute pancreatitis presents a global challenge. The clinical reasoning behind the misuse is poorly understood. Our aim was to investigate current clinical practices and develop recommendations that guide clinicians in prescribing antibiotic treatment in acute pancreatitis.

Methods: Four methods were used. 1) Systematic data collection was performed to summarize current evidence; 2) a retrospective questionnaire was developed to understand the current global clinical practice; 3) five years of prospectively collected data were analysed to identify the clinical parameters used by medical teams in the decision making process, and finally; 4) the UpToDate Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was applied to provide evidence based recommendations for healthcare professionals.

Results: The systematic literature search revealed no consensus on the start of AB therapy in patients with no bacterial culture test. Retrospective data collection on 9728 patients from 22 countries indicated a wide range (31-82%) of antibiotic use frequency in AP. Analysis of 56 variables from 962 patients showed that clinicians initiate antibiotic therapy based on increased WBC and/or elevated CRP, lipase and amylase levels. The above mentioned four laboratory parameters showed no association with infection in the early phase of acute pancreatitis. Instead, procalcitonin levels proved to be a better biomarker of early infection. Patients with suspected infection because of fever had no benefit from antibiotic therapy.

Conclusions: The authors formulated four consensus statements to urge reduction of unjustified antibiotic treatment in acute pancreatitis and to use procalcitonin rather than WBC or CRP as biomarkers to guide decision-making.
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http://dx.doi.org/10.1016/j.pan.2019.04.003DOI Listing
June 2019

G protein-coupled estrogen receptor mediates anti-inflammatory action in Crohn's disease.

Sci Rep 2019 05 1;9(1):6749. Epub 2019 May 1.

Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska St. 141/143, 90-236, Lodz, Poland.

Estrogens exert immunomodulatory action in many autoimmune diseases. Accumulating evidence highlights the meaningful impact of estrogen receptors in physiology and pathophysiology of the colon. However, the significance of G protein-coupled estrogen receptor (GPER) on Crohn's disease (CD), one of the inflammatory bowel disease (IBD) types, is still elusive. Our study revealed GPER overexpression at the mRNA and protein levels in patients with CD. To evaluate the effects of GPER activation/inhibition on colitis development, a murine 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced model of CD was used. We showed that activation of GPER reduces mortality, improves macroscopic and microscopic scores and lowers C-reactive protein (CRP) level. The impact of estrogen signaling on the suppression of the intestinal inflammation was proved by immunohistochemistry. It was demonstrated that GPER activation is accompanied by modulation of extracellular-signal regulated kinase (ERK) signaling pathway and expression level of genes involved in signal transmission and immune response as well as the expression of some microRNAs (miR-145, miR-148-5p and miR-592). Our study revealed that the membrane-bound estrogen receptor GPER mediates anti-inflammatory action and seems to be a potent therapeutic target in maintaining remission in CD.
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http://dx.doi.org/10.1038/s41598-019-43233-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494840PMC
May 2019

The prevalence, characteristics, and determinants of anaemia in newly diagnosed patients with inflammatory bowel disease.

Prz Gastroenterol 2019 12;14(1):39-47. Epub 2019 Mar 12.

Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland.

Introduction: Anaemia is the most common extraintestinal manifestation of inflammatory bowel disease, which has a negative impact on quality of life.

Aim: To determinate the prevalence, risk factors, and aetiology of anaemia in newly diagnosed patients with inflammatory bowel disease (IBD).Material and methods: We included 136 newly diagnosed patients with IBD. We analysed patient age, sex, laboratory tests, endoscopic and radiological examination, length of stay, and the course of hospitalisation.

Results: Anaemia at the time of IBD diagnosis was detected in 89 (65.4%) patients: 51 (57.3%) patients with ulcerative colitis vs. 38 (42.7%) patients with Crohn's disease; = 0.052. Female patients were more frequently anaemic than male patients (59.6% vs. 40.4%; = 0.001). Anaemia was more often diagnosed in Crohn's disease patients with ileocolonic involvement compared to other types of disease location (70.96% vs. 56.52%, respectively; = 0.03). The prevalence of anaemia at the time of diagnosis for ulcerative colitis patients increased with disease extension: for extensive colitis anaemia was diagnosed in 64.71% compared to 35.29% in limited extension ( < 0.05). Anaemic patients were hospitalised for significantly longer than patients with no anaemia (7.95 ±3.8 days vs. 5.88 ±2.7 days for Crohn's disease; = 0.02 and 9.02 ±5.0 days vs. 5.00 ±2.4 days for ulcerative colitis; < 0.05).

Conclusions: Anaemia represents a frequent complication of IBD not only during the long-term course of the disease, but also at the moment of diagnosis. Anaemia is one of the factors extending the time of hospitalisation. Female sex and disease extent are strong determinant factors connected with anaemia.
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http://dx.doi.org/10.5114/pg.2019.83424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444104PMC
March 2019

Diagnostic and therapeutic recommendations in pancreatic ductal adenocarcinoma. Recommendations of the Working Group of the Polish Pancreatic Club.

Prz Gastroenterol 2019 12;14(1):1-18. Epub 2019 Mar 12.

Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland.

These recommendations refer to the current management in pancreatic ductal adenocarcinoma (PDAC), a neoplasia characterised by an aggressive course and extremely poor prognosis. The recommendations regard diagnosis, surgical, adjuvant and palliative treatment, with consideration given to endoscopic and surgical methods. A vast majority of the statements are based on data obtained in clinical studies and experts' recommendations on PDAC management, including the following guidelines: International Association of Pancreatology/European Pancreatic Club (IAP/EPC), American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN) and Polish Society of Gastroenterology (PSG) and The National Institute for Health and Care Excellence (NICE) All recommendations were voted on by members of the Working Group of the Polish Pancreatic Club. Results of the voting and brief comments are provided with each recommendation.
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http://dx.doi.org/10.5114/pg.2019.83422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444110PMC
March 2019

The influence of socio-demographic and clinical factors on the process of acceptance of the disease among patients with ulcerative colitis.

Pol Przegl Chir 2018 Aug;90(6):1-5

Uniwersytet Medyczny w Łodzi  Wydział Wojskowo- Lekarski Klinika Gastroenterologii.

Introduction: Ulcerative colitis (UC) belongs to the group of inflammatory bowel diseases of previously unknown etiology. Although UC may occur at any age, the peak of incidence falls between the ages of 20 and 40 and over 65. It is characterized by alternating periods of remission and exacerbations that hinder the daily functioning of patients. The aim of the study was to determine the degree of acceptance of the disease among WZJG patients, depending on selected socio-demographic and clinical variables.

Material And Methods: The study was conducted on a group of 50 patients with confirmed UC, treated at the General and Colorectal Surgery Clinic of the Medical University in Lodz, and under the care of a specialist Gastroenterological Outpatient Clinic at the University Hospital No. 1 in Łódź. The study was conducted using the own structure questionnaire and the Acceptance of Illness Scale (AIS).

Results: Young people predominated in the study group. The average age of respondents was 38.82. Analysis of the results showed a reduced degree of acceptance of the disease among patients in the phase of exacerbation of the disease. The mean point score of the AIS scale for the study group was 29.65, which indicates the average level of acceptance of the disease among respondents.

Conclusions: People with higher education, professionally active and treated conservatively, accepted their illness to a better extent. The influence of having offspring on better adaptation to the disease has not been demonstrated.
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http://dx.doi.org/10.5604/01.3001.0012.1753DOI Listing
August 2018

Systemic administration of serotonin exacerbates abdominal pain and colitis via interaction with the endocannabinoid system.

Biochem Pharmacol 2019 03 3;161:37-51. Epub 2019 Jan 3.

Department Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland. Electronic address:

Background And Aims: Molecular basis of abdominal pain in IBD is not fully characterized. Serotonin (5-HT) increases visceral pain severity and contributes to exacerbation of inflammation. Moreover, it is well established that decreased anandamide (AEA) signaling in the gut increases visceral pain severity. The aim of this study was to investigate the interplay between 5-HT and endocannabinoid signaling in colitis.

Methods: We used 3% DSS in drinking water to induce colitis in mice. From day 3 5-HT was administered for 5 days and each day visceromotor response to colorectal distention (CRD) was measured. Expression of cannabinoid (CB) receptors as well as enzymes responsible of biosynthesis and degradation of endocannabinoids were investigated. Moreover, endocannabinoid levels were assessed by mass spectrometry. Additionally, we measured the expression of enzymes synthesizing 5-HT and AEA in the colon of IBD patients and healthy controls.

Results: Chronic exposure to 5-HT increased visceromotor response to CRD and worsened colitis, which was associated with decrease of AEA via 5-HT and 5-HT receptors. Moreover, exposure to 5-HT led to the downregulation of CB1 receptors. Colonic levels of N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD), which is responsible for synthesis of AEA, significantly declined after chronic treatment with 5-HT and this effect was reversed by the 5-HT and 5-HT receptor antagonists. NAPE-PLD was also downregulated in the colon of UC patients.

Conclusions: Our study shows a link between 5-HT and endocannabinoid signaling pathways in IBD. Thus, pharmacological blockade of 5-HT signaling or supplementation with endocannabinoids in the gut might be of benefit in severe cases of abdominal pain in IBD.
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http://dx.doi.org/10.1016/j.bcp.2019.01.001DOI Listing
March 2019

Guidelines on the management of irritable bowel syndrome: In memory of Professor Witold Bartnik.

Prz Gastroenterol 2018 19;13(4):259-288. Epub 2018 Sep 19.

Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Subdivision, Central Clinical Hospital of the Ministry of the Interior, Warsaw, Poland.

These guidelines constitute an update of the previous "Recommendations on the management of irritable bowel syndrome" issued in 2008. 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 2008, the aetiology, epidemiology, clinical presentation, diagnostic principles and criteria for the diagnosis, and recommendations for the treatment of irritable bowel syndrome (IBS). The English-language acronym for the syndrome (IBS) has become popular in medical and popular scientific language. It is also widely recognized by patients who identify with this diagnosis. Therefore, in the discussed guidelines, this is what we will use.
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http://dx.doi.org/10.5114/pg.2018.78343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300851PMC
September 2018

Diagnostic and therapeutic recommendations for chronic pancreatitis. Recommendations of the Working Group of the Polish Society of Gastroenterology and the Polish Pancreas Club.

Prz Gastroenterol 2018 17;13(3):167-181. Epub 2018 Sep 17.

Clinical Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Unit, CSK MSWiA, Warsaw, Poland.

This article describes the latest diagnostic and therapeutic recommendations in chronic pancreatitis, developed by the Working Group of the Polish Society of Gastroenterology and the Polish Pancreas Club. The recommendations refer to the diagnosis of chronic pancreatitis, autoimmune pancreatitis, conservative management, treatment of pain, and exocrine and endocrine pancreatic insufficiency, treatment of chronic pancreatitis by endoscopic and surgical methods, and oncological surveillance of chronic pancreatitis. This paper refers to the Polish recommendations published in 2011, which have been updated and supplemented. All recommendations were voted by experts of the Polish Society of Gastroenterology and the Polish Pancreas Club, who evaluated them each time on a five-degree scale, where I meant full acceptance, II - acceptance with some reservation, III - acceptance with serious reservation, IV - rejection with some reservation and V - full rejection. The results of the voting, together with a brief commentary, have been included with each recommendation put to the vote. In addition, the expert group assessed the value of clinical studies on which the statements are based, on a scale where A means high (based on meta-analyses and randomised clinical trials), B means medium (based on clinical trials and observational studies), and C means low (based mainly on expert opinion).
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http://dx.doi.org/10.5114/pg.2018.78067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173070PMC
September 2018

Quality of life and depression in patients with irritable bowel syndrome.

Prz Gastroenterol 2018 16;13(2):102-108. Epub 2018 May 16.

Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland.

Introduction: While irritable bowel syndrome (IBS) is not life-threatening for most, it has enormous influence on quality of life (QOL) and mental health.

Aim: To evaluate the association between QOL and depressive symptoms in IBS patients.

Material And Methods: A total of 87 patients and 56 healthy subjects were enrolled consecutively. All participants were asked to complete self-administered questionnaires: an IBS-specific quality of life (IBS-QOL) questionnaire and the Beck Depression Inventory questionnaire (BDI).

Results: Mean BDI score was higher in IBS group than in controls. IBS-QOL score was significantly lower in IBS patients compared to the control group, in all IBS-QOL domains: dysphoria (DY), interference with activity (IN), body image (BI), health worry (HW), food avoidance (FA), social relation (SR), and sexual (SX) and relationship (RL) issues. QOL DY, IN, and BI scores and overall score were significantly lower in women with IBS compared to men. We found that BDI score was significantly negatively correlated with IBS-QOL score in the domain of DY, IN, HW, FA, SR, and RL scores and overall QOL score. We also found a negative correlation between older age and health worry. RL and IN QOL scores represented the highest correlation with BDI score.

Conclusions: Irritable bowel syndrome is connected with impaired patient quality of life and high prevalence of depression with high correlation rate of both parameter scores. Assessment of depression and QOL should be provided during patient visits in outpatients clinics.
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http://dx.doi.org/10.5114/pg.2018.75819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040097PMC
May 2018

The Role of Insulin-like Growth Factor (IGF) Axis in Early Diagnosis of Pancreatic Adenocarcinoma (PDAC).

J Clin Gastroenterol 2018 08;52(7):569-572

Department of Digestive Tract Diseases.

New-onset diabetes mellitus (DM) is one of the first symptoms of pancreatic adenocarcinoma (PDAC). The frequency of endocrine disorders is estimated between 40% and 80% in patients with pancreatic cancer. DM is a risk factor for cancer development but it may also be a consequence of the tumor growth. Data confirming the existence of a relationship between long standing type 2 DM and an increased risk of PDAC comes from numerous clinical studies. Insulin resistance phenomenon and hyperinsulinemia may result in the increased proliferation of pancreatic islets which in turn may cause a predisposition to cancer development. In contrast, it is proved that new-onset DM among patients over 50 years old significantly increases the risk of PDAC recognition. Insulin-like growth factor 1 (IGF-1) and their complex proteins, IGF binding proteins, which comprise the IGF axis play a crucial role in carbohydrate metabolism disorders and, studies have shown that they may contribute to PDAC growth. Some studies confirm that IGF-1 is connected with early carcinogenesis in animals and humans. Assessing the levels of these proteins may thus be helpful in early recognition of PDAC in patients with recently detected endocrine disorders, especially pancreatic DM.
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http://dx.doi.org/10.1097/MCG.0000000000001073DOI Listing
August 2018