THE ROLE OF FLOW CYTOMETRY IN COMPLICATED CELIAC DISEASE

Background Refractory celiac disease (RCD) is defined as persistence or recurrence of clinical symptoms of malabsorption and histologic signs of villous atrophy despite at least 1 year of strict adherence to a gluten-free diet. Two different entities of RCD have been described: RCD I shows a polyclonal pattern of intraepithelial lymphocytes (IEL), while in RCD II a monoclonal transformation of IEL can be identified (usually detected by means of TCR clonality analysis). Patients with RCD II have a poorer prognosis and a high risk of development of enteropathy-associated T-cell lymphoma (EATL), so that it has recently been proposed to consider RCD II as a form of low-grade intraepithelial lymphoma (pre-EATL). Recently, flow cytometric analysis of isolated intestinal lymphocytes has been introduced as new diagnostic modality for the detection of aberrant intestinal lymphocytes (ILs) and as a stronger predictor of EATL development than gene clonality analysis. Aims The aims of this study were (i) to evaluate the presence of aberrant ILs in a cohort of non-celiac, celiac and RCD patients by means of flow cytometry, (ii) to verify whether there is an association between clinical characteristics of RCD patients and presence of aberrant ILs, (iii) to compare different ILs detection strategies with the purpose of validating a simpler strategy than the ones currently proposed and (iv) to evaluate whether flow cytometric analysis of aberrant ILs could accurately identify RCD II/pre-EATL patients in our cohort. Methods Flow cytometry analysis of intestinal lymphocytes isolated from duodenal biopsy specimens from RCD, uncomplicated CD patients and controls was performed. Several lymphocyte markers (CD3, CD4, CD8, CD7, CD103, TCR\u3b3\u3b4) were applied in order to identify aberrant ILs, defined by means of several gating strategies including cytCD3+surfCD3-CD7+ and surfCD3-CD7+CD103+. Percentages of aberrant ILs as well as clinical characteristics in different patients groups were compared. Results A total of 130 flow cytometry assays were performed on 109 patients, including 42 controls, 21 active CD, 16 CD on GFD and 30 RCD. RCD patients were initially subgrouped according to the presence (TCRclon+, n=17) or absence (TCRclon-, n=13) of TCR clonality: the presence of elevated aberrant ILs was compared between the two subgroups, with elevated ILs detectable exclusively in the RCDclon+. Patients with elevated ILs also showed a significantly more severe malabsorption (assessed by a composite score). A cut-off of 11% aberrant ILs for the most reliable strategy allowed to identify 2 patients with EATL, as well as a small group of high-risk RCD (5/30) that were classified as RCDII/pre-EATL. According to low aberrant ILs levels, the other RCD patients (21/30) were classified as RCD I/low-risk RCD. However, this technique proved negative in 2 cases of overt EATL and was not able to correctly identify as \u201chigh-risk RCD\u201d one patient with ulcerative jejunitis (who later developed a EATL), as well as one patient in whom a diagnosis of gamma-delta T-cell lymphoma was made. In the setting of RCD, aberrant ILs assessment by means of flow cytometry showed a Specificity of 100% but a Sensitivity of 67% for the detection of pre-EATL/EATL Alternative, simpler gating strategies for aberrant ILs showed similar accuracy to the principal strategy, however these results need further validation. Conclusion In routine clinical practice, flow cytometry for the assessment of aberrant ILs could prove a simple and accurate predictor for high-risk RCD. However, its use as a diagnostic strategy to classify patients into RCD I (low risk) and RCD II/pre-EATL could lead to missing cases of RCD patients with elevated risk. In order to prevent the consequences of false negative results, a multifaceted diagnostic approach taking TCR clonality and clinical manifestations (i.e. malabsorption) into account could maximize accuracy

Citalopram amplifies the influence of living conditions on mood in depressed patients enrolled in the STAR*D study

Selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed antidepressant drugs, have a variable and incomplete efficacy. In order to better understand SSRI action, we explored the hypothesis that SSRIs do not affect mood per se but amplify the influence of the living conditions on mood. To this aim, we exploited the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) data set, selected a subpopulation of 591 patients with an overlapping clinical history and analyzed treatment outcome according to dosage −20 or 40 mg per day of citalopram. We found that sociodemographic characteristics affected treatment response in the same direction in the two dose groups, but these effects reached statistical significance only in the 40 mg per day dose group. In the latter, higher improvement rate was associated with having a working employment status (P=0.0219), longer education (P=0.0053), high income (P=0.01) or a private insurance (P=0.0031), and the higher remission rate was associated with having a working employment status (P=0.0326) or longer education (P=0.0484). Moreover, the magnitude of the effect of the sociodemographic characteristics on mood, measured as the percent of patients showing a positive outcome when exposed to favorable living conditions, was much greater—up to 37-fold—in the 40 compared to the 20 mg per day dose group. Overall, our results indicate that citalopram amplifies the influence of the living conditions on mood in a dose-dependent manner. These findings provide a potential explanation for the variable efficacy of SSRIs and might lead to the development of personalized strategies aimed at enhancing their efficacy

Efficacy of a High-Iron Dietary Intervention in Women with Celiac Disease and Iron Deficiency without Anemia : A Clinical Trial

Background and aim: Iron deficiency without anemia (IDWA) is a common finding in celiac disease (CD) and can also persist in case of good compliance and clinical response to a strict gluten-free diet (GFD). This scenario usually presents in CD women of child-bearing age in whom the imbalance between menstrual iron loss and inadequate iron intake from their diet plays the major role. A recommended approach to this condition is yet to be established. This study aimed to compare, in this subset of patients, the efficacy of a dietary approach consisting of an iron-rich diet against the traditional pharmacological oral-replacement therapy. Material and methods: Between February and December 2016, consecutive CD female patients of child-bearing age as referred to our outpatient center with evidence of IDWA (ferritin <15 ng/mL or 15-20 ng/L with transferrin saturation <15%) were enrolled. After the completion of a 7-day weighed food intake recording to assess the usual iron dietary intake, the patients were randomized in two arms to receive a 12-week iron-rich diet (iron intake >20 mg/die) versus oral iron supplementation with ferrous sulfate (FS) (105 mg/day). Blood tests and dietary assessments were repeated at the end of treatment. The degree of compliance and tolerability to the treatments were assessed every month by means of specific questionnaires and symptoms evaluation. Results: A total of 22 women were enrolled and divided in the diet group (n = 10, age 37 \ub1 8 years) and in the FS group (n = 12, age 38 \ub1 10 years). The food intake records demonstrated an inadequate daily intake of iron in all the enrolled subjects. At the end of the treatments, ferritin levels were higher in the FS group (8.5 (5) versus 34 (30.8), p = 0.002). Compliance and tolerability were similar in both treatment groups (89% versus 87%, p = ns). Conclusions: These findings did not support any equivalent efficacy of an iron-rich diet compared to a FS supplementation in non-anemic iron-deficient women affected by CD. However, the diet appeared a well-tolerated approach, and adequate dietary instructions could effectively increase the daily iron consumption, suggesting a role in the long-term management of IDWA, especially in patients who do not tolerate pharmacological supplementation

Is peer support in group clinics as effective as traditional individual appointments? The first study in patients with Celiac disease

INTRODUCTION: Celiac disease (CD) is common, affecting approximately 1% of the population. The cornerstone of management is a gluten-free diet, with dietetic advice being the key to aiding implementation. The aim of the study was to assess group clinics in comparison with traditional individual appointments. METHODS: Patients with a new diagnosis of CD, confirmed histologically, were prospectively recruited over 18 months in Sheffield, United Kingdom. Patients received either a group clinic or traditional one-to-one appointment, led by a dietitian. Quality-of-life questionnaires were completed at baseline, as well as biochemical parameters being recorded. Patients were followed up at 3 months, where adherence scores were assessed as well as biochemical parameters and quality of life questionnaires being completed. RESULTS: Sixty patients with CD were prospectively recruited and received either an individual (n = 30) or group clinic (n = 30). A statistically significant reduction in tissue transglutaminase was noted following group clinics (mean 58.5, SD 43.4 U/mL vs mean 13.2, SD 5.7 U/mL, P < 0.01). No significant differences in baseline and follow-up biochemical parameters between one-to-one and group clinics were noted. At follow-up, there was no statistically significant difference between mean gluten-free diet adherence scores (mean 3.1, SD 0.4 vs mean 3.1, SD 0.7, P = 0.66) between one-to-one and group clinics. DISCUSSION: This first study assessing group clinics in CD demonstrates they are as effective as traditional one-to-one clinics, with the added benefits of peer support and greater efficiency, with an estimated 54% reduction of dietetic resources

Management of Nonceliac Gluten Sensitivity by Gastroenterology Specialists : Data from an Italian Survey

Background and Aim. Nonceliac gluten sensitivity is syndrome characterized by symptoms disappearing after a gluten-free diet. Its existence is still argument of discussion among specialists. Our aim was to evaluate the knowledge about nonceliac gluten sensitivity among gastroenterology specialists. Methods. During October 2013 a questionnaire was sent through a medical newsletter to Italian gastroenterologists. Twelve questions investigated their knowledge on nonceliac gluten sensitivity, including their diagnostic and therapeutic approach. Results. A total of 212 gastroenterologists filled in the questionnaire. The 98.6% were aware of the existence of a syndrome called "nonceliac gluten sensitivity" and 77% believe in its existence. However, only 56% gave a correct definition of the term. The majority of specialists diagnosed gluten sensitive patients and the number of diagnoses was not statistically different from that of celiac disease. Moreover, a gluten-free diet was prescribed by 64% of the specialists and among them the 73% noted an increase of gluten sensitive patients attending their outpatient services. Conclusions. Our study indicated that most of the specialists recognize nonceliac gluten sensitivity and prescribe gluten-free diet, although 44% of the specialists are not able to give its correct definition; underlining the necessity of medical education on this topic is needed

Highly stable Fe3O4/C composite: a candidate material for all solid-state lithium-ion batteries

Fe3O4 nanoparticles synthesized by a base catalyzed method are tested in an All-Solid-State (ASLB) battery using a sulfide electrolyte. The pristine nanoparticles were morphologically characterized showing an average size of 12 nm. The evaluation of the electrochemical properties shows high specific capacity values of 506 mAhg−1 after 350 cycles at a specific current of 250 mAg−1, with very high stability and coulombic efficiency

Tailoring optical properties and stimulated emission in nanostructured polythiophene

Polythiophenes are the most widely utilized semiconducting polymers in organic electronics, but they are scarcely exploited in photonics due to their high photo-induced absorption caused by interchain polaron pairs, which prevents the establishment of a window of net optical gain. Here we study the photophysics of poly(3-hexylthiophene) configured with different degrees of supramolecular ordering, spin-coated thin films and templated nanowires, and find marked differences in their optical properties. Transient absorption measurements evidence a partially-polarized stimulated emission band in the nanowire samples, in contrast with the photo-induced absorption band observed in spin-coated thin films. In combination with theoretical modeling, our experimental results reveal the origin of the primary photoexcitations dominating the dynamics for different supramolecular ordering, with singlet excitons in the nanostructured samples superseding the presence of polaron pairs, which are present in the disordered films. Our approach demonstrates a viable strategy to direct optical properties through structural control, and the observation of optical gain opens the possibility to the use of polythiophene nanostructures as building blocks of organic optical amplifiers and active photonic devices

Sucrosomial Iron Supplementation in Anemic Patients with Celiac Disease Not Tolerating Oral Ferrous Sulfate: A Prospective Study

Patients with celiac disease (CD) frequently suffer from iron deficiency anemia (IDA) and may benefit from iron supplementation. However, intolerance to iron sulfate and duodenal atrophy could reduce the efficacy of this supplementation. This study evaluated the efficacy of a new sucrosomial iron formulation in patients with CD. Consecutive patients with CD and IDA were divided into two groups: patients with a known intolerance to iron sulfate were treated with sucrosomial iron (30 mg of iron/day), while those receiving iron supplementation for the first time were assigned to iron sulfate (105 mg of iron/day). Forty-three patients were enrolled (38 females, mean age 49 \ub1 9 years). After a follow-up of 90 days both groups showed an increase in Hb levels compared to baseline (+10.1% and +16.2% for sucrosomial and sulfate groups, respectively), and a significant improvement in all iron parameters, with no statistical difference between the two groups. Patients treated with sucrosomial iron reported a lower severity of abdominal symptoms, such as abdominal and epigastric pain, abdominal bloating, and constipation, and a higher increase in general well-being (+33% vs. +21%) compared to the iron sulfate group. Sucrosomial iron can be effective in providing iron supplementation in difficult-to-treat populations, such as patients with CD, IDA, and known intolerance to iron sulfate