Characterizing the Prevalence of Obesity Misinformation, Factual Content, Stigma, and Positivity on the Social Media Platform Reddit Between 2011 and 2019: Infodemiology Study.

BACKGROUND: Reddit is a popular social media platform that has faced scrutiny for inflammatory language against those with obesity, yet there has been no comprehensive analysis of its obesity-related content. OBJECTIVE: We aimed to quantify the presence of 4 types of obesity-related content on Reddit (misinformation, facts, stigma, and positivity) and identify psycholinguistic features that may be enriched within each one. METHODS: All sentences (N=764,179) containing "obese" or "obesity" from top-level comments (n=689,447) made on non-age-restricted subreddits (ie, smaller communities within Reddit) between 2011 and 2019 that contained one of a series of keywords were evaluated. Four types of common natural language processing features were extracted: bigram term frequency-inverse document frequency, word embeddings derived from Bidirectional Encoder Representations from Transformers, sentiment from the Valence Aware Dictionary for Sentiment Reasoning, and psycholinguistic features from the Linguistic Inquiry and Word Count Program. These features were used to train an Extreme Gradient Boosting machine learning classifier to label each sentence as 1 of the 4 content categories or other. Two-part hurdle models for semicontinuous data (which use logistic regression to assess the odds of a 0 result and linear regression for continuous data) were used to evaluate whether select psycholinguistic features presented differently in misinformation (compared with facts) or stigma (compared with positivity). RESULTS: After removing ambiguous sentences, 0.47% (3610/764,179) of the sentences were labeled as misinformation, 1.88% (14,366/764,179) were labeled as stigma, 1.94% (14,799/764,179) were labeled as positivity, and 8.93% (68,276/764,179) were labeled as facts. Each category had markers that distinguished it from other categories within the data as well as an external corpus. For example, misinformation had a higher average percent of negations (ß=3.71, 95% CI 3.53-3.90; P<.001) but a lower average number of words >6 letters (ß=-1.47, 95% CI -1.85 to -1.10; P<.001) relative to facts. Stigma had a higher proportion of swear words (ß=1.83, 95% CI 1.62-2.04; P<.001) but a lower proportion of first-person singular pronouns (ß=-5.30, 95% CI -5.44 to -5.16; P<.001) relative to positivity. CONCLUSIONS: There are distinct psycholinguistic properties between types of obesity-related content on Reddit that can be leveraged to rapidly identify deleterious content with minimal human intervention and provide insights into how the Reddit population perceives patients with obesity. Future work should assess whether these properties are shared across languages and other social media platforms.

A randomized study of 2 dose levels of intravenous clofarabine in the treatment of patients with higher-risk myelodysplastic syndrome.

BACKGROUND: Clofarabine is a nucleoside analog with activity in myeloid malignancies. Experience in myelodysplastic syndrome (MDS) is limited. METHODS: The goal of this study was to evaluate the activity and safety of 2 different doses (15 mg/m(2) vs 30 mg/m(2) daily × 5 days) of intravenous clofarabine in patients with higher-risk MDS. Fifty-eight patients with a median age of 68 years (range, 25-89) including 15 patients (28%) with secondary MDS and 35 patients (60%) who received prior DNA methyltransferase (DNMT) inhibitors were adaptively randomized between the 2 dose cohorts. RESULTS: The overall response rate (ORR; based on a modification of International Working Group criteria) was 36% including 26% with complete remission (CR) (ORR, 41% at 15 mg/m(2) and 29% at 30 mg/m(2)). Responses were lower in patients who failed DNMT inhibitors (ORR, 17%; CR rate, 14%). The 8-week mortality rate was 19%. Median survival was 7.4 months for all patients, 13.4 months for responders, and 21.7 months for complete responders. Some adverse events, particularly hepatic and renal, were more severe (grade >2) in patients randomized to 30 mg/m(2) of clofarabine. Myelosuppression and infectious complications were frequent. CONCLUSIONS: Both the lower and higher doses of clofarabine have comparable clinical activity, but the lower dose appeared less toxic. If these results are confirmed, lower doses of clofarabine, possibly in alternative schedules, should be pursued.

XIAP antisense oligonucleotide (AEG35156) achieves target knockdown and induces apoptosis preferentially in CD34+38- cells in a phase 1/2 study of patients with relapsed/refractory AML.

XIAP, a potent caspase inhibitor, is highly expressed in acute myeloid leukemia (AML) cells and contributes to chemoresistance. A multi-center phase 1/2 trial of XIAP antisense oligonucleotide AEG35156 in combination with idarubicin/cytarabine was conducted in 56 patients with relapsed/refractory AML. Herein we report the pharmacodynamic studies of the patients enrolled at M. D. Anderson Cancer Center. A total of 13 patients were enrolled in our institution: five in phase 1 (12-350 mg/m² AEG35156) and eight in phase 2 (350 mg/m² AEG35156) of the protocol. AEG35156 was administered on 3 consecutive days and then weekly up to a maximum of 35 days. Blood samples were collected from patients on days 1 through 5 and on day 28-35 post-chemotherapy for detection of XIAP levels and apoptosis. AEG35156 treatment led to dose-dependent decreases of XIAP mRNA levels (42-100% reduction in phase 2 patients). XIAP protein levels were reduced in all five samples measured. Apoptosis induction was detected in 1/4 phase 1 and 4/5 phase 2 patients. Importantly, apoptosis was most pronounced in CD34+38- AML stem cells and all phase 2 patients showing apoptosis induction in CD34+38- cells achieved response. We conclude that at 350 mg/m², AEG35156 is effective in knocking down XIAP in circulating blasts accompanied by the preferential induction of apoptosis in CD34+38- AML stem cells.

Oral clofarabine in the treatment of patients with higher-risk myelodysplastic syndrome.

PURPOSE: Efficacy and toxicity profile of orally administered clofarabine were evaluated in patients with higher-risk myelodysplastic syndrome (MDS). PATIENTS AND METHODS: Thirty-two patients were treated, of whom 22 had intermediate-2 or high-risk disease (International Prognostic Scoring System). Median age was 70 years (range, 53 to 86), nine patients had secondary MDS, and 20 patients experienced prior therapy failure with hypomethylating agents. Three doses of clofarabine were evaluated: 40 mg/m(2), 30 mg/m(2), and 20 mg/m(2) daily for 5 days. Courses were repeated every 4 to 8 weeks. RESULTS: Eight patients (25%) achieved complete remission (CR), three had (9%) hematologic improvement (HI), and three had (9%) clinical benefit (CB; overall response rate, 43%). Responses in patients who experience treatment failure with hypomethylating agents included CR in two (10%), HI in two (10%), and CB in two patients (10%). No patients died within 6 weeks of induction. Renal failure occurred in four patients in the context of myelosuppression-associated infectious complications. Common adverse events were gastrointestinal and hepatic. Myelosuppression was common, but prolonged myelosuppression (> 42 days) was rare. The toxicity profile was better with lower doses of clofarabine, whereas response rates did not differ significantly. CONCLUSION: Oral clofarabine has achieved a response rate of 43% in patients with higher-risk MDS. The optimal dose and schedule and the appropriate patient population for such therapy remain to be further defined.

Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia.

PURPOSE To determine the efficacy and toxicity of the combination of sorafenib, cytarabine, and idarubicin in patients with acute myeloid leukemia (AML) younger than age 65 years. PATIENTS AND METHODS In the phase I part of the study, 10 patients with relapsed AML were treated with escalating doses of sorafenib with chemotherapy to establish the feasibility of the combination. We then treated 51 patients (median age, 53 years; range, 18 to 65 years) who had previously untreated AML with cytarabine at 1.5 g/m(2) by continuous intravenous (IV) infusion daily for 4 days (3 days if > 60 years of age), idarubicin at 12 mg/m(2) IV daily for 3 days, and sorafenib at 400 mg orally twice daily for 7 days. RESULTS Overall, 38 (75%) patients have achieved a complete remission (CR), including 14 (93%) of 15 patients with mutated FMS-like tyrosine kinase-3 (FLT3; the 15th patient had complete remission with incomplete platelet recovery [CRp]) and 24 (66%) of 36 patients with FLT3 wild-type (WT) disease (three additional FLT3-WT patients had CRp). FLT3-mutated patients were more likely to achieve a CR than FLT3-WT patients (P = .033). With a median follow-up of 54 weeks (range, 8 to 87 weeks), the probability of survival at 1 year is 74%. Among the FLT3-mutated patients, 10 have relapsed and five remain in CR with a median follow-up of 62 weeks (range, 10 to 76 weeks). Plasma inhibitory assay demonstrated an on-target effect on FLT3 kinase activity. CONCLUSION Sorafenib can be safely combined with chemotherapy, produces a high CR rate in FLT3-mutated patients, and inhibits FLT3 signaling.