Randomized controlled pilot study assessing fructose tolerance during fructose reintroduction in non-constipated irritable bowel syndrome patients successfully treated with a low FODMAP diet.

BACKGROUND: Limited data exist to guide FODMAP (fermentable oligo-, di-, monosaccharides, and polyols) reintroduction to assess tolerance following a low FODMAP diet (LFD). Fructose reintroduction is often stepwise up to 7.5 g fructose (e.g., three tsp of honey). We aimed to determine the fructose tolerance threshold in non-constipated, LFD-responsive patients with irritable bowel syndrome (IBS) and assess whether stool microbiome predicted LFD response or fructose tolerance. METHODS: Thirty-nine non-constipated IBS patients (51% women, mean age 33.7 years) completed a 4-week LFD. LFD responders were defined as those who reported adequate relief of IBS symptoms following the LFD. Responders were randomized to one of the three solution groups (100% fructose, 56% fructose/44% glucose, or 100% glucose) and received four doses (2.5, 5, 10, 15 g) for 3 days each. Patients reached their tolerance dose if their mean daily IBS symptom severity (visual analog scale [VAS], 0-100 mm) was >20 mm higher than post-LFD VAS. Stool samples before and after LFD were analyzed using shotgun metagenomics. RESULTS: Seventy-nine percent of patients were LFD responders. Most responders tolerated the 15 g sugar dose. There was no significant difference in mean dose tolerated between solution groups (p = 0.56). Compared to baseline, microbiome composition (beta diversity) significantly shifted and six bacterial genes in fructose and mannose metabolism pathways decreased after LFD, irrespective of LFD response or the solution group. CONCLUSIONS: Non-constipated, LFD-responsive IBS patients should be reintroduced to fructose in higher doses than 15 g to assess tolerance. LFD is associated with significant changes in microbial composition and bacterial genes involved in FODMAP metabolism.

Avoidant Restrictive Food Intake Disorder Prevalent Among Patients With Inflammatory Bowel Disease.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) alter their dietary behaviors to reduce disease-related symptoms, avoid feared food triggers, and control inflammation. This study aimed to estimate the prevalence of avoidant/restrictive food intake disorder (ARFID), evaluate risk factors, and examine the association with risk of malnutrition in patients with IBD. METHODS: This cross-sectional study recruited adult patients with IBD from an ambulatory clinic. ARFID risk was measured using the Nine-Item ARFID Screen. Nutritional risk was measured with the Patient Generated-Subjective Global Assessment. Logistic regression models were used to evaluate the association between clinical characteristics and a positive ARFID risk screen. Patient demographics, disease characteristics, and medical history were abstracted from medical records. RESULTS: Of the 161 participants (Crohn's disease, 45.3%; ulcerative colitis, 51.6%; IBD-unclassified, 3.1%), 28 (17%) had a positive ARFID risk score (≥24). Most participants (92%) reported avoiding 1 or more foods while having active symptoms, and 74% continued to avoid 1 or more foods even in the absence of symptoms. Active symptoms (odds ratio, 5.35; 95% confidence interval, 1.91-15.01) and inflammation (odds ratio, 3.31; 95% confidence interval, 1.06-10.29) were significantly associated with positive ARFID risk. Patients with a positive ARFID risk screen were significantly more likely to be at risk for malnutrition (60.7% vs 15.8%; P < .01). CONCLUSIONS: Avoidant eating behaviors are common in IBD patients, even when in clinical remission. Patients who exhibit active symptoms and/or inflammation should be screened for ARFID risk, with referrals to registered dietitians to help monitor and address disordered eating behaviors and malnutrition risk.

A comparison of the efficacy of weight-shift vs. joystick control of a robotic mobility device by infants ages 5 to 10 months.

The onset of crawling in infants contributes to cognitive, perceptual, social, and emotional development. Conversely, infants with motor impairment that delays or prevents autonomous mobility often have associated developmental delays. Evidence suggests that providing mobility may have positive developmental outcomes, however powered wheelchairs may not be recommended for very young children, due to safety concerns and the child's level of cognitive maturity. The WeeBot is a mobility device controlled by infant weight shifting while seated; infants as young as 5 months have learned to use it. This study compares the efficacy of using the WeeBot vs. using the traditional manual joystick to control a robotic mobility device. Participants were 20 typically developing infants between 5 and 10 months who had not yet achieved independent mobility. A quasi-experimental two-group design was used: The first 10 participants recruited used the WeeBot (weight-shift); the next 10 used the joystick. Results showed that infants learned to use weight-shift control more easily and more skilfully than did infants using the joystick. The ability of infants to use the WeeBot suggests that an intuitive alternative control might allow very early powered mobility for children with disabilities, which might have implications for various aspects of their development.

Human T cells armed with Her2/neu bispecific antibodies divide, are cytotoxic, and secrete cytokines with repeated stimulation.

PURPOSE: Cancer immunotherapy has been limited by anergy of patient T cells, inadequate numbers of precursor tumor-specific CTL, and difficulty in producing therapeutic doses of CTL. To overcome these limitations, bispecific antibodies have been used to create artificial antibody receptors that direct polyclonal activated T cells (ATC) to target tumor antigens. Studies reported herein were designed to characterize bispecific antibody-armed ATC functions during multiple rounds of targeted cell stimulation. EXPERIMENTAL DESIGN: ATCs were generated from human peripheral blood mononuclear cells (PBMC) by culture with anti-CD3 and interleukin 2 for 14 days and armed with anti-CD3 x anti-Her2 bispecific antibody (Her2Bi). In vitro, Her2Bi-armed ATC were examined for a range of functions after repeated stimulation with the Her2/neu-expressing breast cancer cell line SK-BR-3. PBMC isolated from cancer patients treated with Her2Bi-armed ATC were tested ex vivo for cytotoxicity against SK-BR-3. RESULTS: In vitro, armed ATC divided, maintained surface Her2Bi, and expressed a range of activities for extended periods of time. Perforin-mediated cytotoxic activity by armed ATC continued for at least 336 hours, and cytokines and chemokines (i.e., IFN-gamma and regulated on activation, normal T-cell expressed and secreted protein [RANTES]) were secreted during successive rounds of stimulation. Furthermore, PBMC isolated from patients over their courses of immunotherapy exhibited significant cytolytic activity against SK-BR-3 as a function of Her2Bi-armed ATC infusions. CONCLUSIONS: These studies show that armed ATC are specific, durable, and highly functional T-cell populations in vitro. These previously unappreciated broad and long-term functions of armed ATC are encouraging for their therapeutic use in treating cancer.

Anti-CD3 x anti-HER2 bispecific antibody effectively redirects armed T cells to inhibit tumor development and growth in hormone-refractory prostate cancer-bearing severe combined immunodeficient beige mice.

The bispecific antibody (BiAb) anti-CD3 x anti-Her2/neu (Her2Bi), combines Her2/neu targeting with nonmajor histocompatibility complex-restricted cytotoxicity mediated by activated T cells (ATCs). To evaluate this adaptive immunotherapeutic strategy for augmenting antitumor immune response toward hormone-refractory prostate cancer (HRPC), normal donor or patient T cells were activated with anti-CD3, expanded ex vivo in interleukin-2, and then armed with Her2Bi (5-500 ng per million ATCs). In vitro, arming ATCs with Her2Bi increased the percent specific cytotoxicity toward PC-3 prostate adenocarcinoma cells 2-3 fold and increased the secretion of Th1 cytokines granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interferon-gamma when compared with unarmed ATCs or ATCs armed with an irrelevant BiAb. Her2Bi-armed ATCs administered with PC-3 (Winn Assay) or injected intratumorally prevented development or induced remissions, respectively, of PC-3 tumors in severe combined immunodeficient beige mice. Intravenously administered Her2Bi-armed ATCs localized to PC-3 xenografts mediated cytotoxicity toward tumor cells and produced significant tumor growth delay of PC-3 tumors, but not Her2/neu-negative LS174T colon adenocarcinoma xenografts. By flow cytometry analyses, Her2Bi-armed ATCs had a proliferative advantage over unarmed ATCs and persisted in the circulation and tumor tissues longer than unarmed ATCs. These findings suggest that Her2Bi-armed ATC therapy may be an effective, nontoxic, tumor-specific treatment for Her2-positive HRPC.