Coffee and tea consumption, patient-reported, and clinical outcomes in a longitudinal study of patients with breast cancer.

BACKGROUND: Higher consumption of coffee and tea has been associated with improved health outcomes in the general population and improved breast cancer (BC) prognosis. This study investigated patterns of coffee and tea consumption and association with patient-reported outcomes (PROs) and clinical outcomes among survivors of BC. METHODS: The authors included survivors of stage I-III BC enrolled in the CANTO cohort (NCT01993498) that provided post-treatment assessment of coffee and tea consumption from years 1 to 4 after diagnosis. Group-based trajectory modeling clustered patients according to daily consumption of coffee and tea. Multivariable mixed models and Cox models examined associations between consumption, PROs and clinical outcomes. RESULTS: Among 3788 patients, the authors identified four stable patterns of consumption: "Low" (25.8%), "Moderate" (37.6%), "High" (25.3%), and "Very high" (11.3%), corresponding to <1, 2, 3, and ≥ 4 cups of coffee and/or tea per day. Patients in the "Very high" group (vs. "Low"), were more likely to be younger, smokers, with higher monthly income and education. PROs and survival outcomes were similar across the four groups. CONCLUSIONS: Over one in three survivors of BC reported high or very high consumption of coffee and/or tea. The authors found no association between higher consumption of coffee and/or tea, worse PROs and clinical outcomes.

Effects of Different Levels of Weightlifting Training on Bone Mineral Density in a Group of Adolescents.

The aim of the current study was to evaluate the effects of different levels of weightlifting training on bone mineral density (BMD) at different body sites (whole body (WB), lumbar spine (LS), femoral neck (FN), upper limbs (UL) and lower limbs (LL)) in a group of adolescents. Three groups of pubertal boys aged 13-15 years were recruited, including a control group (which included 13 untrained adolescents), a moderately trained group (which included 13 non-elite weightlifters, with four sessions of 2 hours per week) and a highly trained group (which included 13 elite weightlifters, with eight sessions of 2 hours per week). The three groups were paired for age and maturation index (using Tanner stages). Body composition, bone mineral content (BMC) and BMD were evaluated by dual-energy X ray absorptiometry (DXA). Physical performance variables (including weightlifting specific exercises, counter movement jump and squat jump) were measured using validated methods. Results showed that the values of BMD and physical performance variables were greater in the group of elite weightlifters compared to the group of non-elite weightlifters and the control group. In addition, the values of BMD and physical performance variables were higher in the group of the non-elite weightlifters compared to those of the control group. After adjusting for lean mass and squat jump, lumbar spine BMD, FN BMD, UL BMD and LL BMD remained significantly higher in the elite weightlifters' group compared to the two other groups. In conclusion, the current study suggests that elite adolescent weightlifters have greater bone health parameters compared to moderately-trained adolescent weightlifters and untrained adolescents.

Limb Muscular Strength and Bone Mineral Density in Elderly Subjects with Low Skeletal Muscle Mass Index.

The aim of the current study was to investigate the relationships between limb muscular strength and bone mineral density (BMD) in a group of elderly subjects with low skeletal muscle mass index (SMI).55 elderly Lebanese subjects (35 women and 20 men) participated in the current study. Handgrip, one-repetition maximum (1-RM) dumbbell curl (1-RM biceps), 1-RM lying one arm triceps (1-RM triceps), 1-RM calf raise, 1-RM leg extension and 1-RM leg curl were evaluated using validated methods.In both genders, 1-RM biceps, 1-RM triceps, 1-RM leg extension and 1-RM leg curl were positively correlated to total hip BMD. The current study shows that limb muscular strength is positively correlated to hip BMD in elderly subjects with low SMI. This may have clinical implications in the field of osteoporosis prevention in elderly subjects with low SMI.

Sarcopenia negatively affects hip structure analysis variables in a group of Lebanese postmenopausal women.

BACKGROUND: The current study's purpose is to compare hip structural analysis variables in a group of postmenopausal women with sarcopenia and another group of postmenopausal women with normal skeletal muscle mass index. To do so, the current study included 8 postmenopausal women (whose ages ranged between 65 and 84 years) with sarcopenia and 60 age-matched controls (with normal skeletal muscle mass index (SMI)). Body composition and bone parameters were evaluated by dual-energy X-ray absorptiometry (DXA). RESULTS: Weight, lean mass, body mass index, femoral neck cross-sectional area (FN CSA), FN section modulus (Z), FN cross sectional moment of inertia (CSMI), intertrochanteric (IT) CSA, IT Z, IT CSMI, IT cortical thickness (CT), femoral shaft (FS) CSA, FS Z and FS CSMI were significantly greater (p < 0.05) in women with normal SMI compared to women with sarcopenia. In the whole population, SMI was positively associated with IT CSA, IT Z, IT CSMI, IT CT, FS CSA, FS Z, FS CSMI, FS CT but negatively correlated to IT buckling ratio (BR) and FS BR. CONCLUSION: The current study suggests that sarcopenia has a negative effect on hip bone strength indices in postmenopausal women.

Muscular Maximal Strength Indices and Bone Variables in a Group of Elderly Women.

The aim of the present study was to explore the relations between muscular maximal strength indices and bone parameters (bone mineral density [BMD], hip geometry indices, and trabecular bone score [TBS]) in a group of elderly women. This study included 35 healthy elderly women whose ages range between 65 and 75 yr (68.1 ± 3.1 yr). BMD (in gram per square centimeter) was determined for each individual by dual-energy X-ray absorptiometry at the whole body, lumbar spine (L1-L4), total hip (TH), and femoral neck (FN). L1-L4 TBS and hip geometry indices were also evaluated by dual-energy X-ray absorptiometry. Maximal muscle strength of bench press (1-repetition maximum [RM] bench press), maximal muscle strength of leg press (1-RM leg press), and handgrip were measured using validated methods. 1-RM bench press was positively correlated to TH BMD (r = 0.40; p < 0.05), FN BMD (r = 0.41; p < 0.05), FN section modulus (r = 0.33; p < 0.05), and FN cross-sectional moment of inertia (r = 0.35; p < 0.05). 1-RM leg press was positively correlated to TH BMD (r = 0.50; p < 0.01), FN BMD (r = 0.35; p < 0.05), FN cross-sectional area (r = 0.38; p < 0.05), and TBS (r = 0.37; p < 0.05). Handgrip was correlated only to FN cross-sectional moment of inertia (r = 0.43; p < 0.01). This study suggests that 1-RM bench press and 1-RM leg press are positive determinants of BMD in elderly women.

The relationships between bone variables and physical fitness across the BMI spectrum in young adult women.

In this cross-sectional study we aimed to evaluate the relationship between physical fitness and bone variables across the body mass index (BMI) spectrum in women aged 20-35 years. The study included 13 underweight women (BMI < 18.5 kg/m2), 24 normal weight women (BMI 18.5-24.9 kg/m2), and 20 overweight/obese women (BMI ≥ 25 kg/m2) aged between 20 and 35 years. Bone mineral density (BMD) and content (BMC) at the whole body, lumbar spine, and femoral neck, lumbar spine trabecular bone score, femoral neck geometry were assessed using dual-energy X-ray absorptiometry. Cardiorespiratory fitness and lower limb muscle power were estimated using the 20-m shuttle run test and the Sargent jump test, respectively. The associations between bone variables and physical fitness were different according to BMI categories. Correlations between physical fitness and bone parameters are particularly significant in normal BMI and less significant in low and high BMI. Multivariate ANCOVA regression models demonstrated that absolute VO2max (L/min) is a strong determinant of all the bone parameters regardless of BMI. Implementing strategies for increasing VO2max (L/min) by increasing lean mass and promoting resistance and/or high-intensity interval training could be effective to optimize bone health in underweight and overweight young adult women.

Physical Performance Variables and Bone Parameters in a Group of Young Overweight and Obese Women.

The aim of this study was to explore the relationships between physical performance variables and bone parameters such as bone mineral density (BMD), bone mineral content, hip geometry indices, and trabecular bone score in a group of young overweight and obese adult women. Sixty-eight overweight/obese (body mass index ≥25 kg/m2; 25.5-42.4 kg/m2) young women whose ages range from 18 to 35 yr participated in this study. Body composition and bone outcomes were measured by dual-energy X-ray absorptiometry. Maximum oxygen consumption (VO2 max, in liter per minute) was determined indirectly using a progressive shuttle run test. One-repetition-maximum half-squat was directly measured. Vertical jump was measured and maximum power (P max) of the lower limbs was calculated. Lean mass was positively correlated to whole body (WB) BMD, total hip BMD, femoral neck (FN) BMD, femoral neck cross-sectional area (FN CSA) and femoral neck cross sectional moment of inertia (FN CSMI) (p < 0.05). VO2 max (in liter per minute) and muscle power were positively correlated to WB BMD, total hip BMD, FN BMD, FN CSA, and FN CSMI (p < 0.05). One-repetition-maximum half-squat was positively correlated with lumbar spine trabecular bone score, WB BMD, FN BMD, FN CSA and FN CSMI (p < 0.05). This study suggests that lean mass, vertical jump, VO2 max (liter per minute), muscle power and one-repetition-maximum half squat are positive determinants of BMD and hip geometry indices in young overweight and obese women.

Bone Geometric Properties of the Femoral Neck in Underweight Eumenorrheic Women.

The aim of this study was to describe femoral neck (FN) geometry among eumenorrheic underweight women around the age of peak bone mass. Proximal femur geometry and body composition were assessed in 12 underweight women and in 24 healthy controls using dual-energy X-ray absorptiometry. The Hip Structural Analysis program was used to determine bone geometry at the FN. The cross-sectional area (CSA) and the cross-sectional moment of inertia (CSMI) were significantly lower in underweight women than in controls (p < 0.05). There was a trend toward lower sectional modulus (Z) and strength index in underweight women (p < 0.15). Body weight, body mass index, and lean mass (LM) were positively correlated with CSA, CSMI, Z, and neck-shaft angle (r = 0.428-0.611, p < 0.05). After controlling for body weight, body mass index, and LM, the differences in CSA, CSMI, Z, and neck-shaft angle were no more statistically significant between the 2 groups. The multivariate analysis retained LM as the main predictor of CSA, CSMI, and Z in the whole population. The present study suggests that thinness is associated with low resistance to axial forces (CSA) and bending load (Z and CSMI) in adult eumenorrheic women. LM seems to be a key determinant of FN geometry in underweight women.

Vitamin D and Trabecular Bone Score in a Group of Young Lebanese Adults.

The relationship between vitamin D and trabecular bone score (TBS) in young adults remains unclear. The aim of this study was to explore the relationship between 25-hydroxyvitamin D [25(OH)D] serum levels and TBS in a healthy adult population. A total of 54 men and 61 women whose ages range from 18 to 35 participated in the present study. Participants with 25(OH)D insufficiency (between 21 and 29 ng/mL) were 55.7%, and those with 25(OH)D deficiency (≤20 ng/mL) were 11.4%. TBS positively correlated with 25(OH)D in men (r = 0.393; p <0.05) and women (r = 0.324; p < 0.05). In both genders, TBS was significantly higher in 25(OH)D-sufficient participants (≥30 ng/mL). The present study provides evidence that vitamin D positively affects bone health and suggests that maintaining adequate vitamin D status may be essential for optimal TBS values.

Positive Correlations Between Free Vitamin D and Bone Variables in a Group of Young Lebanese Women.

Optimizing bone mass in adulthood is of great importance to prevent the occurrence of osteoporosis in later age. Vitamin D is an essential component of bone health. Low-serum vitamin D is associated with low bone mineral density (BMD), which is an important predictor of fracture risk. However, most cells, apart from renal tubular cells, are exposed to free rather than to total 25-hydroxyvitamin D. Whether free vitamin D would be a better marker than total vitamin D is still under debate. The aim of the present study was to explore the relationships between serum total vitamin D, vitamin D-binding protein (BP), free vitamin D, and bone parameters in a group of young Lebanese women. This study included 88 young female adults aged between 18 and 35 yr. Body composition and BMD were assessed by dual-energy X-ray absorptiometry, and the lumbar spine trabecular bone score was derived. Bone mineral content (BMC) and BMD were measured at the whole body (WB), the lumbar spine (L1-L4), the total hip (TH), and the femoral neck (FN). To evaluate hip bone geometry, dual-energy X-ray absorptiometry scans were analyzed at the FN, the intertrochanteric region, and the femoral shaft by the Hip Structure Analysis program. The cross-sectional area, the index of axial compression strength, and the section modulus (Z), as well as index of bending strength, were measured from bone mass profiles. Composite indices of FN strength (compressive strength index [CSI], bending strength index, and impact strength index [ISI]) were calculated as previously described. Direct measurement of free 25-hydroxyvitamin D concentrations was performed by immunoassay, which detects free vitamin D by ELISA on a microtiter plate. Serum vitamin D BP was measured using a Quantikine ELISA kit, which employed the quantitative sandwich enzyme immunoassay technique. Serum free vitamin D was positively correlated with WB BMC (r = 0.26, p < 0.05), WB BMD (r = 0.29, p < 0.05), L1-L4 BMD (r = 0.28, p < 0.05), TH BMD (r = 0.34, p < 0.01), FN BMD (r = 0.29, p < 0.05), CSI (r = 0.24, p < 0.05), and ISI (r = 0.28, p < 0.05). No positive correlations were detected between the total vitamin D level, the vitamin D BPs, and BMD. The positive associations between free vitamin D and several bone variables (WB BMC, WB BMD, L1-L4 BMD, TH BMD, FN BMD, CSI, bending strength index, and ISI) remained significant after adjustment for weight. In conclusion, the current study suggests that the free vitamin D serum level is a stronger positive determinant of bone parameters and hip bone strength indices in young female adults than total serum vitamin D.

Evaluation of chronic kidney disease in cancer patients: is there a preferred estimation formula?

BACKGROUND: The evaluation of chronic kidney disease (CKD) in cancer patients seems to rely mostly on the Cockcroft-Gault (CG) formula or the creatinine levels to adjust treatment dosages which is a practice refuted by internists. AIMS: We evaluate the overall agreement of the CG, modification of diet in renal disease (MDRD) and CKD-epidemiology collaboration equations (CKD-EPI) equation with the newly devised Janowitz and Williams' (JW) equation. METHODS: The renal function was estimated in 235 cancer patients according to the CG, MDRD, body surface area (BSA)-adjusted MDRD, CKD-EPI, BSA-adjusted CKD-EPI and JW formulae. RESULTS: JW equation was more in agreement with CG and CKD-EPI estimations than the other equations. Taking JW equation as reference, receiver operating characteristic curve analysis showed that CG eGFR had the higher area under the curve when compared with other equations. Hierarchical cluster analysis showed more proximity between CG and JW equations than the other equations. CONCLUSION: The newly proposed JW eGFR estimation was more in agreement with CG equation than the other equations.

Association of Healthy Lifestyle Factors and Obesity-Related Diseases in Adults in the UK.

Importance: A healthy lifestyle is associated with a reduced risk of cardiovascular disease in adults with obesity. Little is known about the associations between a healthy lifestyle and the risk of other obesity-attributable diseases in this population. Objective: To examine the association between healthy lifestyle factors and the incidence of major obesity-related diseases in adults with obesity compared with those with normal weight. Design, Setting, and Participants: This cohort study evaluated UK Biobank participants aged 40 to 73 years and free of major obesity-attributable disease at baseline. Participants were enrolled from 2006 to 2010 and prospectively followed up for disease diagnosis. Exposures: A healthy lifestyle score was constructed using information on not smoking, exercising regularly, no or moderate alcohol consumption, and eating a healthy diet. For each lifestyle factor, participants scored 1 if they met the criterion for a healthy lifestyle and 0 otherwise. Main Outcomes and Measures: The risk of outcomes according to the healthy lifestyle score in adults with obesity compared with those with normal weight were examined using multivariable Cox proportional hazards models with Bonferroni correction for multiple testing. The data analysis was performed between December 1, 2021, and October 31, 2022. Results: A total of 438 583 adult participants in the UK Biobank were evaluated (female, 55.1%; male, 44.9%; mean [SD] age, 56.5 [8.1] years), of whom 107 041 (24.4%) had obesity. During a mean (SD) follow-up of 12.8 (1.7) years, 150 454 participants (34.3%) developed at least 1 of the studied diseases. Compared with adults with obesity and 0 healthy lifestyle factors, individuals with obesity who met all 4 healthy lifestyle factors were at lower risk of hypertension (HR, 0.84; 95% CI, 0.78-0.90), ischemic heart disease (HR, 0.72; 95% CI, 0.65-0.80), arrhythmias (HR, 0.71; 95% 0.61-0.81), heart failure (HR, 0.65; 95% CI, 0.53-0.80), arteriosclerosis (HR, 0.19; 95% CI, 0.07-0.56), kidney failure (HR, 0.73; 95% CI, 0.63-0.85), gout (HR, 0.51; 95% CI, 0.38-0.69), sleep disorders (HR, 0.68; 95% CI, 0.56-0.83), and mood disorders (HR, 0.66; 95% CI, 0.56-0.78). The lifestyle profiles associated with the lowest risks included a healthy diet and at least 1 of the 2 healthy behaviors of physical activity and never smoking. Compared with adults with normal weight, those with obesity were at higher risk of several outcomes, irrespective of the lifestyle score (adjusted HRs ranged from 1.41 [95% CI, 1.27-1.56] for arrhythmias to 7.16 [95% CI, 6.36-8.05] for diabetes for adults with obesity and 4 healthy lifestyle factors). Conclusion and Relevance: In this large cohort study, adherence to a healthy lifestyle was associated with reduced risk of a wide range of obesity-related diseases, but this association was modest in adults with obesity. The findings suggest that although a healthy lifestyle seems to be beneficial, it does not entirely offset the health risks associated with obesity.

Patients' and caregivers' perceptions of bariatric surgery: A France and United States comparative infodemiology study using social media data mining.

Background: People are conversing about bariatric surgery on social media, but little is known about the main themes being discussed. Objective: To analyze discussions regarding bariatric surgery on social media platforms and to establish a cross-cultural comparison of posts geolocated in France and the United States. Methods: Posts were retrieved between January 2015 and April 2021 from general, publicly accessed sites and health-related forums geolocated in both countries. After processing and cleaning the data, posts of patients and caregivers about bariatric surgery were identified using a supervised machine learning algorithm. Results: The analysis dataset contained a total of 10,800 posts from 4,947 web users in France and 51,804 posts from 40,278 web users in the United States. In France, post-operative follow-up (n = 3,251, 30.1% of posts), healthcare pathways (n = 2,171, 20.1% of the posts), and complementary and alternative weight loss therapies (n = 1,652, 15.3% of the posts) were among the most discussed topics. In the United States, the experience with bariatric surgery (n = 11,138, 21.5% of the posts) and the role of physical activity and diet in weight-loss programs before surgery (n = 9,325, 18% of the posts) were among the most discussed topics. Conclusion: Social media analysis provides a valuable toolset for clinicians to help them increase patient-centered care by integrating the patients' and caregivers' needs and concerns into the management of bariatric surgery.

Spin in the Scientific Literature on Bariatric Endoscopy: a Systematic Review of Randomized Controlled Trials.

Bariatric endoscopy (BE) is an emerging treatment option for people with obesity. Spin (i.e., the practice of frequent misrepresentation or overinterpretation of study findings) may lead to imbalanced and unjustified optimism in the interpretation of the results. The aim of this systematic review was to determine the frequency and type of spin in randomized controlled trials (RCTs) of endoscopic primary weight loss techniques with statistically significant and nonsignificant primary outcomes. In conclusion, spin is observed in the abstract and main text of BE reports and can lead to misinterpretation or overinterpretation of the results. Since BE challenges the available non-endoscopic treatments for obesity, further research is needed to better qualify these techniques, as being effective and safe, as well as predefined hypotheses and analyses.

Seventy years of bariatric surgery: A systematic mapping review of randomized controlled trials.

While research publications on bariatric surgery (BS) have grown significantly over the past decade, there is no mapping of the existing body of evidence on this field of research. We performed a systematic review followed by a mapping of randomized controlled trials (RCTs) in BS for people with obesity. From January 2020 to December 2020, we performed a systematic review of RCTs evaluating BS, versus another surgical procedure, or versus a medical control group, through a search of Embase and PubMed. There was no restriction on outcomes for study selection. A total of 114 RCTs were included, most (73.7%) of which were based on a comparison with Roux-en-Y gastric bypass (RYGB) and conducted between 2010 and 2020. Only 15% of the trials were multicenter and few (3.5%) were international. The median number of patients enrolled was 61 (interquartile range [IQR]: 47.3-100). Follow-up time was 1 to 2 years in 36% and 22.8% of the trials, respectively. Weight loss was the most studied criterion (87% of RCTs), followed by obesity-related diseases, and medical and surgical complications (73%, 54%, and 47% of RCTs, respectively). Nutritional deficiency frequency, body composition, and mental health were little studied (20%, 18% and 5% of RCTs, respectively). Our literature review revealed that much research in BS is wasted because of replication of RCTs on subjects for which there is already body of evidence, with small populations and follow-up times mostly below 2 years. Yet several research questions remain unaddressed, and there are few long-term trials. Future studies should take into account the experience of the past 70 years of research in this field.

Surgery for T4 Colorectal Cancer in Older Patients: Determinants of Outcomes.

Background: This study aimed to compare the outcomes of older and younger patients with T4 colorectal cancer (CRC) treated with surgery. Methods: Consecutive patients with T4 CRC treated surgically at Henri Mondor Hospital between 2008 and 2016 were retrospectively analyzed in age subgroups (1) 50−69 years and (2) ≥70 years for overall and relative survival. The multivariable analyses were adjusted for adjusted for age, margin status, lymph node involvement, CEA level, postoperative complications (POC), synchronous metastases, and type of surgery. Results: Of 106 patients with T4 CRC, 57 patients (53.8%) were 70 years or older. The baseline characteristics were generally balanced between the two age groups. Older patients underwent adjuvant therapy less commonly (42.9 vs. 57.1%; p = 0.006) and had a longer delay between surgery and chemotherapy (median 40 vs. 34 days; p < 0.001). A higher trend for POC was reported among the older patients but did not impact the survival outcomes. After adjusting for confounding factors, the overall survival was shorter among the older patients (HR = 3.322, 95% CI 1.49−7.39), but relative survival was not statistically correlated to the age group (HR = 0.873, 95% CI 0.383−1.992). Conclusions: Older patients with CRC were more prone to severe POC, but age did not impact the relative survival of patients with T4 colorectal cancer. Older patients should not be denied surgery based on age alone.

The future of bariatric surgery research: A worldwide mapping of registered trials.

The bariatric surgery (BS) research landscape is a continuous evolving. Since the first described procedure, numerous different techniques have been developed by surgical teams. In this context, we conducted a systematic mapping of upcoming randomized controlled trials (RCTs) in BS for people with obesity. In June 2021, we performed a systematic review of RCTs evaluating BS versus another surgical procedure or versus a medical control group, through a search in ClinicalTrials.gov. There was no restriction on outcomes for study selection. A total of 62 RCTs were included, totaling 10,800 potential individuals to be included, with planned Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy surgeries the most common. The median number of patients planned to be enrolled is 78 (IQR: 50-143). Mean follow-up time is 12 months in 55% of trials and 4 years or more in 23%. The most frequent (81% of RCTs) outcomes to be investigated are obesity-related diseases with the study of type 2 diabetes, followed by weight loss, quality of life, and surgical complications. The rising number of BS procedures around the world has been followed by a subsequent surge in BS research. An increase in interest is observed in outcomes such as obesity-related diseases, intermediate metabolic markers, quality of life, and body composition.

Spin occurs in bariatric surgery randomized controlled trials with a statistically nonsignificant primary outcome: A systematic review.

OBJECTIVES: To systematically identify the strategy and frequency of spin in reports of bariatric surgery randomized controlled trials (RCTs) with statistically nonsignificant primary endpoint. STUDY DESIGN AND SETTING: The use of specific reporting strategies to highlight the beneficial effect of an experimental treatment can affect the reader interpretation of trial results, particularly when the primary endpoint is not statistically significant. A literature search was performed to identify RCTs publications assessing the impact of bariatric surgery on obesity-related comorbidities published over the past 10 years (from January 2020 till December 2020) in MEDLINE and EMBASE. RCTs publications with statistically non-significant primary outcomes were included. RESULTS: Of 46 576 reports screened for title and abstract inclusion, 29 RCT reports met the inclusion criteria for spin analysis. In total, 16 abstracts (55%) and 18 main texts (62%) were classified as having a spin. In abstract results and conclusion sections, the spin was identified in 69% of reports. In main text results, discussion, and conclusion sections, the spin was recognized in 37%, 72%, and 76% of reports respectively. The spin consisted mainly of focusing on within-group improvements and the interpretation of statistically nonsignificant results as showing treatment equivalence. CONCLUSION: Spin occurred in a high proportion of bariatric surgery RCTs with a statistically nonsignificant primary endpoint.

Development and validation of a host-dependent, PDL1-independent, biomarker to predict 6-month progression-free survival in metastatic non-small cell lung cancer (mNSCLC) patients treated with anti-PD1 immune checkpoint inhibitors (ICI) in the CERTIM Cohort: The ELY study.

BACKGROUND: Immune checkpoint inhibitors (ICI) are dramatically active in a minority of non-small cell lung cancer (NSCLC) patients. We studied here the relationship between patients's metabolism and outcome under ICI. METHODS: Metastatic NSCLC patients underwent a nutritional assessment prior to initiating immunotherapy. Resting energy expenditure (REE) was measured (mREE) using ambulatory indirect calorimetry and compared with the theoretical value (tREE) provided by the Harris and Benedict formula. The primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and disease control rate (DCR) based on investigator review per RECIST v1.1. and overall survival (OS). The association of patient's metabolism with 6-month PFS was first explored in a single-center training cohort to estimate the effect size. The relationship between patient's metabolism and 6-month PFS was then tested in an independent non interventional observational prospective cohort (ELY) of 100 patients recruited in two tertiary university centers. FINDINGS: In the entire cohort, the ORR was 14% for the hypermetabolic group (n = 10/74) vs 38% for the normometabolic group (n = 26/68), respectively (estimated difference 25%, 95CI 9-40%, p = 0.001). The DCR was 28% for the hypermetabolic group (n = 21/74) vs 53% for the normometabolic group (n = 36/68), respectively (estimated difference 25%, 95CI 7-42%, p = 0.005). In the validation cohort (100 patients, 2 centers), normometabolic patients (defined as mREE/tREE < 110%) had increased 6-month PFS (57% versus 22%; odds ratio: 4.76; IC95 [1.87 - 12.89]; p<0.001) and improved overall survival (HR 2.20; IC95: 1.41-3.44; p<0.001). The positive and negative predictive values of normometabolism to identify non-progressive patients at 6 months, were 57% and 78% respectively, sensitivity was 72% and specificity was 66%. In multivariate analysis including PD-L1 tumor status, basal metabolism was an independent predictive factor for 6-month PFS. INTERPRETATION: Normometabolism is a new independent parameter to identify mNSCLC patients who will benefit from ICI, with both improved tumor response, 6-month PFS, and survival. FUNDING: This work was supported by Baxter (04012016).