|
1
|
Sandberg-Janzon A, Karling P. Prescription of commonly used drugs in patients with functional bowel disorders. A cross-sectional comparison with the general population. Scand J Gastroenterol 2025; 60:253-261. [PMID: 39862135 DOI: 10.1080/00365521.2025.2458070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/13/2025] [Accepted: 01/19/2025] [Indexed: 01/27/2025]
Abstract
OBJECTIVES Comorbidity with other conditions is common in functional bowel disorders. We aimed to investigate the prescription patterns of commonly used drugs in patients with irritable bowel syndrome (IBS) and functional unspecific bowel disorder, compared to the general population. MATERIAL AND METHODS Prescriptions of commonly used drugs in 2022 were compared between patients and the general population from the same age group and region in Sweden. RESULTS Of 526 patients, 317 were followed up in 2022 (219 women and 98 men) and were compared to 51,001 women and 55,571 men in the general population. The median follow-up time from the first visit to 2022 was 8 years (25th-75th percentile 6-11 years). Female patients were significantly more likely than controls to be prescribed PPIs, antibiotics, NSAIDs, paracetamol, opioids, muscle relaxants, antimigraine drugs, antidepressants and asthma medications. Male patients were significantly more likely than controls to be prescribed PPIs, opioids, antidepressants, and asthma medications. In the year prior diagnosis and through 2022, female patients showed a significant decline in the use of PPIs (38% vs.10%; p < 0.001), antibiotics (27.5% vs. 20.1%; p = 0.0426), NSAIDs (23.3% vs.14.6%; p = 0.012), opioids (20.6% vs. 7.5%; p < 0.001), and a significantly increase in the use of asthma medications (15.5% vs. 24.2%; p = 0.0088). Male patients showed a significant decline in the use of PPIs and NSAIDs. CONCLUSION Patients with functional bowel disorders are more likely to be prescribed medications for conditions other than IBS. Over time, there was a decline in the prescriptions of most drugs, except for antidepressants and asthma medications.
Collapse
Affiliation(s)
| | - Pontus Karling
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| |
Collapse
|
|
2
|
Villalba-Davila P, Aronson S, Lat J, Charles C, Schroeder B, Pittman M, Tang V, Wallach T. Helicobacter pylori infection is associated with significant elevations to fecal calprotectin, systemic inflammatory markers. J Pediatr Gastroenterol Nutr 2025. [PMID: 39831651 DOI: 10.1002/jpn3.12464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 12/12/2024] [Accepted: 12/12/2024] [Indexed: 01/22/2025]
Abstract
OBJECTIVES Fecal calprotectin (FC) is a marker commonly used in the diagnosis and follow-up of inflammatory bowel diseases (IBD). However, other gastrointestinal conditions, like H. pylori (HP) infection, can result in increased neutrophil activity as well. We set out to assess the impact of HP infection on FC and downstream gastrointestinal care via a retrospective study. METHODS In this study, we collected data from two institutions in Brooklyn, NY, in a high immigrant density community. We reviewed data from patients who underwent esophagogastroduodenoscopy (EGD) between January 2017 and October 2022. Patients aged 6-18 years old with an FC level 6 months prior to EGD and HP testing were included. RESULTS Of 129 patients, 37 (28.7%) tested positive for HP infection. The mean FC level was significantly elevated in HP-positive patients (241.2, confidence interval [CI]: 161.0-321.3) as compared with HP-negative patients (88.1, CI: 59.1-117.0) (p < 0.001). Patients with higher FC levels were also more likely to undergo colonoscopies (p = 0.003). DISCUSSION HP infection is associated with increased calprotectin, and calprotectin increases in HP patients are associated with an increased risk of colonoscopy.
Collapse
Affiliation(s)
| | - Stephanie Aronson
- Department of Pediatrics, Maimonides Medical Center, Brooklyn, New York, USA
| | - Jessica Lat
- Department of Pediatrics, Maimonides Medical Center, Brooklyn, New York, USA
| | - Cassandra Charles
- Department of Pediatrics, SUNY Downstate Health Sciences University, Brooklyn, New York, USA
| | - Bryce Schroeder
- Department of Pediatrics, Division of Pediatric Gastroenterology, SUNY Downstate Health Sciences University, Brooklyn, New York, USA
| | - Meredith Pittman
- Department of Pathology, Maimonides Medical Center, Brooklyn, New York, USA
| | - Vivian Tang
- Department of Pediatrics, Division of Pediatric Gastroenterology, Maimonides Medical Center, Brooklyn, New York, USA
| | - Thomas Wallach
- Department of Pediatrics, Division of Pediatric Gastroenterology, SUNY Downstate Health Sciences University, Brooklyn, New York, USA
| |
Collapse
|
|
3
|
Swaminathan A, Day AS, Sparrow MP, Peyrin-Biroulet L, Siegel CA, Gearry RB. Review article: Measuring disease severity in inflammatory bowel disease - Beyond treat to target. Aliment Pharmacol Ther 2024; 60:1176-1199. [PMID: 39403053 DOI: 10.1111/apt.18231] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 08/07/2024] [Accepted: 08/18/2024] [Indexed: 01/11/2025]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) follows a heterogenous disease course and predicting a patient's prognosis is challenging. There is a wide burden of illness in IBD and existing tools measure disease activity at a snapshot in time. Comprehensive assessment of IBD severity should incorporate disease activity, prognosis, and the impacts of disease on a patient. This review investigates the concept of disease severity in adults with IBD to highlight key components contributing to this. METHODS To perform this narrative review, a Medline search was conducted for full-text articles available at 1st March 2024 using search terms which encompassed disease activity assessment, disease severity, prognosis, natural history of Crohn's disease (CD) and ulcerative colitis (UC), and the burden of IBD. RESULTS Current methods of disease assessment in IBD have evolved from a focus on the burden of symptoms to one that includes inflammatory targets, genetic, serological, and proteomic profiles, and assessments of quality-of-life (QoL), disability, and psychosocial health. Longitudinal studies of IBD suggest that the burden of illness is driven by disease phenotype, clinical markers of complicated disease course (previous intestinal resection, corticosteroid use, perianal disease in CD, recent hospitalisations in UC), gut inflammation, and the impact of IBD on the patient. CONCLUSIONS Disease severity in IBD can be difficult to conceptualise due to the multitude of factors that contribute to IBD outcomes. Measurement of IBD severity may better encapsulate the full burden of illness rather than gut inflammation alone at a single timepoint and may be associated with longitudinal outcomes.
Collapse
Affiliation(s)
- Akhilesh Swaminathan
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
- Department of Gastroenterology, Christchurch Hospital, Christchurch, New Zealand
| | - Andrew S Day
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
| | - Miles P Sparrow
- Department of Gastroenterology, Alfred Health and School of Translational Medicine, Monash University, Australia
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandoevre-les-Nancy, France
- Department of Gastroenterology, INFINY Institute, FHU-CURE, INSERM NGERE, Nancy University Hospital, Vandoeuvre-les-Nancy, France
- Groupe Hospitalier privé Ambroise Paré - Hartmann, Paris IBD Center, Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, Quebec, Canada
| | - Corey A Siegel
- Center for Digestive Health, Section of Gastroenterology and Hepatology, Dartmouth Hitchcock Medical Centre, Lebanon, New Hampshire, USA
| | - Richard B Gearry
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
- Department of Gastroenterology, Christchurch Hospital, Christchurch, New Zealand
| |
Collapse
|
|
4
|
Ekoff H, Rydell N, Hellström PM, Movérare R. Fecal and Serum Granulocyte Protein Levels in Inflammatory Bowel Disease and Irritable Bowel Syndrome and Their Relation to Disease Activity. Clin Transl Gastroenterol 2024; 15:e1. [PMID: 38920307 PMCID: PMC11500791 DOI: 10.14309/ctg.0000000000000733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Accepted: 06/11/2024] [Indexed: 06/27/2024] Open
Abstract
INTRODUCTION Neutrophilic calprotectin (CP) and myeloperoxidase (MPO), neutrophil gelatinase-associated lipocalin (NGAL), and eosinophil-derived neurotoxin (EDN) are suggested proxy markers for gut inflammation. However, there are insufficient supporting data for MPO, NGAL, and EDN. METHODS In a cross-sectional investigation including adult patients, we studied the ability of CP, MPO, NGAL, and EDN, measured in fecal and serum samples, to differentiate between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), and to predict disease activity. RESULTS Fifty-nine patients had ulcerative colitis (UC), 38 had Crohn's disease, and 100 patients had IBS. The protein concentrations were higher in patients with IBD in the fecal samples ( P < 0.001) and the serum samples ( P < 0.01), and they correlated weakly (r s ≤0.38) between the sample sources. Fecal EDN was higher in patients with Crohn's disease compared with UC (1.79 vs 0.50 mg/kg, P = 0.016). The neutrophilic proteins were superior to EDN in the fecal samples for differentiating between patients with IBD and IBS. Fecal MPO (cutoff: 0.86 mg/kg) had the highest sensitivity (74.7%) and specificity (84.6%). Combining fecal CP and MPO increased the sensitivity to 82.3% (specificity: 73.6%). NGAL (cutoff: 196.9 μg/L) showed the best discriminating performance in serum (sensitivity: 62.9%; specificity: 68.0%). Serum NGAL (cutoff: 272.4 μg/L) predicted active disease in UC (Partial Mayo Score ≥2) with a sensitivity and specificity of 57.1% and 83.3%, respectively. DISCUSSION Fecal MPO and serum NGAL are promising novel biomarkers, in addition to fecal CP, for differentiating between IBD and IBS. Serum NGAL may also predict disease activity in patients with UC.
Collapse
Affiliation(s)
- Helena Ekoff
- Thermo Fisher Scientific, Uppsala, Sweden
- Department of Medical Sciences: Gastroenterology and Hepatology, Uppsala University, Uppsala, Sweden
| | | | - Per M. Hellström
- Department of Medical Sciences: Gastroenterology and Hepatology, Uppsala University, Uppsala, Sweden
| | - Robert Movérare
- Thermo Fisher Scientific, Uppsala, Sweden
- Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
| |
Collapse
|
|
5
|
Heinzel S, Jureczek J, Kainulainen V, Nieminen AI, Suenkel U, von Thaler AK, Kaleta C, Eschweiler GW, Brockmann K, Aho VTE, Auvinen P, Maetzler W, Berg D, Scheperjans F. Elevated fecal calprotectin is associated with gut microbial dysbiosis, altered serum markers and clinical outcomes in older individuals. Sci Rep 2024; 14:13513. [PMID: 38866914 PMCID: PMC11169261 DOI: 10.1038/s41598-024-63893-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 06/03/2024] [Indexed: 06/14/2024] Open
Abstract
Fecal calprotectin is an established marker of gut inflammation in inflammatory bowel disease (IBD). Elevated levels of fecal calprotectin as well as gut microbial dysbiosis have also been observed in other clinical conditions. However, systemic and multi-omics alterations linked to elevated fecal calprotectin in older individuals remain unclear. This study comprehensively investigated the relationship between fecal calprotectin levels, gut microbiome composition, serum inflammation and targeted metabolomics markers, and relevant lifestyle and medical data in a large sample of older individuals (n = 735; mean age ± SD: 68.7 ± 6.3) from the TREND cohort study. Low (0-50 μg/g; n = 602), moderate (> 50-100 μg/g; n = 64) and high (> 100 μg/g; n = 62) fecal calprotectin groups were stratified. Several pro-inflammatory gut microbial genera were significantly increased and short-chain fatty acid producing genera were decreased in high vs. low calprotectin groups. In serum, IL-17C, CCL19 and the toxic metabolite indoxyl sulfate were increased in high vs. low fecal calprotectin groups. These changes were partially mediated by the gut microbiota. Moreover, the high fecal calprotectin group showed increased BMI and a higher disease prevalence of heart attack and obesity. Our findings contribute to the understanding of fecal calprotectin as a marker of gut dysbiosis and its broader systemic and clinical implications in older individuals.
Collapse
Affiliation(s)
- Sebastian Heinzel
- Department of Neurology, University Medical Centre Schleswig-Holstein (UKSH), Kiel, Germany.
- Institute of Medical Informatics and Statistics, University Medical Centre Schleswig-Holstein (UKSH), Kiel, Germany.
- Department of Neurology, University Medical Centre Schleswig-Holstein, Kiel University, Arnold-Heller-Straße 3, 24105, Kiel, Germany.
| | - Jenna Jureczek
- Department of Neurology, University Medical Centre Schleswig-Holstein (UKSH), Kiel, Germany
- Institute of Medical Informatics and Statistics, University Medical Centre Schleswig-Holstein (UKSH), Kiel, Germany
| | - Veera Kainulainen
- Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Neurology, Helsinki University Hospital, Helsinki, Finland
- Department of Clinical Neurosciences (Neurology), University of Helsinki, Helsinki, Finland
| | - Anni I Nieminen
- Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
| | - Ulrike Suenkel
- Department of Psychiatry and Psychotherapy, German Center of Mental Health, Tübingen University Hospital, Tübingen, Germany
| | | | - Christoph Kaleta
- Institute of Experimental Medicine, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany
| | - Gerhard W Eschweiler
- Department of Psychiatry and Psychotherapy, German Center of Mental Health, Tübingen University Hospital, Tübingen, Germany
- Geriatric Center, University Hospital Tübingen, Tübingen, Germany
| | - Kathrin Brockmann
- Department of Neurodegeneration, Hertie Institute for Clinical Brain Research, German Center for Neurodegenerative Diseases, University of Tübingen, Tübingen, Germany
| | - Velma T E Aho
- Department of Neurology, Helsinki University Hospital, Helsinki, Finland
- Department of Clinical Neurosciences (Neurology), University of Helsinki, Helsinki, Finland
| | - Petri Auvinen
- Institute of Biotechnology, University of Helsinki, Helsinki, Finland
| | - Walter Maetzler
- Department of Neurology, University Medical Centre Schleswig-Holstein (UKSH), Kiel, Germany
| | - Daniela Berg
- Department of Neurology, University Medical Centre Schleswig-Holstein (UKSH), Kiel, Germany
| | - Filip Scheperjans
- Department of Neurology, Helsinki University Hospital, Helsinki, Finland
- Department of Clinical Neurosciences (Neurology), University of Helsinki, Helsinki, Finland
| |
Collapse
|
|
6
|
Liang Y, Meng Z, Ding XL, Jiang M. Effects of proton pump inhibitors on inflammatory bowel disease: An updated review. World J Gastroenterol 2024; 30:2751-2762. [PMID: 38899331 PMCID: PMC11185295 DOI: 10.3748/wjg.v30.i21.2751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 04/26/2024] [Accepted: 05/15/2024] [Indexed: 06/03/2024] Open
Abstract
Inflammatory bowel disease (IBD) is believed to be caused by various factors, including abnormalities in disease susceptibility genes, environmental factors, immune factors, and intestinal bacteria. Proton pump inhibitors (PPIs) are the primary drugs used to treat acid-related diseases. They are also commonly prescribed to patients with IBD. Recent studies have suggested a potential association between the use of certain medications, such as PPIs, and the occurrence and progression of IBD. In this review, we summarize the potential impact of PPIs on IBD and analyze the underlying mechanisms. Our findings may provide insights for conducting further investigations into the effects of PPIs on IBD and serve as an important reminder for physicians to exercise caution when prescribing PPIs to patients with IBD.
Collapse
Affiliation(s)
- Yu Liang
- Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Zhen Meng
- Department of Intervention, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Xue-Li Ding
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Man Jiang
- Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| |
Collapse
|
|
7
|
Fossmark R, Olaisen M. Changes in the Gastrointestinal Microbiota Induced by Proton Pump Inhibitors-A Review of Findings from Experimental Trials. Microorganisms 2024; 12:1110. [PMID: 38930492 PMCID: PMC11205704 DOI: 10.3390/microorganisms12061110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 05/21/2024] [Accepted: 05/27/2024] [Indexed: 06/28/2024] Open
Abstract
The use of proton pump inhibitors (PPIs) has increased considerably in many Western countries, and there is concern that numerous conditions and diseases associated with PPI use may be adverse events. The main function of gastric acid is to defend the organism against orally ingested microorganisms, and there is also concern that alterations not only in the gastric microbiome but also the downstream intestinal microbiome may increase the risk of disease or alter the course of preexisting disease. The current study is a systematic review of the available evidence from experimental trials investigating the effects of PPIs on the gastrointestinal microbiota by next-generation sequencing. Thirteen studies were identified. The effects of PPIs were seen on alterations in diversity and richness in some of the studies, while a larger proportion of the studies detected alterations at various taxonomic levels. The general finding was that PPI use caused an increase in bacteria normally found in the oral microbiota in both the upper and lower GI tract. The most consistent taxonomic alterations seemed to be increases in oral flora along the axis Streptococcaceae and Streptococcus at genus level and various Streptococcus spp., as well as Veillonellaceae, Veillonella and Haemophilus.
Collapse
Affiliation(s)
- Reidar Fossmark
- Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway;
- Centre for Obesity Research, Clinic of Surgery, St. Olav’s University Hospital, 7030 Trondheim, Norway
- Medicus Endoscopy, 7042 Trondheim, Norway
| | - Maya Olaisen
- Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway;
- Department of Gastroenterology, St. Olav’s Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
| |
Collapse
|
|
8
|
Clough J, Colwill M, Poullis A, Pollok R, Patel K, Honap S. Biomarkers in inflammatory bowel disease: a practical guide. Therap Adv Gastroenterol 2024; 17:17562848241251600. [PMID: 38737913 PMCID: PMC11085009 DOI: 10.1177/17562848241251600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 04/12/2024] [Indexed: 05/14/2024] Open
Abstract
Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), is a costly condition in terms of morbidity and healthcare utilization, with an increasing prevalence now approaching 1% in the Western world. Endoscopic assessment of IBD remains the gold standard for diagnosis, evaluation of treatment response and determination of post-operative recurrence, but is expensive and invasive. Biomarkers can facilitate non-invasive disease assessment, with C-reactive protein and faecal calprotectin as the most widely available biomarkers in current clinical practice. This narrative review summarizes the evidence for their use in both UC and CD and offers practical guidance for healthcare providers taking into account the limitations of biomarker interpretation. We present evidence for the future use of novel biomarkers in IBD and discuss how biomarker discovery could deliver the goal of precision medicine in IBD.
Collapse
Affiliation(s)
- Jennie Clough
- St George’s University Hospitals NHS Foundation Trust, London, UK
- School of Immunology and Microbial Sciences, King’s College London, London, UK
| | - Michael Colwill
- St George’s University Hospitals NHS Foundation Trust, London, UK
| | - Andrew Poullis
- St George’s University Hospitals NHS Foundation Trust, London, UK
| | - Richard Pollok
- St George’s University Hospital NHS Foundation Trust
- Institute of Infection and Immunity, St George’s University, London, UK
| | - Kamal Patel
- St George’s University Hospitals NHS Foundation Trust, London, UK
| | - Sailish Honap
- St George’s University Hospitals NHS Foundation Trust, London, UK
- School of Immunology and Microbial Sciences, King’s College London, London, UK
- INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France
| |
Collapse
|
|
9
|
Rodriguez N, Kumar S, Mo J, Hartmann P. Collagenous gastritis with elevated fecal calprotectin in a pediatric patient. JPGN REPORTS 2024; 5:152-157. [PMID: 38756119 PMCID: PMC11093908 DOI: 10.1002/jpr3.12055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 01/11/2024] [Accepted: 02/03/2024] [Indexed: 05/18/2024]
Abstract
Collagenous gastritis is a rare and chronic inflammatory condition of undetermined etiology characterized histologically by thickened subepithelial collagen bands and increased intraepithelial lymphocytes. Here, we present a collagenous gastritis case in a 16-year-old female with chronic abdominal pain, persistently elevated fecal calprotectin (507 and 796 mcg/g), and resolved iron deficiency anemia. The patient's history, laboratory tests, endoscopy, and magnetic resonance imaging ruled out common causes of elevated fecal calprotectin, including Helicobacter pylori and gastrointestinal infections, medications, celiac disease, and inflammatory bowel disease, as well as less common causes such as collagenous colitis. Esophagogastroduodenoscopy revealed significant antral nodularity. Gastric biopsies showed thickened subepithelial collagen band and surface epithelium damage with increased intraepithelial lymphocytes. The ileocolonoscopy was normal. This is among the first reported cases of collagenous gastritis with elevated fecal calprotectin levels that could solely be attributed to this condition.
Collapse
Affiliation(s)
- Natalie Rodriguez
- Department of PediatricsUniversity of California San DiegoLa JollaCaliforniaUSA
| | - Soma Kumar
- Department of PediatricsUniversity of California San DiegoLa JollaCaliforniaUSA
- Division of Gastroenterology, Hepatology & NutritionRady Children's Hospital San DiegoSan DiegoCaliforniaUSA
| | - Jun Mo
- Department of PediatricsUniversity of California San DiegoLa JollaCaliforniaUSA
- Division of PathologyRady Children's Hospital San DiegoSan DiegoCaliforniaUSA
| | - Phillipp Hartmann
- Department of PediatricsUniversity of California San DiegoLa JollaCaliforniaUSA
- Division of Gastroenterology, Hepatology & NutritionRady Children's Hospital San DiegoSan DiegoCaliforniaUSA
| |
Collapse
|
|
10
|
Bjurström O, Karling P. The association between drugs and repeated treatment with budesonide in patients with microscopic colitis: a retrospective observational study. Therap Adv Gastroenterol 2024; 17:17562848241240640. [PMID: 38510459 PMCID: PMC10953108 DOI: 10.1177/17562848241240640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 03/01/2024] [Indexed: 03/22/2024] Open
Abstract
Background Smoking and the use of non-steroidal anti-inflammatory drugs (NSAIDs) acetylsalicylic acid (ASA), proton pump inhibitors (PPIs), serotonin reuptake inhibitors (SSRIs), and statins have been associated with microscopic colitis (MC). Objectives We investigated whether these factors were associated with repeated budesonide treatments in patients diagnosed with MC. Design Retrospective observational study. Methods All patients with a histologically verified diagnosis of MC at our clinic between the years 2006 and 2022 were identified. Baseline factors and drugs prescribed before and after diagnosis were registered. The influence of risk factors on the odds of having a prescription of oral budesonide and the odds of having a second course of budesonide was studied. Results Patients with MC (n = 183) with a mean age of 62.3 years [standard deviation (SD): 13.3 years] were followed for a median of 5 years (25th-75th percentile 4-10 years) after diagnosis. In all, 138 patients (75%) had at least one prescription of budesonide after diagnosis, and 90 patients (49%) had at least one clinical relapse treated with budesonide. Patients who had been prescribed NSAIDs within 1 year before clinical relapse had higher odds for clinical relapse [odds ratio (OR): 3.70, 95% confidence interval (CI): 1.06-12.9] but there was no increased risk for clinical relapse for the use of ASA (OR: 0.99, 95% CI: 0.39-2.90), PPIs (OR: 1.09, 95% CI: 0.45-2.63), SSRI (OR: 1.41, 95% CI: 0.82-2.44), or statins (OR: 0.83, 95% CI: 0.35-1.99). No association was seen between being a smoker and/or being prescribed NSAID, ASA, PPI, SSRI, and statins at baseline and the odds of having a prescription of oral budesonide within 1 year after diagnosis. Conclusion The risk of being prescribed a second course of budesonide is associated with receiving a prescription of NSAIDs but not with the use of ASA, PPIs, SSRIs, and statins.
Collapse
Affiliation(s)
- Oliver Bjurström
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Pontus Karling
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, 901 87, Sweden
| |
Collapse
|
|
11
|
Mathew NE, McCaffrey D, Walker AK, Mallitt KA, Masi A, Morris MJ, Ooi CY. The search for gastrointestinal inflammation in autism: a systematic review and meta-analysis of non-invasive gastrointestinal markers. Mol Autism 2024; 15:4. [PMID: 38233886 PMCID: PMC10795298 DOI: 10.1186/s13229-023-00575-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 11/04/2023] [Indexed: 01/19/2024] Open
Abstract
BACKGROUND Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is associated with elevated gastrointestinal inflammation as studies examining non-invasive faecal biomarkers report conflicting findings. To understand the research landscape and identify gaps, we performed a systematic review and meta-analysis of studies measuring non-invasive markers of gastrointestinal inflammation in autistic and non-autistic samples. Our examination focused on faecal biomarkers as sampling is non-invasive and these markers are a direct reflection of inflammatory processes in the gastrointestinal tract. METHODS We extracted data from case-control studies examining faecal markers of gastrointestinal inflammation. We searched PubMed, Embase, Cochrane CENTRAL, CINAHL, PsycINFO, Web of Science Core Collection and Epistemonikos and forward and backwards citations of included studies published up to April 14, 2023 (PROSPERO CRD42022369279). RESULTS There were few studies examining faecal markers of gastrointestinal inflammation in the autistic population, and many established markers have not been studied. Meta-analyses of studies examining calprotectin (n = 9) and lactoferrin (n = 3) were carried out. A total of 508 autistic children and adolescents and 397 non-autistic children and adolescents were included in the meta-analysis of calprotectin studies which found no significant group differences (ROM: 1.30 [0.91, 1.86]). Estimated differences in calprotectin were lower in studies with siblings and studies which did not exclude non-autistic controls with gastrointestinal symptoms. A total of 139 autistic participants and 75 non-autistic controls were included in the meta-analysis of lactoferrin studies which found no significant group differences (ROM: 1.27 [0.79, 2.04]). LIMITATIONS All studies included in this systematic review and meta-analysis examined children and adolescents. Many studies included non-autistic controls with gastrointestinal symptoms which limit the validity of their findings. The majority of studies of gastrointestinal inflammation focused on children under 12 with few studies including adolescent participants. Most studies that included participants aged four or under did not account for the impact of age on calprotectin levels. Future studies should screen for relevant confounders, include larger samples and explore gastrointestinal inflammation in autistic adolescents and adults. CONCLUSIONS There is no evidence to suggest higher levels of gastrointestinal inflammation as measured by calprotectin and lactoferrin are present in autistic children and adolescents at the population level. Preliminary evidence suggests however that higher calprotectin levels may be present in a subset of autistic participants, who may be clinically characterised by more severe gastrointestinal symptoms and higher levels of autistic traits.
Collapse
Affiliation(s)
- Nisha E Mathew
- School of Clinical Medicine, Discipline of Paediatrics and Child Health, UNSW Medicine and Health, University of New South Wales, Sydney, 2052, Australia
- Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, Randwick, NSW, 2031, Australia
| | - Delyse McCaffrey
- Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, Randwick, NSW, 2031, Australia
- School of Clinical Medicine, Discipline of Psychiatry and Mental Health, UNSW Medicine and Health, University of New South Wales, Sydney, 2052, Australia
| | - Adam K Walker
- Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, Randwick, NSW, 2031, Australia
- School of Clinical Medicine, Discipline of Psychiatry and Mental Health, UNSW Medicine and Health, University of New South Wales, Sydney, 2052, Australia
- Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3800, Australia
| | - Kylie-Ann Mallitt
- School of Clinical Medicine, Discipline of Psychiatry and Mental Health, UNSW Medicine and Health, University of New South Wales, Sydney, 2052, Australia
- Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, 2006, Australia
| | - Anne Masi
- School of Clinical Medicine, Discipline of Psychiatry and Mental Health, UNSW Medicine and Health, University of New South Wales, Sydney, 2052, Australia
| | - Margaret J Morris
- School of Biomedical Sciences, University of New South Wales, Sydney, 2052, Australia
| | - Chee Y Ooi
- School of Clinical Medicine, Discipline of Paediatrics and Child Health, UNSW Medicine and Health, University of New South Wales, Sydney, 2052, Australia.
- Department of Gastroenterology, Sydney Children's Hospital, High Street, Randwick, NSW, 2031, Australia.
| |
Collapse
|
|
12
|
Al-Kuraishy HM, Al-Gareeb AI, Zaidalkiani AT, Alexiou A, Papadakis M, Bahaa MM, Al-Faraga A, Batiha GES. Calprotectin in Parkinsonian disease: Anticipation and dedication. Ageing Res Rev 2024; 93:102143. [PMID: 38008403 DOI: 10.1016/j.arr.2023.102143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 11/13/2023] [Accepted: 11/22/2023] [Indexed: 11/28/2023]
Abstract
Parkinson's disease (PD) is a neurodegenerative disease due to degeneration of dopaminergic neurons (DNs) in the substantia nigra pars compacta (SNpc). PD is characterized by motor and non-motor symptoms. Non-motor symptoms such as constipation and dysfunction of gastrointestinal tract (GIT) motility together with medications used in the management of PD affect gut microbiota. Alterations of gut microbiota with development of gut dyspiosis can induce momentous changes in gut barrier with subsequent systemic inflammation and induction of neuroinflammation. It has been shown that calprotectin which reflect intestinal inflammation and gut barrier injury are augmented in PD. Therefore, this review aims to elucidate the possible role of gut barrier injury and associated dysbiois in PD neuropathology, and how calprotectin reflects gut barrier injury in PD. Benefit of this review was to elucidate that high fecal calprotectin level in PD patients indicated gut dysbiosis and intestinal inflammation. Early increment of fecal calprotectin indicates the development of gut dysbiosis and/or gut-barrier injury which may precede motor symptoms by decades. Thus, fecal calprotectin could be a diagnostic and prognostic biomarker in PD. preclinical and clinical studies are warranted in this regard to emphasize the potential role of fecal calprotectin in PD neuropathology.
Collapse
Affiliation(s)
- Hayder M Al-Kuraishy
- Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq
| | - Ali I Al-Gareeb
- Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq
| | - Ayah Talal Zaidalkiani
- Department of Nutrition, Faculty of Pharmacy and Medical Sciences, University of Petra, 11196 Amman, Jordan
| | - Athanasios Alexiou
- Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW 2770, Australia; AFNP Med, 1030 Wien, Austria
| | - Marios Papadakis
- Department of Surgery II, University Hospital Witten-Herdecke, University of Witten-Herdecke, Heusnerstrasse 40, 42283 Wuppertal, Germany
| | - Mostafa M Bahaa
- Pharmacy Practice Department, Faculty of Pharmacy, Horus University, New Damietta, Egypt.
| | - Ammar Al-Faraga
- Department of Biochemistry, College of Science University of Jeddah, Saudi Arabia
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, AlBeheira 22511, Egypt
| |
Collapse
|
|
13
|
Traini I, Chan SY, Menzies J, Hughes J, Coffey MJ, McKay IR, Ooi CY, Leach ST, Krishnan U. Intestinal dysbiosis and inflammation in children with repaired esophageal atresia. J Pediatr Gastroenterol Nutr 2024; 78:43-51. [PMID: 38291693 DOI: 10.1002/jpn3.12053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 09/23/2023] [Accepted: 09/26/2023] [Indexed: 02/01/2024]
Abstract
OBJECTIVES This study aims to compare the intestinal microbiota and intestinal inflammation of children with esophageal atresia (EA) to matched healthy controls, and to investigate the relationship between these factors and clinical outcomes. METHODS A cross-sectional study of 35 children with EA and 35 matched healthy controls (HC) from a single tertiary pediatric hospital in Australia was conducted. Demographic and dietary data were collected using surveys. Stool samples were analyzed using 16S rRNA sequencing, and fecal calprotectin measurements were used to measure intestinal inflammation. Comparisons were made between the groups, and correlations between the microbiota and clinical factors were investigated in the EA cohort. RESULTS Compared to HC, children with EA had similar alpha diversity, but beta diversity analysis revealed clustering of EA and HC cohorts. Children with EA had a significantly higher relative abundance of the order Lactobacillales, and a lower abundance of the genus uncultured Bacteroidales S24-7. Fecal calprotectin was significantly higher in children with EA compared to HC. In the EA cohort, children taking proton pump inhibitors (PPI's) had lower alpha diversity and higher calprotectin levels compared to those not taking PPI's. There was a negative correlation between calprotectin and length/height-for-age z scores, and children with higher calprotectin levels had a greater burden of gastrointestinal symptoms. CONCLUSIONS Children with EA have an altered intestinal microbiota compared to HC, which is likely related to PPI use, and may be impacting on growth and quality of life. It is important to rationalize PPI use in this cohort.
Collapse
Affiliation(s)
- Isabelle Traini
- Discipline of Pediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Randwick, New South Wales, Australia
| | - Sin Y Chan
- Discipline of Pediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Randwick, New South Wales, Australia
| | - Jessica Menzies
- Department of Nutrition and Dietetics, Sydney Children's Hospital, Randwick, New South Wales, Australia
| | - Jennifer Hughes
- Department of Speech Pathology, Sydney Children's Hospital, Randwick, New South Wales, Australia
| | - Michael J Coffey
- Discipline of Pediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Randwick, New South Wales, Australia
| | - Isabelle R McKay
- Discipline of Pediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Randwick, New South Wales, Australia
| | - Chee Y Ooi
- Discipline of Pediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Randwick, New South Wales, Australia
- Department of Gastroenterology, Sydney Children's Hospital, Randwick, New South Wales, Australia
| | - Steven T Leach
- Discipline of Pediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Randwick, New South Wales, Australia
| | - Usha Krishnan
- Discipline of Pediatrics, School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Randwick, New South Wales, Australia
- Department of Gastroenterology, Sydney Children's Hospital, Randwick, New South Wales, Australia
| |
Collapse
|
|
14
|
Rendek Z, Falk M, Grodzinsky E, Kechagias S, Hjortswang H. Diagnostic value of fecal calprotectin in primary care patients with gastrointestinal symptoms: A retrospective Swedish cohort study. JGH Open 2023; 7:708-716. [PMID: 37908296 PMCID: PMC10615176 DOI: 10.1002/jgh3.12972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 09/02/2023] [Accepted: 09/06/2023] [Indexed: 11/02/2023]
Abstract
Aims To investigate the diagnostic accuracy of fecal calprotectin (FC) for inflammatory bowel disease (IBD) and organic gastrointestinal disease (OGID) in primary care. To examine the association with demographic factors, symptoms and concomitant medical therapy. Methods A retrospective analysis of data on all semiquantitative FC tests from individuals ≥18 years conducted in primary care in Östergötland County in 2010. A 5-year follow-up with inclusion of new gastrointestinal diagnoses. Results A total of 1293 eligible patients were included. IBD was found in 8.8% and other OGID in 30.8% of patients with positive FC. Positive FC was associated with diarrhea, age >60 years, duration <3 months, use of nonsteroidal anti-inflammatory drug (NSAID), and proton pump inhibitor (PPI). Predictors of IBD were positive FC, diarrhea, rectal bleeding, and male sex; predictors of OGID positive FC, age >35 years, abnormal clinical findings, and duration <3 months. FC yielded the highest sensitivity and negative predictive value compared with demographic factors, symptoms, and duration. Use of NSAID and PPI showed a marginal increase in the sensitivity, positive predictive value, and decrease in the specificity of FC. Within 5 years, 4.0% had a new gastrointestinal diagnosis among patients with positive FC (0.6% IBD). Conclusions FC reliably rules out IBD and contradicts the presence of other OGID in primary care patients. Positive FC test together with other predictors, such as diarrhea, rectal bleeding, short duration, or age >35 years, should encourage a prioritized investigation. Use of NSAID, PPI, and ASA may affect the diagnostic accuracy of FC for IBD and OGID.
Collapse
Affiliation(s)
- Zlatica Rendek
- Department of Biomedical and Clinical SciencesLinköping UniversityLinköpingSweden
| | - Magnus Falk
- Department of Health, Medicine and Caring SciencesLinköping UniversityLinköpingSweden
- Primary Health Care Centre KärnaLinköping UniversityLinköpingSweden
| | - Ewa Grodzinsky
- Department of Biomedical and Clinical SciencesLinköping UniversityLinköpingSweden
| | - Stergios Kechagias
- Department of Health, Medicine and Caring SciencesLinköping UniversityLinköpingSweden
- Division of Diagnostics and Specialist Medicine, Department of Health, Medicine and Caring SciencesLinköping UniversityLinköpingSweden
| | - Henrik Hjortswang
- Department of Health, Medicine and Caring SciencesLinköping UniversityLinköpingSweden
- Department of Gastroenterology and Hepatology in Linköping, and Department of Health, Medicine, and Caring SciencesLinköping UniversityLinköpingSweden
| |
Collapse
|
|
15
|
Murray J, Kok KB, Ayling RM. Fecal Calprotectin in Gastrointestinal Disease. Clin Chem 2023:7179811. [PMID: 37228058 DOI: 10.1093/clinchem/hvad051] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 03/14/2023] [Indexed: 05/27/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) comprises a group of chronic conditions characterized by relapsing and remitting inflammation of the gastrointestinal tract. The incidence is increasing worldwide, and the therapeutic options for management are expanding. Endoscopy is the gold standard investigation for diagnosis of IBD and for assessing mucosal healing, which is increasingly being used as a measure of disease control. However, it is an invasive procedure that is unpleasant for patients and expensive and time-consuming for hospitals. Fecal calprotectin has been shown to be an accurate surrogate marker of gastrointestinal inflammation in IBD. CONTENT Fecal calprotectin was initially used for the diagnosis of IBD but is now recognized as having a role in assisting in assessment of disease activity, prediction of relapse, and informing decisions around therapy and may help to minimize requirement for endoscopy. However, there are various preanalytical and analytical factors that can affect interpretation of the results; these need to be understood to optimize clinical care. SUMMARY Preanalytical and analytical factors that can potentially influence fecal calprotectin concentrations are examined, and an overview is provided of clinical situations in which fecal calprotectin is commonly measured.
Collapse
Affiliation(s)
- Jennifer Murray
- Department of Gastroenterology, Barts Health NHS Trust, Royal London Hospital, London, United Kingdom
| | - Klaartje B Kok
- Department of Gastroenterology, Barts Health NHS Trust, Royal London Hospital, London, United Kingdom
| | - Ruth M Ayling
- Department of Clinical Biochemistry, Barts Health NHS Trust, Royal London Hospital, London, United Kingdom
| |
Collapse
|
|
16
|
Bruce H, Osypiw J, Prajapati-Jha G, O'Driscoll S, Brealey M, Benton SC. Comparison of faecal calprotectin using two collection and extraction strategies for the BÜHLMANN CALEX® Cap - possible implications for clinical cut-offs? Ann Clin Biochem 2023:45632231159296. [PMID: 36750426 DOI: 10.1177/00045632231159296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
BACKGROUND Faecal calprotectin has been identified as a useful biochemical marker in the differentiation of inflammatory bowel disease and irritable bowel syndrome. Typically, patients send faecal specimens in a pot for manual extraction by the laboratory. During the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) pandemic, the routine laboratory service was temporarily suspended due to the potential increased risk to staff. In this study we investigated the possibility of patients collecting samples directly into the faecal extraction tubes. METHOD Patients submitted paired faecal samples for calprotectin analysis using a standard faecal container (current practice) and followed instructions for faecal collection using the BÜHLMANN CALEX® Cap device. Samples were returned to the laboratory immediately after collection. Laboratory staff manually extracted the calprotectin from the faecal samples using the CALEX® Cap prior to analysis of both extracts on the Cobas c702. RESULTS 91 paired faecal samples were included in the study. Clinical correlation was found to be 70% with numerical correlation showing a positive bias for the patient-collected CALEX® Cap sample when compared to the laboratory-extracted faecal sample around the clinical decision points 100-250 μg calprotectin/g faeces. CONCLUSION The study shows that collection of a faecal sample using the CALEX® Cap works well and is a good alternative to using standard containers. The correlation gives rise to the possibility that faecal calprotectin is not stable when collected into standard collection containers. Prior to further roll-out of this process, questions surrounding the current cut-offs would need to be addressed.
Collapse
Affiliation(s)
- Helen Bruce
- Department of Clinical Biochemistry, Berkshire and Surrey Pathology Services, Royal Surrey County Hospital, Guildford, UK.,Bowel Cancer Screening Programme Southern Hub, Guildford, UK
| | - Jacqueline Osypiw
- Department of Clinical Biochemistry, Berkshire and Surrey Pathology Services, 6818Royal Berkshire Hospital, Reading, UK
| | - Geeta Prajapati-Jha
- Department of Clinical Biochemistry, Berkshire and Surrey Pathology Services, 6818Royal Berkshire Hospital, Reading, UK
| | | | - Martin Brealey
- Bowel Cancer Screening Programme Southern Hub, Guildford, UK
| | - Sally C Benton
- Department of Clinical Biochemistry, Berkshire and Surrey Pathology Services, Royal Surrey County Hospital, Guildford, UK.,Bowel Cancer Screening Programme Southern Hub, Guildford, UK
| |
Collapse
|
|
17
|
Oral omeprazole and diclofenac intake is associated with increased faecal calprotectin levels: a randomised open-label clinical trial. Eur J Gastroenterol Hepatol 2023; 35:52-58. [PMID: 36468569 DOI: 10.1097/meg.0000000000002473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND AND AIM Nonsteroidal anti-inflammatory drugs and proton pump inhibitors are known to affect the diagnostics of gastrointestinal disorders. The aim of this study was to investigate to what extent omeprazole, diclofenac or co-administration of these affects faecal calprotectin levels and the normalisation interval after cessation. METHODS Participants received 20 mg omeprazole daily for 2 weeks in the first sequence, 50 mg oral diclofenac three times daily for 2 weeks in the second and co-administration of these for 2 weeks in the third, with washout periods in between. The first two sequences were randomised to a different order. Faecal calprotectin was measured on days 0, 4, 7, 14, 21, 28 and 35 and thereafter at 7-day intervals until normalisation in each sequence. RESULTS Thirty-two healthy volunteers were included. During drug intake, 39% on diclofenac (median 70.8 µg/g; range 50.2-1080 µg/g), 53% on omeprazole (median 85.3 µg/g; range 51.1-249 µg/g) and 69% on omeprazole + diclofenac (median 101.5 µg/g; range 51.5-532 µg/g) had faecal calprotectin levels above normal. In the diclofenac sequence, faecal calprotectin returned to normal in all participants within 2 weeks of cessation and in the omeprazole and co-administration sequences, within 3 weeks of cessation. No statistical significant difference was found with respect to drug order. CONCLUSION Short-term intake of omeprazole, diclofenac or co-administration appears to increase faecal calprotectin levels. In patients with increased faecal calprotectin on omeprazole alone or in combination with diclofenac, a repeated faecal calprotectin test is recommended at least 3 weeks after cessation. On diclofenac alone, it is sufficient to repeat the faecal calprotectin test 2 weeks after cessation.
Collapse
|
|
18
|
Hamberg V, Wallman JK, Mogard E, Lindqvist E, Olofsson T, Andréasson K. Elevated fecal levels of the inflammatory biomarker calprotectin in early systemic sclerosis. Rheumatol Int 2022; 43:961-967. [PMID: 36566433 PMCID: PMC10073054 DOI: 10.1007/s00296-022-05264-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 12/17/2022] [Indexed: 12/26/2022]
Abstract
Knowledge on gastrointestinal manifestations in early systemic sclerosis (SSc) is limited. We have investigated gastrointestinal inflammation in SSc at the time of diagnosis using the inflammatory biomarker Fecal calprotectin (F-cal). Consecutive patients with suspected SSc were characterized in relation to the 2013 classification criteria for SSc and classified as SSc or SSc-like disease. F-cal levels were measured with a polyclonal ELISA (Calpro A/S, Lysaker, Norway) and levels above 50 µg/g were considered elevated. F-cal levels were compared to those of control subjects without rheumatic disease. Of 137 patients with suspected SSc, 92 were classified as SSc and 45 as SSc-like disease. Median (interquartile range) disease duration among the SSc participants was 2.5 (1.2, 4.6) years. A substantial proportion of participants classified as SSc (35/92, 38%) and SSc-like disease (14/45, 31%) exhibited elevated F-cal compared to the control group (3/41, 7.3%; p < 0.001 and p = 0.007, respectively). Elevated F-cal was associated with proton pump inhibitor usage (OR 7.14; 95% CI 2.56-29.93; p < 0.001). We conclude that elevated F-cal is present in a subgroup of patients with SSc at the time of diagnosis, suggesting that that GI inflammation may be present in this patient group early in the disease course. F-cal did not exhibit potential to differentiate SSc from SSc-like disease.
Collapse
Affiliation(s)
- Viggo Hamberg
- Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Skane University Hospital, 221 85, Lund, Sweden.
| | - Johan K Wallman
- Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Skane University Hospital, 221 85, Lund, Sweden
| | - Elisabeth Mogard
- Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Skane University Hospital, 221 85, Lund, Sweden
| | - Elisabet Lindqvist
- Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Skane University Hospital, 221 85, Lund, Sweden
| | - Tor Olofsson
- Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Skane University Hospital, 221 85, Lund, Sweden
| | - Kristofer Andréasson
- Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Skane University Hospital, 221 85, Lund, Sweden
| |
Collapse
|
|
19
|
Wrigley-Carr HE, van Dorst JM, Ooi CY. Intestinal dysbiosis and inflammation in cystic fibrosis impacts gut and multi-organ axes. MEDICINE IN MICROECOLOGY 2022. [DOI: 10.1016/j.medmic.2022.100057] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
|
|
20
|
Czerwińska-Rogowska M, Skonieczna-Żydecka K, Kaseja K, Jakubczyk K, Palma J, Bott-Olejnik M, Brzozowski S, Stachowska E. Kitchen Diet vs. Industrial Diets-Impact on Intestinal Barrier Parameters among Stroke Patients. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19106168. [PMID: 35627704 PMCID: PMC9141131 DOI: 10.3390/ijerph19106168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 05/15/2022] [Accepted: 05/16/2022] [Indexed: 12/10/2022]
Abstract
Background and aims: Strokes are the second highest cause of death in the world and the most common cause of permanent disability in adults. Intestinal barrier permeability thus contributes to diminished homeostasis within the body, which further affects the healing process and convalescence. Each stroke patient should be administered with ingredients that support the intestinal barrier (e.g., protein and fiber). The aim of this study was to compare the effect of various types of diet (enteral with or without fiber vs. a mixed kitchen diet) on the metabolic activity of intestinal microbiota, namely short chain fatty acids, and gut barrier integrity parameters (zonulin and calprotectin. Methods: Patients (n = 59), after suffering an ischemic stroke, were randomly allocated to three groups receiving: the kitchen diet (n = 32; 1.2 g fiber in 100 mL); Nutrison Energy® (n = 14; 0.02 g fiber in 100 mL); and Nutrison Diason Energy HP® (n = 13; 1.8 g fiber in 100 mL). The patients underwent anthropometric measurements and blood samples (for prealbumin measurements), and stool samples (for zonulin and calprotectin determinations) were taken twice, on admission and a week later. Results: Industrial diets enriched with fiber maintained nutritional status and had a beneficial effect on intestinal barrier permeability parameters. Patients fed with kitchen diets demonstrated a decreased number of lymphocytes, hemoglobin, erythrocytes, and increased serum concentration of C-reactive protein, but improved gut barrier markers. Proton pump inhibitors were shown to increase the inflammatory process in gut. Conclusions: Stroke patients should be administered with industrial diets enriched with fiber to improve gut barrier integrity and nutritional parameters.
Collapse
Affiliation(s)
- Maja Czerwińska-Rogowska
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University, 71-460 Szczecin, Poland; (M.C.-R.); (K.J.)
| | - Karolina Skonieczna-Żydecka
- Department od Biochemical Sciences, Pomeranian Medical University, 71-460 Szczecin, Poland; (K.S.-Ż.); (J.P.)
| | - Krzysztof Kaseja
- Department of General and Transplant Surgery, Pomeranian Medical University, 71-460 Szczecin, Poland;
| | - Karolina Jakubczyk
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University, 71-460 Szczecin, Poland; (M.C.-R.); (K.J.)
| | - Joanna Palma
- Department od Biochemical Sciences, Pomeranian Medical University, 71-460 Szczecin, Poland; (K.S.-Ż.); (J.P.)
| | - Marta Bott-Olejnik
- Neurology Department Regional Specialist Hospital in Gryfice, 72-300 Gryfice, Poland; (M.B.-O.); (S.B.)
| | - Sławomir Brzozowski
- Neurology Department Regional Specialist Hospital in Gryfice, 72-300 Gryfice, Poland; (M.B.-O.); (S.B.)
| | - Ewa Stachowska
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University, 71-460 Szczecin, Poland; (M.C.-R.); (K.J.)
- Correspondence:
| |
Collapse
|
|
21
|
Mundula T, Russo E, Curini L, Giudici F, Piccioni A, Franceschi F, Amedei A. Chronic systemic low-grade inflammation and modern lifestyle: the dark role of gut microbiota on related diseases with a focus on pandemic COVID-19. Curr Med Chem 2022; 29:5370-5396. [PMID: 35524667 DOI: 10.2174/0929867329666220430131018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 02/01/2022] [Accepted: 02/23/2022] [Indexed: 12/12/2022]
Abstract
Inflammation is a physiological, beneficial and auto-limiting response of the host to alarming stimuli. Conversely, a chronic systemic low-grade inflammation (CSLGI), known as a long-time persisting condition, causes organs and host tissues' damage, representing a major risk for chronic diseases. Currently, a worldwide a high incidence of inflammatory chronic diseases is observed, often linked to the lifestyle-related changes occurred in the last decade's society. The mains lifestyle-related factors are a proinflammatory diet, psychological stress, tobacco smoking, alcohol abuse, physical inactivity, and finally indoor living and working with its related consequences such as indoor pollution, artificial light exposure and low vitamin D production. Recent scientific evidences found that gut microbiota (GM) has a main role in shaping the host's health, particularly as CSLGI mediator. As a matter of facts, based on the last discoveries regarding the remarkable GM activity, in this manuscript we focused on the elements of actual lifestyle that influence the composition and function of intestinal microbial community, in order to elicit the CSLGI and its correlated pathologies. In this scenario, we provide a broad review of the interplay between modern lifestyle, GM and CSLGI with a special focus on the COVID symptoms and emerging long-COVID syndrome.
Collapse
Affiliation(s)
- Tiziana Mundula
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Edda Russo
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Lavinia Curini
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Francesco Giudici
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Andrea Piccioni
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Francesco Franceschi
- Emergency Department, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| |
Collapse
|
|
22
|
Park SY, Lee SP, Kim WJ. Fecal Calprotectin Is Increased in Stroke. J Clin Med 2021; 11:jcm11010159. [PMID: 35011900 PMCID: PMC8745495 DOI: 10.3390/jcm11010159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 12/23/2021] [Accepted: 12/28/2021] [Indexed: 12/14/2022] Open
Abstract
Background: While there have been major advances in unveiling the mechanisms comprising the ischemic cascade of CNS, stroke continues to be a significant burden. There is a need to extend the focus toward peripheral changes, and the brain–gut axis has recently gained much attention. Our study aimed to evaluate gut inflammation and its association with blood variables in stroke using fecal calprotectin (FC). Methods: Fecal samples were obtained from 27 stroke patients and 27 control subjects. FC was quantitatively measured using a commercial ELISA. Laboratory data on the fecal sample collection were also collected, including CBC, ESR, glucose, creatinine, total protein, albumin, transaminases, and CRP. Results: There was a significant increase in FC levels in stroke patients compared to the controls. Furthermore, FC in stroke patients was negatively correlated with the Glasgow Coma Scale. Moreover, FC in stroke patients was positively correlated with CRP and negatively correlated with lymphocyte count and albumin. Conclusions: Our findings show that increased FC is associated with consciousness and systemic response in stroke and warrants further studies to elucidate the usefulness of FC in the management of stroke.
Collapse
Affiliation(s)
- Shin Young Park
- Department of Clinical Laboratory Science, Cheju Halla University, 38 Halladaehak-ro, Jeju-si 63092, Korea;
| | - Sang Pyung Lee
- Brain-Neuro Center, Department of Neurosurgery, Cheju Halla General Hospital, 65 Doryeong-ro, Jeju-si 63127, Korea;
| | - Woo Jin Kim
- Department of Clinical Laboratory Science, Cheju Halla University, 38 Halladaehak-ro, Jeju-si 63092, Korea;
- Department of Laboratory Medicine, EONE Laboratories, 291 Harmony-ro, Yeonsu-gu, Incheon 22014, Korea
- Correspondence: ; Tel.: +82-32-210-2108
| |
Collapse
|
|
23
|
Kmeid M, Arker SH, Petchers A, Lukose G, Li H, Lee EC, Qualia CM, Arslan ME, Lee H. Appendiceal inflammation in colectomy is independently correlated with early pouchitis following ileal pouch anal anastomosis in ulcerative colitis and indeterminate colitis. Ann Diagn Pathol 2021; 55:151838. [PMID: 34626936 DOI: 10.1016/j.anndiagpath.2021.151838] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Revised: 09/23/2021] [Accepted: 09/28/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Appendiceal inflammation in colectomy is one of the histologic predictors of pouchitis in ulcerative colitis (UC) following ileal pouch anal anastomosis (IPAA). Fecal calprotectin level has been shown to increase 2 months prior to the onset of pouchitis. We evaluated whether inflammation and calprotectin expression in appendiceal specimens correlate with early-onset pouchitis in UC and indeterminate colitis (IC). MATERIALS AND METHODS IPAA (2000-2018) cases with appendix blocks available in colectomy specimens were identified (n = 93, 90 UC, 3 IC). Histologic features thought to predict pouchitis were evaluated. The degree of appendiceal inflammation was scored. Calprotectin immunostain was performed on the appendix blocks and the extent of mucosal staining was quantified. Electronic medical records were reviewed for demographics, smoking history, clinical pouchitis, time of onset of pouchitis, and clinical and endoscopic components of the Pouchitis Disease Activity Index (PDAI) score. Follow-up pouch biopsies were reviewed and scored to generate histologic PDAI score, when available. RESULTS Among the patients with clinical pouchitis (n = 73), moderate to severe appendiceal inflammation independently correlated with earlier pouchitis compared to no/mild inflammation (median time to pouchitis 12.0 vs. 23.8, log rank p = 0.016). Calprotectin staining correlated with inflammatory scores of the appendix (Spearman's rho, r = 0.630, p < 0.001) but not with early pouchitis (p > 0.05). CONCLUSIONS The presence of moderate to severe appendiceal inflammation at the time of colectomy was associated with a shorter time to pouchitis following IPAA. Calprotectin immunostain may be used to demonstrate the presence of inflammation in the appendix but its role in predicting early pouchitis remains limited.
Collapse
Affiliation(s)
- Michel Kmeid
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
| | - Soe Htet Arker
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
| | - Adam Petchers
- Department of Surgery, Albany Medical Center, Albany, NY, USA.
| | | | - Hua Li
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
| | - Edward C Lee
- Department of Surgery, Albany Medical Center, Albany, NY, USA.
| | - Cary M Qualia
- Department of Pediatrics, Albany Medical Center, Albany, NY, USA.
| | - Mustafa Erdem Arslan
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
| | - Hwajeong Lee
- Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY, USA.
| |
Collapse
|
|
24
|
Jukic A, Bakiri L, Wagner EF, Tilg H, Adolph TE. Calprotectin: from biomarker to biological function. Gut 2021; 70:1978-1988. [PMID: 34145045 PMCID: PMC8458070 DOI: 10.1136/gutjnl-2021-324855] [Citation(s) in RCA: 226] [Impact Index Per Article: 56.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 06/02/2021] [Indexed: 12/15/2022]
Abstract
The incidence of inflammatory bowel diseases (IBD) emerged with Westernisation of dietary habits worldwide. Crohn's disease and ulcerative colitis are chronic debilitating conditions that afflict individuals with substantial morbidity and challenge healthcare systems across the globe. Since identification and characterisation of calprotectin (CP) in the 1980s, faecal CP emerged as significantly validated, non-invasive biomarker that allows evaluation of gut inflammation. Faecal CP discriminates between inflammatory and non-inflammatory diseases of the gut and portraits the disease course of human IBD. Recent studies revealed insights into biological functions of the CP subunits S100A8 and S100A9 during orchestration of an inflammatory response at mucosal surfaces across organ systems. In this review, we summarise longitudinal evidence for the evolution of CP from biomarker to rheostat of mucosal inflammation and suggest an algorithm for the interpretation of faecal CP in daily clinical practice. We propose that mechanistic insights into the biological function of CP in the gut and beyond may facilitate interpretation of current assays and guide patient-tailored medical therapy in IBD, a concept warranting controlled clinical trials.
Collapse
Affiliation(s)
- Almina Jukic
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Latifa Bakiri
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Erwin F Wagner
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
- Department of Dermatology, Medical University of Vienna, Vienna, Austria
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| | - Timon E Adolph
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medical University of Innsbruck, Innsbruck, Austria
| |
Collapse
|
|
25
|
Guillemard E, Poirel M, Schäfer F, Quinquis L, Rossoni C, Keicher C, Wagner F, Szajewska H, Barbut F, Derrien M, Malfertheiner P. A Randomised, Controlled Trial: Effect of a Multi-Strain Fermented Milk on the Gut Microbiota Recovery after Helicobacter pylori Therapy. Nutrients 2021; 13:nu13093171. [PMID: 34579049 PMCID: PMC8466689 DOI: 10.3390/nu13093171] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 08/27/2021] [Accepted: 09/07/2021] [Indexed: 12/21/2022] Open
Abstract
Helicobacter pylori (Hp) eradication therapy alters gut microbiota, provoking gastrointestinal (GI) symptoms that could be improved by probiotics. The study aim was to assess the effect in Hp patients of a Test fermented milk containing yogurt and Lacticaseibacillus (L. paracasei CNCM I-1518 and I-3689, L. rhamnosus CNCM I-3690) strains on antibiotic associated diarrhea (AAD) (primary aim), GI-symptoms, gut microbiota, and metabolites. A randomised, double-blind, controlled trial was performed on 136 adults under 14-day Hp treatment, receiving the Test or Control product for 28 days. AAD and GI-symptoms were reported and feces analysed for relative and quantitative gut microbiome composition, short chain fatty acids (SCFA), and calprotectin concentrations, and viability of ingested strains. No effect of Test product was observed on AAD or GI-symptoms. Hp treatment induced a significant alteration in bacterial and fungal composition, a decrease of bacterial count and alpha-diversity, an increase of Candida and calprotectin, and a decrease of SCFA concentrations. Following Hp treatment, in the Test as compared to Control group, intra-subject beta-diversity distance from baseline was lower (padj = 0.02), some Enterobacteriaceae, including Escherichia-Shigella (padj = 0.0082) and Klebsiella (padj = 0.013), were less abundant, and concentrations of major SCFA (p = 0.035) and valerate (p = 0.045) were higher. Viable Lacticaseibacillus strains were detected during product consumption in feces. Results suggest that, in patients under Hp treatment, the consumption of a multi-strain fermented milk can induce a modest but significant faster recovery of the microbiota composition (beta-diversity) and of SCFA production and limit the increase of potentially pathogenic bacteria.
Collapse
Affiliation(s)
- Eric Guillemard
- Danone Nutricia Research, Department of Innovation Science and Nutrition, 91767 Palaiseau, France; (M.P.); (F.S.); (L.Q.); (C.R.); (M.D.)
- Correspondence: ; Tel.: +33-6-29-12-63-64
| | - Marion Poirel
- Danone Nutricia Research, Department of Innovation Science and Nutrition, 91767 Palaiseau, France; (M.P.); (F.S.); (L.Q.); (C.R.); (M.D.)
| | - Florent Schäfer
- Danone Nutricia Research, Department of Innovation Science and Nutrition, 91767 Palaiseau, France; (M.P.); (F.S.); (L.Q.); (C.R.); (M.D.)
| | - Laurent Quinquis
- Danone Nutricia Research, Department of Innovation Science and Nutrition, 91767 Palaiseau, France; (M.P.); (F.S.); (L.Q.); (C.R.); (M.D.)
| | - Caroline Rossoni
- Danone Nutricia Research, Department of Innovation Science and Nutrition, 91767 Palaiseau, France; (M.P.); (F.S.); (L.Q.); (C.R.); (M.D.)
| | - Christian Keicher
- Charité Research Organisation GmbH, 10117 Berlin, Germany; (C.K.); (F.W.)
| | - Frank Wagner
- Charité Research Organisation GmbH, 10117 Berlin, Germany; (C.K.); (F.W.)
| | - Hania Szajewska
- Department of Paediatrics, Medical University of Warsaw, 02-091 Warszawa, Poland;
| | | | - Muriel Derrien
- Danone Nutricia Research, Department of Innovation Science and Nutrition, 91767 Palaiseau, France; (M.P.); (F.S.); (L.Q.); (C.R.); (M.D.)
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Magdeburg Clinic, OVGU University, 39120 Magdeburg, Germany;
- Department of Internal Medicine II, LMU University Clinic, 81377 München, Germany
| |
Collapse
|
|
26
|
A multicentre validation study of the diagnostic value of plasma neurofilament light. Nat Commun 2021; 12:3400. [PMID: 34099648 PMCID: PMC8185001 DOI: 10.1038/s41467-021-23620-z] [Citation(s) in RCA: 264] [Impact Index Per Article: 66.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 05/04/2021] [Indexed: 12/13/2022] Open
Abstract
Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King’s College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs. Cerebrospinal fluid neurofilament light (NfL) is a biomarker for neurodegeneration that can also be assessed in blood. Here the authors show in a validation study the potential for plasma NfL as a biomarker for several neurodegenerative diseases.
Collapse
|
|
27
|
Combined Use of Common Fecal and Blood Markers for Detection of Endoscopically Active Inflammatory Bowel Disease. Clin Transl Gastroenterol 2021; 11:e00138. [PMID: 32132451 PMCID: PMC7145039 DOI: 10.14309/ctg.0000000000000138] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Monitoring of disease activity is essential in patients with inflammatory bowel disease. Although endoscopic remission is the ideal therapeutic goal, noninvasive biomarkers (blood and fecal) are more acceptable to patients and are less costly. We evaluated the performance of combinations of fecal and blood markers on the detection of endoscopically active disease.
Collapse
|
|
28
|
Bromke MA, Neubauer K, Kempiński R, Krzystek-Korpacka M. Faecal Calprotectin in Assessment of Mucosal Healing in Adults with Inflammatory Bowel Disease: A Meta-Analysis. J Clin Med 2021; 10:jcm10102203. [PMID: 34069684 PMCID: PMC8161009 DOI: 10.3390/jcm10102203] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 05/12/2021] [Accepted: 05/15/2021] [Indexed: 12/12/2022] Open
Abstract
Achieving mucosal healing in patients with inflammatory bowel disease is related to a higher incidence of sustained clinical remission and it translates to lower rates of hospitalisation and surgery. The assessment methods of disease activity and response to therapy are limited and mainly rely on colonoscopy. This meta-analysis reviews the effectiveness of using faecal calprotectin as a marker for mucosal healing in inflammatory bowel disease. Two meta-analyses were conducted in parallel. The analysis on the use of faecal calprotectin in monitoring mucosal healing in colonic Crohn’s disease is based on 16 publications (17 studies). The data set for diagnostic values of faecal calprotectin in ulcerative colitis is composed of 35 original publications (total 49 studies). The DOR for the use of faecal calprotectin in Crohn’s disease is estimated to be 11.20 and the area under the sROCis 0.829. In cases of ulcerative colitis, the DOR is 14.48, while the AUC sROC is 0.858. Heterogeneity of the studies was moderatetosubstantial. Collected data show overall good sensitivity and specificity of the faecal calprotectin test, as well as a good DOR. Thus, monitoring of mucosal healing with a non-invasive faecal calprotectin test may represent an attractive option for physicians and patients with inflammatory bowel disease.
Collapse
Affiliation(s)
- Mariusz A. Bromke
- Department of Biochemistry and Immunochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368 Wroclaw, Poland;
- Correspondence:
| | - Katarzyna Neubauer
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (K.N.); (R.K.)
| | - Radosław Kempiński
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland; (K.N.); (R.K.)
| | - Małgorzata Krzystek-Korpacka
- Department of Biochemistry and Immunochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368 Wroclaw, Poland;
| |
Collapse
|
|
29
|
Kan YM, Chu SY, Loo CK. Diagnostic accuracy of fecal calprotectin in predicting significant gastrointestinal diseases. JGH OPEN 2021; 5:647-652. [PMID: 34124380 PMCID: PMC8171161 DOI: 10.1002/jgh3.12548] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/07/2021] [Accepted: 04/11/2021] [Indexed: 12/22/2022]
Abstract
Background and Aim It is often unreliable to triage patients for timely endoscopic investigations based on symptoms alone. We need an objective assessment to differentiate between organic gastrointestinal diseases and functional bowel symptoms. We evaluated the diagnostic accuracy of fecal calprotectin (FC) in predicting organic gastrointestinal diseases. Methods In a prospective observational study, consecutive patients referred for colonoscopy to the Department of Medicine and Geriatrics at the Kwong Wah Hospital in Hong Kong were recruited. Stool samples were collected within 24 h before colonoscopy. FC was measured by a commercial kit. Upper endoscopy investigations were then proceeded if normal colonoscopy but elevated FC. Results Two hundred and seventy out of 429 patients had FC above 50 μg/g. Eighty‐six out of 270 with elevated FC had significant colonoscopy pathological findings. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FC test for diagnosing a significant organic colonoscopy or upper endoscopy disease were 91.7, 55.6, 57.0, and 91.2%, respectively. The NPV of FC for colorectal cancer, high risk polyp, and colon inflammation were 98.7, 96.2, and 98.1%, respectively. The NPV of FC in the condition of altered bowel habit or abdominal pain in predicting colorectal cancer and inflammation were 93.8 and 100%, respectively. Conclusions FC is a reliable marker of ruling out organic bowel diseases. A single negative FC test could be used as a triage tool to prioritize the need and urgency of further investigation, particularly in the setting of altered bowel habits and abdominal pain.
Collapse
Affiliation(s)
- Yee Man Kan
- Department of Medicine and Geriatrics Kwong Wah Hospital Kowloon Hong Kong
| | - Sin Yan Chu
- Department of Pathology Kwong Wah Hospital Kowloon Hong Kong
| | - Ching Kong Loo
- Department of Medicine and Geriatrics Kwong Wah Hospital Kowloon Hong Kong
| |
Collapse
|
|
30
|
D'Amico F, Rubin DT, Kotze PG, Magro F, Siegmund B, Kobayashi T, Olivera PA, Bossuyt P, Pouillon L, Louis E, Domènech E, Ghosh S, Danese S, Peyrin‐Biroulet L. International consensus on methodological issues in standardization of fecal calprotectin measurement in inflammatory bowel diseases. United European Gastroenterol J 2021; 9:451-460. [PMID: 33961734 PMCID: PMC8259254 DOI: 10.1002/ueg2.12069] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 02/26/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Fecal calprotectin (FC) is a non-invasive marker of gut inflammation which is frequently used to guide therapeutic decisions in patients with inflammatory bowel diseases (IBD). Each step of FC measurement can influence the results, leading to misinterpretations and potentially impacting the management of IBD patients. To date, there is high heterogeneity between FC measurements and no current method is universally accepted as a standard. AIMS Our aim was to provide clear position statementsabout the pre-analytical and the analytical phases of FC measurement to homogenize FC levels and to minimize variability and risk of misinterpretation through aninternational consensus. MATERIALS & METHODS Fourteen physicians with expertise in the field of IBD and FC from 11 countries attended a virtual international consensus meeting on July 17th, 2020. A systematic literature was conducted and the literature evidence was shared and discussedamong the participants. Statements were formulated, discussed, and voted. Statements were considered approved if all participants agreed. RESULTS Nine statements were formulated and approved. Based on the available evidence, quantitative tests should be preferred for measuring FC. Furthermore, FC measurement, if possible, should always be performed with the same method and factors influencing FC levels should be taken into account when interpreting the results. DISCUSSION FC has an increasingly important role in the management of patients with IBD. However, large multicenter studies should be conducted to define the reproducibility and to confirm the diagnostic accuracy of the available FC tests. CONCLUSION FC concentrations guide clinicians' treatment decisions. Our statements have a relevant impact in daily practice and could be applied in clinical trials to standardize FC measurement.
Collapse
Affiliation(s)
- Ferdinando D'Amico
- Department of Biomedical SciencesHumanitas UniversityMilanItaly
- Department of Gastroenterology and Inserm U1256Nutrition – Genetics and Exposure to Environmental RisksUniversity Hospital of NancyUniversity of LorraineVandoeuvre‐lès‐NancyFrance
| | - David T. Rubin
- Section of Gastroenterology, Hepatology and NutritionUniversity of Chicago Department of MedicineChicagoIllinoisUSA
| | | | - Fernando Magro
- Department of GastroenterologyCentro Hospitalar São JoãoPortoPortugal
| | - Britta Siegmund
- Medizinische Klinik m. S. Gastroenterologie, Infektiologie und RheumatologieCharité ‐ Universitätsmedizin BerlinCorporate Member of Freie Universität BerlinHumboldt‐Universität zu Berlinand Berlin Institute of HealthBerlinGermany
| | - Taku Kobayashi
- Center for Advanced IBD Research and TreatmentKitasato University Kitasato Institute HospitalTokyoJapan
| | - Pablo A. Olivera
- Gastroenterology SectionDepartment of Internal MedicineCentro de Educación Médica e Investigaciones Clínicas (CEMIC)Buenos AiresArgentina
| | - Peter Bossuyt
- Imelda GI Clinical Research CenterImelda General HospitalBonheidenBelgium
| | - Lieven Pouillon
- Imelda GI Clinical Research CenterImelda General HospitalBonheidenBelgium
| | - Edouard Louis
- Department of GastroenterologyCHU Liège University HospitalLiègeBelgium
| | - Eugeni Domènech
- Gastroenterology DepartmentHospital Universitari Germans Trias i PujolBadalonaCataloniaSpain
- Departament de MedicinaUniversitat Autònoma de BarcelonaBarcelonaSpain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)MadridSpain
| | - Subrata Ghosh
- NIHR Biomedical Research CentreUniversity of Birmingham and University Hospitals NHS Foundation TrustBirminghamUK
| | - Silvio Danese
- Department of Biomedical SciencesHumanitas UniversityMilanItaly
- IBD CenterHumanitas Research HospitalIRCCSMilanItaly
| | - Laurent Peyrin‐Biroulet
- Department of Gastroenterology and Inserm U1256Nutrition – Genetics and Exposure to Environmental RisksUniversity Hospital of NancyUniversity of LorraineVandoeuvre‐lès‐NancyFrance
| |
Collapse
|
|
31
|
Westerink F, Huibregtse I, De Hoog M, Bruin S, Meesters E, Brandjes D, Gerdes V. Faecal Inflammatory Biomarkers and Gastrointestinal Symptoms after Bariatric Surgery: A Longitudinal Study. Inflamm Intest Dis 2021; 6:109-116. [PMID: 34124182 DOI: 10.1159/000514576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 12/29/2020] [Indexed: 11/19/2022] Open
Abstract
Background Bariatric surgery induces various gastrointestinal (GI) modifications. We performed the first study longitudinally assessing the effect of bariatric surgery on faecal inflammatory biomarker levels and its relation with GI complaints. Method Faecal calprotectin, lactoferrin, and calgranulin-C levels were determined in 41 patients (34 Roux-en-Y [RYGB], 7 sleeves) before and at 6-16 weeks, 6 months, and 1 year after surgery. Changes in biomarker levels and percentage of patients above reference value were determined. Gastrointestinal symptom rating scale (GSRS) was used to assess GI complaints at corresponding time points. The postoperative relation between GSRS score and biomarker levels above reference value was investigated. Results After RYGB, median calprotectin levels are significantly higher (>188, 104-415 μg/g) than before surgery (40, 19-78 μg/g; p < 0.001), and over 90% of patients have levels above reference value 1 year after surgery. Median lactoferrin was 0.4 (0.2-1.6) μg/g before, and >5.9 (1.8-13.6) μg/g after surgery (p < 0.001). Median calgranulin-C levels remained far below the reference value and were 0.13 (0.05-0.24) μg/g before and <0.23 (0.06-0.33) μg/g after surgery. Similar results were found after sleeve gastrectomy. No difference was seen in GSRS score for patients with calprotectin and lactoferrin levels above reference values. Conclusion Faecal inflammatory biomarkers calprotectin and lactoferrin, but not calgranulin-C, rise above reference values shortly after bariatric surgery and remain elevated in the majority of patients. The discrepancy between calprotectin and calgranulin-C levels suggests no GI inflammation. Furthermore, patients after RYGB with biomarkers above the population reference value do not seem to have more GI complaints.
Collapse
Affiliation(s)
- Floris Westerink
- Department of internal medicine, Amsterdam University Medical Centre, Amsterdam, The Netherlands
| | - Inge Huibregtse
- Department of gastroenterology, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, The Netherlands
| | | | - Sjoerd Bruin
- Department of surgery, Spaarne Gasthuis, Hoofddorp, The Netherlands
| | - Eelco Meesters
- Department of internal medicine, Spaarne Gasthuis, Hoofddorp, The Netherlands
| | - Desiderius Brandjes
- Department of internal medicine, Amsterdam University Medical Centre, Amsterdam, The Netherlands
| | - Victor Gerdes
- Department of internal medicine, Amsterdam University Medical Centre, Amsterdam, The Netherlands.,Department of internal medicine, Spaarne Gasthuis, Hoofddorp, The Netherlands
| |
Collapse
|
|
32
|
Lamot L, Miler M, Vukojević R, Vidović M, Lamot M, Trutin I, Gabaj NN, Harjaček M. The Increased Levels of Fecal Calprotectin in Children With Active Enthesitis Related Arthritis and MRI Signs of Sacroiliitis: The Results of a Single Center Cross-Sectional Exploratory Study in Juvenile Idiopathic Arthritis Patients. Front Med (Lausanne) 2021; 8:650619. [PMID: 33763437 PMCID: PMC7982855 DOI: 10.3389/fmed.2021.650619] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 02/15/2021] [Indexed: 12/22/2022] Open
Abstract
Enthesitis related arthritis (ERA) is a specific subtype of juvenile idiopathic arthritis (JIA), often regarded as an undifferentiated form of juvenile spondyloarthritis (jSpA). While gut is increasingly recognized as origin and/or target of inflammation in adult onset spondyloarthritis (SpA), the incidence of gut involvement in ERA patients is largely unknown. The aim of this study was to measure the concentration of fecal calprotectin (fCAL), a surrogate marker of gut inflammation, in patients with different subtypes of JIA, as well as to correlate the results with various demographic, clinical, laboratory, imaging, and treatment characteristics. The cross-sectional exploratory study involving 71 patients with ERA, other forms of JIA and children complaining musculoskeletal symptoms was therefore conducted. Along with fCAL assessment, a detailed clinical and laboratory examination was performed, including the calculation of a composite disease activity scores. Moreover, MRI of the sacroiliac joints was performed in all ERA and other patients complaining of low back pain. The median concentration of fCAL was highest in ERA patients (33.2 mg/kg, p = 0.02), with a significant difference between those with inactive and active disease (20.0 vs. 57.4, p = 0.01), as well as those with and without MRI signs of sacroiliitis (22.6 vs. 54.3, p = 0.04). The fCAL did not differ depending on the NSAID use (23 vs. 20, p = 0.18), although weak correlation was observed with the treatment duration (r = 0.25, p = 0.03). In conclusion, our findings indicate that a parallel inflammation in musculoskeletal system and gut can occur not just in adults with SpA, but in children with ERA as well.
Collapse
Affiliation(s)
- Lovro Lamot
- Division of Clinical Immunology and Rheumatology, Department of Pediatrics, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia.,Department of Pediatrics, University of Zagreb School of Medicine, Zagreb, Croatia
| | - Marijana Miler
- Universirty Department of Chemistry, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia
| | - Rudolf Vukojević
- Department of Diagnostic and Interventional Radiology, Sestre Milosrdnice University Hospital Center, University of Zagreb, Zagreb, Croatia
| | - Mandica Vidović
- Division of Clinical Immunology and Rheumatology, Department of Pediatrics, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia
| | - Mirta Lamot
- Division of Neonatology, Department of Gynecology and Obstetrics, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia
| | - Ivana Trutin
- Division of Nephrology and Cardiology, Department of Pediatrics, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia
| | - Nora Nikolac Gabaj
- Universirty Department of Chemistry, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia
| | - Miroslav Harjaček
- Division of Clinical Immunology and Rheumatology, Department of Pediatrics, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia.,Department of Pediatrics, University of Zagreb School of Medicine, Zagreb, Croatia
| |
Collapse
|
|
33
|
Hovstadius H, Lundgren D, Karling P. Elevated Faecal Calprotectin in Patients with a Normal Colonoscopy: Does It Matter in Clinical Practice? A Retrospective Observational Study. Inflamm Intest Dis 2021; 6:101-108. [PMID: 34124181 DOI: 10.1159/000513473] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 11/20/2020] [Indexed: 12/24/2022] Open
Abstract
Introduction Faecal calprotectin (FC) is commonly used as a diagnostic tool for patients with gastrointestinal (GI) symptoms. However, there is uncertainty in daily clinical practice how to interpret an elevated FC in patients with a normal colonoscopy. We investigated if patients with a normal colonoscopy but with an elevated FC more often were diagnosed with a GI disease in a 3-year follow-up period. Methods Patients referred for colonoscopy (n = 1,263) to the Umeå University Hospital endoscopy unit between 2007 and 2013 performed a FC test (CALPRO®) on the day before bowel preparation. A medical chart review was performed on all patients who had normal findings on their colonoscopy (n = 585, median age 64 years). Results Thirty-four percent of the patients (n = 202) with normal colonoscopy had elevated FC (>50 μg/g), and these patients were more frequently diagnosed with upper GI disease during the follow-up period than patients with normal FC levels (9.9 vs. 4.7%; p = 0.015). The upper GI diseases were mainly benign (i.e., gastritis). In a binary logistic regression analysis controlling for age, gender, nonsteroid anti-inflammatory drug use, and proton-pump inhibitor use, there was no difference for a new diagnosis of upper GI disease in the follow-up period (multivariate OR 1.70; 95% CI: 0.77-3.74). There was no difference in a new diagnosis of lower GI disease (6.4 vs. 5.2%; p = 0.545) or cardiovascular disease/death (multivariate OR 1.68; 95% CI: 0.83-3.42) in the follow-up period between patients with elevated versus normal FC levels. Conclusions In patients with a normal colonoscopy, a simultaneously measured increased FC level was not associated with an increased risk for significant GI disease during a follow-up period of 3 years.
Collapse
Affiliation(s)
- Henrik Hovstadius
- Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden
| | - David Lundgren
- Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden
| | - Pontus Karling
- Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden
| |
Collapse
|
|
34
|
Lężyk-Ciemniak E, Tworkiewicz M, Wilczyńska D, Szaflarska-Popławska A, Krogulska A. Usefulness of Testing for Fecal Calprotectin in Pediatric Gastroenterology Clinical Practice. Med Princ Pract 2021; 30:311-319. [PMID: 33120396 PMCID: PMC8436627 DOI: 10.1159/000512631] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 10/25/2020] [Indexed: 01/11/2023] Open
Abstract
Gastrointestinal tract symptoms such as abdominal pain, constipation, diarrhea, and fever are common reasons for which parents take children to the pediatrician. An increasing prevalence of chronic diseases of the gastrointestinal tract and a decrease in the median age of their onset indicate the need to search for new diagnostic methods for differentiating inflammatory bowel diseases (IBDs) from other gastrointestinal tract diseases. An example of a novel biomarker is fecal calprotectin (FC), which is considered a noninvasive and useful marker of intestinal inflammation. This review summarizes currently available information on the use of FC in the diagnosis and monitoring of IBD in children. Additionally, it attempts to determine the course of action depending on the concentration of FC. Application of FC determination within the framework of primary medical care can decrease the number of children unnecessarily referred either to endoscopic or radiologic examination. There is a double advantage of calprotectin screening; for patients, it reduces delays in diagnosis and unnecessary exposure to endoscopy, and for doctors, it reduces pressure on endoscopy testing and facilitates decision-making. We emphasize the role of FC as a noninvasive marker, primarily in patients with IBD, in monitoring disease activity, predicting relapse, monitoring therapy efficacy, and monitoring postoperative relapses.
Collapse
Affiliation(s)
- Eliza Lężyk-Ciemniak
- Department of Pediatrics, Allergology and Gastroenterology Collegium Medicum Bydgoszcz, NCU Toruń, Bydgoszcz, Poland
| | - Magdalena Tworkiewicz
- Department of Pediatrics, Allergology and Gastroenterology Collegium Medicum Bydgoszcz, NCU Toruń, Bydgoszcz, Poland
| | - Dominika Wilczyńska
- Department of Pediatrics, Allergology and Gastroenterology Collegium Medicum Bydgoszcz, NCU Toruń, Bydgoszcz, Poland
| | - Anna Szaflarska-Popławska
- Department of Pediatric Endoscopy and Gastrointestinal Function Testing, NCU Toruń, Bydgoszcz, Poland
| | - Aneta Krogulska
- Department of Pediatrics, Allergology and Gastroenterology Collegium Medicum Bydgoszcz, NCU Toruń, Bydgoszcz, Poland
| |
Collapse
|
|
35
|
Ma T, Wu M, Jia S, Yang L. Proton pump inhibitors and the risk of colorectal cancer: a systematic review and meta-analysis of observational studies. Int J Colorectal Dis 2020; 35:2157-2169. [PMID: 32808072 DOI: 10.1007/s00384-020-03717-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/14/2020] [Indexed: 02/04/2023]
Abstract
PURPOSE The increased risk of colorectal cancer (CRC) associated with long-term use of proton pump inhibitors (PPIs) has attracted considerable attention; however, the conclusions of studies evaluating this correlation are inconsistent or even controversial. Therefore, we conducted a systematic review and meta-analysis to determine the association of PPI use with the risk of CRC. METHODS A systematic literature search was conducted in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials to identify relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for the associations between PPI use and the risk of CRC were estimated with a fixed-effects or random-effects model. RESULTS We identified and included 9 observational studies (3 cohort studies and 6 case-control studies) comprising 1,036,438 participants. Overall, there was no statistically significant association between PPI use and the risk of CRC (pooled OR 1.26, 95% CI: 0.90-1.73; p = 0.166) when PPI exposure was assessed as a binary variable. However, a weak association between long-term use of PPIs and CRC was demonstrated (pooled OR 1.19, 95% CI: 1.09-1.31; p < 0.001) when the cumulative duration of PPI exposure was confined to > 5 years. CONCLUSIONS Although the present meta-analysis suggests a weak association between long-term use (> 5 years) of PPIs and CRC, there is not enough statistical power to refute or confirm an association between the use of PPIs and CRC. More high-quality prospective cohort studies are needed to assess this correlation.
Collapse
Affiliation(s)
- Tianyi Ma
- Department of Hepatopancreatobiliary Medicine, The Second Hospital of Jilin University, No. 218 Ziqiang Road, Changchun, Jilin, 130000, China
| | - Meng Wu
- Department of Hepatopancreatobiliary Medicine, The Second Hospital of Jilin University, No. 218 Ziqiang Road, Changchun, Jilin, 130000, China
| | - Shengnan Jia
- Department of Hepatopancreatobiliary Medicine, The Second Hospital of Jilin University, No. 218 Ziqiang Road, Changchun, Jilin, 130000, China
| | - Lanlan Yang
- Department of Hepatopancreatobiliary Medicine, The Second Hospital of Jilin University, No. 218 Ziqiang Road, Changchun, Jilin, 130000, China.
| |
Collapse
|
|
36
|
Ebrahimi B, Nazarinia M, Molayem M. Calprotectin, an available prognostic biomarker in systemic sclerosis: a systematic review. Clin Rheumatol 2020; 40:1709-1715. [PMID: 33044726 DOI: 10.1007/s10067-020-05446-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 10/01/2020] [Accepted: 10/05/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Finding easier and less invasive biologic biomarker in the clinical specimen of systemic sclerosis (SSc) patients can be effective in diagnosing and treating SSc-associated multisystem diseases. The complex of S100A8 and S100A9 (Calprotectin) is an easily available prognostic biomarker that secretes from immune cells and is necessary for initiating the immune response to noninfectious inflammation processes. The present study aims to evaluate the effectiveness of Calprotectin in specimen of SSc patients. We reviewed the evidence for Calprotectin in diagnostic and prognostic of SSc patients. METHODS This systematic review was done to identify studies on "Calprotectin" within "SSc" patients. PubMed, Web of knowledge, and Scopus were searched for this purpose. A standardized form was used to extract diseases, sample size, biomarkers identified, source of biomarker, and its effects. RESULTS Overall, the 16 articles selected show that the main sources of Calprotectin were plasma, bronchoalveolar lavage fluid, and especially stool. CONCLUSION The best source of Calprotectin was fecal Calprotectin that could show the inflammation and small intestinal bacterial overgrowth (SIBO) on SSc patients. Also, the most arguable source is plasma because of its low sample size. Comparing the Calprotectin level in different rheumatic diseases showed the specificity of fecal Calprotectin for SSc disease. Nevertheless, it has to be noted that Calprotectin correlates with some other factors such as age, PIP drug, and nonsteroidal anti-inflammatory drugs.
Collapse
Affiliation(s)
- Bahareh Ebrahimi
- Shiraz Geriatric Research Center, Shiraz University of Medical Sciences, Shiraz, 71936-35899, Iran
| | - MohamadAli Nazarinia
- Shiraz Geriatric Research Center, Shiraz University of Medical Sciences, Shiraz, 71936-35899, Iran.
- Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Mina Molayem
- Shiraz Geriatric Research Center, Shiraz University of Medical Sciences, Shiraz, 71936-35899, Iran
| |
Collapse
|
|
37
|
Scarpignato C, Hongo M, Wu JCY, Lottrup C, Lazarescu A, Stein E, Hunt RH. Pharmacologic treatment of GERD: Where we are now, and where are we going? Ann N Y Acad Sci 2020; 1482:193-212. [PMID: 32935346 DOI: 10.1111/nyas.14473] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 07/20/2020] [Accepted: 07/30/2020] [Indexed: 02/06/2023]
Abstract
The introduction of acid inhibition in clinical practice has revolutionized the management of acid-related diseases, leading to the virtual abolition of elective surgery for ulcer disease and relegating antireflux surgery to patients with gastroesophageal reflux disease (GERD) not adequately managed by medical therapy. Proton pump inhibitors (PPIs) are the antisecretory drugs of choice for the treatment of reflux disease. However, these drugs still leave some unmet clinical needs in GERD. PPI-refractoriness is common, and persistent symptoms are observed in up to 40-55% of daily PPI users. Potassium-competitive acid blockers (P-CABs) clearly overcome many of the drawbacks and limitations of PPIs, achieving rapid, potent, and prolonged acid suppression, offering the opportunity to address many of the unmet needs. In recent years, it has been increasingly recognized that impaired mucosal integrity is involved in the pathogenesis of GERD. As a consequence, esophageal mucosal protection has emerged as a new, promising therapeutic avenue. When P-CABS are used as add-on medications to standard treatment, a growing body of evidence suggests a significant additional benefit, especially in the relief of symptoms not responding to PPI therapy. On the contrary, reflux inhibitors are considered a promise unfulfilled, and prokinetic agents should only be used on a case-by-case basis.
Collapse
Affiliation(s)
- Carmelo Scarpignato
- Department of Health Sciences, United Campus of Malta, Msida, Malta.,Faculty of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong
| | - Michio Hongo
- Department of Comprehensive Medicine, Tohoku University, Sendai, Miyagi, Japan
| | - Justin C Y Wu
- Department of Medicine and Therapeutics, Prince of Wales Hospital, Shatin, Hong Kong, China
| | - Christian Lottrup
- Department of Medicine, Aalborg University Hospital, Hobro, Denmark.,Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmak
| | - Adriana Lazarescu
- Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
| | - Ellen Stein
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland
| | - Richard H Hunt
- Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| |
Collapse
|
|
38
|
Stadlbauer V, Engertsberger L, Komarova I, Feldbacher N, Leber B, Pichler G, Fink N, Scarpatetti M, Schippinger W, Schmidt R, Horvath A. Dysbiosis, gut barrier dysfunction and inflammation in dementia: a pilot study. BMC Geriatr 2020; 20:248. [PMID: 32690030 PMCID: PMC7372911 DOI: 10.1186/s12877-020-01644-2] [Citation(s) in RCA: 110] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Accepted: 07/09/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Dementia is an increasing public health threat worldwide. The pathogenesis of dementia has not been fully elucidated yet. Inflammatory processes are hypothesized to play an important role as a driver for cognitive decline but the origin of inflammation is not clear. We hypothesize that disturbances in gut microbiome composition, gut barrier dysfunction, bacterial translocation and resulting inflammation are associated with cognitive dysfunction in dementia. METHODS To test this hypothesis, a cohort of 23 patients with dementia and 18 age and sex matched controls without cognitive impairments were studied. Gut microbiome composition, gut barrier dysfunction, bacterial translocation and inflammation were assessed from stool and serum samples. Malnutrition was assessed by Mini Nutritional Assessment Short Form (MNA-SF), detailed information on drug use was collected. Microbiome composition was assessed by 16S rRNA sequencing, QIIME 2 and Calypso 7.14 tools. RESULTS Dementia was associated with dysbiosis characterized by differences in beta diversity and changes in taxonomic composition. Gut permeability was increased as evidenced by increased serum diamine oxidase (DAO) levels and systemic inflammation was confirmed by increased soluble cluster of differentiation 14 levels (sCD14). BMI and statin use had the strongest impact on microbiome composition. CONCLUSION Dementia is associated with changes in gut microbiome composition and increased biomarkers of gut permeability and inflammation. Lachnospiraceae NK4A136 group as potential butyrate producer was reduced in dementia. Malnutrition and drug intake were factors, that impact on microbiome composition. Increasing butyrate producing bacteria and targeting malnutrition may be promising therapeutic targets in dementia. TRIAL REGISTRATION NCT03167983 .
Collapse
Affiliation(s)
- Vanessa Stadlbauer
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria. .,Center of Biomarker Research in Medicine (CBmed), Graz, Austria.
| | - Lara Engertsberger
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria
| | - Irina Komarova
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria
| | - Nicole Feldbacher
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.,Center of Biomarker Research in Medicine (CBmed), Graz, Austria
| | - Bettina Leber
- Department of Surgery, Division of Transplantation Surgery, Medical University of Graz, Graz, Austria
| | - Gerald Pichler
- Department of Neurology, Geriatric Health Centers Graz, Albert Schweitzer Hospital, Graz, Austria
| | - Nicole Fink
- Department of Neurology, Geriatric Health Centers Graz, Albert Schweitzer Hospital, Graz, Austria
| | - Monika Scarpatetti
- Department of Neurology, Geriatric Health Centers Graz, Albert Schweitzer Hospital, Graz, Austria
| | - Walter Schippinger
- Department of Neurology, Geriatric Health Centers Graz, Albert Schweitzer Hospital, Graz, Austria
| | - Reinhold Schmidt
- Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria
| | - Angela Horvath
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.,Center of Biomarker Research in Medicine (CBmed), Graz, Austria
| |
Collapse
|
|
39
|
Krzystek-Korpacka M, Kempiński R, Bromke M, Neubauer K. Biochemical Biomarkers of Mucosal Healing for Inflammatory Bowel Disease in Adults. Diagnostics (Basel) 2020; 10:E367. [PMID: 32498475 PMCID: PMC7344443 DOI: 10.3390/diagnostics10060367] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 05/29/2020] [Accepted: 05/30/2020] [Indexed: 02/06/2023] Open
Abstract
Mucosal healing (MH) is the key therapeutic target of inflammatory bowel disease (IBD). The evaluation of MH remains challenging, with endoscopy being the golden standard. We performed a comprehensive overview of the performance of fecal-, serum-, and urine-based biochemical markers in colonic IBD to find out whether we are ready to replace endoscopy with a non-invasive but equally accurate instrument. A Pubmed, Web of Knowledge, and Scopus search of original articles as potential MH markers in adults, published between January 2009 and March 2020, was conducted. Finally, 84 eligible studies were identified. The most frequently studied fecal marker was calprotectin (44 studies), with areas under the curves (AUCs) ranging from 0.70 to 0.99 in ulcerative colitis (UC) and from 0.70 to 0.94 in Crohn`s disease (CD), followed by lactoferrin (4 studies), matrix metalloproteinase-9 (3 studies), and lipocalin-2 (3 studies). The most frequently studied serum marker was C-reactive protein (30 studies), with AUCs ranging from 0.60 to 0.96 in UC and from 0.64 to 0.93 in CD. Fecal calprotectin is an accurate MH marker in IBD in adults; however, it cannot replace endoscopy and the application of calprotectin is hampered by the lack of standardization concerning the cut-off value. Other markers are either not sufficiently accurate or have not been studied extensively enough.
Collapse
Affiliation(s)
| | - Radosław Kempiński
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland;
| | - Mariusz Bromke
- Department of Medical Biochemistry, Wroclaw Medical University, Chalubinskiego 10, 50-368 Wroclaw, Poland;
| | - Katarzyna Neubauer
- Department of Gastroenterology and Hepatology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland;
| |
Collapse
|
|
40
|
Egea Valenzuela J, Iglesias Jorquera E, Álvarez-Higueras FJ, Muñoz Tornero M, Pereñíguez López A, Estrella Díez E, Alberca de las Parras F. Factors associated with the presence of abnormal levels of fecal calprotectin in patients with negative panenteric studies. REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS 2020; 112. [DOI: 10.17235/reed.2020.6508/2019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
|
|
41
|
Kang B. Can proton pump inhibitors cause intestinal inflammation in children? KOREAN JOURNAL OF PEDIATRICS 2019; 62:384-385. [PMID: 31623419 PMCID: PMC6801195 DOI: 10.3345/kjp.2019.00878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 10/02/2019] [Indexed: 11/27/2022]
Affiliation(s)
- Ben Kang
- Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea
| |
Collapse
|
|
42
|
Abstract
Inflammatory bowel disease (IBD) denotes a group of chronic incurable disorders characterized by relapsing-remitting inflammation of the gastrointestinal tract. IBD represents a growing global burden with a prevalence exceeding 0.3% in the Western world and an accelerating incidence in newly industrialized countries. The target for treating IBD has shifted in recent years from symptom control to mucosal healing (MH), which has been shown to be associated with favorable long-term outcomes. The gold standard for ascertaining MH is endoscopic assessment, but endoscopy is limited by its invasive nature, high cost, and finite availability. Surrogate biomarkers are therefore of great utility. Calprotectin, a cytosolic protein derived predominantly from neutrophils, is now widely used in this capacity. Calprotectin is found in various bodily fluids at concentrations proportional to the degree of inflammation, including in feces at levels roughly six times higher than in the blood. Fecal calprotectin (FCP) therefore reflects intestinal inflammation. Various assays, including point-of-care and home-based tests, are now available for measuring FCP. FCP is used for screening purposes, to aid in distinguishing inflammatory from non-inflammatory gastrointestinal conditions like irritable bowel syndrome (IBS), as well as in the monitoring of known IBD. The aims of this review are to provide an overview of the methods used to measure FCP and to review the evidence supporting the use of FCP in IBD, particularly as it pertains to screening, monitoring and predicting disease relapse.
Collapse
Affiliation(s)
- Amanda Ricciuto
- a Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children , University of Toronto , Toronto , Canada
| | - Anne M Griffiths
- a Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children , University of Toronto , Toronto , Canada
| |
Collapse
|