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Background and Aims: The clinical presentation of celiac disease (CD) has changed over time with more patients presenting with non-classical symptoms, extra-intestinal manifestations (EIM) or no symptoms. We aimed to investigate the main symptoms/signs leading to the diagnosis of CD in adult patients. As secondary end-point, we evaluated the outcome of gastrointestinal (GI) symptoms following gluten-free diet (GFD)., Methods: All consecutive CD adult patients referring to our University Hospital from September 2022 to February 2024 were included. Clinical data were retrospectively evaluated., Results: 134 patients, 104 females/30 males, median age at diagnosis 35 years, were included. 79 patients reported GI symptoms (i.e., diarrhea, abdominal bloating, dyspepsia) as the main symptom leading to CD diagnosis. In 40 patients, the leading symptom/sign was an EIM (i.e., iron deficiency anemia, infertility/miscarriages, dermatitis, osteoporosis, elevated transaminase levels). Fifteen patients were asymptomatic, being diagnosed because of a positive family history or concomitant autoimmune hypothyroidism. Of the 79 patients reporting GI symptoms, 20 did not experience complete resolution with the GFD. Among the 17 patients who reported a strict adherence to GFD (vs 1 patient with low-adherence, 2 non-compliant), lactose intolerance and irritable bowel syndrome overlap were diagnosed in 2 and 15 patients, respectively., Conclusion: GI manifestations remain the main symptoms at presentation of CD, however clinicians should be aware of the EIM of CD and the association with other autoimmune disorders. In non-responsive CD patients, an overlap with functional disorders might be considered., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Background: Individuals with Down syndrome (DS) exhibit higher risk for celiac disease (CD) than general population. Although literature suggests CD could be associated with behavioural problems in both paediatric and adult age, such association has been poorly explored in children and adolescents DS. Therefore, the current study aimed to investigate differences in emotional/behavioural difficulties, adaptive skills and sleep problems between children with DS with and without CD., Methods: Data were retrospectively collected from a database including data from 381 individuals with DS (3-18 years). The final sample included 65 participants, 27 with co-occurring CD and 38 age, IQ, sex and body mass index-matched controls without CD. Emotional/behavioural difficulties, adaptive skills and sleep problems were assessed through parent report questionnaires., Results: No group differences emerged in emotional/behavioural difficulties, whereas participants in the CD group showed better adaptive skills in the practical domain than control group. Weak differences emerged in sleep problems., Conclusions: Youth with DS and co-occurring CD do not exhibit more emotional and behavioural problems than youth with DS without co-occurring CD but exhibit better adaptive skills in the practical domain., (© 2024 The Authors. Journal of Intellectual Disability Research published by John Wiley & Sons and MENCAP.)

Background: Celiac Disease (CD) is characterized by small intestine involvement. However, cardiac manifestations may also be seen in the clinical course. The significance of the QRS prolongation and the presence of QRS fragmentation (fQRS) has been previously studied in many chronic inflammatory disorders as an independent predictor of cardiac manifestations. The study aimed to evaluate the QRS duration and presence of fQRS in patients with CD. Methods: 164 patients with CD and 162 healthy controls were included in the present study. QRS duration and presence of fQRS were calculated from the 12-lead electrocardiogram and compared between groups. The association between these parameters and disease duration was also evaluated. Results: QRS duration was found to be higher in the CD group compared to the control group (83 (76.8-93) vs. 91 (84-94), p<0.001). The presence of fQRS was demonstrated to be higher in the CD group (n=68 (41.5%) vs n=42 (25.9%), p=0.003). Notably, QRS duration was positively correlated with disease duration (Spearman's Rho= 0.47, p<0.001). In addition, disease duration was significantly higher in the fQRS (+) group (60 (23,5-144) vs. 28,5 (15-71,5), p=0.002). Conclusion: This study revealed that QRS prolongation and the presence of fQRS were higher in patients with CD. The presence of these findings may be an indicator of early subclinical cardiac involvement, especially in those with long disease duration. Thus, patients with these ECG findings can be considered for further cardiac evaluation., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Low bone mineral density (BMD) is common in adults with coeliac disease (CD), even in individuals adhering to a gluten-free diet (GFD). Women are more likely to have low BMD and have an increased risk of osteoporosis, so women with pre-existing low BMD related to CD are at an even higher risk. BMD assessed by dual X-ray absorptiometry (DXA) and bone quality assessed through quantitative ultrasound (QUS) were investigated in 31 premenopausal women with CD consuming a GFD, and 39 matched healthy controls from the Lower North Island, New Zealand. In addition, bone metabolism and nutrient status were assessed, and four-day diet diaries were used to estimate nutrient intake. No statistically significant differences were found in BMD assessed by DXA between the two groups at the hip, lumbar spine or forearm. However, the parameters measured by the QUS were significantly lower in CD participants. Dietary data indicated significantly lower intakes of energy, dietary fibre, magnesium and phosphorus in women with CD, likely as a result of a reduced intake of wholegrain foods, and suggested that both groups had inadequate intake of calcium. No significant differences were demonstrated in biochemical parameters. BMD and bone biomarkers indicated no differences between coeliac and healthy women in New Zealand. However, these findings suggest that QUS may be more sensitive for the coeliac population, due to the disease's affect on the trabecular bone, and warrant further research.

Background and Aim: Abnormalities in the reproductive functions are often ignored while evaluating a patient with celiac disease (CeD). We evaluated the entire reproductive functions in female patients with CeD., Methods: In a case control study between 2020 and 2021 using detailed questionnaire, we evaluated reproductive functions (age at menarche, menstrual pattern, fertility, pregnancy outcome and menopause) in biopsy-proven female patients with CeD of age >10 years. The questionnaire was administered either in person or telephonically. Age-matched healthy female controls (twice the number) were also recruited., Results: Of 1086 CeD patients, 470 were females and 288 were included. As compared with controls (n = 586), females with CeD had higher age at menarche (14.6 ± 2.0 vs 13.6 ± 1.5 years; P = 0.001), delayed menarche (30.8% vs 11.4%; P = 0.001), abnormal menstrual pattern (39.7% vs 25.8%; P < 0.001), involuntary delay in conception at > 1 year (33.8% vs 11.8%; P = 0.01), current infertility rate (10.5% vs 5.2%;P = 0.028), and poorer overall pregnancy outcomes (abortion [23.5% vs 12.8%; P = 0.001], pre-term birth [16.3% vs 3.7%; P = 0.001])., Conclusions: Either one or more aspect of reproductive functions and pregnancy outcome is affected adversely in three-fourth female patients with CeD., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: The present study aims to investigate the potential impact of celiac disease (CD) on hearing functions and assess the effect of a gluten-free diet (GFD) on this condition., Materials and Methods: The study included 55 children with CD (110 ears) and 25 healthy controls (50 ears) matched for age and gender. The CD group was divided into adherent (n = 31) and nonadherent (n = 24) to GFD. Participants underwent tympanometry and pure tone audiometry assessments covering frequencies from 500 to 4000 Hz., Results: Patients with CD showed significantly higher air and bone conduction hearing averages compared to the control group at frequencies of 500, 1000, 2000, and 4000 Hz for air conduction, and at 500 Hz for bone conduction (P < 0.05). Celiac patients, those who fully adhered to GFD, had notably higher air conduction hearing averages at 500, 2000, and 4000 Hz compared to healthy controls (P < 0.05). However, there was no difference in bone conduction hearing averages between the two groups. In contrast, celiac patients who did not comply with GFD had statistically significantly higher air and bone conduction hearing averages than the control group (P < 0.05), at frequencies of 500, 1000, and 4000 Hz for air conduction, and at 500 and 1000 Hz for bone conduction (P < 0.05)., Conclusions: The study suggests that nonadherence to GFD may elevate the risk of hearing loss in children with CD. As a result, it is recommended to conduct hearing screenings for children with CD and underscore the importance of complying with GFD to mitigate further detrimental effects on hearing functions., (Copyright © 2024 Copyright: © 2024 Nigerian Journal of Clinical Practice.)

Celiac disease (CeD) is likely to be associated with growth impairment and poor weight gain. However, long-term growth patterns following diagnosis are poorly characterized. We evaluated long-term anthropometric changes in a large cohort of pediatric patients with CeD. A retrospective chart review of patients diagnosed with CeD between 1999 and 2018 was conducted. Demographic and clinical data were collected, and anthropometrics were analyzed from diagnosis and throughout follow-up. The study included 500 patients (59.8% females, median (IQR) age at diagnosis 5.7 (3.7-8.9) years), with a mean follow-up of 5.5 (range 1.5-16.2) years. Weight, height, and BMI Z-score-for-age (WAZ, HAZ, and BMIZ) increased significantly from a mean (± SD) of - 0.82 (± 1.21), - 0.73 (± 1.16), and - 0.32 (± 1.11) at diagnosis to - 0.41 (± 1.23), - 0.45(± 1.16), and - 0.17 (± 1.14) at last follow-up, respectively (p < 0.001 for WAZ and HAZ and p = 0.002 for BMIZ). The largest improvements were observed in patients diagnosed before 3 years of age (p < 0.01). Patients for whom the final adult height was available (n = 86) improved from HAZ mean (± SD) - 0.89 ± 1.37 at diagnosis to - 0.51 ± 1.28 at adulthood measurement, p < 0.05. Wasting was present in 19.7% and stunting in 16.4% of the cohort at diagnosis and normalized in 77.3% and 64.8%, respectively, within a median (IQR) time of 0.79 (0.42-4.24) and 2.3 (0.72-6.02) years, respectively. Gluten-free diet adherence and frequency of visits were not associated with normalization of wasting or stunting in all age groups.  Conclusion: Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. Younger age at diagnosis is associated with greater improvement in weight and linear growth, emphasizing the importance of early diagnosis of CeD. What is Known: • Celiac disease (СeD) is likely to be associated with growth impairment and poor weight gain. • Long-term changes in anthropometric indices after diagnosis of CeD are not well characterized. What is New: • Over a long-term follow-up, pediatric patients with CeD demonstrate significant increases in weight, height, and BMI-for-age. • Young age at diagnosis is associated with larger improvement in weight and linear growth., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Brain fog is a subjective cognitive impairment commonly reported in coeliac disease. A standardised tool to define and assess it is an important unmet need., Aims: To develop a patient-informed tool to assess brain fog in coeliac disease to support clinical care, research and drug development., Methods: A pilot online study defined patient descriptors of brain fog. A second study evaluated the factor structure and performance of the scale across two-time points ('Now' and in the 'Past week'). One month later, participants were invited to repeat the study with two online cognitive processing tests, the Stroop task and the trail making test., Results: Among adults with treated coeliac disease, 37 (91.9% F) participated in the pilot study and 510 (88.8% F) in the second study of whom 99 repeated the study 1 month later with 51 completing cognitive testing. The most common brain fog descriptors were 'difficulty focusing', 'difficulty thinking' and 'difficulty finding the right words and communicating'. The 12-item scale reflects 'cognitive impairment' and 'somatic and affective experience' and demonstrates strong psychometric properties. It tracked with patients report of brain fog being present or absent across two-time points. It did not significantly correlate with the cognitive tests., Conclusion: The brain fog assessment and severity scale is the first patient-informed clinical outcomes assessment tool measuring brain fog in coeliac disease. It is brief and validated for two time-based formats. Further research coupling it with biomarker discovery is needed to confirm its validity as a predictor of cognitive performance., (© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Studies suggest an association between a gluten-free diet (GFD) and bone health in celiac disease (CD). However, the evidence on this relationship in children and adolescents is limited. Thus, this systematic review and meta-analysis aimed to analyze the effect of GFD on the bone health and anthropometric profile of children and adolescents with CD. Five databases were searched up to January, 2022 to identify relevant studies. The studies' methodological quality was evaluated using two scales. The Hedge's g standardized mean differences (SMD) with 95% confidence intervals were estimated using a random-effects model. The GRADE approach was used to assess the quality of evidence. Twenty-eight studies were included in the final review. GFD increased bone mineral content (BMC) (SMD = 0.39; 95%CI = 0.16, 0.62) and bone mineral density (BMD) (SMD = 0.29; 95%CI = 0.10, 0.47) in CD individuals. Difference in mean BMC and BMD between children and adolescents with CD versus healthy individuals was -0.49 (95%CI = -0.76, -0.22) and -0.47 (SMD = -95%CI = -0.72, -0.22), respectively. There was no difference in BMI and body fat among celiac children and adolescents versus healthy controls. In conclusion, GFD was associated with higher BMC and BMD in children and adolescents with CD.

Background: Although intestinal fungi are known to interact with the immune system, the relationship between intestinal fungi and childhood celiac disease (CeD), an immune-mediated condition, has rarely been reported., Aims: The aim of this study was to describe gut fungal profiles in a cohort of children with new-onset CeD., Methods: Mucosal and fecal samples were collected from children with CeD and controls and subjected to metagenomics analysis of fungal microbiota communities. DNA libraries were sequenced using Illumina HiSeq platform 2 × 150 bp. Bioinformatic analysis was performed to quantify the relative abundance of fungi. Shannon alpha diversity metrics and beta diversity principal coordinate (PCo) analyses were calculated, and DESeq tests were performed between celiac and non-celiac groups., Results: Overall more abundant taxa in samples of children with CeD included Tricholomataceae, Saccharomycetaceae, Saccharomycetes Saccharomyces cerevisiae, and Candida, whereas less abundant taxa included Pichiaceae, Pichia kudriavzevii, Pneumocystis, and Pneumocystis jirovecii. Alpha diversity between CeD and control individuals did not differ significantly, and beta diversity PCo analysis showed overlap of samples from CeD and controls for both fecal or mucosal samples; however, there was a clear separation between mucosal and fecal overall samples CONCLUSIONS: We report fungal dysbiosis in children with CeD, suggesting a possible role in the pathogenesis of CeD. Further larger, controlled, prospective and longitudinal studies are needed to verify the results of this study and clarify the functional role of fungi in CeD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Celiac disease (CD) is now viewed as a systemic disease with multifaceted clinical manifestations. Among the extra-intestinal features, neurological and neuropsychiatric symptoms are still a diagnostic challenge, since they can precede or follow the diagnosis of CD. In particular, it is well known that some adults with CD may complain of cognitive symptoms, that improve when the gluten-free diet (GFD) is started, although they may re-appear after incidental gluten intake. Among the neurophysiological techniques, motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) can non-invasively probe in vivo the excitation state of cortical areas and cortico-spinal conductivity, being also able to unveil preclinical impairment in several neurological and psychiatric disorders, as well as in some systemic diseases affecting the central nervous system (CNS), such as CD. We previously demonstrated an intracortical disinhibition and hyperfacilitation of MEP responses to TMS in newly diagnosed patients. However, no data are available on the central cholinergic functioning indexed by specific TMS measures, such as the short-latency afferent inhibition (SAI), which might represent the neurophysiological correlate of cognitive changes in CD patients, also at the preclinical level., Methods: Cognitive and depressive symptoms were screened by means of the Montreal Cognitive Assessment (MoCA) and the 17-item Hamilton Depression Rating Scale (HDRS), respectively, in 15 consecutive de novo CD patients and 15 healthy controls. All patients were on normal diet at the time of the enrolment. Brain computed tomography (CT) was performed in all patients. SAI, recorded at two interstimulus intervals (2 and 8 ms), was assessed as the percentage amplitude ratio between the conditioned and the unconditioned MEP response. Resting motor threshold, MEP amplitude and latency, and central motor conduction time were also measured., Results: The two groups were comparable for age, sex, anthropometric features, and educational level. Brain CT ruled out intracranial calcifications and clear radiological abnormalities in all patients. Scores at MoCA and HDRS were significantly worse in patients than in controls. The comparison of TMS data between the two groups revealed no statistically significant difference for all measures, including SAI at both interstimulus intervals., Conclusions: Central cholinergic functioning explored by the SAI of the motor cortex resulted to be not affected in these de novo CD patients compared to age-matched healthy controls. Although the statistically significant difference in MoCA, an overt cognitive impairment was not clinically evident in CD patients. Coherently, to date, no study based on TMS or other diagnostic techniques has shown any involvement of the central acetylcholine or the cholinergic fibers within the CNS in CD. This finding might add support to the vascular inflammation hypothesis underlying the so-called "gluten encephalopathy", which seems to be due to an aetiology different from that of the cholinergic dysfunction. Longitudinal studies correlating clinical, TMS, and neuroimaging data, both before and after GFD, are needed., Competing Interests: The authors have declared that no competing interests exist.

Background and Aim: We aimed to describe the socio-demographic, behavioral and clinical profiles of adult patients with newly diagnosed celiac disease (CeD) and their possible association with QoL and psychological symptoms., Methods: Adults newly diagnosed with CeD and residents in the Veneto region were included. Their sociodemographic characteristics, clinical presentation, mode of diagnosis, duration of symptoms before diagnosis and comorbidities were recorded. All patients completed the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI) and Short Form Health Survey (SF-36) questionnaires., Results: Between 2016 and 2019, 110 CeD patients (81% females, mean age 37.5) were recruited. At diagnosis, patients were categorized into classical (n = 56), nonclassical CeD (n = 49) and asymptomatic (n = 5) groups. Patients with classical presentation had a lower QoL than nonclassical patients, who were found to be more depressed. We observed a diagnosis delay of more than 7 months in more than 60% of patients with both classical and nonclassical presentations and we found that a longer duration of GI symptoms decreased the self-reported SF36 scores in the physical health (p = 0.002), social functioning (p = 0.03) and general health (p = 0.009) domains. Women had an overall lower self-perceived QoL., Conclusions: Symptomatic presentation at CeD diagnosis, diagnostic delay and sex may affect QoL and psychological disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Progress has been made in understanding coeliac disease, a relatively frequent and underappreciated immune-mediated condition that occurs in genetically predisposed individuals. However, several gaps remain in knowledge related to diagnosis and management. The gluten-free diet, currently the only available management, is not curative or universally effective (some adherent patients have ongoing duodenal injury). Unprecedented numbers of emerging therapies, including some with novel tolerogenic mechanisms, are currently being investigated in clinical trials. In March 2020, the Celiac Disease Foundation and the Society for the Study of Celiac Disease convened a consensus workshop to identify high-yield areas of research that should be prioritized. Workshop participants included leading experts in clinical practice, academia, government and pharmaceutical development, as well as representatives from patient support groups in North America. This Roadmap summarizes key advances in the field of coeliac disease and provides information on important discussions from the consensus approach to address gaps and opportunities related to the pathogenesis, diagnosis and management of coeliac disease. The morbidity of coeliac disease is often underestimated, which has led to an unmet need to improve the management of these patients. Expanded research funding is needed as coeliac disease is a potentially curable disease., (© 2021. Springer Nature Limited.)

Celiac disease (CD) may cause numerous nutrient deficiencies that a proper gluten-free diet (GFD) should compensate for. The study group consists of 40 children, aged 8.43 years (SD 3.5), on average, in whom CD was diagnosed on the basis of clinical symptoms, immunological and histopathological results. The patients' height, weight, diet and biochemical tests were assessed three times: before diagnosis, after six months, and following one year of GFD. After one year, the patients' weight and height increased but nutritional status (body mass index, BMI percentile) did not change significantly. The children's diet before diagnosis was similar to that of the general Polish population: insufficient implementation of the dietary norm for energy, fiber, calcium, iodine, iron as well as folic acid, vitamins D, K, and E was observed. Over the year, the GFD of the children with CD did not change significantly for most of the above nutrients, or the changes were not significant for the overall assessment of the diet. Celiac patients following GFD may have a higher risk of iron, calcium and folate deficiencies. These results confirm the need for personalized nutritional education aimed at excluding gluten from the diet, as well as balancing the diet properly, in patients with CD.

Aim: Celiac disease (CD) is an immune-mediated disorder with various manifestations. The aim of this study was to evaluate the prevalence of gastrointestinal (GI) and extra-intestinal symptoms of celiac patients, especially migraine, and compare it with healthy individuals., Methods: We compared 1000 celiac subjects (CS) registered at our celiac center with the control group for headache-based on International Classification of Headache Disorders, third edition criteria and their GI symptoms. Besides, CS with migraine and non-migrainous headache were compared in terms of GI symptoms and accompanied conditions., Results: Headache was more common in CS than controls (34% vs 27% respectively, P value<0.001) and more prevalent in females (71.9% in females vs 28% in males, P value = 0.004). Moreover, the prevalence of migraine in CS was higher than controls (20.7 vs 11.9% respectively, P value<0.001). Furthermore, migraine was more prevalent in females with CD (80% in females vs 19% in males, P value = 0.033), and often without aura (76%). Abdominal pain (76.9%, P value = 0.025), diarrhea (54.9%, P value = 0.002), and constipation (42.9%, P value = 0.011) were the most common GI symptoms in CS with headache and more prevalent in CS with migraine. Conversely, type 1 diabetes mellitus was less common in CS with migraine than in CS with non-migrainous headache. (P value = 0.001). On multivariate logistic regression analysis, female sex (OR 1.50, 95%CI 1.22-1.83, P value < 0.001), and CD (OR 1.36, 95%CI 1.12-1.65, P value = 0.002) were independent predictors of headache, whereas age more than 60 years (OR 0.70, 95%CI 0.50-0.97, P value = 0.032) had a protective effect., Conclusion: Headache especially migraine is more prevalent in CS than healthy controls. In addition, abdominal pain, diarrhea, and constipation are more common in CS with migraine than in CS with non-migrainous headaches. Therefore, evaluation of CD in patients with migraine and these simultaneous GI symptoms seems reasonable., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Angiotensin receptor blocker-associated enteropathy (ARB-e) is an increasingly recognised clinical entity with symptoms and histological findings identical to coeliac disease (CD). There is evidence to suggest immune-mediated mucosal injury in ARB-e with a high prevalence of DQ2/DQ8; however, as IgA anti-tissue transglutaminase (anti-TTG) is usually negative, an insult other than TTG-mediated injury is suspected. The impact of ARBs on disease activity in patients with CD is not known., Objective: To assess the effect of ARB exposure on patients with established CD., Methods: A patient record search of 1142 individual patients attending a dedicated coeliac clinic from 2010 to the present identified 59 patients treated with ARB. Those with CD confirmed by serology (TTG + ve/EMA + ve) and histopathology (Marsh criteria) were included (n = 40, 0.52%). Data collected included disease duration, compliance with gluten-free diet (GFD), reported symptoms (diarrhoea, weight loss and abdominal pain), surrogate markers of absorption (Vitamin D, Iron, Calcium and Haemoglobin), in addition to anti-TTG titre and histological grade at last follow up. Patients were age and sex-matched in a 1:2 ratio with CD patients not taking ARBs (controls), with comparable rates of disease duration and compliance with GFD., Results: The ARB and control groups were matched in terms of age (mean 66.2 years) and gender (female 63%). Strict compliance with GFD was reported in 55% and 56%, respectively. Persistent symptoms were reported in 10/40 (25%) of the ARB group compared with 7/82 (9%) of controls (p = 0.0181). There were lower rates of mucosal healing (Marsh grade 0) in the ARB group (36% n = 11) compared to controls (55%, n = 33). There was no significant difference in anti-TTG titres. Surrogate markers of absorption were comparable across the groups, except for Vitamin D which was lower in those taking olmesartan (p = 0.0015)., Conclusions: ARBs may aggravate the enteropathy and lead to increased symptoms in patients with bone fide diagnosed CD following a GFD., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Celiac disease (CD) is a chronic autoimmune disorder of small intestine against dietary gluten, among genetically predisposed individuals. Monocytes are versatile innate immune cells involved in the regulation of inflammation, and strongly involved in the intestinal immunity. However, the role of monocytes and their subtypes in CD is not well demonstrated., Methods: Here, we assessed the polarization of CD14+ monocytes by evaluating the M1 (CD16) and M2 (CD163) markers by flowcytometry, their soluble forms (sCD16 and sCD163), and the serum levels of IL-10, IL-12, TGF-β, and TNF-α cytokines using ELISA method, among 30 CD patients and 30 sex- and age-matched healthy subjects (HS). We also analyzed the diagnostic values of all variables with significant differences., Results: CD14+CD163+ monocytes were more frequent in CD patients than HS, while CD14+CD16+ monocytes were higher in HS. IL-10and TNF-α increased, and TGF-β expression was decreased among CD patients. The sCD16 serum levels were elevated in patients, while sCD163 was higher but not significant among CD patients. CD163+/CD16+ and IL-10/IL-12 ratios were higher in CD patients, and TGFβ/TNFα ratio was higher in HS group. IL-10, CD14+CD163+, TNF-α, and IL-10/IL-12 ratios with the AUC over 0.7 were introduced as fair diagnostic markers. Our findings revealed that the M2 (CD14+CD163+) monocytes were more frequent among CD patients, and the cytokine balance was disturbed., Conclusion: According to the significant functional diversities of monocyte subtypes between CD patients and HS group, these immunologic markers could be introduced as specific diagnostic biomarkers for CD., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Both celiac disease (CD) and type 1 diabetes (T1D) are autoimmune diseases resulting from a complex interplay between genetic susceptibility and environmental factors., Aim: In this retrospective study, we determined the frequency of auto-antibodies of T1D in adult patients with active CD., Materials and Methods: Eighty adult patients with active CD were included in our study. Ninety healthy blood donors (HBD) served as control group. Anti-glutamic acid decarboxylase IgG antibodies (GAD-Ab), anti-tyrosine phosphatase IgG antibodies (IA2-Ab), and anti-zinc transporter IgG antibodies (Zn-T8-Ab) were determined by enzyme-linked immunosorbent assay (ELISA) for patients and control group. For statistical analysis, we used Chi-square or Fisher's exact test., Results: Out of 80 patients, 10 (12.50%) had auto-antibodies of T1D vs. only one in control group (1.11%) (p = 0.003). Simultaneous presence of GAD-Ab, IA2-Ab, and Zn-T8-Ab was found in one patient (1.25%). Nine patients had only GAD-Ab. IA2-Ab and Zn-T8-Ab were absent in all HBD. The frequency of GAD-Ab was significantly higher in CD patients than in HBD (12.5% vs 1.11%, p = 0.003)., Conclusion: The present study has shown that CD is associated with a high frequency of auto-antibodies of T1D. Screening for T1D in this population, at risk for other autoimmune diseases, may be useful., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental conditions whose etiopathogenesis derives from a complex interaction between genetic liability and environmental factors. In this framework, mounting evidence suggests that immune system dysfunction could be a risk factor contributing to the development of ASD in at least a subpopulation of individuals. In particular, some studies suggest an association between celiac disease (CD)-a long-term autoimmune disorder that primarily affects the small intestine triggered by the ingestion of gluten-and ASD, while others hypothesized a random link. This investigation aimed to evaluate the prevalence of CD in a large sample of school-aged children with ASD and to characterize their clinical profile., Methods: Medical records of 405 children with ASD aged 5-11 years (mean age: 7.2 years; SD: 1.8 years) consecutively referred to a tertiary-care university hospital between January 2014 and December 2018 were reviewed; among them, 362 had carried out serological testing for CD., Results: Nine patients with positive CD serology were identified, eight of which satisfied the criteria for CD diagnosis. The estimated CD prevalence in ASD children was 2.18% (95% CI, 0.8-3.7), which was not statistically different (1.58%; p = 0.36) from that of an Italian population, matched for age range, considered as a control group (95% CI, 1.26-1.90). Three out of the eight ASD patients with CD did not have any symptoms suggestive of CD., Conclusions: Our findings did not show a higher prevalence of CD in ASD children than in the control population, but could suggest the utility of routine CD screening, given its frequent atypical clinical presentation in this population.

Celiac disease (CD) is a chronic autoimmune disorder of the small intestine, whose only effective treatment is a gluten-free diet (GFD). It is characterized by the atrophy of the intestinal villi that leads to altered nutrient absorption. This study describes the nutritional imbalances which may be found in adults with CD following a GFD. During the first year of treatment, deficiencies will overcome as the intestinal mucosa recovers. Thus, biochemical data will show this progression, together with the decrease in symptoms. In contrast, in the long term, when a strict GFD is followed and mucosal recovery is achieved, analyzing nutrient intake makes more sense. Macronutrient consumption is characterized by its low complex carbohydrate and fiber intakes, and high fat (especially SFA) and sugar intakes. This profile has been related to the consumption of GFP and their nutritional composition, in addition to unbalanced dietary habits. The most notable deficiencies in micronutrients are usually those of iron, calcium and magnesium and vitamin D, E and some of group B. It is necessary to follow up patients with CD and to promote nutritional education among them, since it could help not only to achieve a gluten free but also a balanced diet.

Our understanding of the pathophysiology of celiac disease has progressed greatly over the past 25 years; however, some fallacies about the clinical characteristics and management persist. Worldwide epidemiologic data are now available showing that celiac disease is ubiquitous. An elevated body mass index is common at the time of the diagnosis. The gluten-free diet (GFD) is an imperfect treatment for celiac disease; not all individuals show a response. This diet is widely used by people without celiac disease, and symptomatic improvement on a GFD is not sufficient for diagnosis. Finally, the GFD is burdensome, difficult to achieve, and thus has an incomplete efficacy, opening exciting opportunities for novel, nondietary treatments., (Copyright © 2021 by The American College of Gastroenterology.)

We have previously shown that 67% of patients with newly diagnosed coeliac disease (CD) presenting to gastroenterologists have evidence of neurological dysfunction. This manifested with headache and loss of co-ordination. Furthermore 60% of these patients had abnormal brain imaging. In this follow-up study, we re-examined and re-scanned 30 patients from the original cohort of 100, seven years later. There was significant reduction in the prevalence of headaches (47% to 20%) but an increase in the prevalence of incoordination (27% to 47%). Although those patients with coordination problems at baseline reported improvement on the gluten free diet (GFD), there were 7 patients reporting incoordination not present at baseline. All 7 patients had positive serology for one or more gluten-sensitivity related antibodies at follow-up. In total, 50% of the whole follow-up cohort were positive for one or more gluten-related antibodies. A comparison between the baseline and follow-up brain imaging showed a greater rate of cerebellar grey matter atrophy in the antibody positive group compared to the antibody negative group. Patients with CD who do not adhere to a strict GFD and are serological positive are at risk of developing ataxia, and have a significantly higher rate of cerebellar atrophy when compared to patients with negative serology. This highlights the importance of regular review and close monitoring.

The iron absorption process developsmainly in the proximal duodenum. This portion of the intestine is typically destroyed in celiac disease (CD), resulting in a reduction in absorption of iron and subsequent iron deficiency anemia (IDA). In fact, the most frequent extra-intestinal manifestation (EIM) of CD is IDA, with a prevalence between 12 and 82% (in relation with the various reports) in patients with new CD diagnosis. The primary treatment of CD is the gluten-free diet (GFD), which is associated with adequate management of IDA, if present. Iron replacement treatment historically has been based on oral products containing ferrous sulphate (FS). However, the absorption of FS is limited in patients with active CD and unpredictable in patients on a GFD. Furthermore, a poor tolerability of this kind of ferrous is particularly frequent in patients with CD or with other inflammatory bowel diseases. Normalization from anemic state typically occurs after at least 6 months of GFD, but the process can take up to 2 years for iron stores to replenish.

Background: Celiac disease (CD) may present or be complicated by neurological and neuropsychiatric manifestations. Transcranial magnetic stimulation (TMS) probes brain excitability non-invasively, also preclinically. We previously demonstrated an intracortical motor disinhibition and hyperfacilitation in de novo CD patients, which revert back after a long-term gluten-free diet (GFD). In this cross-sectional study, we explored the interhemispheric excitability by transcallosal inhibition, which has never been investigated in CD., Methods: A total of 15 right-handed de novo, neurologically asymptomatic, CD patients and 15 age-matched healthy controls were screened for cognitive and depressive symptoms to the Montreal Cognitive Assessment (MoCA) and the 17-item Hamilton Depression Rating Scale (HDRS), respectively. TMS consisted of resting motor threshold, amplitude, latency, and duration of the motor evoked potentials, duration and latency of the contralateral silent period (cSP). Transcallosal inhibition was evaluated as duration and latency of the ipsilateral silent period (iSP)., Results: MoCA and HDRS scored significantly worse in patients. The iSP and cSP were significantly shorter in duration in patients, with a positive correlation between the MoCA and iSP., Conclusions: An intracortical and interhemispheric motor disinhibition was observed in CD, suggesting the involvement of GABA-mediated cortical and callosal circuitries. Further studies correlating clinical, TMS, and neuroimaging data are needed.

Background & Aims: Environmental enteric dysfunction (EED) limits the Sustainable Development Goals of improved childhood growth and survival. We applied mucosal genomics to advance our understanding of EED., Methods: The Study of Environmental Enteropathy and Malnutrition (SEEM) followed 416 children from birth to 24 months in a rural district in Pakistan. Biomarkers were measured at 9 months and tested for association with growth at 24 months. The duodenal methylome and transcriptome were determined in 52 undernourished SEEM participants and 42 North American controls and patients with celiac disease., Results: After accounting for growth at study entry, circulating insulin-like growth factor-1 (IGF-1) and ferritin predicted linear growth, whereas leptin correlated with future weight gain. The EED transcriptome exhibited suppression of antioxidant, detoxification, and lipid metabolism genes, and induction of anti-microbial response, interferon, and lymphocyte activation genes. Relative to celiac disease, suppression of antioxidant and detoxification genes and induction of antimicrobial response genes were EED-specific. At the epigenetic level, EED showed hyper-methylation of epithelial metabolism and barrier function genes, and hypo-methylation of immune response and cell proliferation genes. Duodenal coexpression modules showed association between lymphocyte proliferation and epithelial metabolic genes and histologic severity, fecal energy loss, and wasting (weight-for-length/height Z < -2.0). Leptin was associated with expression of epithelial carbohydrate metabolism and stem cell renewal genes. Immune response genes were attenuated by giardia colonization., Conclusions: Children with reduced circulating IGF-1 are more likely to experience stunting. Leptin and a gene signature for lymphocyte activation and dysregulated lipid metabolism are implicated in wasting, suggesting new approaches for EED refractory to nutritional intervention. ClinicalTrials.gov, Number: NCT03588013. (https://clinicaltrials.gov/ct2/show/NCT03588013)., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: non-autoimmune thyroid disorder is a common finding in celiac patients, more frequent than in the general population. An impairment of iodine absorption has been hypothesized, but it has never been investigated so far. We aimed to evaluate the iodine absorption in children and adolescents with newly diagnosed celiac disease. Methods: 36 consecutive celiac patients (age 7.4 years, range 2.4-14.5 years) before starting a gluten-free diet (GFD) were enrolled. We assayed the urinary iodine concentration (UIC) in a 24-h urine sample, at baseline (T0) after 3 (T1) and 12 months (T2) of GFD. Results: UIC at T0 was 64 μg/L (IQR 45-93.25 μg/L) with an iodine deficiency rate of 77.8%. UIC was not different according to histological damage, clinical presentation (typical vs atypical); we found no correlation with the thyroid function tests and auxological parameters. UIC was not statistically different at T1 (76 μg/L) and T2 (89 μg/L) vs T0. UIC at T2 was similar between patients with positive and negative anti-transglutaminase antibodies at T2. No patients presented overt hypothyroidism during the study. Conclusions : We found that iodine absorption in celiac children is impaired compared to the general population; it increases slightly, but not significantly, during the GFD. We should regularly reinforce the need for a proper iodine intake in celiac disease patients to reduce iodine deficiency risk.

We aimed to assess Health-Related Quality of Life (HRQoL) of Italian children and their parents with coeliac disease (CD) using the Coeliac Disease Dutch Questionnaire (CDDUX). The CDDUX underwent a cross-cultural adaptation in a multi-step process, according to international guidelines. A total of 224 children aged between 8-18 years and their parents were prospectively recruited. Cronbach α coefficient was determined as a measure of internal consistency of the questionnaire and inter-children/parent reliability by intraclass correlation coefficient. Univariate and bivariate regression models were used to evaluate correlations between clinical variables and children and parents subclasses of CDDUX and overall mean Paediatric Quality of Life Inventory (PedsQL). The Italian CDDUX proved to be valid and reliable, mean CDDUX total score revealing a neutral evaluation of the quality of life in children 52.6 ± 17.2 and parents 49.5 ± 17.9 ( p = 0.07) with strong correlation with PedsQL. The only clinical variable which appeared to affect significantly quality of life both in children and parents was the lower age. A comparison with our results showed remarkable differences in the HRQoL of populations of various nationalities. The Italian version of the CDDUX questionnaire is a simple and reliable tool for assessing the HRQoL in children and adolescents with CD.

The World Health Organization declared coronavirus disease-2019 (COVID-19) a global pandemic in March 2020. Since then, there are more than 34 million cases of COVID-19 leading to more than 1 million deaths worldwide. Numerous studies suggest that celiac disease (CeD), a chronic immune-mediated gastrointestinal condition triggered by gluten, is associated with an increased risk of respiratory infections. 1-3 However, how it relates to the risk of COVID-19 is unknown. To address this gap, we conducted a cross-sectional study to evaluate whether patients with self-reported CeD are at an increased risk of contracting COVID-19., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The intestinal epithelium limits host-luminal interactions and maintains gut homeostasis. Breakdown of the epithelial barrier and villous atrophy are hallmarks of coeliac disease. Besides the well characterized immune-mediated epithelial damage induced in coeliac mucosa, constitutional changes and early gluten direct effects disturb intestinal epithelial cells. The subsequent modifications in key epithelial signaling pathways leads to outnumbered immature epithelial cells that, in turn, facilitate epithelial dysfunction, promote crypt hyperplasia, and increase intestinal permeability. Consequently, underlying immune cells have a greater access to gluten, which boosts the proinflammatory immune response against gluten and positively feedback the epithelial damage loop. Gluten-free diet is an indispensable treatment for coeliac disease patients, but additional therapies are under development, including those that reinforce intestinal epithelial healing. In this chapter, we provide an overview of intestinal epithelial cell disturbances that develop during gluten intake in coeliac disease mucosa., (© 2021 Elsevier Inc. All rights reserved.)

Assessment of adherence to gluten-free diet (GFD) represents the cornerstone in the management of coeliac disease. The primary aim of this study was to assess diet adherence through a questionnaire adapted to children. The secondary aim was to identify influencing factors and outcomes related to diet adherence. In this study, data about diagnosis, education, quality of life (QoL) and anti-transglutaminase (anti-TG2) titers of 160 coeliac children were collected. For the assessment of diet adherence, all participants completed the questionnaire modified from Leffler et al. (2009), while a random sample of 37 also underwent an extensive dietary interview. According to the questionnaire, diet adherence was excellent in 95 (59.4%), fair in 46 (28.8%) and low in 19 (11.9%) patients. Children diagnosed with biopsy showed better adherence than those with a biopsy-sparing approach ( p = 0.036). Adherence to GFD tended to worsen during the follow up, with the average length of follow up being associated with lower scores of diet adherence ( p = 0.009). Moreover, adherence to GFD decreased throughout school career, dropping from elementary until high school ( p = 0.037). A positive correlation was observed between adherence to GFD and growth percentiles, which increased when higher scores of adherence were achieved. Diet adherence positively correlated with QoL ( p = 0.001). In conclusion, the questionnaire displayed good sensitivity in detecting problems in diet adherence, being useful as a screening tool. Better comprehension of influencing factors and outcomes may allow the development of new strategies to improve diet adherence.

Malabsorption due to celiac disease (CD) may contribute to postmenopausal osteoporosis. This study aimed to survey participants with CD regarding their bone density, fractures, and bone-preserving medications; to compare tolerance of bone-preserving medications in participants with and without CD; and to review the evidence for CD screening and osteoporosis therapies in the setting of CD. We recruited 131 participants with CD and 102 participants without CD. Of those with CD, 87% were diagnosed in adulthood and 40% had no recognized gastrointestinal symptoms. In 21% CD was diagnosed after the diagnosis of osteoporosis and in 9% after a fracture. No difference was found in the tolerability of bone medications between participants with CD and those without. Review of the literature found that, although monitoring of bone health is recommended for patients with CD, screening for CD is not generally accepted for patients with osteoporosis, although studies of the prevalence of CD in osteoporosis had incomplete ascertainment methods. There is a lack of well-conducted studies and therefore insufficient data for the efficacy and tolerability of bone medication in CD. In conclusion, both CD and menopause lead to bone loss. Identifying CD in postmenopausal women should lead to modification of osteoporosis management.

The aims of the present study were to estimate the celiac disease (CD) prevalence in Denmark and the relevance of the test for human leukocyte antigen DQ2 and DQ8 haplotypes (HLA-DQ2/DQ8) for diagnosing CD. The plasma IgA transglutaminase antibody (TGA-IgA) and HLA-DQ2/DQ8 tests should normally be positive for a CD diagnosis. First, we estimated the CD and HLA-DQ2/DQ8 prevalence in the available blood samples collected at the North Zealand Hospital. Out of a total of 9754 patients, with symptoms suggestive of CD (such as malabsorption, diarrhea, steatorrhea, ion-deficiency anemia, and weight loss or growth failure), 153 patients had TGA-IgA positive results (i.e. TGA-IgA > 10 U/mL). In this cohort, the prevalence of CD was 0.912% and the prevalence of HLA-DQ2/DQ8 positive patients was estimated to be 62%. Based on the distribution of HLA-DQ2/DQ8 positive individuals in the general Danish population, a calculation of CD prevalence in Denmark was found to be maximum 0.77%. Second, we analysed for the HLA-DQ2/DQ8 haplotypes in 293 positive plasma TGA-IgA samples. Nearly all (99%) of the CD patients and non-CD patients were HLA-DQ2/DQ8 positive.

Experimental and epidemiological evidence has shown that modifications of the intrauterine environment can have deleterious consequences for individuals, expressed as an increased risk of suffering non-communicable pathologies in adult life, which is known as the hypothesis of the early origin of diseases or fetal programming. On the other hand, changes in gene expression patterns through epigenetic modifications can be the basis for long-term maintenance of the effects of fetal programming. In this sense, epigenetics comprises the study of intrauterine disturbances, which develop diseases in the adult, including celiac disease (CD). In addition, early feeding practices could influence the risk of CD development, such as breastfeeding timing and duration and age of gluten introduction in the diet. Gluten acts as a trigger for CD in genetically predisposed subjects, although approximately 30% of the world population has HLA DQ2 or DQ8, the prevalence of the disease is only 1-3%. It is not known what factors act to modify the risk of disease in genetically at-risk subjects. Taking into account all these considerations, the aim of the current review is to elucidate the role of early programming and the effect of early nutrition on the development and progression of CD. It is logical that attention has been paid to gluten as a key element in preventing the disease. However, there is no strong evidence in favor of the protective factor of breastfeeding, timing of introduction of gluten during lactation, and the development of CD. Diet, genetic risk, microbiota, and environmental interaction are possible triggers of the change in tolerance to an immune response to gluten, but large-scale cohort studies are needed. Emerging scientific concepts, such as epigenetics, may help us establish the role of these factors.

Purpose: The aim of the study was to determine whether celiac disease affects ovarian reserve assessed by antral follicle counting, ovarian volume, and anti-müllerian hormone in adolescent patients., Methods: This case-control multicenter trial was performed from January 1, 2017 to May 31, 2018 and included 45 girls. On days 2-5 of the menstrual cycle, measurements of serum follicle stimulating hormone, luteinizing hormone, estradiol, prolactin, and anti-müllerian hormone were performed. Antral follicle counts and ovarian volumes were determined on the same day., Results: Evaluation was made of 21 (47.7%) celiac patients with a mean age of 15.8 ± 1.3 years, and 24 (52.3%) healthy control subjects with a mean age of 16.2 ± 1.2. There was no difference between the groups in respect of right and left ovarian volumes (p = 0.790 and p = 0.670, respectively). Serum levels of anti-müllerian hormone of the celiac patients and controls were found comparable [(3.7 ± 2.9 (0.5-12) and 3.6 ± 1.8 (1.2-8.1)] ng/mL, respectively, p = 0.915)., Conclusions: Celiac disease may not affect the ovarian reserve determined with established ovarian reserve markers including antral follicle counting, ovarian volume, and anti-müllerian hormone in adolescent patients., Trial Registration: ClinicalTrials.gov identifier (NCT number): NCT04024449 https://clinicaltrials.gov/ct2/show/NCT04024449.

Coeliac disease (CD) and noncoeliac wheat or gluten sensitivity (NCWS/NCGS) are common gluten-related disorders. Both conditions can present with gastrointestinal and extraintestinal manifestations, which can be a challenge for physicians to discern between. Whilst coeliac serology and histological assessment are required for the diagnosis of CD, there are no clear biomarkers for the diagnosis of NCGS. The management of both conditions is with a gluten-free diet (GFD), although the duration, as well as strictness of adherence to a GFD in NCGS, is unclear. Adherence to a GFD in CD can also be challenging, with recent developments of noninvasive assessments, although histological assessment via duodenal biopsies remains the gold standard. The management of refractory coeliac disease remains particularly challenging, often requiring specialist input. Whilst wheat is noted to be a trigger for symptom generation in NCGS, it is unclear which components of wheat are responsible for symptom generation in this group, with further research required to elucidate the pathophysiology., (© 2020 The Association for the Publication of the Journal of Internal Medicine.)

Introduction: Many patients with celiac disease (CD) experience persistent symptoms despite adhering to the gluten-free diet. Different studies have assessed the use of probiotics as an adjuvant treatment for CD. We performed a systematic review and meta-analysis to evaluate the efficacy of probiotics in improving gastrointestinal (GI) symptoms and quality of life (QOL) in patients with CD., Methods: We searched EMBASE, MEDLINE, CINAHL, Web of Science, CENTRAL, and DARE databases up to February 2019 for randomized controlled trials (RCTs) evaluating probiotics compared with placebo for treating CD. We collected data on GI symptoms, QOL, adverse events, serum tumor necrosis factor-α, intestinal permeability, and microbiota composition., Results: We screened 2,831 records and found that 7 articles describing 6 RCTs (n = 279 participants) were eligible for quantitative analysis. Probiotics improved GI symptoms when assessed by the GI Symptoms Rating Scale (mean difference symptom reduction: -28.7%; 95% confidence interval [CI] -43.96 to -13.52; P = 0.0002). There was no difference in GI symptoms after probiotics when different questionnaires were pooled. The levels of Bifidobacteria increased after probiotics (mean difference: 0.85 log colony-forming units (CFU) per gram; 95% CI 0.38-1.32 log CFU per gram; P = 0.0003). There were insufficient data on tumor necrosis factor-a levels or QOL for probiotics compared with placebo. No difference in adverse events was observed between probiotics and placebo. The overall certainty of the evidence ranged from very low to low., Discussion: Probiotics may improve GI symptoms in patients with CD. High-quality clinical trials are needed to improve the certainty in the evidence (see Visual abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B595).

Introduction: Growth impairment has often been described in children who develop coeliac disease (CD). Based on data from the multicentre, longitudinal PreventCD study, we analysed the growth patterns of infants at genetic risk of CD, comparing those who developed CD by 6 years of age (CD 'cases', 113 infants) versus those who did not develop CD by 6 years (no CD 'controls', 831 infants)., Methods: Weight and length/height were measured using a longitudinal protocol. Raw measurements were standardised, computing z-scores for length/height and weight; a linear mixed model was fitted to the data in order to compare the rate of growth in the two cohorts., Results: Neither cases nor controls had significant growth failure. However, when the mean z-scores for weight and height were analysed, there was a difference between the two groups starting at fourth month of life. When the growth pattern in the first year was analysed longitudinally using mixed models, it emerged that children who develop CD had a significantly lower growth rate in weight z-score (-0.028/month; 95% CI -0.038 to -0.017; p<0.001) and in length/height z-score (-0.018/month; 95% CI -0.031 to -0.005; p=0.008) than those who do not develop CD. When the whole follow-up period was analysed (0-6 years), differences between groups in both weight and length/height z-scores were confirmed., Conclusion: The growth of children at risk of CD rarely fell below 'clinical standards'. However, growth rate was significantly lower in cases than in controls. Our data suggest that peculiar pathways of growth are present in children who develop CD, long before any clinical or serological signs of the disease appear., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Aims: Aberrations in body composition are expected in children suffering from chronic inflammatory conditions. The objective is to examine whether children with inflammatory bowel disease (IBD: Crohn's disease and ulcerative colitis), coeliac disease, asthma and juvenile idiopathic arthritis (JIA) have an altered body composition as compared to healthy children., Methods: A systematic review, registered in Prospero (registration number: CRD42018107645), was conducted according to PRISMA guidelines. We conducted a search of three databases, Pubmed, Cochrane and Scopus. An assessment of the quality of the study was performed., Results: Data from 50 studies, 32 with IBD, 8 with coeliac disease, 2 with asthma and 8 with JIA, involving 2399 children were selected for review after applying the eligibility criteria. In all but 4 studies, children with Crohn's disease exhibited decreased amounts of fat mass and fat free mass. Reductions in fat mass were also evident in studies in children with coeliac disease. It is uncertain whether body composition is altered in children with asthma or JIA., Conclusions: Children with Crohn's disease manifest with lowered adiposity and lean mass and therefore are likely to be at risk for suffering malnutrition-related clinical complications. Apart from Crohn's disease, data examining body composition in children with chronic inflammatory conditions are scarce and there is a paucity of reports examining the relationship between inflammation and body composition. Interpretation of the current study results is hampered by the low quality of the studies and due to the fact that the analyses have been habitually secondary outcomes., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

In literature, there are conflicting opinions on the development of cardiovascular disease risk in patients with coeliac disease (CD). The aim of the research was to identify in young subjects without cardiovascular risk factor and newly diagnosed CD, alterations in different instrumental parameters that are associated with an augmented cardiovascular risk. Twenty-one consecutive young adults with a new diagnosis of CD and without cardiovascular risk factors were prospectively enrolled and underwent transthoracic echocardiography to analyse ascending aorta elastic properties [including tissue Doppler imaging strain (TDI-ε)] and left ventricular 2D strains (global longitudinal, radial and circumferential), and applanation tonometry by SphygmoCor. Cases were compared with 21 age- and sex-matched healthy controls. Mean age of the cases was 38 ± 9 years and 15 of them (71%) were female. Brachial and central blood pressure was higher in the CD group. Elastic properties of the ascending aorta were all impaired in the CD group: TDI-ε was altered in 57% of cases (0% of controls, p < 0.001). Concentric remodelling and grade I diastolic dysfunction were present in 38% and 24% of cases, respectively (0% of controls, p < 0.001). Global longitudinal strain was normal in all subjects, while radial and circumferential strain were altered in 67% and 35%, respectively (0% of controls, p < 0.001). In young subjects without cardiovascular risk factor, a newly diagnosed CD is associated with altered aortic elastic properties, left ventricular concentric remodelling and diastolic dysfunction and altered radial and circumferential strain.

Context: Consensus regarding diagnosis and management of osteoporosis in premenopausal women (PW) is still lacking due to few studies carried out in this population., Design: The European Calcified Tissue Society and the International Osteoporosis Foundation convened a working group to produce an updated review of literature published after 2017 on this topic., Results: Fragility fractures in PW are rare and mostly due to secondary osteoporosis (ie, in presence of an underlying disease such as hormonal, inflammatory, or digestive disorders). In absence of another disorder, low bone mineral density (BMD) together with fragility fractures qualifies as idiopathic osteoporosis. In contrast, low BMD alone does not necessarily represent osteoporosis in absence of bone microarchitectural abnormalities. BMD increases in PW with osteoporosis when the underlying disease is treated. For example, in celiac disease, an increase of 9% in radius trabecular volumetric density was achieved after 1 year of gluten-free diet, while anti-tumor necrosis factor alpha improved BMD in PW with inflammatory bowel diseases. In amenorrhea, including anorexia nervosa, appropriately delivered estrogen replacement therapy can also improve BMD. Alternatively, antiresorptive or anabolic therapy has been shown to improve BMD in a variety of conditions, the range of improvement (3%-16%) depending on skeletal site and the nature of the secondary cause. No studies were powered to demonstrate fracture reduction. The effects of bisphosphonates in childbearing women have been scantly studied and caution is needed., Conclusion: The majority of PW with osteoporosis have an underlying disease. Specific therapy of these diseases, as well as antiresorptive and anabolic drugs, improve BMD, but without evidence of fracture reduction., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The objectives of this scoping review were to identify and characterize studies examining nutrition assessment, interventions, and measures to monitor gluten-free diet (GFD) adherence/compliance in patients with celiac disease (CD). An electronic literature search of four databases (Cochrane Database for systematic reviews, CINAHL, Embase, and Ovid MEDLINE) was conducted to identify articles examining nutrition care in CD individuals. Except for narrative review, grey literature, and case study/report, all types of peer-reviewed articles published between January 2007 and August 2018 were eligible. There were a total of 10,823 records; 10,368 were excluded during the first round of screening due to irrelevancy and/or duplication. Of the 455 full-text articles that were assessed, 292 met the criteria and were included. Most of the studies were observational studies (n=212), followed by experimental trials (n=50), evidence-based practice guideline (EBPG)/report/statement (n=16), and systematic review (SR) (n=14). Nine original studies examined assessment, focusing mainly on different tools/ways to assess GFD adherence. The majority of the included original articles (n=235) were in the nutrition intervention category with GFD, oats, and prebiotics/probiotics as the top-three most studied interventions. There were eight SRs on GFD and five on oats. One SR and 21 original studies investigated the effectiveness of different measures to monitor GFD adherence/compliance. Although recent CD EBPGs were identified, different methods with varying levels of rigor, in terms of literature search and assessment of evidence strength, were used. Based on this scoping review, interventions focused on gluten-free diet and oats have been significantly covered by either SRs or EBPGs. Studies related to prebiotics/probiotics and education program/counseling focused interventions, as well as assessment, in CD patients have increased in recent years. Thus, it might be beneficial to conduct SRs/EBPGs focused on these topics to guide practitioners., (Copyright © 2020 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Coeliac disease is a common small bowel enteropathy arising in genetically predisposed individuals and caused by ingestion of gluten in the diet. Great advances have been made in understanding the role of the adaptive immune system in response to gluten peptides. Despite detailed knowledge of these adaptive immune mechanisms, the complete series of pathogenic events responsible for development of the tissue lesion remains less certain. This review contributes to the field by discussing additional mechanisms which may also contribute to pathogenesis. These include the production of cytokines such as interleukin-15 by intestinal epithelial cells and local antigen presenting cells as a pivotal event in the disease process. A subset of unconventional T cells called gamma/delta T cells are also persistently expanded in the coeliac disease (CD) small intestinal epithelium and recent analysis has shown that these cells contribute to pathogenic inflammation. Other unconventional T cell subsets may play a local immunoregulatory role and require further study. It has also been suggested that, in addition to activation of pathogenic T helper cells by gluten peptides, other peptides may directly interact with the intestinal mucosa, further contributing to the disease process. We also discuss how myofibroblasts, a major source of tissue transglutaminase and metalloproteases, may play a key role in intestinal tissue remodeling. Contribution of each of these factors to pathogenesis is discussed to enhance our view of this complex disorder and to contribute to a wider understanding of chronic immune-mediated disease., (Copyright © 2020 Dunne, Byrne, Chirdo and Feighery.)

Introduction: Duodenal eosinophilia is a key feature of functional dyspepsia, particularly in those with early satiety. Duodenal eosinophilia is also recognised in coeliac disease, although its relevance to symptoms is not understood. We aimed to determine if duodenal eosinophilia is present in patients with coeliac disease presenting with dyspepsia, and whether other histological characteristics were associated with clinical features on presentation. Methods: The coeliac study population comprised 61 patients with a new presentation of coeliac disease to a single centre from 2003 to 2013. A standard symptom assessment was documented for all patients. The control population (55 adults) presenting for endoscopy without coeliac disease was drawn from the same centre with similar demographics for age and gender. Duodenal biopsies from both groups were assessed for eosinophil counts and histological features. Results: Dyspepsia was present in 18.0% of coeliac patients and early satiety in 24.6%. The eosinophil counts were significantly higher in the stomach (12.1/mm 2 vs. 4.0/mm 2 , p  < .001) and duodenum (60.4/mm 2 vs. 18.0/mm 2 , p  < .001) of coeliac patients compared with controls. There was no significant difference in the mean duodenal eosinophil count in coeliac disease with and without early satiety (55.4/mm 2 vs. 66.9/mm 2 , p  = .51). Duodenal eosinophilia was not associated with the severity of coeliac enteropathy. The degree of villous atrophy was associated with iron deficiency at presentation ( p  = .01), but not symptoms. Conclusions: Although duodenal eosinophil counts are higher in coeliac disease than controls, we were not able to demonstrate an association with presenting symptoms or markers of disease severity.

Objectives: Celiac disease is an autoimmune disorder that develops because of sensitivity to gluten-containing grains in genetically disposed individuals. Nasal mucociliary clearance is the most important protective factor that protects the upper and lower airways from foreign particulates. This study aimed to investigate the effect of celiac disease on nasal mucociliary clearance., Methods: The study included patients with celiac disease and healthy children. Nasal mucociliary clearance time was measured using the saccharin test. The children's saccharin taste time was recorded in seconds., Results: Overall, 65 children were included: 43 patients with celiac disease (66.2%) and 22 healthy children (33.8%). Of all the children, 42 (64.6%) were female, and the average age was 11.8 ± 4 years. Nasal mucociliary clearance time of patients with celiac disease (531 ± 155 s) was significantly prolonged in comparison to that of healthy children (448 ± 80 s) (p = 0.006). No relationships were found between the diagnosis age, celiac type, and histopathological phase and compliance with the gluten-free diet and nasal mucociliary clearance time of patients with celiac disease., Conclusions: This study showed that nasal mucociliary clearance was prolonged in patients with celiac disease. A defect in nasal mucociliary clearance increases the risk of infection and inflammation in small airways. Studies reported a high prevalence of respiratory tract infection in patients with celiac disease, which was associated with malnutrition, vitamin deficiency, and hyposplenism. The findings of the present study indicated that impairment of nasal mucociliary clearance could play a role in the development of frequent lung infections in patients with celiac disease., Competing Interests: Declaration of competing interest No conflict of interest was declared by the authors., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction . Celiac disease, an autoimmune enteropathy, occurs in susceptible individuals and is treatable with a gluten-free diet. These may not be supplemented with vitamins. Objective . To assess the nutritional health of children who have biopsy-proven celiac disease. Methods . Charts were reviewed between July 1, 2007, and June 30, 2017. Results . A total of 252 children ages 0 to 21 years had biopsy-proven celiac disease, mean age 11 ± 4.1 years. Body mass index Z -score was 0.2 ± 1.2 at diagnosis. Except for vitamin D, few had deficiencies at diagnosis. At 1-year follow-up, there was no significant change in anthropomorphics or vitamin status. Adherence to follow-up was poor; at 5 years after diagnosis, 39% adhered to follow-up. Conclusion . Despite a rigorous, proactive protocol for contacting and following children with celiac disease, adherence to follow-up was poor. New strategies, such as follow-up through the primary care provider, are needed.

Context: Celiac disease is characterized by deficits in bone mineral accrual and longitudinal growth., Objective: The purpose of this study was to determine the differences in bone health and stature among children and adolescents with celiac disease versus healthy controls., Data Sources: Articles published before February 27, 2018 were located using searches of the Physical Education Index (n = 186), PubMed (n = 180), Scopus (n = 3), SPORTDiscus (n = 3), and Web of Science (n = 4)., Study Selection: Bone mineral content (BMC) and areal bone mineral density (aBMD) were assessed via dual-energy X-ray absorptiometry, and height was measured using a stadiometer., Data Extraction: Effect sizes (ES) were calculated as follows: the mean difference of the celiac disease group and healthy control group, divided by the pooled standard deviation. The inverse variance weight was used to calculate the overall mean ES. Random-effects models were used to aggregate a mean ES, 95% confidence intervals (CIs) and to identify potential moderators., Results: The results of 30 effects gathered from 12 studies published between 1996 and 2017 indicated BMC (ES = -0.54, 95% CI: -0.69 to -0.40; p < 0.0001) and aBMD (ES = 0.72, 95% CI: -0.96 to -0.47; p < 0.0001) were lower in youth with celiac disease., Limitations: These results were limited to only cross-sectional and baseline data from longitudinal studies reporting BMC and BMD, however did not assess changes in bone health over time., Conclusion: Children and adolescents with celiac disease have suboptimal bone health and shorter stature., (Copyright © 2019 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)