-
Journal of Gastrointestinal and Liver... Jun 2024The environmental factors, apart from gluten ingestion predisposing to coeliac disease are poorly known. Smoking is associated with many immune-mediated diseases, but...
BACKGROUND AND AIMS
The environmental factors, apart from gluten ingestion predisposing to coeliac disease are poorly known. Smoking is associated with many immune-mediated diseases, but research on coeliac disease is scarce. This study aims to investigate how smoking affects the clinical presentation, presence of comorbidities and response to gluten-free diet in coeliac disease.
METHODS
Altogether 815 adults with coeliac disease participated in a nationwide cross-sectional study. Participants were interviewed and smoking habits (never, former, or current smoker), clinical presentation of coeliac disease and presence of comorbidities were elicited. Serology and severity of small bowel mucosal lesions at diagnosis were gathered from the participants' medical records and follow-up serology was measured. Gastrointestinal symptoms and psychological well-being were assessed using validated questionnaires.
RESULTS
Current smokers were more often male and were diagnosed at younger ages than never or former smokers. There were no differences between the groups in clinical presentation, severity of symptoms or mucosal lesions at diagnosis or in dietary compliance and clinical, serological, and histological recovery. Musculoskeletal disorders, particularly osteoporosis and osteopenia, were more common in never smokers than in other groups (14.5% vs. 5.1% and 4.1%, p<0.001), and cardiovascular disorders were diagnosed more often in former smokers (36.2% vs. 23.5% and 21.9%, p=0.003).
CONCLUSIONS
Smoking does not seem to have an impact on the clinical presentation, severity of symptoms or mucosal damage in coeliac disease. Histological and clinical recovery as well as seroconversion on gluten-free diet are not affected by smoking status.
Topics: Humans; Celiac Disease; Male; Female; Cross-Sectional Studies; Middle Aged; Diet, Gluten-Free; Adult; Cigarette Smoking; Aged; Treatment Outcome; Comorbidity; Risk Factors; Smokers; Ex-Smokers; Intestinal Mucosa
PubMed: 38944862
DOI: 10.15403/jgld-5364 -
Journal of Medical Microbiology Jun 2024Avian reovirus (ARV) is associated with arthritis/tenosynovitis and malabsorption syndrome in chickens. The σC and σB proteins, both exposed to the virus capsid, are...
Avian reovirus (ARV) is associated with arthritis/tenosynovitis and malabsorption syndrome in chickens. The σC and σB proteins, both exposed to the virus capsid, are highly immunogenic and could form the basis for diagnostic devices designed to assess the immunological status of the flock. Commercial ARV ELISAs cannot distinguish between vaccinated and infected animals and might not detect circulating ARV strains. We aimed to develop a customized test to detect the circulating field ARV strains as well as distinguish between vaccinated and unvaccinated animals. We developed ELISA assays based on recombinant (r) σB, σC and the nonstructural protein σNS and tested them using antisera of vaccinated and unvaccinated chickens as well as negative controls. Fragments of σB and σC proteins were also used to study regions that could be further exploited in diagnostic tests. Vaccinated and unvaccinated birds were positive by commercial ELISA, with no difference in optical density values. In contrast, samples of unvaccinated animals showed lower absorbance in the rσB and rσC ELISA tests and higher absorbance in the rσNS ELISA test than the vaccinated animals. Negative control samples were negative in all tests. Fragmentation of σB and σC proteins showed that some regions can differentiate between vaccinated and unvaccinated animals. For example, σB amino acids 128-179 (σB-F4) and σC amino acids 121-165 (σC-F4) exhibited 85 and 95% positivity among samples of vaccinated animals but only 5% and zero positivity among samples of unvaccinated animals, respectively. These data suggest that unvaccinated birds might have been exposed to field strains of ARV. The reduction in absorbance in the recombinant tests possibly reflects an increased specificity of our test since unvaccinated samples showed less cross-reactivity with the vaccine proteins immobilized on ELISAs. The discrepant results obtained with the protein fragment tests between vaccinated and unvaccinated animals are discussed in light of the diversity between ARV strains.
Topics: Animals; Orthoreovirus, Avian; Enzyme-Linked Immunosorbent Assay; Chickens; Reoviridae Infections; Poultry Diseases; Recombinant Proteins; Antibodies, Viral; Capsid Proteins; Viral Proteins
PubMed: 38935078
DOI: 10.1099/jmm.0.001836 -
Neurogastroenterology and Motility Jun 2024Several organizations have proposed guidelines or clinical decision tools for the management of patients with disorders of gut-brain interactions (DGBI) affecting the... (Review)
Review
BACKGROUND
Several organizations have proposed guidelines or clinical decision tools for the management of patients with disorders of gut-brain interactions (DGBI) affecting the lower digestive tract including irritable bowel syndrome and chronic idiopathic constipation. Such algorithms are based on sequential therapeutic trials and modifying the treatment strategy based on efficacy and adverse events.
PURPOSE
The aims of this review are to evaluate the evidence for efficacy of second- and third-line pharmacotherapies and to assess the evidence for the alternative option to manage subgroups of patients with symptoms suggestive of lower DGBI based on diagnostic tests or documented dysfunctions. The preeminent tests to identify such subgroups that present with symptoms that overlap with lower DGBI are detailed: digital rectal examination as well as anorectal manometry and balloon expulsion for evacuation disorders, detailed measurements of colonic transit, and diagnosis of bile acid diarrhea or carbohydrate malabsorption based on biochemical measurements. The review also addresses the cost implications of screening to exclude alternative diagnoses and the costs of therapy associated with the therapeutic options following an algorithmic approach to treatment from the perspective of society, insurer, or patient. Finally, the costs of the diagnostic tests to identify actionable biomarkers and the evidence of efficacy of individualized therapy based on formal diagnosis or documentation of abnormal functions are detailed in the review.
PubMed: 38934414
DOI: 10.1111/nmo.14856 -
Nutrients Jun 2024Approximately 30% of milk protein is β-casein. We aimed to determine whether lactose maldigesters who chronically consumed two cups of A1/A2 milk (containing 75% A1... (Randomized Controlled Trial)
Randomized Controlled Trial
Approximately 30% of milk protein is β-casein. We aimed to determine whether lactose maldigesters who chronically consumed two cups of A1/A2 milk (containing 75% A1 β-casein and 25% A2 β-casein) would adapt to have fewer intolerance symptoms, lower serum inflammatory markers, and/or altered glutathione levels similar to those consuming A2 milk (containing 100% A2 β-casein). A double-blinded, randomized, crossover trial was conducted. Sixteen confirmed lactose maldigesters consumed 250 mL of A1/A2 milk and A2 milk twice daily with meals for two weeks. At the end of the adaptation period on day 15, lactose maldigestion was measured after a challenge with the same milk used for adaptation (0.5 g of lactose per kg of body weight) with a hydrogen breath test. Fecal urgency was higher during the two-week consumption of A1/A2 milk compared to A2 milk ( = 0.04, = 16). Bloating ( = 0.03, = 16) and flatulence ( = 0.02, = 16) were also higher on the 15th day with A1/A2 milk compared to A2 milk challenge. However, day-to-day symptoms, hydrogen, serum inflammatory markers, and antioxidant concentrations were not different after A1/A2 and A2 milk consumption adaptation periods. Adaptation over two weeks did not improve lactose digestion or tolerance of A1/A2 milk to match that of A2 milk.
Topics: Humans; Lactose Intolerance; Caseins; Milk; Cross-Over Studies; Female; Double-Blind Method; Adult; Animals; Male; Lactose; Middle Aged; Biomarkers; Flatulence; Breath Tests; Adaptation, Physiological
PubMed: 38931316
DOI: 10.3390/nu16121963 -
Nutrients Jun 2024Skin autofluorescence (sAF) measurement is a non-invasive method used to assess tissue advanced glycation end product (AGE) accumulation. This study aims to characterize...
Assessment of Skin Autofluorescence and Its Association with Glycated Hemoglobin, Cardiovascular Risk Markers, and Concomitant Chronic Diseases in Children with Type 1 Diabetes.
UNLABELLED
Skin autofluorescence (sAF) measurement is a non-invasive method used to assess tissue advanced glycation end product (AGE) accumulation. This study aims to characterize sAF's association with (1) glycated hemoglobin (HbA1c) values, (2) cardiovascular risk markers, and (3) common comorbidities (autoimmune thyroiditis, celiac disease) in children with type 1 diabetes (T1D).
MATERIALS AND METHODS
A total of 348 children with T1D aged 3-18 years and 85 age- and gender-matched control subjects were enrolled. sAF was quantified using an AGE Reader (Diagnoptics BV, The Netherlands). The analysis covered HbA1c, blood lipid, and C-reactive protein (CRP) levels, ambulatory blood pressure monitoring records, and body composition parameters. The associations between variables and sAF were assessed using the Mann-Whitney U test and Spearman correlation.
RESULTS
We observed significantly higher sAF values in the T1D group compared to the control (1.40 [1.27-1.53] vs. 1.20 [1.07-1.30, AU]; = 0.004), consistent across all tested age groups. In the T1D group, sAF was positively correlated with current HbA1c, mean of historical HbA1c values, and T1D duration (r values, respectively: 0.27, 0.22, 0.14, all < 0.01). Percentage of body fat was positively correlated with sAF (r = 0.120; = 0.044). No significant correlations were found between sAF and lipid fractions, Z-score of BMI, parameters from 24 h ambulatory blood pressure monitoring, or the amount of albumin excreted in urine. sAF was positively correlated with CRP (r = 0.17, < 0.05). sAF was significantly higher in patients with concomitant celiac disease (1.53 [1.43-1.63] vs. 1.40 [1.27-1.53, AU], = 0.001).
CONCLUSION
Among young T1D patients with relatively brief diabetes duration, sAF effectively mirrors prior glycemic control, as presented by historical average HbA1c. However, associations with conventional CV risk markers are not evident. The higher sAF values in patients with celiac disease warrant further exploration.
Topics: Humans; Child; Glycated Hemoglobin; Diabetes Mellitus, Type 1; Female; Male; Adolescent; Skin; Child, Preschool; Glycation End Products, Advanced; Heart Disease Risk Factors; Biomarkers; Cardiovascular Diseases; Chronic Disease; Optical Imaging; C-Reactive Protein; Case-Control Studies; Celiac Disease; Comorbidity
PubMed: 38931293
DOI: 10.3390/nu16121940 -
Nutrients Jun 2024Celiac disease (CeD) is an autoimmune disease with a strong association with human leukocyte antigen (HLA), characterized by the production of specific autoantibodies... (Review)
Review
Celiac disease (CeD) is an autoimmune disease with a strong association with human leukocyte antigen (HLA), characterized by the production of specific autoantibodies and immune-mediated enterocyte killing. CeD is a unique autoimmune condition, as it is the only one in which the environmental trigger is known: gluten, a storage protein present in wheat, barley, and rye. How and when the loss of tolerance of the intestinal mucosa to gluten occurs is still unknown. This event, through the activation of adaptive immune responses, enhances epithelial cell death, increases the permeability of the epithelial barrier, and induces secretion of pro-inflammatory cytokines, resulting in the transition from genetic predisposition to the actual onset of the disease. While the role of gastrointestinal infections as a possible trigger has been considered on the basis of a possible mechanism of antigen mimicry, a more likely alternative mechanism appears to involve a complex disruption of the gastrointestinal microbiota ecosystem triggered by infections, rather than the specific effect of a single pathogen on intestinal mucosal homeostasis. Several lines of evidence show the existence of intestinal dysbiosis that precedes the onset of CeD in genetically at-risk subjects, characterized by the loss of protective bacterial elements that both epigenetically and functionally can influence the response of the intestinal epithelium leading to the loss of gluten tolerance. We have conducted a literature review in order to summarize the current knowledge about the complex and in part still unraveled dysbiosis that precedes and accompanies CeD and present some exciting new data on how this dysbiosis might be prevented and/or counteracted. The literature search was conducted on PubMed.gov in the time frame 2010 to March 2024 utilizing the terms "celiac disease and microbiota", "celiac disease and microbiome", and "celiac disease and probiotics" and restricting the search to the following article types: Clinical Trials, Meta-Analysis, Review, and Systematic Review. A total of 364 papers were identified and reviewed. The main conclusions of this review can be outlined as follows: (1) quantitative and qualitative changes in gut microbiota have been clearly documented in CeD patients; (2) intestinal microbiota's extensive and variable interactions with enterocytes, viral and bacterial pathogens and even gluten combine to impact the inflammatory immune response to gluten and the loss of gluten tolerance, ultimately affecting the pathogenesis, progression, and clinical expression of CeD; (3) gluten-free diet fails to restore the eubiosis of the digestive tract in CeD patients, and also negatively affects microbial homeostasis; (4) new tools allowing targeted microbiota therapy, such as the use of probiotics (a good example being precision probiotics like the novel strain of (20220303-A2) begin to show exciting potential applications.
Topics: Celiac Disease; Humans; Gastrointestinal Microbiome; Glutens; Dysbiosis; Intestinal Mucosa
PubMed: 38931237
DOI: 10.3390/nu16121882 -
Nutrients Jun 2024Folate is a water-soluble B vitamin involved in the synthesis of purines and pyrimidines and is one of the essential vitamins for human growth and reproduction. Folate... (Review)
Review
Folate is a water-soluble B vitamin involved in the synthesis of purines and pyrimidines and is one of the essential vitamins for human growth and reproduction. Folate deficiency due to low dietary intake, poor absorption of folate, and alterations in folate metabolism due to genetic defects or drug interactions significantly increases the risk of diseases such as neural tube defects, cardiovascular disease, cancer, and cognitive dysfunction. Recent studies have shown that folate deficiency can cause hyperhomocysteinemia, which increases the risk of hypertension and cardiovascular disease, and that high homocysteine levels are an independent risk factor for liver fibrosis and cirrhosis. In addition, folate deficiency results in increased secretion of pro-inflammatory factors and impaired lipid metabolism in the liver, leading to lipid accumulation in hepatocytes and fibrosis. There is substantial evidence that folate deficiency contributes to the development and progression of a variety of liver diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), viral hepatitis, hepatic fibrosis, and liver cancer. Here we review key studies on the role of folate in the pathophysiology of liver diseases, summarize the current status of studies on folate in the treatment of liver diseases, and speculate that folate may be a potential therapeutic target for liver diseases.
Topics: Humans; Folic Acid; Folic Acid Deficiency; Liver Diseases; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis; Liver; Animals; Liver Neoplasms; Hyperhomocysteinemia; Homocysteine; Lipid Metabolism
PubMed: 38931227
DOI: 10.3390/nu16121872 -
Nutrients Jun 2024Millions of children and adults worldwide suffer from undiagnosed and untreated celiac disease (CeD). The clinical picture of CeD is highly heterogeneous and comprises... (Review)
Review
Millions of children and adults worldwide suffer from undiagnosed and untreated celiac disease (CeD). The clinical picture of CeD is highly heterogeneous and comprises manifestations that can affect almost the whole body. This narrative overview is aimed at characterizing diseases and complaints that are associated with unrecognized CeD and that frequently involve sites other than the gastrointestinal (G.I.) tract, i.e., dental, otorhinolaryngological, and ocular complications; skin and hair abnormalities; afflictions of the bones, joints, and muscles; cardiovascular affectations; kidney diseases; neuro-psychiatric disorders; and gynecological-obstetrical manifestations. The association between CeD and extra-GI manifestations is frequently overlooked, which leads to a delay in diagnosis. Most CeD-mediated disorders can be treated with a strict gluten-free diet (GFD), but some of them are irreversible unless CeD is diagnosed in time. Some manifestations can be classified as risk factors for CeD, and CeD screening tests for affected patients should be selectively considered. Apart from gastroenterologists, specialists in other medical disciplines can play an important role in identifying people with unrecognized CeD and may help prevent its progress and long-term complications. Further comprehensive investigations are necessary to clarify the pathogenesis of extra-GI manifestations and the effect of a GFD.
Topics: Humans; Celiac Disease; Diet, Gluten-Free; Risk Factors; Female
PubMed: 38931169
DOI: 10.3390/nu16121814 -
Children (Basel, Switzerland) Jun 2024Shwachman Diamond Syndrome (SDS) is a multi-system disease characterized by exocrine pancreatic insufficiency with malabsorption, infantile neutropenia and aplastic... (Review)
Review
Lethal Complications and Complex Genotypes in Shwachman Diamond Syndrome: Report of a Family with Recurrent Neonatal Deaths and a Case-Based Brief Review of the Literature.
Shwachman Diamond Syndrome (SDS) is a multi-system disease characterized by exocrine pancreatic insufficiency with malabsorption, infantile neutropenia and aplastic anemia. Life-threatening complications include progression to acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), critical deep-tissue infections and asphyxiating thoracic dystrophy. In most patients, SDS results from biallelic pathogenic variants in the gene, different combinations of which contribute to heterogenous clinical presentations. Null variants are not well tolerated, supporting the theory that the loss of SBDS expression is likely lethal in both mice and humans. A novel complex genotype (SBDS:c.[242C>G;258+2T>C];[460-1G>A]/WFS1:c.[2327A>T];[1371G>T]) was detected in a family with recurrent neonatal deaths. A female neonate died three hours after birth with hemolytic anemia, and a male neonate with severe anemia, thrombocytopenia and neutropenia succumbed on day 40 after infection. A subsequent review of the literature focused on fatal complications, complex SBDS genotypes and/or unusual clinical presentations and disclosed rare cases, of which some had unexpected combinations of genetic and clinical findings. The impact of pathogenic variants and associated phenotypes is discussed in the context of data sharing towards expanding scientific expert networks, consolidating knowledge and advancing an understanding of novel underlying genotypes and complex phenotypes, facilitating informed clinical decisions and disease management.
PubMed: 38929284
DOI: 10.3390/children11060705 -
The Spine Journal : Official Journal of... Jun 2024Copper deficiency myelopathy (CDM) is a rare disease that can present with spastic quadriparesis and sensory ataxia. As a result, it can precisely mimic cervical... (Review)
Review
BACKGROUND AND CONTEXT
Copper deficiency myelopathy (CDM) is a rare disease that can present with spastic quadriparesis and sensory ataxia. As a result, it can precisely mimic cervical spondylitic myelopathy (CSM). Copper deficiency may be seen following gastric bypass surgery, malabsorption syndromes such as celiac disease, and with excessive exogenous zinc intake. We present a systematic review of the literature for CDM and an illustrative case .
PURPOSE
Provide a systematic review of CDM to highlight the importance of recognizing the consideration of CDM in patients presenting to a spine surgeon with myelopathy that progress despite adequate surgical decompression, or myelopathy concomitant with cytopenia, thus requiring further workup.
STUDY DESIGN/SETTING
Retrospective medical record review and systematic review of the literature PATIENT SAMPLE: PubMed and Ovid-Embase database search was conducted in July 2022 OUTCOME MEASURES: Self-reported measures include PRISMA flow diagram for retrospective review; Physiological measures include retrospective review of MRI imaging of cervical spine; alternate demographic and laboratory value data extracted via literature review METHODS: A PubMed and Ovid-Embase database search was conducted in July 2022 searching for "copper deficiency myelopathy [MeSH]" from 2000 to 2022 via PRISMA guidelines. Following title and abstract review, the following data was extracted from full text: age, sex, etiology, hematological values upon presentation (mean corpuscular volume, white blood count, platelet count, and hemoglobin level), metal serum studies (serum copper, ceruloplasmin, and zinc), 24-hour collection of copper and zinc, and distinct radiographic findings on MRI.
RESULTS
A total of 116 studies were included in this review which contained 198 cases of copper deficiency myelopathy. The mean age was 53.57 ± 14.14 years, with the majority being females (63.8%). The most common etiology was prior gastric surgery (n=55, 36.2 %) followed by excessive zinc consumption from the use of zinc denture cream (n=39, 19.9%)The mean serum copper was 15.67 ± 17.84 (normal=80.0-155.0) mcg/dL and mean ceruloplasmin was 6.43 ± 5.25 (normal=16-45) mg/dL. In spite of appropriate treatment with copper supplementation, only 47 cases (24%) reported improvement in neurological status, and only 10 (5.1%) recovered to baseline. A hyperintense T2 signal abnormality resembling an inverted "v" in the dorsal columns was the most common radiographic abnormality.
CONCLUSION
Pertinent risk factors for copper deficiency myelopathy include prior upper gastrointestinal surgery, zinc excess, and malabsorption. Characteristic laboratory and imaging findings include cytopenia, low serum copper and ceruloplasmin, and distinct inverted "v" T2 signal hyperintensity in the dorsal columns. The neurologic deterioration with copper deficiency will progress in spite of decompressive surgery, and can be devastating and irreversible even with copper supplementation, reinforcing the importance of early detection. We thus recommend patients with myelopathy presenting with a history of gastric bypass, malabsorption syndromes, excessive zinc exposure, cytopenia, or imaging resembling an inverted "v" shaped hyperintense T2 MRI signal in the dorsal columns, should first undergo blood tests for copper, ceruloplasmin, and B12 levels prior to surgical consideration.
PubMed: 38909910
DOI: 10.1016/j.spinee.2024.06.018