Interhemispheric reactivity of the subthalamic nucleus sustains progressive dopamine neuron loss in asymmetrical parkinsonism.

Parkinson's disease (PD) is characterized by the progressive and asymmetrical degeneration of the nigrostriatal dopamine neurons and the unilateral presentation of the motor symptoms at onset, contralateral to the most impaired hemisphere. We previously developed a rat PD model that mimics these typical features, based on unilateral injection of a substrate inhibitor of excitatory amino acid transporters, L-trans-pyrrolidine-2,4-dicarboxylate (PDC), in the substantia nigra (SN). Here, we used this progressive model in a multilevel study (behavioral testing, in vivo 1H-magnetic resonance spectroscopy, slice electrophysiology, immunocytochemistry and in situ hybridization) to characterize the functional changes occurring in the cortico-basal ganglia-cortical network in an evolving asymmetrical neurodegeneration context and their possible contribution to the cell death progression. We focused on the corticostriatal input and the subthalamic nucleus (STN), two glutamate components with major implications in PD pathophysiology. In the striatum, glutamate and glutamine levels increased from presymptomatic stages in the PDC-injected hemisphere only, which also showed enhanced glutamatergic transmission and loss of plasticity at corticostriatal synapses assessed at symptomatic stage. Surprisingly, the contralateral STN showed earlier and stronger reactivity than the ipsilateral side (increased intraneuronal cytochrome oxidase subunit I mRNA levels; enhanced glutamate and glutamine concentrations). Moreover, its lesion at early presymptomatic stage halted the ongoing neurodegeneration in the PDC-injected SN and prevented the expression of motor asymmetry. These findings reveal the existence of endogenous interhemispheric processes linking the primary injured SN and the contralateral STN that could sustain progressive dopamine neuron loss, opening new perspectives for disease-modifying treatment of PD.

Study of the relationship between psychoactive substance use and pain in cancer patients and cancer survivors: A French nationwide cross-sectional study.

Pain is a prevalent symptom among cancer patients and survivors. Psychoactive substance use (PSU) is associated with both the presence and severity of pain. However, little is known about this association in the context of cancer. The primary objective was to compare the prevalence of PSU and its relationship with pain during and after cancer. PSU was defined as the use of nonmedication substances (alcohol, tobacco, e-cigarettes, cannabidiol, and cannabis), with frequency categorized as at least yearly, monthly, weekly, or daily. Secondary objectives aimed to explore the relationships between PSU and pain characteristics, health-related quality of life, anxiety, depression, deprivation, and individual characteristics. Among the 1041 individuals included, pain prevalence was 44.7% (95% confidence interval [CI] 41.6%-47.8%). The overall prevalence of PSU at least monthly was 67.0% (95% CI 64.0%-69.8%). The proportions of chronic and neuropathic pains were higher for at least monthly use of cannabidiol compared to nonuse (70.0% vs. 39.3% and 55.7% vs. 28.1%, p < .001). In multivariate analysis, the monthly uses of tobacco and cannabidiol were higher in painful individuals than in nonpainful ones (odds ratio: 2.85 [95% CI 1.22-6.64] and 3.76 [95% CI 1.13-12.44], p < .05). From the point of view of the patient care, the study underscores the need for physicians to prioritize smoking cessation and pay attention to the use of cannabidiol during and after cancer.

Development and Validation of a Score to Assess Transmural Healing and Response in Patients with Crohn's Disease.

BACKGROUND & AIMS: Because transmural healing (TH) could be the best therapeutic target in Crohn's disease (CD), we aimed to build and validate a score to assess TH and transmural response (TR), and to confirm their association with favorable CD outcomes. METHODS: DEVISE-CD project encompassed 2 retrospective cohorts (274 and 224 patients with CD for development and validation phase, retrospectively) and 1 multicenter prospective validation cohort (N = 46 patients). A step-by-step process was used to build the modified Clermont score (C-score). The primary end points were time to bowel damage progression, and steroid-free clinical remission with fecal calprotectin <250 at 1 year for retrospective and prospective validation cohorts, respectively. RESULTS: Edema, ulcer, contrast enhancement, diffusion-weighted hyperintensity, fat wrapping, bowel thickening (>3 mm), and enlarged lymph nodes were associated to higher risk of bowel damage progression (P < .01). Edema, diffusion-weighted hyperintensity, post-gadolinium contrast enhancement, and bowel thickening were highly coexistent (>95%) and collinear (P < .0001). Bowel thickness had the highest sensitivity to change after treatment (standardized mean difference = 0.30 ± 1.0; P = .001). C-score was calculated as 0.2x(bowel thickness-3mm) + 1.5x enlarged lymph nodes + 2x ulcer. TH (C-score <0.5; hazard ratio [HR], 0.28 [0.13-0.63]; P = .002; adjusted HR [aHR], 0.15 [0.04-0.53]; P = .003), TR50 (50% decrease of C-score; HR, 0.30 [0.15-0.63]; P = .001; aHR, 0.36 [0.14-0.88]; P = .025), or TR25 (25% decrease of C-score; HR, 0.37 [0.19-0.71]; P = .003; aHR, 0.46 [0.23-0.94]; P = .034) prevented bowel damage progression in development and validation cohorts, respectively. In the prospective validation cohort, achieving TH (OR, 4.6 [1.3-15.6]; P = .016), TR50 (OR, 6.9 [1.8-26.0]; P = .008), or TR25 (OR, 6.0 [1.6-22.3]; P = .008) after 12 weeks of anti-tumor necrosis factor therapy led to higher rate of corticosteroid-free remission at 1 year. CONCLUSIONS: C-score is a validated, reliable, and easy-to-use tool to assess TH and TR in patients with CD.

Neoadjuvant Chemotherapy Does Not Improve Survival in cT2N0M0 Gastric Adenocarcinoma Patients: A Multicenter Propensity Score Analysis.

BACKGROUND: According to current international guidelines, stage cT2N0M0 gastric adenocarcinoma warrants preoperative chemotherapy followed by surgery. However, upfront surgery is often preferred in clinical practice, depending on patient clinical status and local treatment preferences. OBJECTIVE: The aim of the present study was to assess the impact of neoadjuvant chemotherapy in overall survival (OS) and disease-free survival (DFS) of cT2N0M0 patients. METHODS: A retrospective analysis was performed among 32 centers, including gastric adenocarcinoma patients operated between January 2007 and December 2017. Patients with cT2N0M0 stage were divided into upfront surgery (S) and neoadjuvant chemotherapy followed by surgery (CS) groups. Inverse probability of treatment weighting (IPTW) was used to compensate for baseline differences between the groups. RESULTS: Among the 202 patients diagnosed with cT2N0M0 stage, 68 (33.7%) were in the CS group and 134 (66.3%) were in the S group. CS patients were younger (mean age 62.7 ± 12.8 vs. 69.8 ± 12.1 years for S patients; p < 0.001) and had a better health status (World Health Organization performance status = 0 in 60.3% of CS patients vs. 34.5% of S patients; p = 0.006). During follow-up, recurrence occurred in 27.2% and 19.6% of CS and S patients, respectively, after IPTW (p = 0.32). Five-year OS was similar between CS and S patients (78.9% vs. 68.3%; p = 0.42), as was 5-year DFS (70.4% vs. 68.5%; p = 0.96). Neoadjuvant chemotherapy was associated with neither OS nor DFS in multivariable analysis after IPTW. CONCLUSIONS: Patients with cT2N0M0 gastric adenocarcinoma did not present a survival or recurrence benefit if treated with perioperative chemotherapy followed by surgery as opposed to surgery alone.

Is large for gestational age in singletons born after frozen embryo transfer associated with freezing technique or endometrial preparation protocol? A longitudinal national French study.

STUDY QUESTION: Is large for gestational age (LGA) observed in babies born after frozen embryo transfer (FET) associated with either the freezing technique or the endometrial preparation protocol? SUMMARY ANSWER: Artificial cycles are associated with a higher risk of LGA, with no difference in rate between the two freezing techniques (vitrification versus slow freezing) or embryo stage (cleaved embryo versus blastocyst). WHAT IS KNOWN ALREADY: Several studies have compared neonatal outcomes after fresh embryo transfer (ET) and FET and shown that FET is associated with improved neonatal outcomes, including reduced risks of preterm birth, low birthweight, and small for gestational age (SGA), when compared with fresh ET. However, these studies also revealed an increased risk of LGA after FET. The underlying pathophysiology of this increased risk remains unclear; parental infertility, laboratory procedures (including embryo culture conditions and freezing-thawing processes), and endometrial preparation treatments might be involved. STUDY DESIGN, SIZE, DURATION: A multicentre epidemiological data study was performed through a retrospective analysis of the standardized individual clinical records of the French national register of IVF from 2014 to 2018, including single deliveries resulting from fresh ET or FET that were prospectively collected in fertility centres. Complementary data were collected from the participating fertility centres and included the vitrification media and devices, and the endometrial preparation protocols. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected from 35 French ART centres, leading to the inclusion of a total of 72 789 fresh ET, 10 602 slow-freezing FET, and 39 062 vitrification FET. Main clinical outcomes were presented according to origin of the transferred embryos (fresh, slow frozen, or vitrified embryos) and endometrial preparations for FET (ovulatory or artificial cycles), comparing five different groups (fresh, slow freezing-ovulatory cycle, slow freezing-artificial cycle, vitrification-ovulatory cycle, and vitrification-artificial cycle). Foetal growth disorders were defined in live-born singletons according to gestational age and sex-specific weight percentile distribution: SGA and LGA if <10th and ≥90th percentiles, respectively. Analyses were performed using linear mixed models with the ART centres as random effect. MAIN RESULTS AND THE ROLE OF CHANCE: Transfers led to, respectively, 19 006, 1798, and 9195 deliveries corresponding to delivery rates per transfer of 26.1%, 17.0%, and 23.5% after fresh ET, slow-freezing FET, and vitrification FET, respectively. FET cycles were performed in either ovulatory cycles (n = 21 704) or artificial cycles (n = 34 237), leading to 5910 and 10 322 pregnancies, respectively, and corresponding to pregnancy rates per transfer of 31.6% and 33.3%. A significantly higher rate of spontaneous miscarriage was observed in artificial cycles when compared with ovulatory cycles (33.3% versus 21.4%, P < 0.001, in slow freezing groups and 31.6% versus 21.8%, P < 0.001 in vitrification groups). Consequently, a lower delivery rate per transfer was observed in artificial cycles compared with ovulatory cycles both in slow freezing and vitrification groups (15.5% versus 18.9%, P < 0.001 and 22.8% versus 24.9%, P < 0.001, respectively). Among a total of 26 585 live-born singletons, 16 413 babies were born from fresh ET, 1644 from slow-freezing FET, and 8528 from vitrification FET. Birthweight was significantly higher in the FET groups than in the fresh ET group, with no difference between the two freezing techniques. Likewise, LGA rates were higher and SGA rates were lower in the FET groups compared with the fresh ET group whatever the method used for embryo freezing. In a multivariable analysis, the risk of LGA following FET was significantly increased in artificial compared with ovulatory cycles. In contrast, the risk of LGA was not associated with either the freezing procedure (vitrification versus slow freezing) or the embryo stage (cleaved embryo versus blastocyst) at freezing. Regarding the vitrification method, the risk of LGA was not associated with either the vitrification medium used or the embryo stage. LIMITATIONS, REASONS FOR CAUTION: No data were available on maternal context, such as parity, BMI, infertility cause, or maternal comorbidities, in the French national database. In particular, we cannot exclude that the increased risk of LGA observed following FET with artificial cycles may, at least partially, be associated with a confounding effect of some maternal factors. No information about embryo culture and incubation conditions was available. Most of the vitrification techniques were performed using the same device and with two main vitrification media, limiting the validity of a comparison of risk for LGA according to the device or vitrification media used. WIDER IMPLICATIONS OF THE FINDINGS: Our results seem reassuring, since no potential foetal growth disorders following embryo vitrification in comparison with slow freezing were observed. Even if other factors are involved, the endometrial preparation treatment seems to have the greatest impact on LGA risk following FET. FET during ovulatory cycles could minimize the risk for foetal growth disorders. STUDY FUNDING/COMPETING INTEREST(S): This work has received funding from the French Biomedicine Agency (Grant number: 19AMP002). None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

The initial molecular response predicts the deep molecular response but not treatment-free remission maintenance in a real-world chronic myeloid leukemia cohort.

In chronic myeloid leukemia, the identification of early molecular predictors of stable treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) discontinuation is challenging. The predictive values of residual disease (BCR::ABL1 quantification) at months 3 and 6 and more recently, BCR::ABL1 transcript halving time (HT) have been described, but no study compared the predictive value of different early parameters. Using a real-world cohort of 408 patients, we compared the performance of the ELTS score, BCR::ABL1 HT, and residual disease at month 3 and 6 to predict the molecular response, achievement of the TKI discontinuation criteria, and TFR maintenance. The performances of BCR::ABL1 HT and residual disease at month 3 were similar. Residual disease at month 6 displayed the best performance for predicting the optimal response (area under the ROC curve between 0.81 and 0.92; cut-off values: 0.11% for MR4 at month 24 and 0.12% for MR4.5 at month 48). Conversely, no early parameter predicted reaching the TKI discontinuation criteria and TFR maintenance. We obtained similar results when patients were divided in subgroups by first-line treatment (imatinib vs second generation TKI, 2G-TKI). We identified a relationship between ELTS score, earlier milestones and TFR maintenance only in the 2G-TKI group. In conclusion, this first comparative study of early therapeutic response parameters showed that they are excellent indicators of TKI efficacy (BCR::ABL1 transcript reduction) and best responders. Conversely, they did not predict the achievement of the TKI discontinuation criteria and TFR maintenance, suggesting that other parameters are involved in TFR maintenance.

Value of combining biological age with assessment of individual frailty to optimize management of cancer treated with targeted therapies: model of chronic myeloid leukemia treated with tyrosine kinase inhibitors (BIO-TIMER trial).

BACKGROUND: In the era of targeted therapies, the influence of aging on cancer management varies from one patient to another. Assessing individual frailty using geriatric tools has its limitations, and is not appropriate for all patients especially the youngest one. Thus, assessing the complementary value of a potential biomarker of individual aging is a promising field of investigation. The chronic myeloid leukemia model allows us to address this question with obvious advantages: longest experience in the use of tyrosine kinase inhibitors, standardization of therapeutic management and response with minimal residual disease and no effect on age-related diseases. Therefore, the aim of the BIO-TIMER study is to assess the biological age of chronic myeloid leukemia or non-malignant cells in patients treated with tyrosine kinase inhibitors and to determine its relevance, in association or not with individual frailty to optimize the personalised management of each patient. METHODS: The BIO-TIMER study is a multi-center, prospective, longitudinal study aiming to evaluate the value of combining biological age determination by DNA methylation profile with individual frailty assessment to personalize the management of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. Blood samples will be collected at diagnosis, 3 months and 12 months after treatment initiation. Individual frailty and quality of life will be assess at diagnosis, 6 months after treatment initiation, and then annually for 3 years. Tolerance to tyrosine kinase inhibitors will also be assessed during the 3-year follow-up. The study plans to recruit 321 patients and recruitment started in November 2023. DISCUSSION: The assessment of individual frailty should make it possible to personalize the treatment and care of patients. The BIO-TIMER study will provide new data on the role of aging in the management of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors, which could influence clinical decision-making. TRIAL REGISTRATION: ClinicalTrials.gov , ID NCT06130787; registered on November 14, 2023.

Robot-assisted gait training improves walking and cerebral connectivity in children with unilateral cerebral palsy.

BACKGROUND: Robot-assisted gait training (RAGT) is promising to help walking rehabilitation in cerebral palsy, but training-induced neuroplastic effects have little been investigated. METHODS: Forty unilateral cerebral palsy children aged 4-18 years were randomly allocated in a monocentric study to ten 20-minute RAGT sessions with the G-EO system, five days a week (n = 20) or to a control group (who continued conventional care with six 30-minute physiotherapy sessions, three days a week) (n = 20), two weeks running, from September 2020 to December 2021. Clinical and MRI outcomes were compared before and one month after therapy. The primary outcome was gait speed. Secondary outcomes were a 6-minute walking test distance, Gross Motor Function Measure-88 (GMFM-88) dimensions D and E, Patient Global Impression of Improvement, resting-state functional connectivity within the sensorimotor network, and structural connectivity in the corticospinal tracts. RESULTS: Gait speed and the 6-minute walking test distance improved more after RAGT. Resting-state functional connectivity increased after RAGT but decreased in controls between superior and lateral healthy or lateral injured sensorimotor networks. GMFM-88 and structural connectivity in corticospinal tracts were unchanged. Impression of improvement in children was better after RAGT. CONCLUSION: Short-term benefit of repetitive RAGT on walking abilities and functional cerebral connectivity was found in unilateral cerebral palsy children. IMPACT STATEMENT: Short-term repetitive robot-assisted gait training improves gait speed and walking resistance and increases cerebral functional connectivity in unilateral cerebral palsy. GMFM dimensions D and E were unchanged after short-term repetitive robot-assisted gait training in unilateral cerebral palsy.

Augmented Reality Guided Laparoscopic Liver Resection: A Phantom Study With Intraparenchymal Tumors.

INTRODUCTION: Augmented reality (AR) in laparoscopic liver resection (LLR) can improve intrahepatic navigation by creating a virtual liver transparency. Our team has recently developed Hepataug, an AR software that projects the invisible intrahepatic tumors onto the laparoscopic images and allows the surgeon to localize them precisely. However, the accuracy of registration according to the location and size of the tumors, as well as the influence of the projection axis, have never been measured. The aim of this work was to measure the three-dimensional (3D) tumor prediction error of Hepataug. METHODS: Eight 3D virtual livers were created from the computed tomography scan of a healthy human liver. Reference markers with known coordinates were virtually placed on the anterior surface. The virtual livers were then deformed and 3D printed, forming 3D liver phantoms. After placing each 3D phantom inside a pelvitrainer, registration allowed Hepataug to project virtual tumors along two axes: the laparoscope axis and the operator port axis. The surgeons had to point the center of eight virtual tumors per liver with a pointing tool whose coordinates were precisely calculated. RESULTS: We obtained 128 pointing experiments. The average pointing error was 29.4 ± 17.1 mm and 9.2 ± 5.1 mm for the laparoscope and operator port axes respectively (P = 0.001). The pointing errors tended to increase with tumor depth (correlation coefficients greater than 0.5 with P < 0.001). There was no significant dependency of the pointing error on the tumor size for both projection axes. CONCLUSIONS: Tumor visualization by projection toward the operating port improves the accuracy of AR guidance and partially solves the problem of the two-dimensional visual interface of monocular laparoscopy. Despite a lower precision of AR for tumors located in the posterior part of the liver, it could allow the surgeons to access these lesions without completely mobilizing the liver, hence decreasing the surgical trauma.

CX3CL1/Fractalkine as a biomarker for early pregnancy prediction of preterm premature rupture of membranes.

OBJECTIVES: The objective of our study was to evaluate serum CX3CL1/Fractalkine, a monocyte/macrophage chemoattractant expressed in cytotrophoblasts and decidual cells, as a predictive biomarker for the occurrence of preterm premature rupture of membranes (PPROM). METHODS: A case-control study of 438 pregnancies including 82 PPROM cases and 64 preterm labor with intact membranes cases with blood samples collected at first trimester, second trimester and delivery was conducted. The predictive ability of CX3CL1 and maternal risk factors for the occurrence of PPROM was assessed by receiver operating characteristic curve analysis. A second, independent cohort was prospectively constituted to confirm the case-control study results. RESULTS: First trimester CX3CL1 was significantly increased in PPROM cases when compared to matched controls. Multivariate regression analysis highlighted a significant difference for CX3CL1 measured during the first trimester (p<0.001). Alone, CX3CL1 predicts PPROM with a 90 % sensitivity and a specificity around 40 %. The area under the receiver operating characteristic curve for PPROM prediction were 0.64 (95% confidence interval: 0.57-0.71) for first trimester CX3CL1, and 0.61 (95% confidence interval: 0.54-0.68) for maternal risk factors (body mass index<18.5 kg/m2, nulliparity, tobacco use and the absence of high school diploma). The combination of CX3CL1 and maternal risk factors significantly improved the area under the curve: 0.72 (95% confidence interval: 0.66-0.79) (p<0.001). The results were confirmed on a second independent cohort. CONCLUSIONS: CX3CL1 is a promising blood biomarker in the early (first trimester) prediction of PPROM.

Physiological effects and safety of bed verticalization in patients with acute respiratory distress syndrome.

BACKGROUND: Trunk inclination in patients with Acute Respiratory Distress Syndrome (ARDS) in the supine position has gained scientific interest due to its effects on respiratory physiology, including mechanics, oxygenation, ventilation distribution, and efficiency. Changing from flat supine to semi-recumbent increases driving pressure due to decreased respiratory system compliance. Positional adjustments also deteriorate ventilatory efficiency for CO2 removal, particularly in COVID-19-associated ARDS (C-ARDS), indicating likely lung parenchyma overdistension. Tilting the trunk reduces chest wall compliance and, to a lesser extent, lung compliance and transpulmonary driving pressure, with significant hemodynamic and gas exchange implications. METHODS: A prospective, pilot physiological study was conducted on early ARDS patients in two ICUs at CHU Clermont-Ferrand, France. The protocol involved 30-min step gradual verticalization from a 30° semi-seated position (baseline) to different levels of inclination (0°, 30°, 60°, and 90°), before returning to the baseline position. Measurements included tidal volume, positive end-expiratory pressure (PEEP), esophageal pressures, and pulmonary artery catheter data. The primary endpoint was the variation in transpulmonary driving pressure through the verticalization procedure. RESULTS: From May 2020 through January 2021, 30 patients were included. Transpulmonary driving pressure increased slightly from baseline (median and interquartile range [IQR], 9 [5-11] cmH2O) to the 90° position (10 [7-14] cmH2O; P < 10-2 for the overall effect of position in mixed model). End-expiratory lung volume increased with verticalization, in parallel to decreases in alveolar strain and increased arterial oxygenation. Verticalization was associated with decreased cardiac output and stroke volume, and increased norepinephrine doses and serum lactate levels, prompting interruption of the procedure in two patients. There were no other adverse events such as falls or equipment accidental removals. CONCLUSIONS: Verticalization to 90° is feasible in ARDS patients, improving EELV and oxygenation up to 30°, likely due to alveolar recruitment and blood flow redistribution. However, there is a risk of overdistension and hemodynamic instability beyond 30°, necessitating individualized bed angles based on clinical situations. Trial registration ClinicalTrials.gov registration number NCT04371016 , April 24, 2020.

The association between obesity severity and food reward in adolescents with obesity: a one-stage individual participant data meta-analysis.

BACKGROUND: Food reward and cue reactivity have been linked prospectively to problematic eating behaviours and excess weight gain in adults and children. However, evidence to date in support of an association between degree of adiposity and food reward is tenuous. A non-linear relationship between reward sensitivity and obesity degree has been previously proposed, suggesting a peak is reached in mild obesity and decreases in more severe obesity in a quadratic fashion. OBJECTIVE: To investigate and characterise in detail the relationship between obesity severity, body composition, and explicit and implicit food reward in adolescents with obesity. METHODS: Data from seven clinical trials in adolescents with obesity were aggregated and analysed in an independent participant data meta-analysis. Linear and curvilinear relationships between the degree of obesity and explicit and implicit reward for sweet and high fat foods were tested in fasted and fed states with BMI-z score as a continuous and discrete predictor using clinically recognised partitions. RESULTS: Although positive associations between obesity severity and preference for high-fat (i.e. energy dense) foods were observed when fasted, none reached significance in either analysis. Conversely, adiposity was reliably associated with lower reward for sweet, particularly when measured as implicit wanting (p = 0.012, ηp2 = 0.06), independent of metabolic state. However, this significant association was only observed in the linear model. Fat distribution was consistently associated with explicit and implicit preference for high-fat foods. CONCLUSIONS: A limited relationship was demonstrated between obesity severity and food reward in adolescents, although a lower preference for sweet could be a signal of severe obesity in a linear trend. Obesity is likely a heterogenous condition associated with multiple potential phenotypes, which metrics of body composition may help define. CLINICAL TRIAL REGISTRATIONS: NCT02925572: https://classic. CLINICALTRIALS: gov/ct2/show/NCT02925572 . NCT03807609: https://classic. CLINICALTRIALS: gov/ct2/show/NCT03807609 . NCT03742622: https://classic. CLINICALTRIALS: gov/ct2/show/NCT03742622 . NCT03967782: https://classic. CLINICALTRIALS: gov/ct2/show/NCT03967782 . NCT03968458: https://classic. CLINICALTRIALS: gov/ct2/show/NCT03968458 . NCT04739189: https://classic. CLINICALTRIALS: gov/ct2/show/NCT04739189 . NCT05365685: https://www. CLINICALTRIALS: gov/study/NCT05365685?tab=history .

Motor disorders related to oxaliplatin-induced peripheral neuropathy: long-term severity and impact on quality of life.

PURPOSE: Sensory chemotherapy-induced peripheral neuropathy (CIPN) is well-recognized, but motor CIPN remains understudied. This secondary analysis focused on the long-term severity and impact of motor disorders, their relation to sensory CIPN, neuropathic pain, psychological distress, and health-related quality of life (HRQoL) after oxaliplatin-based chemotherapy in colorectal cancer (CRC) survivors. METHODS: Data from a multicenter, cross-sectional study were re-analyzed to explore motor CIPN among CRC survivors up to 5 years post-chemotherapy, with no longitudinal follow-up. Questionnaires assessed sensory and motor CIPN (QLQ-CIPN20), neuropathic pain (DN4), anxiety and depression (HADS), and HRQoL (QLQ-C30). RESULTS: Among 405 CRC survivors, 31.1% had sensory CIPN as previously described. When categorizing the 405 CRC survivors based on the years since their last oxaliplatin-based chemotherapy, the motor scores derived from the QLQ-CIPN20 showed no significant difference between years (p = 0.08). Motor CIPN scores correlated with female gender, higher oxaliplatin dose intensity, sensory CIPN, and neuropathic pain. Motor CIPN also linked to decreased HRQoL and increased psychological distress. CONCLUSION: The study underscores the detrimental impact of motor disorders on CRC survivors post-oxaliplatin-based chemotherapy. Oncologists should prioritize assessing and managing motor manifestations alongside sensory symptoms to enhance post-cancer quality of life. TRIAL REGISTRATION: NCT02970526 (2016-11-22). https://classic. CLINICALTRIALS: gov/ct2/show/NCT02970526?term=NCT02970526&draw=2&rank=1 .

Intestinal Ultrasonography as an Alternative to Fecal Calprotectin to Monitor Patients with Crohn's Disease: Experience from a Novice Sonographer.

BACKGROUND: While fecal calprotectin (Fcal) is now recommended, the positioning of intestinal ultrasonography (IUS) is still unknown to monitor patients with CD. AIMS: To assess the agreement between IUS performed by a novice sonographer and Fcal to detect active CD and to compare these two monitoring tools to determine the need for therapeutic escalation. METHODS: In this cross-sectional prospective study, we consecutively included CD patients ≥ 18 years-old with concomitant IUS and Fcal testing within 7 days. IUS was performed by a novice sonographer. The endpoints were the agreement between IUS and Fcal (> 150 µg/g) to detect active CD and the need for therapeutic escalation. RESULTS: Among 66 patients undergoing IUS, 56 patients had also Fcal testing. The agreement between IUS and Fcal to detect an active CD was 80.4% (κ-coefficient = 0.536 ± 0.127). Fcal, IUS or both had respectively the following positive (76.9%[54.0-99.8], 70.0%[49.9-90.1], and 81.8%[59.0-100.0]) and negative (81.4%[69.8-93.0], 88.9%[78.6-99.2], and 80.0%[68.3-91.7]) predictive values to detect active CD requiring therapeutic escalation. Using a 10 points-acceptability numerical scale, IUS presented with a better acceptability than Fcal (9.5 ± 1.2 vs 8.0 ± 2.3, p < 0.0001). Contrary to the agreement with Fcal and the performances of IUS to identify the need for therapeutic escalation, the duration of IUS procedure decreased over time (correlation coefficient = - 0.54, p = 0.001) and plateaued between 15 and 20 min-long from the 24th procedure. CONCLUSION: IUS and fecal calprotectin do not give the same information and could be complementary to monitor patients with CD.

Eicosanoids and Oxylipin Signature in Hereditary Hemochromatosis Patients Are Similar to Dysmetabolic Iron Overload Syndrome Patients but Are Impacted by Dietary Iron Absorption.

INTRODUCTION: Oxylipins are mediators of oxidative stress. To characterize the underlying inflammatory processes and phenotype effect of iron metabolism disorders, we investigated the oxylipin profile in hereditary hemochromatosis (HH) and dysmetabolic iron overload syndrome (DIOS) patients. METHODS: An LC-MS/MS-based method was performed to quantify plasma oxylipins in 20 HH and 20 DIOS patients in fasting conditions and 3 h after an iron-rich meal in HH patients. RESULTS: Principal component analysis showed no separation between HH and DIOS, suggesting that the clinical phenotype has no direct impact on oxylipin metabolism. 20-HETE was higher in DIOS and correlated with hypertension (p = 0.03). Different oxylipin signatures were observed in HH before and after the iron-rich meal. Discriminant oxylipins include epoxy fatty acids derived from docosahexaenoic acid and arachidonic acid as well as 13-HODE and 9-HODE. Mediation analysis found no major contribution of dietary iron absorption for 16/22 oxylipins significantly affected by the meal. DISCUSSION: The oxylipin profiles of HH and DIOS seemed similar except for 20-HETE, possibly reflecting different hypertension prevalence between the two groups. Oxylipins were significantly affected by the iron-rich meal, but the specific contribution of iron was not clear. Although iron may contribute to oxidative stress and inflammation in HH and DIOS, this does not seem to directly affect oxylipin metabolism.

Constitutional thinness might be characterized by physiologically adapted and not impaired muscle function and architecture: new results from the NUTRILEAN study.

PURPOSE: While muscle mass and skeletal muscle fibers phenotype have been shown atypical in constitutional thinness (CT), force production capacities and its architectural determinants have never been explored. The present study compared muscle functionality and architecture between participants with CT and their normal-weight (NW) counterparts. METHODS: Anthropometry, body composition (Dual-X-ray Absorptiometry), physical activity/sedentary behavior (ActiGraph wGT3X-BT), ultrasound recording of the Vastus Lateralis (2D-ultrasound system), and functional capacities at maximal isometric and isokinetic voluntary contractions (MVCISO and MVCCON) during knee extension (isokinetic dynamometer chair Biodex) have been measured in 18 women with CT (body mass index < 17.5 kg/m2) and 17 NW women. RESULTS: A lower fat-free mass (ES: -1.94, 95%CI: -2.76 to -1.11, p < 0.001), a higher sedentary time, and a trend for a lower time spent at low-intensity physical activity, were observed in CT vs NW participants. While absolute MVCISO, MVCCON, rate of torque development (RTD), and torque work were all markedly lower in CT, these differences disappeared when normalized to body or muscle mass. Muscle thickness and fascicle length were found lower in CT (ES: -1.29, 95%CI: -2.03 to -0.52, p < 0.001; and ES: -0.87, 95%CI: -1.58 to -0.15, p = 0.02, respectively), while pennation angle was found similar. CONCLUSION: Despite lower absolute strength capacities observed in CT, present findings support the hypothesis of physiological adaptations to the low body and muscle mass than to some intrinsic contractile impairments. These results call for further studies exploring hypertrophy-targeted strategies in the management of CT.

Similar maximal aerobic capacity but lower energy efficiency during low-to-moderate exercise in women with constitutional thinness: new results from the NUTRILEAN study.

PURPOSE: Individuals with constitutional thinness have been presented with a lower muscular energy metabolism at the cellular level but their effective aerobic capacities and exercise-related energy efficiency remains unexplored. The present study compares maximal and sub-maximal aerobic capacities between subjects with constitutional thinness and age-matched normal-weight ones. METHODS: Anthropometric measures, body composition (Dual-X-ray absorptiometry), physical activity and sedentary time (GT3x actigraphs), and maximal aerobic capacities (cycling V ˙ O 2peak test) were assessed in 18 constitutionally thin (CT-body mass index < 17.5 kg m-2) and 17 normal-weight (NW-body mass index between 20 and 25 kg m-2) women. Energy efficiency was assessed during a submaximal cycling test and a walking exercise. RESULTS: CT had a lower body mass and body mass index compared to NW. Absolute peak oxygen uptake and maximal aerobic power were lower in CT subjects compared to NW (ES: - 1.63 [- 2.40; - 0.86] and - 1.32 [- 2.05; - 0.58], p < 0.001). V ˙ O 2peak related to body mass was not different between groups. Gross and net efficiency (ES: - 0.78 [- 1.48; - 0.06], p = 0.03 and ES: - 0.73 [- 1.43; - 0.01], p = 0.05) were lower in CT compared to NW during the submaximal cycling exercise. The gross energy cost of walking related to body mass was lower in subjects with CT (ES: - 1.80 [- 2.60; - 0.97, p = 0.05), with no difference for the net one. Perceived exertion was similar between groups in responses to both submaximal exercises. CONCLUSION: Constitutionally thin women do not show impaired aerobic capacities at moderate to maximal intensities despite lower energy efficiency while cycling and walking at low-to-moderate intensities.

Individual variability and consistency of post-exercise energy and macronutrient intake, appetite sensations, and food reward in healthy adults.

Limited evidence is available about the variability of appetitive responses within individuals after an acute bout of exercise. The present study aimed to assess the consistency and individual variability of post-exercise appetitive responses in healthy individuals. Twenty participants (10 females, 23.9 ± 4.1 years, 22.5 ± 2.0 kg m-2) joined the laboratory to perform four sessions separated by a minimum of 5 days: i) a control session with a rest period before and an ad libitum lunch (REST), and ii) three identical exercise sessions (EX) with a 30-min moderate-intensity (60-70% of predicted maximal heart rate) walking bout ending 25 min before the ad libitum lunch. Subjective appetite sensations were assessed before and after the meal at regular intervals, and satiety quotients were calculated. Food reward was assessed by the Leeds Food Preference Questionnaire before and after lunch. For each EX session, the difference with the REST session was calculated (Δ = EX - REST). Energy and macronutrient intake were consistent in response to exercise (all intraclass correlation coefficients (ICC) > 0.8) while results showed that post-exercise subjective appetite sensations and satiety quotients varied across the three EX sessions (almost all ICC < 0.7). Food reward was overall consistent in response to exercise before the test meal but not after. When considering the changes (Δ), the results showed no or poor consistency for most of the appetitive outcomes. To conclude, energy and macronutrient intake, as well as pre-meal food reward, are consistent after exercise in healthy individuals, while subjective appetite sensations are not stable within individuals across the sessions. Regarding the variations from REST to EX sessions, the results suggest that the individual changes observed are only random day-to-day variations.

Post-exercise energy replacement might lead to reduced subsequent energy intake in women with constitutional thinness: Exploratory results from the NUTRILEAN project.

While people with Constitutional Thinness (CT) declare a deep willingness to gain weight, there appetitive responses to energy balance manipulations remain unclear. The present work compares the effect of an acute exercise combined or not with an energy replacement load, on subsequent energy intake, appetite and food reward, between normal weight and women with CT. Anthropometric measurements, body composition (Dual X-ray absorptiometry-DXA) and aerobic capacity (VO2max) were assessed in 10 normal-weight (Body Mass Index-BMI): 20-25 kg/m2) and 10 C T (BMI<17.5 kg/m2) women (18-30 years). They randomly performed i) a resting session (CON); ii) an exercise session (EX); iii) an exercise session with energy replacement (EX + R). Their subsequent ad libitum intake, appetite feelings and food reward were evaluated (Leeds-Food-Preference-Questionnaire). CT showed a lower weight (p < 0,001), BMI(p < 0,001), Fat-Mass (%) (p = 0,003) and Fat-Free Mass (kg) (p < 0,001). CT showed a lower ad libitum energy intake on EX + R compared with CON (p = 0,008) and a higher Relative Energy Intake (REI) on CON compared with EX (p = 0,007) and EX + R (p < 0,001). A lower was observed during EX and EX + R compared with CON (p = 0,006,p = 0,009 respectively) in CT. No condition nor group effect was found for hunger. NW only showed a higher pre-meal fullness on EX + R compared to CON and EX (p < 0,001). Choice (p = 0,030), Explicit Liking (p = 0,016), Explicit Wanting (p = 0,004) and Implicit Wanting (p = 0,035) for taste were higher on EX + R than CON and EX. The decreased EI observed in CT when the exercise-induced energy expenditure is compensated by the ingestion of an equivalent energy load, might contribute to explain the difficulty to increase their energy balance and then induce weight gain. Further studies are needed to better understand their energy balance regulation to propose adapted weight gain strategies.

Age related impairments in ingestion from a large population based-sample.

OBJECTIVES: Epidemiological data regarding the evolution of problems related to mastication and swallowing with age are lacking. This study aims to (i) describe changes in oral function with age, using data from a large French population, (ii) validate online, self-report uses of an ICF questionnaire in older persons, and (iii) assess whether impairment is related to avoidance of certain foods, xerostomia, body mass index (BMI) and oral health related quality of life (OHRQoL). METHODS: Volunteers aged ≥18 years with internet access completed a series of questionnaires on sociodemographic, anthropometric and oral health characteristics (oral function, Xerostomia Index (XI), OHRQoL, reasons for avoidance of certain food). Oral function was assessed using items derived from the International Classification of Functioning (ICF). Five ICF items related to ingestion function and six items related to activities and participation were used. A validation study was undertaken to identify those with poor chewing ability and low salivary flow amongst older participants reporting impairment. FINDINGS: 39 597 individuals were included. The prevalence of individuals with impairment for ICF items related to ingestion function and oral activity (eating, drinking and speaking), and the percentage of participants with poor OHRQoL increased significantly with age (p < 0.001). Each ICF item was significantly associated with OHRQoL (p < 0.001), XI (p < 0.001), BMI (p < 0.001) and avoidance of certain food due to chewing or swallowing difficulties. CONCLUSION: Overall, 21.5% and 13.5% of the study population had chewing and/or biting impairments respectively, which might affect food selection and consumption. These findings raise individual and population-based issues. Further studies are needed to assess whether impairment in oral function might increase frailty in older individuals, and also to compare data with those from other countries.