Publications by authors named "Kamran Rostami"

102 Publications

Prevalence and outcome of COVID-19 among Iranian celiac patients.

Gastroenterol Hepatol Bed Bench 2022 ;15(2):153-157

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aim: This study aimed to evaluate the prevalence and outcome of COVID-19 among Iranian celiac disease patients.

Background: Patients with celiac disease (CD) might be at greater risk for opportunistic viral infections. Coronavirus disease-2019 (COVID-19) is a new coronavirus (SARS-CoV-2) cause of respiratory disorder which spread around the world at the end of 2019. The question is does COVID-19 infection increase the risk of severe outcome and/or a higher mortality in treated celiac disease?.

Methods: Data regarding demographic details, clinical history, and COVID-19 infection symptoms among treated celiac disease patients was collected from July 2020 to January 2021 and analyzed using SPSS version 25.

Results: A total of 455 celiac disease patients were included in this study. The prevalence of Covid-19 infection among celiac disease patients was 2.4%. Infection among women (72.7%) was higher than the men, and only one overweight man who smoked was hospitalized. Among COVID-19 infected celiac disease patients, the most common symptoms were myalgia 90.9% (10/11), fever, body trembling, headache, shortness of breath, loss of smell and taste, and anorexia (72.7%). Treatments for COVID-19, included antibiotics (90.9%), pain analgesics (54.5%), antihistamines (27.3%), antivirals (9.1%) and hydroxychloroquine (9.1%).

Conclusion: This study shows that treated celiac disease is not a risk factor for severity or higher mortality in patients infected with COVID-19. Women, however, might need extra-protection to prevent COVID-19 infection.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275738PMC
January 2022

Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.

Nutrients 2022 Jun 15;14(12). Epub 2022 Jun 15.

Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN 55907, USA.

Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in μm), crypt depth (CrD, in μm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. The median VH in NCGS was significantly shorter (600, IQR: 400-705) than controls (900, IQR: 667-1112) ( < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390-620) vs. 427 µm (IQR: 348-569, = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls ( < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. : NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.
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http://dx.doi.org/10.3390/nu14122487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230100PMC
June 2022

Is duodenal biopsy always necessary for the diagnosis of coeliac disease in adult patients with high anti-tissue transglutaminase (TTG) antibody titres?

Frontline Gastroenterol 2022 25;13(4):287-294. Epub 2021 Jun 25.

Gastroenterology and Hepatology, Middlemore Hospital - Counties Manukau DIstrict Health Board (CMDH), Auckland, New Zealand.

Objective: Avoiding duodenal biopsy in adults for coeliac disease (CD) diagnosis is controversial. Some retrospective and prospective studies have shown that CD can be reliably diagnosed in adults with serology rather than duodenal biopsies. This study aimed to check the accuracy of a cut-off value of ≥10 upper limit of normal of anti-tissue transglutaminase antibody (anti-TTG IgA) titres for CD diagnosis in adult patients.

Method: We retrospectively analysed adult patients (≥16 years) who underwent gastroscopy from 2013 to 2018 for positive coeliac serology. The relationship between titres and disease was determined by using linear models, whereas sensitivity and specificity were assessed by receiver operator curve.

Results: We analysed 144 newly anti-TTG antibody-positive adult patients with a median age of 48.5 years (IQR 32-62); among them, 86 (60%) patients had CD (Marsh III: n=68 and Marsh II and I: n=18) with a higher prevalence in females (n=59 (69%)) and Europeans (n=60 (70%)). Fifty (58%) patients with CD had colonoscopy and five (6%) had imaging; only six patients were diagnosed with additional conditions. An anti-TTG IgA titre cut-off value of 150 U/L was 100% specific for CD in our dataset, with 70% (95% CI: 60% to 88%) sensitivity for this patient group.

Conclusion: Coeliac serology using anti-TTG IgA with titres ≥10× normal value is an excellent predictor of CD, irrespective of age, gender and ethnicity. Duodenal biopsy may not be necessary in selected adult patients with CD, especially younger than 50 years of age without additional gastrointestinal red-flag signs and symptoms.
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http://dx.doi.org/10.1136/flgastro-2020-101728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9186042PMC
June 2021

Nomenclature and diagnosis of seronegative coeliac disease and chronic non-coeliac enteropathies in adults: the Paris consensus.

Gut 2022 Jun 8. Epub 2022 Jun 8.

Dipartimento di Medicina Interna e Terapia Medica, University of Pavia, Pavia, Italy.

Objective: Differential diagnosis of villous atrophy (VA) without coeliac antibodies in adults includes seronegative coeliac disease (CD) and chronic enteropathies unrelated to gluten, ie. non-coeliac enteropathies (NCEs). There is currently no international consensus on the nomenclature and diagnostic criteria for these enteropathies. In this work, a Delphi process was conducted to address this diagnostic and clinical uncertainty.

Design: An international task force of 13 gastroenterologists from six countries was recruited at the 16th International Coeliac Disease Symposium, Paris, 2019. Between September 2019 and July 2021, a Delphi process was conducted through mail surveys to reach a consensus on which conditions to consider in the differential diagnosis of VA with negative coeliac serology and the clinical diagnostic approaches required for these conditions. A 70% agreement threshold was adopted.

Results: Chronic enteropathies characterised by VA and negative coeliac serology can be attributed to two main clinical scenarios: forms of CD presenting with negative serology, which also include seronegative CD and CD associated with IgA deficiency, and NCEs, with the latter recognising different underlying aetiologies. A consensus was reached on the diagnostic criteria for NCEs assisting clinicians in differentiating NCEs from seronegative CD. Although in adults seronegative CD is the most common aetiology in patients with VA and negative serology, discriminating between seronegative CD and NCEs is key to avoid unnecessary lifelong gluten-free diet, treat disease-specific morbidity and contrast poor long-term outcomes.

Conclusion: This paper describes the Paris consensus on the definitions and diagnostic criteria for seronegative CD and chronic NCEs in adults.
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http://dx.doi.org/10.1136/gutjnl-2021-326645DOI Listing
June 2022

Toward finding the difference between untreated celiac disease and COVID-19 infected patients in terms of CD4, CD25 (IL-2 Rα), FOXP3 and IL-6 expressions as genes affecting immune homeostasis.

BMC Gastroenterol 2021 Dec 11;21(1):462. Epub 2021 Dec 11.

Research Laboratories, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy.

Background: Coronavirus disease 2019 (COVID-19) is defined as an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 and celiac disease (CD) is one of the autoimmune multiorgan diseases, which can be accompanied by an increased risk of viral infections. CD patients, especially untreated subjects, may be at greater risk of infections such as viral illnesses. Interleukin (IL)-6, CD4, CD25, and FOXP3 are known as genes affecting immune homeostasis and relate to the inflammation state. This study aimed to compare the expression levels of aforementioned genes in peripheral blood samples of CD and severe COVID-19 patients.

Methods: Sixty newly diagnosed CD patients with median age (mean ± SD) of 35.40 ± 24.12 years; thirty confirmed severe COVID-19 patients with median age (mean ± SD) of 59.67 ± 17.22, and 60 healthy subjects with median age (mean ± SD) of 35.6 ± 13.02 years; were recruited from March to September 2020. Fresh whole blood samples were collected, total RNA was obtained and cDNA synthesis was carried out. RNA expression levels of IL-6, CD4, CD25, and FOXP3 genes were assessed using real-time quantitative RT-PCR according to the 2 formula. Statistical analysis was performed using SPSS (V.21) and GraphPad, Prism (V.6).

Results: While increased expression of CD4, CD25, and FOXP3 was observed in CD patients compared to the control group (p = 0.02, p = 0.03, and p < 0.0001 respectively) and COVID-19 patients group (p < 0.0001 for all of them), their expression levels in COVID-19 patients decreased compared to controls (p < 0.0001, p = 0.01, p = 0.007, respectively). Increased IL-6 expression was observed in both groups of patients compared to controls (p < 0.0001 for both of them).

Conclusions: Although untreated CD patients may be at greater risk of developing into severe COVID-19 if they are infected by SARS-CoV-2 virus (due to their high expression of IL-6), increased expression of anti-inflammatory markers in these patients may be beneficial for them with the ability of reducing the severity of COVID-19 disease, which needs to be proven in future studies involving celiac patients infected with COVID-19.
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http://dx.doi.org/10.1186/s12876-021-02056-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665626PMC
December 2021

Symptomatic giant gastric hyperplastic polyp: a case report.

Gastroenterol Hepatol Bed Bench 2021 ;14(2):181-184

Department of Gastroenterology, Palmerston North Hospital, New Zealand.

Herein we describe a rare case of a 59-year-old male who was diagnosed with giant hyperplastic polyps after referring with symptoms of abdominal pain and vomiting, and associated red-flag symptoms of unintentional weight loss and early satiety.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101519PMC
January 2021

An elemental diet is effective in the management of diversion colitis.

Gastroenterol Hepatol Bed Bench 2021 ;14(1):81-84

Department of Gastroenterology, Palmerston North Hospital, New Zealand.

The use of an elemental diet in the management of inflammatory gastroenterological diseases has long been accepted as standard management and has shown to both induce and maintain remission in Crohn's disease, but the evidence is lacking for its use in diversion colitis. An elemental diet is one which provides all the required nutrition in a more easily absorbed and hypoallergenic form. In this case report, we present a patient who had a flare of diversion colitis treated with diet alone. She had a significant improvement in her symptoms with a decrease in bowel motions, rectal discharge and pain. This case suggests that there may be some role for the use of an elemental diet in the management of diversion colitis. We also examine some potential mechanisms which may lead to the benefit observed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035536PMC
January 2021

An algorithm for differentiating food antigen-related gastrointestinal symptoms.

Gastroenterol Hepatol Bed Bench 2021 ;14(1):8-16

Grigore T Popa" University of Medicine and Pharmacy, Iasi, Romania.

Aim: The aim of this clinical audit was to assess patient-reported outcomes on the effect of dietary intervention, to enhance our understanding of possible treatment options in irritable bowel syndrome (IBS).

Background: A large number of food-related gastro-intestinal disorders have been attributed to IBS for decades.

Methods: Patient-reported outcomes from the records of 149 IBS patients treated at secondary and tertiary Gastroenterology outpatients in two UK hospitals between January 2014 and July 2016 were audited. Patients all presented with symptoms fulfilling Rome III-IV criteria for IBS had negative coeliac serology and did not have other gastrointestinal (GI) conditions. A modified version of a low FODMAP diet had been recommended (gluten and lactose free diet (G/LFD)) and was implemented for 6 weeks. Outcomes and dietary adherence were recorded during outpatient's consultations.

Results: A total of 134 patients complied with the diet optimally. The majority had an improvement rate >70% and continued with the diet. Fifty-three percent became completely or almost asymptomatic, while 27.6% had a poor response to the diet (scoring < 30%) to G/LFD. The improvement was excellent in patients with normal BMI and good in overweight and obese and where BMI <18. Over 50% did not require any follow-up within 12 months.

Conclusion: Although it is unclear whether symptoms are triggered by gluten, fructans or lactose, elimination of gluten and lactose proved to be an effective treatment in patients with IBS. Multidisciplinary team management and implementation of detailed nutrition therapy using the audit algorithm might prove to be both cost effective and efficacious a treatment option in IBS.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035543PMC
January 2021

Neurological manifestation of coeliac disease with particular emphasis on gluten ataxia and immunological injury: a review article.

Gastroenterol Hepatol Bed Bench 2021 ;14(1):1-7

Dudley Group of Hospitals NHSF Trust, UK.

Coeliac disease (CD) is a gluten-induced enteropathy affecting 1% of the population and has extra intestinal manifestations. One such expression involves nervous system, and CD may present as gluten ataxia (GA), peripheral neuropathy and epileptiform disorder among others. Considerable controversy exists on the exact pathophysiological mechanism of gluten leading to ataxia. It is, however, clear that in intestinal axis tissue transglutaminase 2 (tTG2) is the primary target but in the nervous system, tTG6 may be the causative antigen although its exact role is not clear. Furthermore, it has also been postulated that anti-gangliodise antibodies may play a role in the emergence of central pathology if not the key contender. Moreover, the association of neurological injury with non-coeliac gluten sensitivity (NCGS), a related but pathologically different condition implies an independent mechanism of neuronal injury by gluten in the absence of CD. This review will touch on the salient features of CD and the nervous system and will highlight current controversies in relation to gluten and GA.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035534PMC
January 2021

The Gluten Gene: Unlocking the Understanding of Gluten Sensitivity and Intolerance.

Appl Clin Genet 2021 11;14:37-50. Epub 2021 Feb 11.

Department of Gastroenterology, MidCentral DHB, Palmerston North, New Zealand.

Wheat flour is one of the most important food ingredients containing several essential nutrients including proteins. Gluten is one of the major protein components of wheat consisted of glutenin (encoded on chromosome 1) and gliadin (encoded on chromosome 1 and 6) and there are around hundred genes encoding it in wheat. Gluten proteins have the ability of eliciting the pathogenic immune responses and hypersensitivity reactions in susceptible individuals called "gluten-related disorders (GRDs)", which include celiac disease (CD), wheat allergy (WA), and non-celiac gluten sensitivity (NCGS). Currently removing gluten from the diet is the only effective treatment for mentioned GRDs and studies for the appropriate and alternative therapeutic approaches are ongoing. Accordingly, several genetic studies have focused on breeding wheat with low immunological properties through gene editing methods. The present review considers genetic characteristics of gluten protein components, focusing on their role in the incidence of gluten-related diseases, and genetic modifications conducted to produce wheat with less immunological properties.
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http://dx.doi.org/10.2147/TACG.S276596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886246PMC
February 2021

Prevalence of celiac disease in low and high risk population in Asia-Pacific region: a systematic review and meta-analysis.

Sci Rep 2021 01 27;11(1):2383. Epub 2021 Jan 27.

Gastroenterology and Liver Disease Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Science, Tehran, Iran.

This systematic review and meta-analysis study was conducted to estimate the pooled prevalence of CD in low and high risk groups in this region. Following keywords were searched in the Medline, PubMed, Scopus, Web of Science and Cochrane database according to the MeSH terms; celiac disease, prevalence, high risk population and Asian-Pacific region. Prevalence studies published from January 1991 to March 2018 were selected. Prevalence of CD with 95% confidence interval (CI) was calculated using STATA software, version 14. The pooled sero-prevalence of CD among low risk group in Asia-Pacific region was 1.2% (95% CI 0.8-1.7%) in 96,099 individuals based on positive anti-tissue transglutaminase (anti-t-TG Ab) and/or anti-endomysial antibodies (EMA). The pooled prevalence of biopsy proven CD in Asia-Pacific among high and low risk groups was 4.3% (95% CI 3.3-5.5%) and 0.61% (95% CI 0.4-0.8%) in 10,719 and 70,344 subjects, respectively. In addition, the pooled sero-prevalence and prevalence of CD in general population was significantly higher in children compared with adults and it was significantly greater in female vs. male (P < 0.05). Our results suggest high risk individuals of CD are key group that should be specifically targeted for prevention and control measures, and screening may prove to have an optimal cost-benefit ratio.
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http://dx.doi.org/10.1038/s41598-021-82023-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841177PMC
January 2021

Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts.

Gut 2021 05 2;70(5):876-883. Epub 2020 Nov 2.

Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield, UK

Objective: We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients.

Design: The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD.

Results: Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively.

Conclusion: Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD.
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http://dx.doi.org/10.1136/gutjnl-2020-320913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040155PMC
May 2021

The correlation between vitamin D levels and demographics in patients with gastrointestinal disorders; a cross-sectional study.

Gastroenterol Hepatol Bed Bench 2020 ;13(3):223-231

Department of Gastroenterology Palmerston North Hospital, New Zealand.

Aim: The aim of the present study was to evaluate vitamin D levels, in correlation with age, body mass index (BMI), gender and ethnicity, in patients with gastrointestinal disorders (GID).

Background: Vitamin D deficiency (VDD) is a global health issue, affecting over 1 billion people. A great body of evidence has shown that it can lead to increased morbidity and mortality. Furthermore, latitude, sedentary lifestyle, limited sunlight exposure, ageing and the presence of comorbidities and chronic illnesses, places patients at an increased risk of VDD.

Methods: 305 consecutive patients, with GID, were assessed for vitamin D levels, using a two-step competitive binding immunoenzymatic assay. Patients were then classified as adequate (50-150nmol/l), insufficient (25-50nmol/l) and deficient (<25nmol/l).

Results: 62% of the investigated subjects had low vitamin D levels. From this group, 132 patients (43.3%) had insufficient vitamin D levels, 57 (18.7%) had deficient levels and 116 (38%) had adequate levels. Age was not significantly different in the 3 groups (p=0.29). Interestingly, vitamin D levels were significantly lower in men (39.23±23.62) compared to women (50.68±24.46) (p=0.0001). The BMI was significantly higher in patients with insufficient vitamin D levels. Being of Asian ethnicity had a positive influence on vitamin D levels (B=0.076) (p<0.0001). 71.4% of patients, with IBD, and 60% of patients, with abnormal liver function, had low vitamin D levels.

Conclusion: VDD has a high prevalence in patients with GID in particular IBD and liver disease in the United Kingdom. Routine vitamin D testing and supplementations in the case of deficiency and suboptimal level of vitamin D for patients with hepatobiliary, pancreatic, kidney, malabsorptive and restrictive diseases/surgeries is recommended.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417489PMC
January 2020

Serum Level and Gene Expression of Interleukin-15 Do Not Correlate with Villous Atrophy in Celiac Disease Patients.

Genet Test Mol Biomarkers 2020 Aug 17;24(8):502-507. Epub 2020 Jul 17.

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Interleukin-15 (IL-15) is a key player in the pathogenesis of celiac disease (CD). We investigated the functional role of IL-15 in the process of epithelial cell phenotypic modification at different stages of CD. In this study, we looked for correlations between the mRNA levels in duodenal tissue and serum protein levels in a cohort of Iranian patients affected by CD based on the degree of histopathology. Ninety-five formalin-fixed, paraffin-embedded duodenal tissue specimens were collected: 23 with a Marsh I value; 30 with a Marsh II value; 32 with a Marsh III value; and 10 normal controls. The expression levels of the gene in these biopsy specimens were determined by real-time quantitative polymerase chain reaction (qPCR), and IL-15 serum protein concentrations were determined by enzyme-linked immunosorbent assay and compared to tissue expression. The IL-15 mRNA levels were higher in patients with Marsh II compared with the control group, and the Marsh I, and Marsh III groups. The differences between the Marsh II and Marsh I patients were statistically significant ( = 0.03). Similarly, the serum concentration of IL-15 was higher in Marsh II patients compared to those with Marsh I and Marsh III lesions, although the differences were not statistically significant ( = 0.221). Our results demonstrate that IL-15 gene expression might be elevated only in the early stages of CD onset (and histological damage) and that IL-15 serum levels do not significantly correlate with its tissue expression whatever the degree of histopathology.
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http://dx.doi.org/10.1089/gtmb.2019.0265DOI Listing
August 2020

Citation classics in general medical journals: assessing the quality of evidence; a systematic review.

Gastroenterol Hepatol Bed Bench 2020 ;13(2):101-114

Department of Emergency Medicine, Inselspital, University Hospital of Bern, Bern, Switzerland.

Aim: This review provides a comprehensive overview of more than 100 of the most cited studies in general medical journals and evaluates whether citations predict the quality of a scientific article.

Background: The number of citations is commonly used as a measure of the quality and impact of a scientific article. However, it is often criticised that the number of citations is in fact a poor indicator of the true quality, as it can be influenced by different factors such as current trends.

Methods: This review was conducted in line with the PRISMA guidelines. The Journal Citation Report (JCR) within Incites allowed the evaluation and comparison of articles, published in general medical journals, using far-reaching citation data drawn from scholarly and technical journals and conference proceedings. All steps of the review were performed in duplicate and conflicts were resolved through consensus.

Results: The 100 most cited articles published from 1963 until the end of 2018 were identified. The number of citations ranged from 4012 to 31853. Most of the articles were published in the 2000's, followed by the 1990's, 1980's, 1970's and 1960's, respectively. All of the articles were published in five journals. There were 50 studies at level II, 28 at level V, 10 at level IV, 7 at level III, and 5 at Level I.

Conclusion: This systematic review provides an overview of the most cited articles, published in general medical journals. The number of citations provides an indication of the quality of evidence. However, researchers and clinicians should use standardized assessment tools rather than solely rely on the number of citations in order to judge the quality of published articles.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149815PMC
January 2020

The value of a biopsy in celiac disease follow up: assessment of the small bowel after 6 and 24 months treatment with a gluten free diet.

Rev Esp Enferm Dig 2020 Feb;112(2):101-108

Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Iran.

Introduction: a routine small bowel biopsy (SBB) during the follow up of celiac disease (CD) is controversial. Little information is available regarding the histological changes during (gluten free diet (GFD) in the long term.

Objectives: the aim of the study was to evaluate a novel criterion to compare duodenal histology in CD patients after six months and two years of gluten withdrawal.

Methods: this was a cross-sectional study of 200 patients with confirmed Marsh I-III who were under the six months (group A, n = 100) and 24 months (group B, n = 100) of a GFD. Nineteen patients were excluded due to an inadequate adherence to the GFD and another 23 patients were excluded as they were unwilling to undergo a re-endoscopy and did not comply with the necessary criteria. Endoscopy with a duodenal biopsy, serological assays and clinical evaluation were performed and compared with baseline data in the remaining 58 patients (20 patients in group A and 38 patients in group B).

Results: a significant complete histological recovery was found in 47.4% of patients in group B compared to 30% in group A (p = 0.026). A partial histological recovery was reported in seven (35%) and eleven (28.9%) patients in groups A and B, respectively. Any changes in mucosal histology after GFD was observed in 35% of patients in group A and 23.7% in group B. Serological assessment and endoscopic appearance normalized in 78.9% vs 75.0% in group B and 68.4% vs 65.0% in group A, respectively. However, this improvement did not reach statistical significance (p > 0.05).

Conclusions: the results of this study show that histological recovery in patients with Marsh ≥ III is slow and does not correlate with symptomatic improvement. We suggest that the long-term effects of a GFD can play an important role in achieving histological improvement, especially in older patients.
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http://dx.doi.org/10.17235/reed.2019.5947/2018DOI Listing
February 2020

Lack of health care professional's awareness for management of celiac disease may contribute to the under diagnosis of celiac disease.

Gastroenterol Hepatol Bed Bench 2019 ;12(3):203-208

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Aim: We assessed the knowledge of physicians regarding diagnosis and treatment of celiac disease (CD).

Background: Specialists as the main therapist group of CD patients may play crucial role in the diagnosis and treatment of CD. Therefore, training and ensuring their capabilities is important.

Methods: The population was specialists including Gastroenterologist, GI fellow, consultants, residents and general practitioners graduated in Medical Sciences Universities in Iran. The examination was the experts made and aimed to assess the educational needs of physicians and explore their failures in the diagnosis and treatment of CD with the key feature approach. Data was collected using a questionnaire that its validity and reliability was confirmed by experts (r = 91.6%). The total score was 150 with the classification of participants to the following categories: good (112- 150), intermediate (39-112) and weak ( ≤38).

Results: Out of 300 participants, 197 questionnaires were returned (Response rate = 66%). The mean age of the participants was 42.67 years (SD = 7.9 years) with majority were male (63.6%). Average score of participates who had less than three year's experience was significantly higher than others (P≤0.05). Only 12.1% and 9.8% of specialists have got the excellent score for diagnosis and treatment, respectively.

Conclusion: It may conclude that specialists have had performance gap and around 90% needed training based on the principles of instructional design in order to improve their knowledge and skills to do and practice their assigned tasks. Therefore, development of training packages according to the principles of instructional design is suggested.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668761PMC
January 2019

The role of CXCR3 and its ligands CXCL10 and CXCL11 in the pathogenesis of celiac disease.

Medicine (Baltimore) 2019 Jun;98(25):e15949

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The chemokine receptor CXCR3 and its ligands CXCL10 and CXCL11 have been suggested to give rise to the most relevant chemokine axis able to facilitate the entrance of immune cells into inflamed tissues and be activated in different inflammatory disorders, such as celiac disease (CD).The aim of this study was to investigate the expression level of CXCR3, CXCL10, and CXCL11 genes in celiac patients compared to healthy controls. Both cohorts have been recruited from the Iranian population.In this case-control study, biopsy specimens were collected from 71 celiac patients (60.5% female) and 90 control subjects (57% female) during 2016. Total RNA was extracted and mRNA expression levels of CXCR3, CXCL10, and CXCL11 genes were investigated by SYBR green qPCR.Based on qPCR and relative quantification method, the mRNA expression levels of CXCR3, CXCL10, and CXCL11 were significantly higher in duodenal biopsies of celiac patients compared to healthy controls in the study population (P = .038, P = .021, and P = .012 respectively).The result of this study showed that CXCR3/CXCL10/CXCL11 signaling axis is overexpressed in the small intestinal mucosa of CD patients compared to controls. This finding might explain the specific enrollment of the main cell populations that infiltrate the epithelium.
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http://dx.doi.org/10.1097/MD.0000000000015949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636963PMC
June 2019

Semi-elemental diet is effective in managing high output ileostomy; a case report.

Gastroenterol Hepatol Bed Bench 2019 ;12(2):169-173

Department of Gastroenterology, Milton Keynes University Hospital, Milton Keynes, UK.

A notable proportion of surgically created stomas develop high output. Ongoing monitoring and treatment of hight stoma output is imperative to avoid risk of complications. Prevailing management guidelines focus mainly on supportive measures and medications that alter bowel motility. However, some patients fail to respond to these measures, leaving few substitutes. This report documents the use of semi-elemental diet in the management of a high-output ileostomy case. A 58-year-old patient underwent multiple bowel resections that resulted in a small intestine measuring 90 cm, with an end ileostomy being performed. He was on home parenteral nutrition (HPN) for over 9 years and was admitted to the hospital with an episode of sepsis from an infected line. One day prior to the hospital admission, the stoma was producing 7.2 litres/day. The Patient was advised to start Vital 1.5 10-15/day (2.5-3 litres/day) exclusively, in addition to his 1.5 litres of IV fluid, based on the nutritional requirement as calculated by a dietitian. Following the introduction of the semi-elemental diet, the ileostomy output dropped swiftly to 2 litres/day, 9 days post admission, and the BMI remained stable. This report suggests a possible role for semi-elemental diet in the management of ileostomies with short bowel syndrome. Based on our previous experience and this case, elemental or semi-elemental diet may both be used as a mono-therapy, in patients with high ileostomy output, even in cases with small bowel length as short as 90cm.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536019PMC
January 2019

Prevalence of gluten-related disorders in Asia-Pacific region: a systematic review.

J Gastrointestin Liver Dis 2019 Mar;28(1):95-105

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background And Aims: The epidemiology of gluten-related disorders (GRDs) is still an open field to be explored. We conducted this systematic review based on the current epidemiology knowledge of GRDs, focusing on the changing prevalence of GRDs reported in the Asia-Pacific region.

Methods: We searched Medline, PubMed, Scopus, Web of Science and Cochrane database with the following MeSH terms and keywords: celiac disease (CD), wheat allergy (WA), non-celiac gluten sensitivity (NCGS), dermatitis herpetiformis (DH) and gluten ataxia (GA) and the prevalence studies published from January 1991 to January 2018. Each article was cross-referenced with "Asia-Pacific region" and countries in this region such as Australia, New Zealand, India, Pakistan, Turkey, Iran and others.

Results: We included 66 studies, which reported the prevalence of GRDs in the Asia-Pacific region. Prevalence of celiac disease was 0.32%-1.41% in healthy children and 0.05%-1.22% in the adult population, while the prevalence in the high risk population was higher (0.6%-11.8%). Previous studies have shown a very low incidence of dermatitis herpetiformis (DH) (<0.001%) and gluten ataxia (GA) in this area. Few studies on NCGS outbreaks have been found in this area due to the lack of specific diagnostic biomarkers. Wheat allergy (WA), although uncommon in most Asian-Pacific countries, is the most common cause of anaphylaxis in this region.

Conclusion: The results of this systematic review suggest the need to plan further proper epidemiological studies in order to understand the natural history of GRDs and to assess its burden on health systems.
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http://dx.doi.org/10.15403/jgld.2014.1121.281.sysDOI Listing
March 2019

Coeliac disease novel histological quantification.

Comput Biol Med 2019 03 28;106:149. Epub 2018 Nov 28.

Department of Pathology, Brigham & Women's Hospital, Boston, USA.

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http://dx.doi.org/10.1016/j.compbiomed.2018.11.023DOI Listing
March 2019

Contribution of HLA-DQ2/DQ8 haplotypes in type one diabetes patients with/without celiac disease.

J Diabetes Complications 2019 01 25;33(1):59-62. Epub 2018 Oct 25.

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Based on lack of data on the distribution of the related alleles in the T1D population in Iranian population, we assessed the frequency of HLA DQ2 and DQ8 haplotypes in patients with T1D with/without CD compared to healthy population.

Materials And Methods: 70 patients with T1D without celiac disease, 60 T1D cases with CD were compared to 150 healthy individuals during 2016. Ten mililiter Gheparinized blood samples were collected, genomic DNA was extracted and alleles were genotyped by Real-time PCR using SYBR Green as a low-resolution method.

Results: HLA-DQ2 and/or HLA-DQ8 genotypes was presented in 51% and 23% of T1D patients without CD respectively. Twenty one percent of those patients carried both alleles and 5% were negative for both alleles. T1D patients with CD had much higher DQ2 frequency (72%) and lower DQ8 (11.6%), than T1D patients without CD and controls, 14% carried both alleles and 3% were negative for both. The frequencies of DQ2 and DQ8 alleles in Iranian healthy population were 19 and 5% respectively.

Conclusion: According to the same genetic background for CD and T1D we suggest that HLA-typing can be a very useful screening tool for CD in patients with type one diabetes.
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http://dx.doi.org/10.1016/j.jdiacomp.2018.10.001DOI Listing
January 2019

Mood Disorders and Gluten: It's Not All in Your Mind! A Systematic Review with Meta-Analysis.

Nutrients 2018 Nov 8;10(11). Epub 2018 Nov 8.

Department of Gastroenterology, Mid-Central District Health Board, Palmerston North Hospital, Palmerston North 4442, New Zealand.

Gluten elimination may represent an effective treatment strategy for mood disorders in individuals with gluten-related disorders. However, the directionality of the relationship remains unclear. We performed a systematic review of prospective studies for effects of gluten on mood symptoms in patients with or without gluten-related disorders. Six electronic databases (CINAHL, PsycINFO, Medline, Web of Science, Scopus and Cochrane Library) were searched, from inception to 8 August 2018, for prospective studies published in English. Meta-analyses with random-effects were performed. Three randomised-controlled trials and 10 longitudinal studies comprising 1139 participants fit the inclusion criteria. A gluten-free diet (GFD) significantly improved pooled depressive symptom scores in GFD-treated patients (Standardised Mean Difference (SMD) -0.37, 95% confidence interval (CI) -0.55 to -0.20; < 0.0001), with no difference in mean scores between patients and healthy controls after one year (SMD 0.01, 95% CI -0.18 to 0.20, = 0.94). There was a tendency towards worsening symptoms for non-coeliac gluten sensitive patients during a blinded gluten challenge vs. placebo (SMD 0.21, 95% CI -0.58 to 0.15; = 0.25). Our review supports the association between mood disorders and gluten intake in susceptible individuals. The effects of a GFD on mood in subjects without gluten-related disorders should be considered in future research.
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http://dx.doi.org/10.3390/nu10111708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266949PMC
November 2018

Serum cytokines profile in treated celiac disease compared with non-celiac gluten sensitivity and control: a marker for differentiation.

J Gastrointestin Liver Dis 2018 Sep;27(3):241-247

School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background And Aims: There is increasing evidence regarding elevated serum levels of inflammatory cytokines in patients with celiac disease (CD), but little is known about their levels in patients with non-celiac gluten sensitivity (NCGS). The aim of this study was to evaluate the serum levels of inflammatory cytokines in Iranian patients with CD and NCGS and to compare them with those of healthy individuals.

Methods: A total of 110 treated CD, 15 with NCGS, and 46 healthy subjects were enrolled during 2016. Serum levels of IL-1, IL-6, IL-8, IL-15 and IFN-γ were measured using ELISA, and compared between groups. The correlation of the severity of mucosal damage and clinical symptoms with serum levels of cytokines was also assessed.

Results: The mean serum levels of IFN-γ (p = 0.04) and IL-6 (p = 0.007) were significantly different between the patients in the CD and control groups, and IL-8 was significantly higher in the CD group compared with patients in the NCGS group (p = 0.04). Statistically significant correlations were observed between the serum levels of IFN-γ and abortion (p = 0.01), IL-1 and weight loss (p = 0.043) and infertility (p = 0.0001) in CD patients, and between IFN-γ and abortion (p = 0.01) and infertility (p = 0.01) in the NCGS patients. Moreover, no significant relationship was observed between the severity of mucosal damage and the serum level of the studied cytokines.

Conclusions: Inflammatory cytokines are implicated in the pathogenesis of CD, and their serum levels might help to identify a diagnostic marker to differentiate CD from NCGS. However, further studies with a larger sample size are recommended.
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http://dx.doi.org/10.15403/jgld.2014.1121.273.heyDOI Listing
September 2018

Diverse Profiles of Toll-Like Receptors 2, 4, 7, and 9 mRNA in Peripheral Blood and Biopsy Specimens of Patients with Celiac Disease.

J Immunol Res 2018 2;2018:7587095. Epub 2018 Jul 2.

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background And Aims: Both adaptive and innate immunity are involved in the development of celiac disease (CD). Altered Toll-like receptors (TLR) expression and activation may be partially responsible for the inflammation and subsequently crypt hyperplasia, but the main driver for inflammation is gliadin-reactive T-cells. Therefore, the aim of this study was to investigate the TLRs 2, 4, 7, and 9 gene expressions in both peripheral blood and intestinal mucosa of patients with celiac disease compared to healthy control (HC).

Material And Methods: Blood samples from 120 confirmed active CD patients and 120 age- and sex-matched healthy volunteers served as control group were collected during 2015-2016. Also, 20 biopsy specimens from the study group were randomly collected. Total RNA was isolated using a standard commercial kit. The mRNA expression of TLRs was quantified by relative qPCR with 2 microglobulin (2m) as a reference gene.

Results: TLR4 ( = 0.01) and TLR9 ( = 0.02) mRNA were significantly elevated in blood samples from CD patients compared to the healthy controls. Moreover, TLR2 ( = 0.03) and TLR4 ( = 0.0003) expression level was increased in CD biopsy specimens compared to controls, whereas expression of TLR9 mRNA was significantly decreased in CD patients. There was no significant difference in the expression of TLR7 in biopsy and blood specimens.

Conclusions: The alteration of TLR4 and TLR9 expression in the blood and biopsy samples of patients with CD supports the critical role of the innate immune system in the pathogenesis of this disease. Upregulation of TLR4 and TLR9 suggests the contribution of gut microbiota or dysregulation of the immune response to commensal flora in small bowel mucosa in celiac patients.
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http://dx.doi.org/10.1155/2018/7587095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051003PMC
November 2018

Post pancreatitis/cholecystectomy gluten intolerance.

Gastroenterol Hepatol Bed Bench 2018 ;11(3):273-275

Department of Gastroenterology, Hepatology and Nutrition, Milton Keynes University Hospital, United Kingdom.

This case report describes the journey of a patient who suffered from life-limiting gastrointestinal symptoms after an acute bout of pancreatitis following ERCP for cholelithiasis bile following a ductal stone, and subsequent cholecystectomy. She was diagnosed and treated for IBS with medication without significant improvement. On implementation of a simple gluten and lactose exclusion diet she recovered to her premorbid state, and trials of gluten challenge triggered flares of symptoms. This case report will go on to discuss current evidence for use of gluten and lactose exclusion diets in some gluten sensitive patients misdiagnosed with IBS.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040032PMC
January 2018

Non celiac gluten sensitivity and diagnostic challenges.

Gastroenterol Hepatol Bed Bench 2018 ;11(3):197-202

Allied Health and Social Sciences, University of Worcester, UK.

Non-celiac gluten sensitivity (NCGS), also referred to as non-celiac wheat sensitivity (NCWS), is a clinical syndrome characterized by both intestinal and extra-intestinal symptoms responsive to the withdrawal of gluten-containing food from the diet. The aim of this review is to summarize recent advances in research and provide a brief overview of the history of the condition for the benefit of professionals working in gastroenterology. Academic databases such as PubMed and Google Scholar were searched using key words such as "non-celiac gluten sensitivity", "gluten related disorders", and the studies outlined in reference page were selected and analysed. Most of the analysed studiers agree that NCGS would need to be diagnosed only after exclusion of celiac disease and wheat allergy, and that a reliable serological marker is not available presently. The mechanisms causing symptoms in NCGS after gluten ingestion are largely unknown, but recent advances have begun to offer novel insights. The estimated prevalence of NCGS, at present, varies between 0.6 and 6%. There is an overlap between irritable bowel syndrome and NCGS with regard to the similarity of gastrointestinal symptoms. The histologic characteristics of NCGS are still under investigation, ranging from normal histology to slight increase in the number of T lymphocytes in the superficial epithelium of villi. Positive response to gluten free diet for a limited period (e.g., 6 weeks), followed by the reappearance of symptoms after gluten challenge appears, at this moment, to be the best approach for confirming diagnosis. The Salerno expert criteria may help to diagnose NCGS accurately in particular for research purposes but it has limited applicability in clinical practice.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040028PMC
January 2018

Seronegative coeliac disease: Are they coeliac? When biopsy in adult can be avoided?

Gastroenterol Hepatol Bed Bench 2018 ;11(3):178-180

Department of Gastroenterology, VU University Medical Center Amsterdam.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040025PMC
January 2018

A rare cause of hematemesis.

Gastroenterol Hepatol Bed Bench 2018 ;11(2):172-173

Department of Colorectal Surgery, Milton Keynes University Hospital, Milton Keynes, UK.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990916PMC
January 2018

Contributions of HLA haplotypes, IL8 level and Toxoplasma gondii infection in defining celiac disease's phenotypes.

BMC Gastroenterol 2018 May 18;18(1):66. Epub 2018 May 18.

Celiac Disease Department, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: It is not clear why some patients with coeliac disease (CD) present with severe symptoms and small intestinal mucosal damages while others present with milder symptoms and no frank enteropathy. There is no study to assess the associated factors with mild/severe symptoms and enteropathy. The terminologies like latent, silent and potential are difficult to use and are unrepresentative. In the present study we describe coeliac disease's phenotypes based on HLA haplotypes, IL8 production and past infection with Toxoplasma gondii (T. gondii) infection.

Methods: In this case-control study, sera originating from 150 healthy subjects and 150 patients diagnosed with CD during the years 2013-14 were analyzed for the presence of antibodies specific T. gondii of the IgG and IgM subclasses. The level of IL8 were measured and HLA-DQ2 and HLA-DQ8 alleles were genotyped. The correlation between these parameters and the damages in intestinal mucosal were assessed using an accepted histopathological classification.

Results: High levels of IgG antibodies against T. gondii were found in the sera of control group compared to the CD group (52.6% vs. 39.4%, P = 0.02). Mean serum levels of IL8 was significantly higher in CD patients compared with control (P ≤ 0.05). By comparing the level of anti- T. gondii IgG and mucosal damage in celiac disease, we found a significant relationship between the severity of mucosal damages and anti- T. gondii IgG level (P = 0.02). No correlation was detected between Toxoplasma gondii infection and types of HLA (P > 0.05). However, patients with severely abnormal histology carried HLA-DQ2 risk alleles (92 patients (61%)) more often than the controls and those with mild histological abnormalities.

Conclusions: CD patients with severe histological changes had more often Toxoplasma gondii infection than those affected with mild histological features. This suggests that CD's phenotypes are correlated to additional factors like infections and to particular HLA DQ2 alleles that may need additional investigations and potentially will require additional treatment.
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http://dx.doi.org/10.1186/s12876-018-0796-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960085PMC
May 2018
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