Age-Related Patterns in Clinical Presentations and Gluten-Related Issues Among Children and Adolescents With Celiac Disease

OBJECTIVES: Celiac disease (CD) is common and often cited as an “iceberg” phenomenon (i.e., an assumed large number of undiagnosed cases). Recently, atypical or asymptomatic manifestations are becoming more commonly described in older children and adolescents. Moreover, CD diagnosis in children can be complicated by several factors, including its diverse clinical presentations, delay in recognizing CD signs and symptoms, and premature dietary gluten avoidance before the formal diagnosis of CD. To date, few studies have directly examined age-related differences in clinical characteristics and gluten-related issues among children with CD. The aim of this study was to determine age-related patterns in clinical characteristics and gluten-related issues among children with confirmed CD. METHODS: We performed a structured medical record review of biopsy-proven CD patients, aged 0–19 years, between 2000 and 2010 at a large Boston teaching hospital. Data collection included demographics, medical history, gluten-related issues, and diagnostic investigations (CD-specific serology, upper gastrointestinal endoscopy, and small intestinal biopsy). The first positive duodenal biopsy with Marsh III classification defined age of diagnosis. Patients were divided into three age groups for comparisons of the aforementioned characteristics: infant-preschool group (0–5 years), school-aged group (6–11 years), and adolescence group (12–19 years). RESULTS: Among 411 children with biopsy-proven CD, the mean age was 9.5 (s.d. 5.1) years. Most were female (63%) and white (96%). All children had positive CD-specific serology. Most children presented with either abdominal complaints or bowel movement changes. Overall, boys were more common among infant-preschool group compared with the other age groups. More distinct clinical manifestations (vomiting, bowel movement changes, and weight issues) were apparent in the youngest group, whereas school-aged children had more subjective abdominal complaints at the initial presentation. Conversely, the adolescents were most likely to present without any gastrointestinal (GI) symptoms, but not when this was combined with absence of weight issues. Age of diagnosis was not associated with atypical extraintestinal CD presentations. Regarding the gluten-related issues, 10% of school-aged children avoided dietary gluten before the formal CD diagnosis, and 27% of the adolescents reported dietary gluten transgression within the first 12 months of diagnosis, significantly higher than the other age groups. Age differences in histopathology were also found. Whereas the infant-preschool group had a higher proportion of total villous atrophy, the older children were more likely to have gross duodenal abnormalities and chronic duodenitis suggestive of CD at the time of diagnosis. CONCLUSIONS: Children and adolescents with CD have age-related patterns in both the clinical presentations and gluten-related issues. More pronounced clinical and histological features were determined in younger children, whereas older children more commonly presented with solely subjective abdominal complaints or even without any GI symptoms. However, silent and atypical extraintestinal CD presentations were comparable between age groups. In addition to the aforementioned presentations, the higher rates of dietary gluten avoidance and transgression in older children make CD diagnosis and management particularly challenging. These age-related patterns may further increase awareness, facilitate early diagnosis, and improve patient care of pediatric CD

Low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet improves symptoms in adults suffering from irritable bowel syndrome (IBS) compared to standard IBS diet: A meta-analysis of clinical studies

BACKGROUND: Irritable bowel syndrome (IBS) and functional digestive tract disorders, e.g. functional bloating, carbohydrate maldigestion and intolerances, are very common disorders frequently causing significant symptoms that challenge health care systems. A low Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols (FODMAP) diet is one of the possible therapeutic approaches for decreasing abdominal symptoms and improving quality of life. OBJECTIVES: We aimed to meta-analyze data on the therapeutic effect of a low-FODMAP diet on symptoms of IBS and quality of life and compare its effectiveness to a regular, standard IBS diet with high FODMAP content, using a common scoring system, the IBS Symptom Severity Score (IBS-SSS). METHODS: A systematic literature search was conducted in PubMed, EMBASE and the Cochrane Library as well as in the references in a recent meta-analysis. Adult patients diagnosed with IBS according to the Rome II, Rome III, Rome IV or NICE criteria were included in the analysis. STATISTICAL METHODS: Mean differences with 95% confidence intervals were calculated from studies that contained means, standard deviation (SD) or mean differences and SD of differences and p-values. A random effect model was used because of the heterogeneity (Q test (chi2) and I2 indicator). A p-value of less than 0.05 was chosen to indicate a significant difference. RESULTS: The literature search yielded 902 publications, but only 10 were eligible for our meta-analysis. Both regular and low-FODMAP diets proved to be effective in IBS, but post-diet IBS-SSS values were significantly lower (p = 0.002) in the low-FODMAP group. The low-FODMAP diet showed a correlation with the improvement of general symptoms (by IBS-SSS) in patients with IBS. CONCLUSIONS: This meta-analysis provides high-grade evidence of an improved general symptom score among patients with irritable bowel syndrome who have maintained a low-FODMAP diet compared to those on a traditional IBS diet, therefore showing its superiority to regular IBS dietary therapy. These data suggest that a low-FODMAP diet with dietitian control can be a candidate for first-line therapeutic modality in IBS. Because of a lack of data, well-planned randomized controlled studies are needed to ascertain the correlation between improvement of separate key IBS symptoms and the effect of a low-FODMAP diet

Spectrum of gluten-related disorders: consensus on new nomenclature and classification

A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that is generating great confusion among health care professionals. The number of individuals embracing a gluten-free diet (GFD) appears much higher than the projected number of celiac disease patients, fueling a global market of gluten-free products approaching $2.5 billion (US) in global sales in 2010. This trend is supported by the notion that, along with celiac disease, other conditions related to the ingestion of gluten have emerged as health care concerns. This review will summarize our current knowledge about the three main forms of gluten reactions: allergic (wheat allergy), autoimmune (celiac disease, dermatitis herpetiformis and gluten ataxia) and possibly immune-mediated (gluten sensitivity), and also outline pathogenic, clinical and epidemiological differences and propose new nomenclature and classifications

The Application of the Rare Earths to Magnesium and Titanium Metallurgy in Australia

Rare earth elements (REEs) have found application in metallurgical processes for nearly a century due to their unique chemical and physical properties but have gained increased attention in recent decades. Notably, the use of these elements may assist in the development of advanced magnesium and titanium products for applications spanning biomedicine, aerospace, and the automotive industry. To this end, current progress in this area, highlighting work done in Australian research organizations with particular academic expertise, is reviewed. Two areas that require further research are identified: the application of Sc and the heavy lanthanides to the development of novel magnesium alloys and the use of REEs as additives in the development of additive manufacturing of titanium parts

A new look at biomedical Ti-based shape memory alloys

Shape memory alloys (SMAs) are materials that exhibit a distinct thermomechanical coupling, one that gives rise to a wide variety of applications across a broad range of fields. One of the most successful roles is in the construction of novel medical implants. Unfortunately, concerns have been raised about the biocompatibility of the most popular SMA, nitinol (NiTi), due to the known toxic, allergenic and carcinogenic properties of nickel. Given the unique capabilities of SMAs, it is apparent that there is a need for a new class of alloys - alloys that exhibit the full range of shape memory abilities yet are also free of any undesirable side effects. This article reviews the literature surrounding SMAs and identifies the metals Ti, Au, Sn, Ta, Nb, Ru and Zr as candidates for the production of thoroughly biocompatible SMAs. Hf and Re are also promising, though more research is necessary before a definitive statement can be made. Further, the Ti-(Ta,Nb)-(Zr,Hf) alloy system is particularly suited for orthopaedic implants due to a reduced Young's modulus. However, concerns over this system's shape memory properties exist, and should be taken into consideration. Alternate alloy systems that demonstrate higher bulk moduli may still be considered, however, if they are formed into a porous structure. Due to the nature of the alloying components, blended elemental powder metallurgy is recommended for the manufacture of these alloys, particularly due to the ease with which it may be adapted to the formation of porous alloy

Effects of selected metallic and interstitial elements on the microstructure and mechanical properties of beta titanium alloys for orthopedic applications

Metallic biomaterials are widely used for orthopedic application to resolve pain and improve patients quality of life. Among these biomaterials, beta (β)phase titanium (Ti) alloys have received intense interest over last two decades. Unfortunately, the issue of insufficient mechanical properties of biocompatible β Ti alloys is still significant, including low tensile strength (UTS) and high Young's modulus (E), which causes the early failure of the implant and degradation of natural bone, respectively. Thus, this article reviews the effects of some commonly used alloying elements on UTS, E and microstructure of Ti alloys for orthopedic application. Niobium is highlighted as the optimum βstabilizer addition, with other elements such as tantalum and molybdenum also somewhat suitable. Tin and zirconium, although not βstabilizers, are also suggested for their effects on microstructure. Additionally, the effects of four interstitial elements have been discussed; oxygen and nitrogen are noted to show significant effects on microstructure and phase transformations in β alloys, and so are of interest in developing highstrength novel Ti alloys, though further research is needed. Carbon is less beneficial, but is not harmful if carbide formation is avoided. Hydrogen is solely detrimental, and should be limited as much as possible

Optimized Fabrication and Characterization of TiO2Nb2O5ZrO2 Nanotubes on β-Phase TiZr35Nb28 Alloy for Biomedical Applications via the Taguchi Method

The nanostructured surface modification of metallic implants is increasingly gaining attention for biomedical applications. Among such nanostructured surfaces, oxide nanotube (NT) structures have received significant consideration in the biomedical and clinical fields, particularly because of their unique biological characteristics. This experimental study is based on the optimization and characterization of TiO2Nb2O5ZrO2 nanotubes (NTs) on newly developed β phase TiZr35Nb28 alloy. The effects of the anodization process parameters on the inner diameter (Di) of the NTs were investigated. The experiment was conducted using the Taguchi experimental design with an L9 (33) orthogonal array, with three control factors targeted for optimization: (i) applied voltage, (ii) water content of the electrolyte solution, and (iii) anodization time. The chemical composition, morphology, and hydrophilic properties of TiO2Nb2O5ZrO2 NTs after optimization were characterized by energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and water contact angle measurement. The results showed that a large Di of NTs was achieved using an applied voltage of 40 V, water content of 5%, and anodization time of 120 min, with the applied voltage identified as the most effective parameter for the growth of TiO2Nb2O5ZrO2 NTs based on signal-to-noise (S/N) ratio analysis. The Pareto ANOVA and confirmation test results showed that the Taguchi method was successful in optimizing the larger Di for NTs; moreover, the optimized nanotubular surface exhibited the highest surface roughness and an increased hydrophilic nature. The above findings may contribute to the development of high-performance nanostructured coatings for biomedical applications