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Background: Gastric lymphoma of mucosa-associated lymphoid tissue (MALT) is related to Helicobacter pylori infection and may depend on this infection for growth.Objective: To determine the response of gastric MALT lymphoma to antibiotic treatment.Design: Prospective, uncontrolled treatment trial.Setting: University hospital referral center and three collaborating university and community hospitals.Patients: 34 patients with stage I or stage II N1 gastric MALT lymphoma.Intervention: Two of three oral antibiotic regimens--1) amoxicillin, 750 mg three times daily, and clarithromycin, 500 mg three times daily; 2)tetracycline, 500 mg four times daily, and clarithromycin, 500 mg three times daily; or 3) tetracycline, 500 mg four times daily, and metronidazole, 500 mg three times daily--were administered sequentially (usually in the order written) for 21 days at baseline and at 8 weeks, along with a proton-pump inhibitor (lansoprazole or omeprazole) and bismuth subsalicylate.Measurements: Complete remission was defined as the absence of histopathologic evidence of lymphoma on endoscopic biopsy. Partial remission was defined as a reduction in endoscopic tumor stage or 50% reduction in the size of large tumors.Results: 34 patients were followed for a mean (+/-SD) of 41 +/- 16 months (range, 18 to 70 months) after antibiotic treatment. Of 28 H. pylori-positive patients, 14 (50% [95% CI, 31% to 69%]) achieved complete remission, 8 (29%) achieved partial remission (treatment eventually failed in 4 of the 8), and 10 (36% [CI, 19% to 56%]) did not respond to treatment. Treatment failed in all 6 (100% [CI, 54% to 100%]) H. pylori-negative patients. Patients with endoscopic appearance of gastritis (stage I T1 disease) were most likely to achieve complete remission within 18 months. Tumors in the distal stomach were associated with more favorable response than tumors in the proximal stomach.Conclusions: A subset of H. pylori-positive gastric MALT lymphomas, including infiltrative tumors, may respond to antibiotics. The likelihood of early complete remission seems to be greatest for superficial and distal tumors. [ABSTRACT FROM AUTHOR]

Background: A multicenter, double blinded, randomized phase III trial of the therapeutic cancer vaccine STn-KLH was completed in an international cohort of 1,028 women with metastatic breast cancer who had either no evidence of disease or nonprogressive disease following first-line chemotherapy. This trial is registered with ClinicalTrials.gov (No. NCT00003638 ). The outcomes showed that STn-KLH was safe and relatively well tolerated but had neither a positive nor negative effect on time to progression (TTP) or overall survival (OS) duration in the intent-to-treat population when compared with KLH control alone. The purpose of this post hoc analysis is to explore the potential benefit of combining an antiestrogen with MUC1 vaccines in metastatic breast cancer patients. Methods: The data were further explored to determine if a retrospective, reassigned endocrine subset patient stratification produces subgroups that may have experienced benefit in TTP or survival compared with the phase III trial ITT analysis. Results: Women treated with concomitant endocrine therapy, a pre stratified subset comprising approximately one third of the original study population, achieved a clinical benefit both in terms of TTP and survival compared with women who did not receive endocrine therapy. Moreover, women in the endocrine-treatment subset who mounted a median or greater antibody response (titer >1:320 toward bovine submaxillary mucin) to the STn-KLH vaccine experienced significantly longer median survival than their trial counterparts who mounted a below-median antibody response. Conclusion: Unlike maintenance chemotherapy, with its associated cumulative toxicity, the combination of endocrine and STn-KLH therapy may offer clinical benefit with few adverse effects for women with metastatic breast cancer. [ABSTRACT FROM AUTHOR]

The objectives of this pilot study were to examine fecal microbiota composition of pediatric patients with celiac disease (CD) before and after a 1-year gluten-free diet (GFD) and to determine the association with symptoms and anti-tissue transglutaminase (aTTG) antibody., Methods: Stool samples were obtained from pediatric patients with CD and from healthy controls. Patients were classified by the presence (diarrhea, abdominal pain, weight loss) or absence (asymptomatic, headache, fatigue, etc.) of typical CD gastrointestinal symptoms and by aTTG normalization post-GFD intervention (< 7 U/mL). Fecal microbial composition was measured using 16S ribosomal RNA gene amplicon sequencing of the V3-V4 region., Results: At diagnosis, 13 of 22 patients with CD had typical gastrointestinal symptoms, the remaining patients having atypical or asymptomatic presentations. After a 1-year GFD, all symptomatic patients improved and 9 of 19 had normalized aTTG. Prior to GFD, no distinct microbial signature was observed between patients and controls ( P = 0.39). Post-GFD, patients with CD had a unique microbial signature with reductions in known fiber-degrading bacteria, including Blautia , Dorea , Lactobacillus , and Prevotella compared with controls. Within the patients with CD, microbial composition was not associated with reported symptom presentation or aTTG normalization., Conclusions: Pediatric patients with CD only had a unique microbial signature compared with healthy controls when placed on the GFD. These results suggest that pediatric patients with CD may not have a unique fecal microbial signature indicative of inherent dysbiosis, in contrast to that suggested for older patients. In children with CD, diet may play a role in shaping microbial composition more so than disease status., Competing Interests: D. Sample received funding from Women and Children’s Health Research Institute; Maternal Newborn Child Youth Strategic Clinical Network. Dr Fouhse received funding from Natural Sciences and Engineering Research Council Post Doctoral Fellowship. Drs Huynh and Dieleman received funding from Broad Foundation—Medical Research Program Grant Number MOP 0243. Dr Willing received funding from Canada Research Chairs program. The remaining authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: Celiac disease (CD) is a gluten-triggered autoimmune disorder of the small intestine, which can occur in genetically susceptible individuals at any age. A strict life-long gluten free diet (GFD) is the only medically approved treatment, and non-adherence is associated with significant morbidity. However, gluten use is widespread, complicating efforts to follow the diet. Youth with CD are especially challenged with dietary adherence, as they strive for peer acceptance and personal autonomy in the context of managing a chronic disease., Methods: A scoping review was conducted to identify mechanisms to assist youth with remaining gluten free., Results: There is a paucity of literature regarding best approaches to improve diet adherence by youth, however, lessons can also be learned by borrowing ideas from self-management approaches of other chronic diseases. Several mechanisms for improving GFD adherence among youth are identified, including regular engagement of the youth with CD and their family with an experienced multidisciplinary team, electronic tool utilization and awareness of accurate resources for self-guided education and resources., Conclusions: Improvement in GFD adherence by youth is achievable and may influence long-term health outcomes., (©2019 Walter de Gruyter GmbH, Berlin/Boston.)

Importance: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for colorectal polyps and cancer. A combination of sulindac and erlotinib led to a 71% reduction in duodenal polyp burden in a phase 2 trial., Objective: To evaluate effect of sulindac and erlotinib on colorectal adenoma regression in patients with FAP., Design, Setting, and Participants: Prespecified secondary analysis for colorectal adenoma regression was carried out using data from a double-blind, randomized, placebo-controlled trial, enrolling 92 patients with FAP, conducted from July 2010 to June 2014 in Salt Lake City, Utah., Interventions: Patients were randomized to sulindac, 150 mg twice daily, and erlotinib, 75 mg daily (n = 46), vs placebo (n = 46) for 6 months., Main Outcomes and Measurements: The total number of polyps in the intact colorectum, ileal pouch anal anastomosis, or ileo-rectum were recorded at baseline and 6 months. The primary outcomes were change in total colorectal polyp count and percentage change in colorectal polyps, following 6 months of treatment., Results: Eighty-two randomized patients (mean [SD] age, 40 [13] years; 49 [60%] women) had colorectal polyp count data available for this secondary analysis: 22 with intact colon, 44 with ileal pouch anal anastomosis and 16 with ileo-rectal anastomosis; 41 patients received sulindac/erlotinib and 41 placebo. The total colorectal polyp count was significantly different between the placebo and sulindac-erlotinib group at 6 months in patients with net percentage change of 69.4% in those with an intact colorectum compared with placebo (95% CI, 28.8%-109.2%; P = .009)., Conclusion and Relevance: In this double-blind, placebo-controlled, randomized trial we showed that combination treatment with sulindac and erlotinib compared with placebo resulted in significantly lower colorectal polyp burden after 6 months of treatment. There was a reduction in polyp burden in both those with an entire colorectum and those with only a rectal pouch or rectum., Trial Registration: clinicaltrials.gov Identifier: NCT01187901.

Background: Carpal tunnel syndrome (CTS) is the most common form of peripheral nerve injury, affecting approximately 3 % of the population. While surgery is effective in mild and moderate cases, nerve and functional recovery are often not complete in severe cases. Therefore, there is a need for adjuvant methods to improve nerve regeneration in those cases. Acetyl-L-carnitine (ALCAR) is involved in lipid transport, vital for mitochondrial function. Although it has been shown to be effective in various forms of neuropathies, it has not been used in traumatic or compressive peripheral nerve injury., Methods: In this pilot study we will utilize a double-blind, randomized, placebo-controlled design. Inclusion criteria will include adult patients with severe CTS. This will be confirmed by nerve conduction studies and motor unit number estimation (MUNE). Only those with severe motor unit loss in the thenar muscles (2 standard deviations [SD] below the mean for the age group) will be included. Eligible patients will be randomized to receive 3,000 mg/day of ALCAR orally or placebo following carpal tunnel release surgery for 2 months. The primary outcome will be MUNE with supplementary secondary outcome measures that include: 1) two-point discrimination; 2) Semmes-Weinstein monofilaments for pressure sensitivity; 3) cold and pain threshold for small fiber function; 4) Boston self-assessment Carpal Tunnel Questionnaire and 5) Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire for symptom severity; and 6) Purdue Pegboard Test for hand functional performance. To follow post treatment recovery and monitor safety, patients will be seen at 3 months, 6 months and 1 year. The outcome measures will be analyzed using two-way ANOVA, with treatment assignment and time points being the independent factors. If significant associations are detected, a post hoc analysis will be completed. We aim to recruit ten patients into each of the two groups. Data from this pilot will provide the basis for power calculation for a full-scale trial., Discussion: ALCAR is a physiologic peptide crucial for fatty acid transport. ALCAR has been shown to be effective in neuroprotection in the central nervous system and increase peripheral nerve regeneration. This has been applied clinically to various systemic peripheral neuropathies including diabetic neuropathy, antiretroviral toxic neuropathy, and chemotherapy-induced peripheral neuropathy. While animal evidence exists for the benefit of ALCAR in compression neuropathy, there have been no human studies to date. This trial will represent the first use of ALCAR in peripheral nerve injury/compression neuropathy., Trial Registration: NCT02141035 ; 20 April 2015.

Importance: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal polyps and cancer. Surgical and endoscopic management of duodenal neoplasia is difficult and chemoprevention has not been successful., Objective: To evaluate the effect of a combination of sulindac and erlotinib on duodenal adenoma regression in patients with FAP., Design, Setting, and Participants: Double-blind, randomized, placebo-controlled trial, enrolling 92 participants with FAP, conducted from July 2010 through June 2014 at Huntsman Cancer Institute in Salt Lake City, Utah., Interventions: Participants with FAP were randomized to sulindac (150 mg) twice daily and erlotinib (75 mg) daily (n = 46) vs placebo (n = 46) for 6 months., Main Outcomes and Measures: The total number and diameter of polyps in the proximal duodenum were mapped at baseline and 6 months. The primary outcome was change in total polyp burden at 6 months. Polyp burden was calculated as the sum of the diameters of polyps. The secondary outcomes were change in total duodenal polyp count, change in duodenal polyp burden or count stratified by genotype and initial polyp burden, and percentage of change from baseline in duodenal polyp burden., Results: Ninety-two participants (mean age, 41 years [range, 24-55]; women, 56 [61%]) were randomized when the trial was stopped by the external data and safety monitoring board because the second preplanned interim analysis met the prespecified stopping rule for superiority. Grade 1 and 2 adverse events were more common in the sulindac-erlotinib group, with an acne-like rash observed in 87% of participants receiving treatment and 20% of participants receiving placebo (P < .001). Only 2 participants experienced grade 3 adverse events. [table: see text]., Conclusions and Relevance: Among participants with FAP, the use of sulindac and erlotinib compared with placebo resulted in a lower duodenal polyp burden after 6 months. Adverse events may limit the use of these medications at the doses used in this study. Further research is necessary to evaluate these preliminary findings in a larger study population with longer follow-up to determine whether the observed effects will result in improved clinical outcomes., Trial Registration: clinicaltrials.gov Identifier: NCT 01187901., Competing Interests: Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Samadder reports being a consultant for Cook Medical. Dr Jasperson reports being an employee of Ambry Genetics. Dr Burt reports being a consultant for Myriad Genetics and receiving personal fees from Thetis Pharmaceuticals. No other disclosures were reported.

Grassland bird habitat has declined substantially in the United States. Remaining grasslands are increasingly fragmented, mostly privately owned, and vary greatly in terms of habitat quality and protection status. A coordinated strategic response for grassland bird conservation is difficult, largely due to the scope and complexity of the problem, further compounded by biological, sociological, and economic uncertainties. We describe the results from a collaborative Structured Decision Making (SDM) workshop focused on linking social and economic drivers of landscape change to grassland bird population outcomes. We identified and evaluated alternative strategies for grassland bird conservation using a series of rapid prototype models. We modeled change in grassland and agriculture cover in hypothetical landscapes resulting from different landowner decisions in response to alternative socio-economic conservation policy decisions. Resulting changes in land cover at all three stages of the annual cycle (breeding, wintering, and migration) were used to estimate changes in grassland bird populations. Our results suggest that successful grassland bird conservation may depend upon linkages with ecosystem services on working agricultural lands and grassland-based marketing campaigns to engage the public. With further development, spatial models that link landowner decisions with biological outcomes can be essential tools for making conservation policy decisions. A coordinated non-traditional partnership will likely be necessary to clearly understand and systematically respond to the many conservation challenges facing grassland birds.

Background: A multicenter, double blinded, randomized phase III trial of the therapeutic cancer vaccine sialy1-Tn (STn) conjugated to keyhole-limpet Hemocyanin (KLH) was completed in an international cohort of 1,028 women with metastatic breast cancer who had nonprogressive disease or no evidence of disease after first-line chemotherapy (ClinicalTrials.gov, (NCT00003638). STn-KLH was safe and relatively well tolerated but did not affect time to progression (TTP) or overall survival (OS) duration. The purpose of this post hoc analysis was to explore whether patients who received concurrent endocrine therapy and STn-KLH had a TTP or OS benefit., Methods: A retrospective, blinded review of the data from the phase III trial of STn-KLH was performed to ensure that strata assignments were appropriate. We then studied the effect of concomitant endocrine therapy and STn-KLH or KLH on TTP and OS in the cohort described above. We also assessed the TTP and OS by antibody responses in patients who received endocrine therapy., Results: The women treated with concomitant endocrine therapy, a pre-stratified subset comprising approximately one-third of the original study population, and STn-KLH had longer TTP and OS than the control group of women who received KLH alone. Moreover, of the women who received endocrine therapy, those who had a median or greater antibody response (titer >1:320 toward ovine sub maxillary mucin) to the STn-KLH vaccine had significantly longer median OS than those who had a below-median antibody response., Conclusion: Adding STn-KLH to endocrine therapy may improve clinical outcomes with few adverse effects for women with metastatic breast cancer.

Epidemiological and experimental evidence indicates that aspirin can protect against colorectal cancer. Aspirin inhibits cyclooxygenase enzymes and blocks prostaglandin (PG) biosynthesis. Using rectal PGE(2) levels as a mucosal biomarker, we sought to determine the optimal aspirin dose that would significantly suppress PGE(2) levels for chemoprevention trials. We conducted a randomized, double-blinded study in 60 subjects with prior sporadic colorectal adenoma(s) and evaluated three aspirin doses (81, 325, and 650 mg) or placebo taken daily for 4 weeks. PGE(2) levels in rectal biopsies performed at baseline and week 4 were analyzed by competitive immunoassay. Plasma salicylate levels, pill counts, and subject calendars were used to assess compliance. The 81-mg aspirin dose significantly suppressed PGE(2) levels relative to placebo (P = 0.005) and did so to an equivalent extent as did higher doses (P > 0.4) in evaluable subjects (n = 55) over a 4-week treatment period. Serum salicylate levels were associated with aspirin dose (P = 0.0002). Pill counts and calendars indicated that >98% of doses were taken by all subjects. No adverse events occurred in this short-term study. The 81-mg daily aspirin dose suppressed PGE(2) levels to an equivalent extent as did the 650-mg dose and supports the use of this dose for chemoprevention trials.

Patients with phonological alexia (difficulty reading pseudowords) frequently have concomitant difficulty reading functor words and verbs compared with concrete nouns. The current study compares two techniques for helping two patients with phonological alexia regain the ability to read functors and verbs. One technique follows the approach of reorganization of function, while the other relies on the stimulation approach. Study 1, employing a reorganization approach, resulted in both patients increasing their reading accuracy from approximately 10 to 90% or greater. Study 2, using a stimulation approach, resulted in significant improvement, however neither patient was able to achieve accuracy greater than 59%. Study 3 reverted back to the reorganization approach using the same words from Study 2. Both patients demonstrated significant success, achieving 90% or greater accuracy. Whereas the reorganization approach meets with far greater success than the stimulation approach, both approaches can be seen as instances of paired associate learning. An explanation of the advantage of the reorganization approach is developed which focuses on the nature of the pairings in the paired associate learning paradigm: it is proposed that pairings within the same level of representation are easier to learn than pairings that cut across levels of representation.

Background: When to do a neck dissection as part of the surgical treatment for a patient with squamous carcinoma of the oral tongue is controversial, particularly when the primary can be resected without entering the neck. If the patient who is at high risk for having occult nodal disease in the neck can be identified, node dissection with the glossectomy could be justified. To better identify patients for this procedure, we correlated various tumor and patient factors along with preoperative diagnostic studies with the presence or absence of pathologically positive nodes in a group of patients who underwent node dissection., Methods: Ninety-one previously untreated patients with biopsy-proved squamous carcinoma of the oral tongue were prospectively studied. All patients had a glossectomy and neck dissection as their initial treatment. The pathology findings (ie, lymph nodes with squamous cancer) were correlated with many preoperative and intraoperative factors, and a statistical analysis was made., Results: The use of computed tomography and ultrasound was not better than the clinical examination in determining the presence or absence of nodal metastases. The best predictors were depth of muscle invasion, double DNA aneuploidy, and histologic differentiation of the tumor., Conclusions: All patients with stage T2-T4 squamous cancers of the oral tongue should have an elective dissection of the neck. Patients with T1N0 cancer who have a double DNA-aneuploid tumor, depth of muscle invasion > 4 mm, or have a poorly differentiated cancer should definitely undergo elective neck dissection. Ultrasound and computed tomography are of little value in predicting which patients have positive nodes.

Variability in DNA repair capability may be a determinant of interindividual difference in susceptibility to carcinogenic exposures. A cytogenetic assay which quantifies chromosomal breakage induced by in vitro exposure to a clastogen provides an indirect measure of repair. We report the results of a case-control study of upper aerodigestive tract cancers assessing differences in mutagen sensitivity based on this assay. There were 108 cases with previously untreated squamous cell cancers and 108 age and sex frequency-matched controls selected from blood donors to The University of Texas M. D. Anderson Cancer Center. Sixty-nine% of the cases, compared with 44% of the controls, were classified as mutagen sensitive (breaks per cell > or = 0.8). On multivariate analysis, mutagen sensitivity [odds ratio (OR), 2.5], heavy cigarette smoking (OR, 4.8), and heavy alcohol consumption (OR, 3.1) were associated with significantly increased risk. Stratified analyses showed that the combined effects of cigarette smoking (OR, 8.1) and mutagen sensitivity (OR, 3.2) were suggestive of a multiplicative effect (OR, 23.0). The combined estimate for alcohol use (OR, 3.0) and mutagen sensitivity (OR, 3.0) was 5.8. These data confirm those of a previously published preliminary study of upper aerodigestive cancers and underscore the importance of considering interindividual susceptibility in cancer risk characterization, even for those cancers with well quantified exposures.

This study evaluated the relationship between family history of cancer and bleomycin-induced mutagen sensitivity. The study included 108 patients who registered at The University of Texas M.D. Anderson Cancer Center from June 1987 to June 1991 with histologically confirmed and previously untreated squamous cell carcinoma of the upper aerodigestive tract. All patients underwent the mutagen sensitivity assay and completed a self-administered risk evaluation questionnaire, including a detailed family history. The patients reported having 650 first-degree relatives, including 54 cases with cancers. The patients were classified as mutagen sensitive (> or = 1 chromosome break/cell) or not mutagen sensitive (< or = 0.99 chromosome breaks/cell). Odds ratios (ORs) were calculated to test for significant associations between mutagen sensitivity and family history of cancer. We found a significant OR (OR = 2.63; 95% confidence interval = 1.06-6.53) for patients who were mutagen sensitive and had one first-degree relative affected with cancer. For mutagen-sensitive patients with two or more first-degree relatives affected with cancer, the OR increased to 6.59 (95% confidence interval = 1.69-25.72). Although 88% of the patients were ever smokers, cigarette smoking was not found to be related to mutagen sensitivity. The study findings suggest that patients who have defective DNA repair capability as evidenced by the mutagen sensitivity assay are significantly more likely to report a family history of cancer than patients who are not mutagen sensitive. Further studies are needed to confirm that mutagen-sensitive individuals have inherited an increased risk of cancer.

Quantitative measurements of serum C1q-binding macromolecules (C1qBM) and immunoglobulin A (IgA) were done on 162 patients using previously described methodology. The measurements were compared to a previously described head and neck cancer population. Using the Cox Proportional Hazards model, the prognostic implications regarding high C1qBM and subsequent death with disease (P = .02), and regional recurrence (P = .0094) were validated, but not our previous IgA-related prognostic implications. When both study populations were combined, C1qBM was predictive of survival in those patients treated with induction chemotherapy (P = .0001). C1qBM was not a significant predictor of survival in patients treated with surgery plus postoperative radiation therapy in either this second "test" population or in the original "training" population. The findings demonstrate the confounding influence of treatment modalities and the importance of model validation.