Low-dose lung radiotherapy for COVID-19 lung disease: a preclinical efficacy study in a bleomycin model of pneumonitis

AbstractPurposeLow-dose whole lung radiotherapy (LDLR) has been proposed as a treatment for patients with acute respiratory distress syndrome associated with SARS-CoV-2 infection and clinical trials are underway. There is an urgent need for preclinical evidence to justify this approach and inform dose, scheduling and mechanisms of action.Materials and methodsFemale C57BL/6 mice were treated with intranasal bleomycin sulphate (7.5 or 11.25 units/kg, day 0), then exposed to whole lung radiation therapy (0.5, 1.0, 1.5 Gy or sham, day 3). Bodyweight was measured daily and lung tissue harvested for histology and flow cytometry on day 10. Computed tomography (CT) lung imaging was performed pre-radiation (day 3) and pre-endpoint (day 10).ResultsBleomycin caused pneumonitis of variable severity which correlated with weight loss. LDLR at 1.0 Gy was associated with a significant increase in the proportion of mice recovering to 98% of initial bodyweight and a proportion of these mice exhibited less severe histopathological lung changes. Mice experiencing moderate initial weight loss were more likely to respond to LDLR than those experiencing severe initial weight loss. Additionally, LDLR (1.0 Gy) significantly reduced bleomycin-induced increases in interstitial macrophages, CD103+ dendritic cells and neutrophil-DC hybrids. Overall,bleomycin-treated mice exhibited significantly higher percentages of non-aerated lung in left than right lungs and LDLR (1.0 Gy) prevented further reductions in aerated lung volume in right but not left lungs. LDLR at 0.5 and 1.5 Gy did not modulate bodyweight or flow cytometric readouts of bleomycin-induced pneumonitis.ConclusionsOur data support the concept that LDLR can ameliorate acute inflammatory lung injury, identify 1.0 Gy as the most effective dose and provide preliminary evidence that it is more effective in the context of moderate than severe pneumonitis. Mechanistically, LDLR at 1.0 Gy significantly suppressed bleomycin-induced accumulation of pulmonary interstitial macrophages, CD103+ dendritic cells and neutrophil-DC hybrids.

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Impact of the COVID‐19 pandemic on initial weight loss in a digital weight management program: A natural experiment

Obesity ◽

10.1002/oby.23233 ◽

2021 ◽

Author(s):

Tiffany Bullard ◽

Adam Medcalf ◽

Chad Rethorst ◽

Gary D. Foster

Keyword(s):

Weight Loss ◽

Weight Management ◽

Natural Experiment ◽

Management Program ◽

Weight Management Program ◽

Initial Weight ◽

Initial Weight Loss

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Abstract MP003: Development and Validation of a Prediction Model of Weight Loss Maintenance or Regain at 4 Years in the Look AHEAD Trial

Circulation ◽

10.1161/circ.135.suppl_1.mp003 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Samantha E Berger ◽

Gordon S Huggins ◽

Jeanne M McCaffery ◽

Alice H Lichtenstein

Keyword(s):

Machine Learning ◽

Type 2 Diabetes ◽

Weight Loss ◽

Logistic Regression ◽

Prediction Model ◽

Weight Regain ◽

Initial Weight ◽

Initial Weight Loss ◽

Look Ahead

Introduction: The development of type 2 diabetes is strongly associated with excess weight gain and can often be partially ameliorated or reversed by weight loss. While many lifestyle interventions have resulted in successful weight loss, strategies to maintain the weight loss have been considerably less successful. Prior studies have identified multiple predictors of weight regain, but none have synthesized them into one analytic stream. Methods: We developed a prediction model of 4-year weight regain after a one-year lifestyle-induced weight loss intervention followed by a 3 year maintenance intervention in 1791 overweight or obese adults with type 2 diabetes from the Action for Health in Diabetes (Look AHEAD) trial who lost ≥3% of initial weight by the end of year 1. Weight regain was defined as regaining <50% of the weight lost during the intervention by year 4. Using machine learning we integrated factors from several domains, including demographics, psychosocial metrics, health status and behaviors (e.g. physical activity, self-monitoring, medication use and intervention adherence). We used classification trees and stochastic gradient boosting with 10-fold cross validation to develop and internally validate the prediction model. Results: At the end of four years, 928 individuals maintained ≥50% of their initial weight lost (maintainers), whereas 863 did not met that criterion (regainers). We identified an interaction between age and several variables in the model, as well as percent initial weight loss. Several factors were significant predictors of weight regain based on variable importance plots, regardless of age or initial weight loss, such as insurance status, physical function score, baseline BMI, meal replacement use and minutes of exercise recorded during year 1. We also identified several factors that were significant predictors depending on age group (45-55y/ 56-65y/66-76y) and initial weight loss (lost 3-9% vs. ≥10% of initial weight). When the variables identified from machine learning were added to a logistic regression model stratified by age and initial weight loss groups, the models showed good prediction (3-9% initial weight loss, ages 45-55y (n=293): ROC AUC=0.78; ≥10% initial weight loss, ages 45-55y (n=242): ROC AUC=0.78; (3-9% initial weight loss, ages 56-65y (n=484): ROC AUC=0.70; ≥10% initial weight loss, ages 56-65y (n=455): ROC AUC = 0.74; 3-9% initial weight loss, ages 66-76y (n=150): ROC AUC=0.84; ≥10% initial weight loss, ages 66-76y (n=167): ROC AUC=0.86). Conclusion: The combination of machine learning methodology and logistic regression generates a prediction model that can consider numerous factors simultaneously, can be used to predict weight regain in other populations and can assist in the development of better strategies to prevent post-loss regain.

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Effect of a vegetable-oil emulsion on body composition; a 12-week study in overweight women on a meal replacement therapy after an initial weight loss: a randomized controlled trial

European Journal of Nutrition ◽

10.1007/s00394-010-0131-x ◽

2010 ◽

Vol 50 (4) ◽

pp. 235-242 ◽

Cited By ~ 8

Author(s):

Johan Olsson ◽

Birgitta Sundberg ◽

Annika Viberg ◽

Arvo Haenni

Keyword(s):

Weight Loss ◽

Randomized Controlled Trial ◽

Body Composition ◽

Replacement Therapy ◽

Controlled Trial ◽

Initial Weight ◽

Initial Weight Loss ◽

Oil Emulsion ◽

Overweight Women ◽

Randomized Controlled

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Maintenance programs help sustain the initial weight loss in overweight children

The Journal of Pediatrics ◽

10.1016/j.jpeds.2007.12.006 ◽

2008 ◽

Vol 152 (3) ◽

pp. 443-444 ◽

Cited By ~ 1

Author(s):

John G. Frohna

Keyword(s):

Weight Loss ◽

Overweight Children ◽

Initial Weight ◽

Initial Weight Loss

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MON-LB101 5-Year Data of an Aggressive Pharmacological Approach to Moderate and Morbid Obesity: Is Prevention of Bariatric Surgery Feasible in the Long Run?

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2340 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Flavio Cadegiani

Keyword(s):

Bariatric Surgery ◽

Morbid Obesity ◽

Weight Loss ◽

Body Weight ◽

Weight Regain ◽

Morbidly Obese ◽

Biochemical Profile ◽

Initial Weight ◽

Initial Weight Loss

Abstract Background: Maintenance of weight loss in patients that undergo weight loss interventions is highly challenging, irrespective of the type of approach to obesity (whether surgical, pharmacological, or non-pharmacological). We proposed a protocol of an aggressive clinical treatment for obesity aiming to prevent the need of bariatric surgery, in patients unwilling to undergo this procedure, by proposing a protocol that included the combination of different anti-obesity medications and non-pharmacological modalities, for longer duration, and with an active approach to prevent weight regain. Our initial 2-year data showed that 93% (40 of 43 patients) with moderate and morbid obesity were able to avoid the need of bariatric surgery, with concomitant improvements of the biochemical profile. However, whether these patients would maintain their successful rates after five years was uncertain. Our objective is to describe the efficacy and safety of a long term (5-year data) pharmacological and multi-modal treatment for moderate and severe obesity. Methods: The 40 patients that were successful in the two-year approach in our obesity center (Corpometria Institute, Brasilia, DF, Brazil) were enrolled. A long-term anti-obesity protocol was employed, with continuous or intermittent use of anti-obesity drugs, trimestral body composition analysis, psychotherapy, visit to a nutritionist every four months, and both resistance and endurance exercises at least four times a week. Body weight (BW), total weight excess (TWE), body fat, markers of lipid and glucose metabolism, liver function, and inflammation were analyzed. Subjects that dropped out were considered as weight regain. Therapeutic success for the 5-year follow-up included as the maintenance of >20% loss of the initial BW loss, and no weight regain (or < 20% of the initial weight loss). Results: A total of 27 patients (67.5%) were able to maintain the body weight, seven dropped out, and six regained more than 20% of the initial weight loss. Of these, 21 (77.8%) had significant further increase of muscle mass and decrease of fat loss, while 17 (63.0%) had further weight loss (p < 0.05), compared to the 2-year data. Improvements on the biochemical profile persisted in all 27 patients, and had significant further improvements in 24 (88.9%) of these patients. Conclusion: The risk of weight regain five years after a weight loss treatment for obesity was significantly lower compared to previous literature, and comparable to the long-term outcomes of bariatric procedures. An aggressive, structured, and long-term clinical weight loss approach has been shown to be feasible, even for morbidly obese patients.

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