title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
|---|---|---|---|---|
4.3. Prediction Model | Currently, the usual management for overweight and obesity is done by calculating energy expenditure, establishing daily nutritional requirements, and performing caloric restriction, in addition to giving recommendations for lifestyle changes specific to each individual [ | PMC10746100 | ||
4.4. BMI Percentage Loss Prediction Model Based on the MHP and LF Diets’ Methylation Data | BMI loss, weight loss | The model that predicts the percentage of BMI loss was made with a total methylation score that was constructed considering the MHP diet methylation score, in which the 15 CpG sites that were better associated with the reduction of BMI percentage were selected and 11 CpG sites for the LF diet. With this model, it was possible to predict with which diet the highest percentage of BMI would be lost for 75 participants, corresponding to 37.3% of the total population of this study. We consider that this total methylation score could be used to predict which diet is more appropriate for each individual. If not significant, the predictive model indicates that these subjects would lose a similar percentage of BMI with both diets. In this case, and in order to increase the adherence to the treatment, the individuals could choose by dietary preference.The potential of DNA methylation to predict BMI loss has been described before, as demonstrated in a study in which a prediction score was performed based on 83 CpG sites that was associated with BMI; the result they obtained was a prediction that represented 29% of the variation in BMI in the population they studied [To conclude, it is important to mention that this pioneer prediction model can be improved by adding other information, because the use of other variables for the prediction of the decrease in anthropometric measurements with a dietary intervention has been evidenced. For example, a useful weight loss prediction model using gut microbiota data and urine metabolites in a nutritional intervention has been recently published [ | PMC10746100 | |
4.5. Strengths and Limitations | obesity | OBESITY | One of the main strengths of this pilot research is that it was carried out within the framework of a randomized clinical study in which more than 200 people were characterized. A methylation array was used to analyze around 850,000 methylation sites in each individual at baseline. Multiple methylation sites were identified as associated with the reduction in BMI percentage after the intervention with the two types of diets, thus demonstrating the impact that epigenetics has on the response and regulation of anthropometric measures and suggesting that epigenetic markers can be very useful in the precision dietary treatment of obesity. Furthermore, although a pilot study, it was a robust study, since the association of CpG sites with the dietary intervention response was not affected by potential confounding factors, as the model was adjusted for age, sex, and cell composition.The designed epigenetic model successfully predicted the percentage of BMI loss with each of the two diets (MHP and LF). For this model, blood was used as the study tissue, which is an accessible, easy, minimally invasive tissue. Therefore, the designed methylation score can be used as biomarkers in the future using blood samples. On the other hand, with the results obtained, future research can be developed, and the model can also allow the integration of new variables for improvement.It is important to mention that the information obtained from the methylation data of these subjects refers to the methylation situation at that moment and of the tissue that was studied, but this information may vary with time and the tissue analyzed.Another limitation of this pioneer study was the expression of the genes in which the methylation sites identified in this research were located, as it was not analyzed.It would be interesting to know if the changes in methylation have any real influence on the expression levels. It should be taken into account that this research was carried out in a Spanish population, mostly of Caucasian origin, so the data obtained cannot be extrapolated to a demographically different population. It is important to point out that several studies suggest that epigenetic marks are dependent on race, origin, and many lifestyle factors, including perinatal factors, and there are many factors that influence the degree of individual methylation, so that small differences in methylation can be found between individuals. As DNA methylation somewhat shows a maternal inheritance, another limitation is that we did not have twins in the study.On the other hand, there are technological limitations that can influence methylation values, as they are dependent on the equipment used; reagents; and sample handling (blood preservation, cell isolation, DNA extraction, bisulfite treatment, etc.). For this reason, it is difficult to compare between different studies. | PMC10746100 |
5. Conclusions | weight loss | This pioneer research demonstrates that DNA methylation is an individual characteristic that can be used to have greater precision in the nutritional treatment of BMI reduction. The model designed based on the methylation information through the linear mixed effect model allows predicting the percentage of BMI loss and could be useful in determining which diet is more adequate for weight loss for each individual. | PMC10746100 | |
Supplementary Materials | The following supporting information can be downloaded at Click here for additional data file. | PMC10746100 | ||
Author Contributions | Conceptualization, F.I.M. and J.A.M.; methodology, F.I.M. and J.I.R.-B.; formal analysis, J.I.R.-B. and S.G.-C.; investigation, N.C.G.-Á. and S.G.-C.; resources, F.I.M. and J.A.M.; data curation, J.I.R.-B.; writing—original draft preparation, N.C.G.-Á.; writing—review and editing, F.I.M., J.I.R.-B., J.A.M. and S.G.-C.; supervision, F.I.M. and S.G.-C.; project administration, F.I.M. and S.G.-C.; funding acquisition, F.I.M. and J.A.M. All authors have read and agreed to the published version of the manuscript. | PMC10746100 | ||
Institutional Review Board Statement | The study was performed in line with the guidelines of the Declaration of Helsinki and received approval by the Ethics Committee of the University of Navarra (ref. 132/2015). | PMC10746100 | ||
Informed Consent Statement | Informed consent was obtained from all subjects involved in the study. Written informed consent has been obtained from the patients to publish this paper. | PMC10746100 | ||
Data Availability Statement | Data will be available upon request by contacting the corresponding author. | PMC10746100 | ||
Conflicts of Interest | The authors declare that they have no conflict of interest. | PMC10746100 | ||
References | TNF-α, tumor necrosis | REGRESSION, INSULIN RESISTANCE, TUMOR NECROSIS | Flow chart of the participants who started and completed the intervention.Flow chart for the design of the prediction model based on DNA methylation.Flow chart for the selection of methylation sites (CpG) used for the prediction model.Prediction model of the percentage of BMI loss according to the total methylation score of each individual. “Y” axis: percentage of BMI loss and “X” axis: methylation score. According to the total score, it can be predicted with which diet the greatest percentage of BMI is achieved for each individual.Representation of the distribution of the Representation of the population distribution with respect to the total methylation score. “X” axis shows the total methylation score. “Y” axis shows the number of participants.Biological role of genes that have functions in metabolism, the immune system, and cell function and that contain the CpG sites selected for the MHP diet prediction model.Biological role of genes that have functions in metabolism, the immune system, and cell function and that contain the CpG sites selected for the LF diet prediction model.Baseline anthropometric and biochemical data from the groups with a moderately high-protein (MHP) and a low-fat (LF) diet.Values correspond to the mean ± SEM. BMI: body mass index, HOMA-IR: insulin resistance index. HDL: high-density lipoprotein, LDL: low-density lipoprotein, ox-LDL: oxidized low-density lipoprotein, Alt: alanine aminotransferase, Ast: aspartate aminotransferase, and TNF-α: tumor necrosis factor alpha. Anthropometric and biochemical changes that occurred with the interventions with each of the two diets (MHP and LF) after 4 months and the differences between them.Values correspond to the baseline mean and mean changes after caloric restriction treatment ± SEM. BMI: body mass index. HOMA-IR: insulin resistance index. HDL: high-density lipoprotein, LDL: low-density lipoprotein, ox-LDL: oxidized low-density lipoprotein, and Alt: alanine aminotransferase. Ast: aspartate aminotransferase. TNF-α: tumor necrosis factor alpha. Spearman’s correlations between methylation of the significant CpG sites (Spearman’s correlations between methylation of the significant CpG sites and the percentage of BMI loss of the 201 subjects. Spearman’s correlations between methylation of the significant CpG sites (Spearman’s correlation of CpG sites with the percentage of BMI loss. Multiple linear regression for MHP diet prediction model showing an association between methylation of the CpG sites and BMI difference (Multiple linear regression model using the percentage of BMI loss as the dependent variable and the CpG sites for the MHP diet as independent variables. SEM: standard error. Beta values represent changes in results for the increasing number of BMI percent loss units.Multiple linear regression for the LF diet prediction model showing an association between methylation of the CpG sites and BMI difference (Linear regression model using the percentage of BMI loss as the dependent variable and the CpG sites for the LF diet as independent variables. SEM: standard error. Beta values represent changes in results for the increasing number of BMI percent loss units.Design of weighted sub-scores for the diet MHP, LF, and total score.Linear mixed effect model for the prediction of the percentage of BMI loss.Dependent variable percentage of BMI loss, fixed effect variable diet, total score, and interaction of the diet and total score. Adjusted for age and sex. Diet## total score indicates the interaction between both variables. SEM: standard error.Information from the 15 methylation sites associated with the MHP diet selected for the prediction model.Information from methylation sites of the MHP diet prediction model by using the “Illumina MethylationEPIC array”. The location on the chromosome, the related gene, and the region in which each CpG is found were analyzed for each methylation site. Gene Information from the 11 methylation sites associated with the LF diet selected for the prediction model.Information from the methylation sites of the LF diet prediction model by using the “Illumina MethylationEPIC array”. The location on the chromosome, the related gene, and the region in which each CpG is found was analyzed for each methylation site. Gene | PMC10746100 |
Background | obesity, NAFLD, appetite | OBESITY, NONALCOHOLIC FATTY LIVER DISEASE | Academic Editor: Cornelia Amălinei This trial assessed the effects of a calorie-restricted diet (CRD) with hydroxycitric acid (HCA) supplementation on appetite-regulating hormones, obesity indices, body composition, and appetite in women with nonalcoholic fatty liver disease (NAFLD). | PMC10356186 |
Methods | NAFLD | This study was carried out on 44 overweight/obese women with NAFLD. The patients were randomly assigned into two groups, namely, “ | PMC10356186 | |
Results | obesity | OBESITY | Forty patients completed the trial. At the end of the trial, although significant reductions were found in most of the studied obesity indices in the intervention group, there was only a significant decrease in waist circumference and waist-to-height ratio in the control group. Fat mass and muscle mass significantly decreased in the intervention group ( | PMC10356186 |
Conclusion | weight loss diet | HCA plus weight loss diet could significantly reduce visceral adipose tissue without any significant changes in serum leptin and adiponectin levels. | PMC10356186 | |
1. Introduction | NAFLD | NONALCOHOLIC FATTY LIVER DISEASE, CHRONIC LIVER DISEASE | Nonalcoholic fatty liver disease (NAFLD) is recognized as the most frequent chronic liver disease globally [
| PMC10356186 |
2. Methods | PMC10356186 | |||
2.1. Study Design and Participants | LIVER DISEASES, COMPLICATIONS | In this single-blind, controlled, and randomized clinical trial, 142 female patients aged between 18 and 50 years and BMI = 27.5–40 kg/mThis paper is a part of already published studies [Those who were pregnant or lactating, had menopause, were alcohol drinker, or smoker, followed a weight-loss diet, and took dietary supplements or any medication affecting lipid and glucose metabolism as well as those suffering from liver diseases, inflammatory conditions, and metabolic complications were excluded. | PMC10356186 | |
2.2. Sample Size | The sample size was determined based on the mean and standard deviation (SD) of serum leptin level at baseline reported by Vasques et al. [ | PMC10356186 | ||
2.3. Randomization, Blinding, and Intervention | weight loss | The patients were randomly assigned to one of the two study groups (1 : 1). The randomized block procedure of size 4 was applied, and the sequence was generated using the random allocation software (RAS). Randomization was stratified by age (18–35 yrs. To assess habitual diet for each subject, a validated 169-item food frequency questionnaire (FFQ) was fulfilled at baseline. LCD was defined as individual calorie-restricted diet for each patient using daily energy requirement (calculated based on Mifflin-St. Joer formula) minus 500 kcal to reach weight loss. The proportions of carbohydrates, fats, and proteins from energy were 55%, 30%, and 15%, respectively.Those in “ | PMC10356186 | |
2.4. Measures and Assessments | To assess dietary intakes, the subjects completed three food records (two nonconsecutive weekdays and a weekend) and data on food intake were analyzed by Nutritionist IV software (First Databank, USA) modified for Iranian foods. Appetite status was assessed using a validated 6-item questionnaire based on 100 mm visual analog scoring (VAS). Six variables, hunger, satiety, desire to eat any food, and specific food including salty, sweet, and fatty foods were recorded subjectively [Intravenous blood samples (5 ml) were collected from patients at the beginning and end of the study after 12 hours of fasting. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST) concentrations were measured at baseline and endpoint of the study using the International Federation of Clinical Chemistry (IFCC)-approved method [ | PMC10356186 | ||
2.5. Statistical Analysis | Data analysis was conducted using SPSS 25.0 software (SPSS Inc., Chicago, IL, USA). The Kolmogorov–Smirnov test was used for checking the normality of the data distribution. Between-group comparisons at baseline were tested using the independent samples | PMC10356186 | ||
3. Results | Forty patients completed the trial.
Appetite status assessed by VAS is presented in
Changes in serum levels of leptin and adiponectin over the trial are presented in
| PMC10356186 | ||
4. Discussion | obesity | OBESITY | Results of this trial showed significant reductions in obesity indices and total and visceral fat without any significant change in serum leptin and adiponectin levels. Although energy and macronutrient intakes decreased in both groups, greater reductions were observed in the control group than in the intervention group (In the present study, although there were slight reductions in mean concentrations of leptin and adiponectin as well as an increase in leptin to adiponectin ratio in both groups, intergroup differences were not statistically significant after the trial, even after adjusting for the confounding factors (In the present study, lack of using placebo, studying only female subjects, and relatively short duration of the trial are considered as limitations. However, to the best of our knowledge, this trial is considered as one of the limited human studies to have examine the effect of HCA extract derived from | PMC10356186 |
5. Conclusion | NAFLD, LCD | OBESE | It is concluded that HCA plus LCD in obese women with NAFLD could significantly reduce visceral adipose tissue without any significant changes in serum leptin and adiponectin levels. | PMC10356186 |
Acknowledgments | The authors sincerely thank the patients who participated in this clinical trial. The authors would like to appreciate the cooperation of the Clinical Research Development Unit of Imam Reza General Hospital, Tabriz, Iran, in conducting this research. This study was written based on the data obtained from the M.Sc. Thesis of Solmaz Nomi-Golzar (Ethics code: TBZMED. REC.1394.324). The present clinical trial was supported by the Vice Chancellor of Research of Tabriz University of Medical Sciences. | PMC10356186 | ||
Data Availability | The datasets used and analyzed during the current study are not publicly available due to our center's patient confidentiality policies, but they are available from the corresponding author on reasonable request. | PMC10356186 | ||
Conflicts of Interest | The authors declare that they have no conflicts of interest. | PMC10356186 | ||
Authors' Contributions | NAFLD, Obesity, obesity, skeletal muscle mass, FM, HT | OBESITY, NONALCOHOLIC FATTY LIVER DISEASE, OBESITY | The authors' responsibilities were as follows: MEM contributed to the conception of the article; SA, SNG, and HT wrote the original paper; MEM contributed to the statistical analysis; and MEM and HT contributed to the final revision of the manuscript. All authors read and approved the final version of the manuscript.Flow chart of the study.Baseline characteristic of the study patients.NAFLD, nonalcoholic fatty liver disease; ALT, alanine transaminase; AST, aspartate transaminase. This table has been previously published. Energy and macronutrient intakes of the study participants throughout the study.
Appetite status of the study participants throughout the study.
Obesity indices and body composition of the study participants throughout the study.BMI, body mass index; WHR, waist to hip ratio; WhtR, waist to height ratio; FM, fat mass; SMM, skeletal muscle mass; VAT, visceral adipose tissue. Anthropometric measures in this table have been previously published [Associations between percent of changes in obesity indices and body composition with percent of changes in serum leptin and adiponectin and their ratios.VAT, visceral adipose tissue; FM, fat mass; wc, waist circumference; BMI, body mass index; WHR, waist-to-hip ratio; WHtR, waist-to-height ratio; Lep/Adp, leptin to adiponectin ratio; | PMC10356186 |
1. Introduction | obese, endotoxemia, cancer, weight reduction, metabolic diseases, overweight, post-prandial endotoxemia | METABOLIC DISEASES, CANCER, OBESE, ENDOTOXEMIA | Sugar-rich diets, but also the use of intense sweeteners, may alter intestinal barrier function. Here, we assessed the effect of sucrose and sucralose on post-prandial endotoxemia in a randomized placebo-controlled single-blinded crossover-designed study. Following a 2-day standardization of their diet, healthy men and women received a beverage containing either sucrose, sucralose (iso-sweet) or an isocaloric combination of sucralose + maltodextrin. Plasma endotoxin levels were measured after consumption of the respective beverages. Moreover, the effect of sucrose and sucralose on intestinal permeability was assessed in Caco-2 cells and ex vivo in an everted gut sac model. The nutritional standardization recommended by nutrition societies was associated with a significant decrease in plasma endotoxin levels. The intake of the sucrose-sweetened beverage resulted in a significant increase in plasma endotoxin levels while being unchanged after the intake of sucralose-sweetened beverages. In Caco-2 cells, the challenge with sucrose but not with sucralose significantly increased the permeation of the bacterial endotoxin across the cell monolayer. Xylose permeation in small intestinal everted tissue sacs was significantly higher upon the challenge with sucrose while remaining unchanged in sucralose-challenged sacs. Our data suggest that an acute intake of physiologically relevant amounts of sucrose but not of sucralose can result in post-prandial endotoxemia.Despite ever-increasing weight reduction intervention programs worldwide, the number of overweight and obese individuals is still increasing, as are instances of metabolic diseases and cancer [Sugar-sweetened beverages have been identified as one major source of added sugars across all age groups in several epidemiological studies and countries [Sucralose, being frequently used either solely or in combination in beverages [Starting from this background, the aim of the present single-blinded crossover-designed study was to assess the effects of an acute intake of sucralose in physiological doses compared to an iso-sweet intake of sucrose on post-prandial endotoxemia in healthy young adults. | PMC10537596 |
2. Materials and Methods | PMC10537596 | |||
2.1. Study Participants | post-prandial endotoxemia | This randomized controlled prospective human intervention study in crossover design was approved by the Ethics Committee of the University of Vienna (reference number: 00585) and was carried out in accordance with the ethical standards laid down in the Declaration of Helsinki. Originally, it was planned to investigate the effect of an acute (only once) and a two-day long intake of sucralose and sucrose on post-prandial endotoxemia in healthy subjects. Due to the COVID-19 pandemic situation and the associated restrictions, we were not able to conduct the study as originally planned and therefore focused on the acute intervention only. The study is registered at ClinicalTrials.gov (NCT04788680) and obtained approval to be carried out between 2021 and 2022. Sample size was calculated based on previous studies [ | PMC10537596 | |
2.2. Intervention Study | The study design is summarized in | PMC10537596 | ||
2.3. Anthropometry, Blood Pressure and Metabolic Parameters | BLOOD | At the beginning and over the course of the study, anthropometric data and blood pressure were determined. Blood lipids were measured using a commercially available measuring instrument (Swiss Point of Care, LJ IJsselstein, The Netherlands). Blood sugar levels were assessed in capillary blood obtained from the fingertip by using a finger-stick glucometer before and after standardization and during the intervention. | PMC10537596 | |
2.4. Bacterial Endotoxin | To assess the effect of the standardized nutrition as well as of the different beverages on bacterial endotoxin levels in plasma of participants over time, a limulus amebocyte lysate assay was used (Charles River, Ecully, France) as detailed previously [ | PMC10537596 | ||
2.5. Caco-2 Cells In Vitro Experiments | Differentiated Caco-2 cells (ACC 169, DSMZ, Braunschweig, Germany) were grown in trans-wells by using DMEM medium containing 10% fetal bovine serum (Pan-Biotech GmbH, Aidenbach, Germany) and 100 µg/mL streptomycin and 100 U/mL penicillin (Pan-Biotech GmbH, Aidenbach, Germany) in a 5% carbon dioxide atmosphere. After reaching confluency, cells were treated with sucralose (0.016 mM) or sucrose (10 mM) in the apical compartment of the trans-well for 2 h. Lipopolysaccharide (LPS, 100 ng/mL) was added to the apical side after 2 h for another 1 h and bacterial endotoxin levels were measured in the media of the basolateral compartment. | PMC10537596 | ||
2.6. Enzyme-Linked Immunosorbent Assay (ELISA) | Intestinal fatty acid | Intestinal fatty acid binding protein (iFABP) concentrations were analyzed in cell culture supernatant of the apical side of the Caco-2 cell trans-well model using a commercially available ELISA kit (Bio-Techne Corp., Minneapolis, MN, USA). | PMC10537596 | |
2.7. Ex Vivo Everted Gut Sac Experiments and Xylose Permeation Measurement | SMALL INTESTINE | Small intestine ( | PMC10537596 | |
2.8. Statistical Analysis | Data are presented as means ± SEM. To test for normality, a Shapiro–Wilk normality test was performed. Grubb’s test was used before statistical analysis to identify outliers. To assess the effects between two paired groups, a paired | PMC10537596 | ||
3. Results | PMC10537596 | |||
3.1. Baseline Characteristics and Nutritional Standardization | corona infections | Of the 18 normal-weight, healthy men and women enrolled in the study, 11 participants finished the study and were analyzed. Seven participants did not start the study as they dropped out of the study due to corona infections ( | PMC10537596 | |
3.2. Effect of an Acute Intake of Sucralose, Sucrose and an Isocaloric Combination of Sucralose and Maltodextrin, Respectively, on Post-Prandial Bacterial Endotoxin Levels in Blood | After the intake of the sucrose-sweetened beverage, plasma endotoxin levels increased significantly when compared with baseline levels (120 min: +~45%, 180 min: +~36% compared with baseline, | PMC10537596 | ||
3.3. Effect of Sucralose and Sucrose on Bacterial Endotoxin Permeation and Protein Levels of iFABP in Differentiated Caco-2 Cells | To further assess if the increase in bacterial endotoxin levels found after the intake of sucrose was related to changes in intestinal barrier function and to compare these effects with those of sucralose, a model of the intestinal barrier, e.g., differentiated Caco-2 cells grown on trans-well inserts was employed in which cells were incubated with sucrose or sucralose in iso-sweet, physiological doses (see | PMC10537596 | ||
3.4. Effect of Sucralose and Sucrose on Markers of Intestinal Barrier Function in Small Intestinal Everted Tissue Sacs of C57BL/6J Mice | When challenging small intestinal everted tissue sacs with sucrose, the permeation of xylose significantly increased compared with tissue sacs only incubated with 1× Krebs–Henseleit buffer. In contrast, the intestinal permeation of xylose was not altered when tissue sacs were challenged with sucralose ( | PMC10537596 | ||
4. Discussion | weight gain | DISEASES | Intense sweeteners widely used in human nutrition as substitutes for sugars like sucrose or high-fructose corn syrup may have beneficial effects with regard to body weight gain and the development of some non-communicable diseases [In line with our previous findings [ | PMC10537596 |
Limitations | MASLD, metabolic abnormalities | TYPE 2 DIABETES | Our study is not without limitations that need to be considered when interpreting the data. A major limitation of our study is the sample size of only 11 subjects and the focus on young, healthy adults. The results might differ in a larger cohort and in another age group as well as in subjects with metabolic abnormalities, e.g., type 2 diabetes or metabolic dysfunction-associated steatotic liver disease (MASLD). This needs to be assessed in future studies. Another limitation is that the subjects consumed the different beverages only once. Therefore, from the present study, no estimation regarding the long-term effects of an intake of sucralose, especially of large amounts, on intestinal barrier function can be made. Additionally, in the present study, no direct measurements of intestinal permeability, e.g., through a xylose or lactose-mannitol test were included. However, these tests require not only the ingestion of an additional beverage but also urine collection over several hours. As the dietary interventions were rather rigid and participants had to consume a large amount of liquid in a rather short period of time on the day of the study, these additional tests would have resulted in lower compliance and therefore decreased the number of participants even further. | PMC10537596 |
5. Conclusions | intestinal barrier dysfunction | METABOLIC DISEASES, INTESTINAL BARRIER DYSFUNCTION, TYPE 2 DIABETES | In summary, our data suggest that the intake of a sucralose-sweetened beverage in a physiological amount, e.g., 1 L, has no effect on intestinal barrier function in healthy young adults. To our knowledge, this is the first study which examines the effect of an acute intake of sucralose on endotoxin levels in healthy, normal-weight human subjects. However, whether an intake of sucralose over an extended period of time and at higher doses or in individuals suffering from health impairments has similar limited effects on intestinal barrier function needs to be determined in future studies. The results of our study also add further weight to the hypothesis that dietary sugars like sucrose may be critical in the development of intestinal barrier dysfunction suggested to contribute to the development of various metabolic diseases like MASLD and type 2 diabetes [ | PMC10537596 |
Author Contributions | Conceptualization, I.B.; Formal analysis, R.S.; Funding acquisition, I.B. and A.B.; Investigation, R.S., V.S. and A.B.; Visualization, R.S. and A.B.; Writing—original draft, R.S., I.B. and A.B., Writing—review & editing, R.S., V.S., I.B. and A.B. All authors have read and agreed to the published version of the manuscript. | PMC10537596 | ||
Institutional Review Board Statement | The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the University of Vienna (protocol code 00585, 13 January 2021). | PMC10537596 | ||
Informed Consent Statement | Informed consent was obtained from all subjects involved in the study. | PMC10537596 | ||
Data Availability Statement | Data are made available upon reasonable request. | PMC10537596 | ||
Conflicts of Interest | The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analysis or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. | PMC10537596 | ||
References | Design of the randomized controlled single-blinded crossover-designed human intervention study.Effect of a beverage containing either sucrose, sucralose or sucralose + maltodextrin on bacterial endotoxin levels in peripheral blood 60, 120 and 180 min after the consumption of the respective beverage. Values are means ± SEM, (Composition of breakfast on day of study.E%: percentage of energy.Characteristics of healthy male and female participants.Values are means ± SEM, Nutritional intake of participants before and during the nutritional standardization according to the recommendations of the German, Austrian and Swiss Nutrition societies (D-A-CH) prior to each intervention.Values are means ± SEM, Effect of the nutritional standardization following the recommendations of the German, Austrian and Swiss Nutrition societies (D-A-CH) on anthropometric and clinical parameters as well as bacterial endotoxin levels in healthy participants.Values are means ± SEM, | PMC10537596 | ||
Purpose | fracture, weight loss, bone loss | BONE LOSS | Intentional weight loss has been shown to increase bone loss short term but the long-term effects are not known. Data from the Look AHEAD clinical trial shows that a long term intentional weight loss intervention was associated with greater bone loss at the hip in men.Intentional weight loss has been shown to increase bone loss short term and increase frailty fracture risk, but the long-term effects on bone mineral density (BMD) are not known. | PMC10348976 |
Methods | weight loss, bone loss | BONE LOSS | Data from a subgroup from the Look AHEAD (LA) multicenter, randomized clinical trial was used to evaluate whether a long term intentional weight loss intervention would increase bone loss. In a preplanned substudy, BMD was assessed at 5 of the 16 LA clinical centers using dual-energy X-ray absorptiometry at baseline, year 8, and the observational visit 12.6–16.3 years after randomization (year 12–16). | PMC10348976 |
Results | At year 8, bone density loss (%) was greater in the Intensive Lifestyle Intervention (ILI) group compared with the control group (DSE) for the femoral neck ( | PMC10348976 | ||
Conclusion | fracture, weight loss | BONE LOSS | Long term intentional weight loss was associated with greater bone loss at the hip in men. These results taken with the previously published Look AHEAD data from the entire clinical trial showing increased frailty fracture risk with weight loss in the ILI group suggest that when intentional weight loss is planned, consideration of bone density preservation and fracture prevention strategies is warranted. | PMC10348976 |
Trial Registration | Clinicaltrials.gov Identifier: NCT00017953. June 21, 2001 | PMC10348976 | ||
Supplementary Information | The online version contains supplementary material available at 10.1007/s11657-023-01303-0. | PMC10348976 | ||
Keywords | PMC10348976 | |||
Introduction | overweight / obesity, DM, weight loss, diabetes | DIABETES | Among the US population, it is estimated that over 34 million people have diabetes and this risk increases with age and increasing body mass index (BMI) [Therefore, the purpose of this analysis is to examine whether this long term intentional weight loss intervention resulted in sustained bone density loss, beyond four years, as measured by dual-energy X-ray absorptiometry (DXA) in older persons with overweight / obesity living with type 2 DM in the Look AHEAD randomized clinical trial. | PMC10348976 |
Methods | DM, Fracture, fracture | The Look AHEAD randomized clinical trial involved 16 clinical sites across the US (Clinicaltrials.gov Identifier: NCT00017953). The methods and baseline characteristics of the study population have been published and the protocol is available (Intervention curricula for both ILI and DSE were developed centrally and have been described in detail [Look AHEAD was approved by local Institutional Review Boards and all participants provided informed consent. Look AHEAD complied with the World Medical Association Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects.Major eligibility criteria for Look AHEAD included the following: 45–76 years of age; type 2 DM; body mass index (BMI) of ≥ 25.0 kg/mRandomization occurred from August 2001 through April 2004 with an allocation ratio of 1:1 and stratification by clinical site. At baseline and annual clinic visits, weight and height were measured with a digital scale and a standard wall-mounted stadiometer respectively. BMI was calculated from the measured weights and heights. Questionnaires were used to collect demographic characteristics, medical history, smoking history, and alcohol use. Fracture data was collected as previously described in the Look AHEAD fracture paper [ | PMC10348976 | |
Dual-energy X-ray absorptiometry (DXA) substudy | SECONDARY | Look AHEAD was also designed to examine secondary outcomes including areal BMD changes. In a preplanned substudy, total hip, lumbar spine, and whole body DXA scans were obtained at baseline, year 1, year 4, year 8, and at the observational visit which occurred 12.6 – 16.3 years after randomization (year 12–16) at five clinical centers (Baton Rouge, Boston, Houston, Los Angeles, and Seattle). This paper extends the BMD findings previously published to the year 8 and year 12–16 visit [Consort diagram for the Look AHEAD DXA substudy participants | PMC10348976 | |
Fracture ascertainment | fracture, fractures, primary fracture | EVENTS, SECONDARY | During annual visits and telephone calls every 6 months, staff members who were unaware of study-group assignments (blinded) queried participants about all medical events and hospitalizations including incident fractures. Hospital and other records such as outpatient medical records and x-ray reports were reviewed for potential incident fracture events, with adjudication according to standard criteria by a central review committee of trained physicians who were blinded to study-group assignment. The primary fracture outcome was prespecified as the first occurrence of a fracture. Self-reported fractures of the fingers, toes, face, neck (c-spine), sternum, ribs, and skull were not centrally adjudicated and are not included in the fracture events for this manuscript. Only confirmed centrally adjudicated incident fracture events are included in these analyses. As a secondary fracture outcome, a frailty fracture endpoint was created a priori and is a composite of the first occurrence of a hip, pelvis, upper arm or shoulder fracture [ | PMC10348976 |
Statistical analysis | bone loss | BONE LOSS | Baseline characteristics were summarized with means and standard deviations for continuous variables, and frequencies and percents for categorical variables, stratified by randomization arm and gender. Comparisons between randomization arms were made with t-tests or chi-square tests of association as appropriate with a p value of < 0.05 accepted as significant. Absolute changes in BMD were compared across ILI and DSE groups. Analyses are also presented stratified by gender because of well-described gender differences in BMD and bone loss. Differences by randomization assignment were tested with longitudinal linear models to account for within-subject correlation. All models are adjusted for study site, age, race/ethnicity, baseline total bone mass, use of bone positive agents, use of bone negative agents, and baseline value of the BMD outcome. Overall models are also adjusted for gender. Gender differences in percent changes in BMD by visit are explored in overall models that also include an interaction term. Adjusted mean change from baseline and standard errors are reported. Analyses were carried out using SAS v 9.4 (SAS Institute, Cary, NC). | PMC10348976 |
Discussion | obesity, fracture, weight loss, bone loss | OSTEOPOROTIC FRACTURES, OBESITY, SECONDARY, BONE LOSS | In the Look AHEAD clinical trial in persons with overweight and obesity and with DM, we previously found that an intensive lifestyle intervention that resulted in intentional long term weight loss and improved fitness increased the risk of frailty fracture [Our finding of increased bone loss with weight loss is consistent with other reports from the Osteoporotic Fractures in Men Study which found that weight loss regardless of intentionality is associated with an increase in bone loss [We did not observe any differences in bone density changes at the lumbar spine, comparing the two treatment groups. Interestingly, men in both groups experienced increased BMD of the lumbar spine a finding that is consistent with reports from other studies of increasing spine BMD as measured by DXA with aging [The total number of bariatric surgeries in the DXA subgroup was very small and thus we were not able to examine this surgical procedure’s effect on bone by treatment assignment in the current paper. Although beyond the scope of this paper, it is worth noting that bariatric surgery is an increasingly utilized weight loss strategy in this population [The strengths of the Look AHEAD clinical trial include randomization to group assignment, high levels of retention during longitudinal follow-up, a racially and geographically diverse participant population, and successfully producing long-term intentional weight loss and improvements in physical activity and fitness. Further, the DXA measurement in the DXA substudy and fracture ascertainment in the whole Look AHEAD group were preplanned secondary outcomes of the trial. The DXA data was also rigorously monitored by the DXA quality assurance center and longitudinal performance was assessed with regular scanning of spine and whole body phantoms on each densitometer.There are several considerations to put interpretation of our findings in context. Look AHEAD did not collect information regarding calcium and vitamin D intake in the DXA subgroup, thus we are unable to examine the observed bone changes in relation to these variables that are known to be important for bone health in both men and women [Another limitation of the substudy is use of a DXA scanner in the setting of weight change. With obesity, the long-term precision of the DXA scanner is reduced which may result in attenuation of associations between changes in weight and BMD [ | PMC10348976 |
Conclusion | fracture, weight loss | BONE LOSS | Long term intentional weight loss was associated with greater bone loss at the hip in men long term and in women in the shorter term. These results taken with the previously published Look AHEAD fracture data from the entire clinical trial showing increased frailty fracture risk in the ILI group with intentional weight loss suggest that when intentional weight loss is planned, consideration of bone density preservation and fracture prevention strategies is warranted. | PMC10348976 |
Funding | Bartter, Johnson & Johnson Company, Digestive, Diabetes | LUNG, KIDNEY DISEASES, DIABETES, BLOOD, HEART, DISEASE | Funded by the National Institutes of Health through cooperative agreements with the National Institute on Aging: AG058571 and National Institute of Diabetes and Digestive and Kidney Diseases: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992. Additional funding was provided by the National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; NIH Office of Research on Women’s Health; and the Centers for Disease Control and Prevention. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service (I.H.S.) provided personnel, medical oversight, and use of facilities. The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the I.H.S. or other funding sources. Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center (M01RR01066); the Harvard Clinical and Translational Science Center (RR025758-04); the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (GCRC) (M01RR000056), the Clinical Translational Research Center (CTRC) funded by the Clinical & Translational Science Award (UL1 RR 024153) and NIH grant (DK 046204); the VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; and the Frederic C. Bartter General Clinical Research Center (M01RR01346). The following organizations have made major contributions to Look AHEAD: FedEx Corporation; Health Management Resources; LifeScan, Inc., a Johnson & Johnson Company; OPTIFAST® of Nestle HealthCare Nutrition, Inc.; Hoffmann-La Roche Inc.; Abbott Nutrition; and Slim-Fast Brand of Unilever North America. | PMC10348976 |
Data Availability | Digestive, Diabetes | KIDNEY DISEASES, DIABETES | Data that support the findings from the Look AHEAD trial (Action for Health in Diabetes) can be accessed through application to the National Institute of Diabetes and Digestive and Kidney Diseases; NIDDK Central Repository: | PMC10348976 |
Declarations | PMC10348976 | |||
Ethical approval | All procedures performed in the Look AHEAD study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. | PMC10348976 | ||
Informed consent | Informed consent was obtained from all individual participants included in the study. | PMC10348976 | ||
Competing interests | Andrea Anderson | SCHWARTZ | The authors have disclosed the following financial and non-financial competing interests and funding.Karen C. Johnson, MD, MPH – The author declares that they have no conflict of interest.Andrea Anderson, MS—The author declares that they have no conflict of interest.Kristen M. Beavers, PhD—The author declares that they have no conflict of interest.Carolyn J. Crandall, MD, MS, CCD—The author declares that they have no conflict of interest.Helen P. Hazuda, PhD—The author declares that they have no conflict of interest.Cora E. Lewis, MD, MSPH – Reports serving on a Data Safety Monitoring Board for Rush University Medical Center.Edward Lipkin MD, PhD—The author declares that they have no conflict of interest.Ann V. Schwartz, PhD, MPH—The author declares that they have no conflict of interest.F.X. Pi-Sunyer, MD—The author declares that they have no conflict of interest.Qi Zhao, MD, PhD | PMC10348976 |
Human and animal rights | The Look AHEAD study was approved by the appropriate institutional research ethics committees and was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. | PMC10348976 | ||
References | PMC10348976 | |||
Background | cancer, Inflammation | CANCER, DISEASE, MALIGNANCIES, INFLAMMATION | Edited by: Luisa Giaccone, University of Turin, ItalyReviewed by: Elisabetta Metafuni, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Italy; Sakhila Ghimire, University Medical Center Regensburg, GermanyThis article was submitted to Alloimmunity and Transplantation, a section of the journal Frontiers in ImmunologyIn allogeneic hematopoietic stem cell transplantation (allo-HSCT), prognostic indicators effectively predict survival. The Disease conditions prior to transplantation dramatically affects the outcome of HSCT. Optimization of the pre-transplant risk assessment is critical for enhancing allo-HSCT decision-making. Inflammation and nutritional status play significant roles in cancer genesis and progression. As a combined inflammatory and nutritional status biomarker, the C-reactive protein/albumin ratio (CAR) can accurately forecast the prognosis in various malignancies. This research sought to examine the predictive value of CAR and develop a novel nomogram by combining biomarkers and evaluating their importance following HSCT. | PMC9974829 |
Methods | comorbidity | DISEASE | Analyses were conducted retroactively on a cohort of 185 consecutive patients who underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) at Wuhan Union Medical College Hospital during the period from February 2017 to January 2019. Of these patients, 129 were randomly assigned to the training cohort, and the remaining 56 patients constituted the internal validation cohort. Univariate and multivariate analyses were carried out to examine the predictive significance of clinicopathological factors in the training cohort. Subsequently, the survival nomogram model was developed and compared with the disease risk comorbidity index (DRCI) using the concordance index (C-index), calibration curve, receiver operating characteristics (ROC) curve, and decision curve analysis (DCA). | PMC9974829 |
Results | Comorbidity | DISEASE | Patients were separated into low and high CAR groups using a cutoff of 0.087, which independently predicted overall survival (OS). Based on risk factors, CAR, the Disease Risk Index(DRI), and the Hematopoietic Cell Transplantation–specific Comorbidity Index(HCT-CI), the nomogram was developed to predict OS. The C-index and area under the ROC curve confirmed the improved predictive accuracy of the nomogram. The calibration curves revealed that the observed probabilities agreed well with those predicted by the nomogram in training, validation and entire cohort. It was confirmed by DCA that the nomogram offered greater net benefits than DRCI among all cohorts. | PMC9974829 |
Conclusion | CAR is an independent prognostic indicator for haplo-HSCT outcomes. Higher CAR was related to worse clinicopathologic characteristics and poorer prognoses in patients underwent haplo-HSCT. This research provided an accurate nomogram for predicting the OS of patients following haplo-HSCT, illustrating its potential clinical utility. | PMC9974829 | ||
Introduction | hematologic malignancies, Comorbidity | DISEASE, COMPLICATION, HEMATOLOGIC MALIGNANCIES, MALNUTRITION, DISEASE CHARACTERISTIC, COMPLICATIONS | One of the most promising treatments for patients with hematologic malignancies is allogeneic hematopoietic stem cell transplantation (allo-HSCT) (It can be challenging to select patients who will benefit from HSCT because survival after transplantation can vary greatly and rely on many factors. Various factors, including age at HSCT, complications, the donor type, the disease status as well as the conditioning regimen, can affect outcomes (To provide a score for pre-transplant risk and to better predict outcomes after allo-HSCT, several prognostic models have been performed. The Hematopoietic Cell Transplantation–specific Comorbidity Index (HCT-CI) and its derivation, the Comorbidity–Age Index, are derived from the complication condition of the patient (A thorough pre-transplant evaluation is essential at the time of assessing the risks and advantages of haplo-HCT. Therefore, It would be of tremendous clinical benefit for patients undergoing haplo-HSCT to develop a well-rounded pre-HSCT prognostic system that considers the risk elements associated with the patient and the disease. According to our knowledge, the prognostic implications of CAR in patients who received haplo-HSCT is unknown. Therefore, we hypothesized that integration of the inflammatory state, malnutrition, disease characteristics and comorbidities could provide a more comprehensive and precise prediction of overall survival (OS) than DRCI. | PMC9974829 |
Materials and methods | PMC9974829 | |||
Study patients | malignant hematologic disease | This research comprised all consecutive adult patients (aged >18 years) with malignant hematologic disease who underwent haplo-HSCT within the period of February 2017 to January 2019 at Wuhan Union Medical College Hospital. All patients who received haplo-HSCT as their initial allogeneic transplant were included in the risk assessment score and outcome analysis. Patients who received a second or third HSCT and those with incomplete medical records were omitted from this work. The flow diagram of the patient is illustrated in Patient flow diagram. HSCT, Hematopoietic Stem Cell Transplantation. AHSCT, Autologous Hematopoietic Stem Cell Transplantation. | PMC9974829 | |
Definitions | inflammation | INFLAMMATION | All data were collected directly within 10 days of the allo-HSCT conditioning regimen to assess the inflammatory and nutritional status before transplantation. We investigated CRP as a marker of inflammation and albumin as an indicator of nutritional status. CAR was counted by dividing the serum CRP level by the serum albumin level as a combination marker. DRI was applied by the criteria according to Armand et al ( | PMC9974829 |
CRP and albumin level measurement | 5 ml of cubital vein whole blood was extracted from all patients in the morning on an empty stomach. Serum CRP level measurements were included in the routine clinical tests using an automated biochemical analyzer | PMC9974829 | ||
Donor selection, transplant regimens, and GVHD prophylaxis and treatment | Donor selection method in accordance with the non-HLA system ( | PMC9974829 | ||
Development of a prognostic model | REGRESSION | In total, 185 patients were randomized into two groups (training and validation cohorts) based on a ratio of 7 to 3. the following medical characteristics were evaluated to identify the predictive factors of survival in the training cohort: age at HSCT, sex, DRI, HCT-CI, CAR, donor–recipient relationship, donor–recipient sex match, donor–recipient blood type match, number of HLA mismatches and conditioning regimens. The construction of nomograms is based on multivariate regression models (such as Cox and logistic regression models), which can may simplify and visualize complex regression equations, and making the results of prediction model more readable and valuable for use.Variables significant at P < 0.10 in univariate analysis as underlying survival risk elements were selected for multivariate Cox proportional risk regression to Identify independent prognostic factors. According to the above results, Statistically significant parameters (P<0.05) were incorporated into a nomogram to predict OS in patients after haplo-HSCT. | PMC9974829 | |
Model validation and clinical use | The predictive capability of the nomogram was evaluated by assessing discrimination power and calibration in the training, validation, and entire cohorts. The concordance index (C-index) was computed to evaluate the discriminative ability of the novel nomogram in all cohorts. A higher C-index suggests superior capability to differentiate patients according to survival status. Calibration curve produced from 1000 bootstrap replicates was used to examine the conformity between the model-predicted probability and the actual condition. In addition, to further evaluate the predictive performance of the nomogram for OS, ROC curve was plotted over the total score of the nomogram for OS for each patient, and AUC analyses was computed. Finally, the net benefit of the novel nomogram was measured with decision curve analysis (DCA). | PMC9974829 | ||
Statistical analysis | Categorical features were presented as counts and proportions and examined by the chi-squared test. Continuously parameterized characteristics were reported as the median and interquartile range (IQR), and comparisons of continuous variables between cohorts were determined using the Mann–Whitney U test. In these tests, a two-tail P value of 0.05 was deemed to be statistically significant. Based on the maximum Youden index, the best cutoff value for continuous variables was determined by ROC curve analysis. OS rates were estimated using the Kaplan–Meier method, and Disparities between groups were evaluated by log-rank test. The prognostic index was calculated | PMC9974829 | ||
Results | PMC9974829 | |||
Optimal cutoff of CAR for predicting all-cause mortality following haplo-HSCT | death | The median CAR among 185 patients was 0.087 (range, 0.00667–2.67352). With all-cause patient death as the outcome variable, a 3-year time-dependent ROC curve was created, and the maximum Youden index for OS was utilized to determine the optimal cutoff. The optimal cutoff of CAR was finally regarded as 0.109. Patients were then separated into low CAR and high CAR groups based on the appropriate cutoff for CAR. Kaplan–Meier survival curves demonstrated that patients in the high CAR group had a higher mortality rate (P < 0.0001, Kaplan–Meier plots of OS according to patient groups with low CAR or high CAR.The relationship between CAR and clinical characteristics. | PMC9974829 | |
Baseline clinical features of the research cohort | isohemagglutinins | The baseline clinical features of the training and validation cohorts are depicted in Patients’ baseline features.Minor ABO mismatch demonstrated the donor had isohemagglutinins against the recipient’s red blood cells, including the following blood group combinations: O (donor) into A, B, or AB (recipient); A or B (donor) into AB (recipient) (recipient). Major ABO mismatched indicated that the recipient had isohemagglutinin resistant to donor red blood cells and included the following blood group combinations: A, B, or AB (donor) became O (recipient), and AB (donor) became A or B (recipient). Major-minor mismatched suggest that both the donor and the recipient share isohemagglutinins: A to B and vice versa. | PMC9974829 | |
Construction of the novel nomogram of OS | REGRESSION | In univariate analysis, OS was related to DRI (P < 0.001), HCT-CI (P = 0.038), and CAR (P < 0.001). In multivariate Cox regression analysis, DRI (P < 0.001), HCT-CI (P = 0.011), and CAR (P =0.017) were independent predictors of OS following haplo-HSCT (Univariate and multivariate Cox analysis for OS in patients with haplo-HSCT in training cohort.Nomogram of OS for patients with haplo-HSCT. Low CAR: ≤0.109; High CAR: >0.109. | PMC9974829 | |
Validation of the novel nomogram | The C-indices of the novel nomogram for 3-year OS in the training cohort by bootstrap resampling was 0.671 (95% CI = 0.5923–0.7496). Meanwhile, it was found that the calibration plot displayed good similarity between the predicted and actual survival rates (Calibration curves for predicting 3-year OS in training cohort | PMC9974829 | ||
Comparison of the nomograms and DRCI | Comparisons between DRCI and the nomograms were also conducted. For the three cohorts shown in the figure, the AUCs of the nomogram were greater than those of DRCI [0.715 (95% CI:0.617–0.812) Area under the ROC curves of nomogram and DRCI of OS in training cohort Comparison of the decision curves between the nomogram and the DRCI in the training | PMC9974829 | ||
Discussion | acute myeloid leukemia, tumor, inflammation, Comorbidity, malnutrition | ACUTE MYELOID LEUKEMIA, CANCER PROGRESSION, TUMOR, PROLIFERATION, INFLAMMATION, DISEASE, INVASIVE CANCER, MYELODYSPLASTIC SYNDROMES, MALNUTRITION, HEMATOLOGICAL MALIGNANCY | DRI, HCT-CI, and CAR were the components of the developed OS nomogram. Previous studies using multivariate analysis also demonstrated significant associations between these prognostic variables and OS in patients following haplo-HSCT. Our results reconfirmed the conclusions of these investigations. In this research, we found that CAR was negatively correlated with OS following haplo-HSCT. Furthermore, we proposed a nomogram for stratifying patients at the time of haplo-HSCT by incorporating CAR into the established DRCI scoring system. The nomogram outperformed the DRCI in predicting OS in haplo-HSCT cohorts, which gave clinicians more flexibility in making personalized decisions about the medical management of patients after haploidentical HSCT.DRI, which originated from the underlying hematological malignancy, cytogenetics for acute myeloid leukemia and myelodysplastic syndromes, and disease status at the time of transplantation, is a validated tool commonly used to predict survival outcomes following HSCT. This score is available for patients receiving HSCT independently of age, the pretreatment intensity regimen, and the graft source (The HCT-CI is a modified version of the Charlson Comorbidity Index (According to studies, malnutrition and systemic inflammation are significantly associated with worse outcomes in patients who underwent HSCT (The cutoff of CAR has differed among studies (The precise mechanism underlying the role of CAR in cancer progression is uncertain and potentially complex. Our investigation demonstrated that high CAR was significantly related to DRI. (P = 0.0015), suggesting that higher CAR is correlated with more invasive cancer behavior in patients following haplo-HSCT. This might be explained by the possibility that tumor cells release cytokines that induce CRP elevation or that CRP elevation is a substituted marker for the active release of cytokines that promote tumor cell proliferation (There are some limitations to this study, despite our nomogram incorporating CAR having significantly better predictive accuracy than DRCI. First, This research is retrospective rather than prospective, which might have resulted in data bias. Furthermore, the study relied on clinical data from our single center database, and there was no external validation. Third, during the duration of the study, nutritional interferences, for example, using intravenous supplementation for patients with decreased food intake, was an integral element of the standard treatment. However, In this study, it was not possible to analyze the influences of these interferences on inflammatory and nutritional conditions and transplantation outcomes. Thus, the results of our research require additional confirmation | PMC9974829 |
Conclusion | To our knowledge, none of the existing scoring systems considers the pre-transplant inflammatory and nutritional status. This is the first study to demonstrate the predictive power of pre-transplant CAR for survival outcomes following haplo-HSCT. Compared with DRCI, the nomogram incorporating CAR displayed substantially improved predictive accuracy. It has been proven that a high CAR at diagnosis is associated with a poor prognosis following haplo-HSCT, and this important finding can lead to further investigation. | PMC9974829 | ||
Data availability statement | The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author. | PMC9974829 | ||
Ethics statement | The studies involving human participants were reviewed and approved by the Ethics Committee of Tongji Medical College of Huazhong University. The patients/participants provided their written informed consent to participate in this study. | PMC9974829 | ||
Author contributions | KW collected, analyzed the data, and wrote the paper. XJ and ZX researched the literature and revised the paper. All authors contributed to the article and approved the submitted version. | PMC9974829 | ||
Acknowledgments | The authors of this study would like to thank all the study participants for their contributions. | PMC9974829 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.