DEPTOR at the Nexus of Cancer, Metabolism, and Immunity.

DEP domain-containing mechanistic target of rapamycin (mTOR)-interacting protein (DEPTOR) is an important modulator of mTOR, a kinase at the center of two important protein complexes named mTORC1 and mTORC2. These highly studied complexes play essential roles in regulating growth, metabolism, and immunity in response to mitogens, nutrients, and cytokines. Defects in mTOR signaling have been associated with the development of many diseases, including cancer and diabetes, and approaches aiming at modulating mTOR activity are envisioned as an attractive strategy to improve human health. DEPTOR interaction with mTOR represses its kinase activity and rewires the mTOR signaling pathway. Over the last years, several studies have revealed key roles for DEPTOR in numerous biological and pathological processes. Here, we provide the current state of the knowledge regarding the cellular and physiological functions of DEPTOR by focusing on its impact on the mTOR pathway and its role in promoting health and disease.

Human gut microbiota after bariatric surgery alters intestinal morphology and glucose absorption in mice independently of obesity.

OBJECTIVE: Bariatric surgery is an effective treatment for type 2 diabetes (T2D) that changes gut microbial composition. We determined whether the gut microbiota in humans after restrictive or malabsorptive bariatric surgery was sufficient to lower blood glucose. DESIGN: Women with obesity and T2D had biliopancreatic diversion with duodenal switch (BPD-DS) or laparoscopic sleeve gastrectomy (LSG). Faecal samples from the same patient before and after each surgery were used to colonise rodents, and determinants of blood glucose control were assessed. RESULTS: Glucose tolerance was improved in germ-free mice orally colonised for 7 weeks with human microbiota after either BPD-DS or LSG, whereas food intake, fat mass, insulin resistance, secretion and clearance were unchanged. Mice colonised with microbiota post-BPD-DS had lower villus height/width and crypt depth in the distal jejunum and lower intestinal glucose absorption. Inhibition of sodium-glucose cotransporter (Sglt)1 abrogated microbiota-transmissible improvements in blood glucose control in mice. In specific pathogen-free (SPF) rats, intrajejunal colonisation for 4 weeks with microbiota post-BPD-DS was sufficient to improve blood glucose control, which was negated after intrajejunal Sglt-1 inhibition. Higher Parabacteroides and lower Blautia coincided with improvements in blood glucose control after colonisation with human bacteria post-BPD-DS and LSG. CONCLUSION: Exposure of rodents to human gut microbiota after restrictive or malabsorptive bariatric surgery improves glycaemic control. The gut microbiota after bariatric surgery is a standalone factor that alters upper gut intestinal morphology and lowers Sglt1-mediated intestinal glucose absorption, which improves blood glucose control independently from changes in obesity, insulin or insulin resistance.

Hypoabsorptive surgeries cause limb-dependent changes in the gut endocannabinoidome and microbiome in association with beneficial metabolic effects.

OBJECTIVE: To determine whether the metabolic benefits of hypoabsorptive surgeries are associated with changes in the gut endocannabinoidome (eCBome) and microbiome. METHODS: Biliopancreatic diversion with duodenal switch (BPD-DS) and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) were performed in diet-induced obese (DIO) male Wistar rats. Control groups fed a high-fat diet (HF) included sham-operated (SHAM HF) and SHAM HF-pair-weighed to BPD-DS (SHAM HF-PW). Body weight, fat mass gain, fecal energy loss, HOMA-IR, and gut-secreted hormone levels were measured. The levels of eCBome lipid mediators and prostaglandins were quantified in different intestinal segments by LC-MS/MS, while expression levels of genes encoding eCBome metabolic enzymes and receptors were determined by RT-qPCR. Metataxonomic (16S rRNA) analysis was performed on residual distal jejunum, proximal jejunum, and ileum contents. RESULTS: BPD-DS and SADI-S reduced fat gain and HOMA-IR, while increasing glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) levels in HF-fed rats. Both surgeries induced potent limb-dependent alterations in eCBome mediators and in gut microbial ecology. In response to BPD-DS and SADI-S, changes in gut microbiota were significantly correlated with those of eCBome mediators. Principal component analyses revealed connections between PYY, N-oleoylethanolamine (OEA), N-linoleoylethanolamine (LEA), Clostridium, and Enterobacteriaceae_g_2 in the proximal and distal jejunum and in the ileum. CONCLUSIONS: BPD-DS and SADI-S caused limb-dependent changes in the gut eCBome and microbiome. The present results indicate that these variables could significantly influence the beneficial metabolic outcome of hypoabsorptive bariatric surgeries.

Strategies to prevent long-term opioid use following trauma: a Canadian practice survey.

PURPOSE: To evaluate how Canadian clinicians involved in trauma patient care and prescribing opioids perceive the use and effectiveness of strategies to prevent long-term opioid therapy following trauma. Barriers and facilitators to the implementation of these strategies were also assessed. METHODS: We conducted a web-based cross-sectional survey. Potential participants were identified by trauma program managers and directors of the targeted departments in three Canadian provinces. We designed our questionnaire using standard health survey research methods. The questionnaire was administered between April 2021 and November 2021. RESULTS: Our response rate was 47% (350/744), and 52% (181/350) of participants completed the entire survey. Most respondents (71%, 129/181) worked in teaching hospitals. Multimodal analgesia (93%, 240/257), nonsteroidal anti-inflammatory agents (77%, 198/257), and physical stimulation (75%, 193/257) were the strategies perceived to be the most frequently used. Several preventive strategies were perceived to be very effective by over 80% of respondents. Of these, some that were reported as not being frequently used were perceived to be among the most effective ones, including guidelines or protocols, assessing risk factors for opioid misuse, physical health follow-up by a professional, training for clinicians, patient education, and prescription monitoring systems. Staff shortages, time constraints, and organizational practices were identified as the main barriers to the implementation of the highest ranked preventive strategies. CONCLUSIONS: Several strategies to prevent long-term opioid therapy following trauma are perceived as being effective by those prescribing opioids in this population. Some of these strategies appear to be commonly used in everyday practice and others less so. Future research should focus on which preventive strategies should be given higher priority for implementation before assessing their effectiveness.

RéSUMé: OBJECTIF: Évaluer comment les cliniciens canadiens impliqués dans les soins aux patients traumatisés et prescrivant des opioïdes perçoivent l'utilisation et l'efficacité des stratégies visant à prévenir le traitement prolongé par opioïde après un traumatisme. Les obstacles et facilitateurs de la mise en œuvre de ces stratégies ont aussi été analysés. MéTHODES: Nous avons réalisé une enquête transversale via le Web. Les participants potentiels ont été identifiés par les gestionnaires et directeurs de programmes de traumatologie des départements ciblés dans trois provinces canadiennes. Nous avons conçu notre questionnaire en utilisant la méthodologie de recherche usuelle des enquêtes de santé. Le questionnaire a été administré entre avril 2021 et novembre 2021. RéSULTATS: Notre taux de réponse a été de 47 % (350/744) et 52 % (181/350) des participants ont complété l'enquête dans sa totalité. La majorité des personnes interrogées (71 %, 129/181) travaillait dans des hôpitaux universitaires. L'analgésie multimodale (93 %, 240/257), les anti-inflammatoires non stéroïdiens (77 %, 198/257) et la stimulation physique (75 %, 193/257) étaient les stratégies perçues comme étant le plus fréquemment utilisées. Plusieurs stratégies préventives étaient perçues comme étant très efficaces par plus de 80 % des répondants. Parmi celles-ci, certaines étaient signalées comme n'étant pas utilisées très souvent, mais perçues comme étant les plus efficaces, notamment les lignes directrices et protocoles évaluant les facteurs de risque d'utilisation abusive des opioïdes, le suivi de la santé physique par un professionnel, la formation des cliniciens, l'éducation des patients et les systèmes de suivi des prescriptions. La pénurie de personnels, les contraintes de temps et les pratiques de l'établissement ont été identifiées comme étant les principaux obstacles à la mise en place des stratégies préventives classées parmi les premières. CONCLUSIONS: Plusieurs stratégies de prévention du traitement par opioïdes à long terme après un traumatisme sont perçues comme efficaces par ceux qui les prescrivent à cette population de patients. Certaines de ces stratégies apparaissent comme couramment utilisées dans la pratique quotidienne et d'autres moins souvent. La recherche future devrait se concentrer sur la détermination des stratégies préventives auxquelles il faudrait accorder la plus grande priorité de mise en œuvre avant d'évaluer leur efficacité.

Optoelectronic Pressure Sensor Based on the Bending Loss of Plastic Optical Fibers Embedded in Stretchable Polydimethylsiloxane.

We report the design and testing of a sensor pad based on optical and flexible materials for the development of pressure monitoring devices. This project aims to create a flexible and low-cost pressure sensor based on a two-dimensional grid of plastic optical fibers embedded in a pad of flexible and stretchable polydimethylsiloxane (PDMS). The opposite ends of each fiber are connected to an LED and a photodiode, respectively, to excite and measure light intensity changes due to the local bending of the pressure points on the PDMS pad. Tests were performed in order to study the sensitivity and repeatability of the designed flexible pressure sensor.

Impact of weight loss on brain age: Improved brain health following bariatric surgery.

Individuals living with obesity tend to have increased brain age, reflecting poorer brain health likely due to grey and white matter atrophy related to obesity. However, it is unclear if older brain age associated with obesity can be reversed following weight loss and cardiometabolic health improvement. The aim of this study was to assess the impact of weight loss and cardiometabolic improvement following bariatric surgery on brain health, as measured by change in brain age estimated based on voxel-based morphometry (VBM) measurements. We used three distinct datasets to perform this study: 1) CamCAN dataset to train the brain age prediction model, 2) Human Connectome Project (HCP) dataset to investigate whether individuals with obesity have greater brain age than individuals with normal weight, and 3) pre-surgery, as well as 4, 12, and 24 month post-surgery data from participants (n = 87, age: 44.0 ± 9.2 years, BMI: 43.9 ± 4.2 kg/m2) who underwent a bariatric surgery to investigate whether weight loss and cardiometabolic improvement as a result of bariatric surgery lowers the brain age. As expected, our results from the HCP dataset showed a higher brain age for individuals with obesity compared to individuals with normal weight (T-value = 7.08, p-value < 0.0001). We also found significant improvement in brain health, indicated by a decrease of 2.9 and 5.6 years in adjusted delta age at 12 and 24 months following bariatric surgery compared to baseline (p-value < 0.0005 for both). While the overall effect seemed to be driven by a global change across all brain regions and not from a specific region, our exploratory analysis showed lower delta age in certain brain regions (mainly in somatomotor, visual, and ventral attention networks) at 24 months. This reduced age was also associated with post-surgery improvements in BMI, systolic/diastolic blood pressure, and HOMA-IR (T-valueBMI=4.29, T-valueSBP=4.67, T-valueDBP=4.12, T-valueHOMA-IR=3.16, all p-values < 0.05). In conclusion, these results suggest that obesity-related brain health abnormalities (as measured by delta age) might be reversed by bariatric surgery-induced weight loss and widespread improvements in cardiometabolic alterations.

Consistent gut bacterial and short-chain fatty acid signatures in hypoabsorptive bariatric surgeries correlate with metabolic benefits in rats.

OBJECTIVE: The study aimed at comparing how changes in the gut microbiota are associated to the beneficial effects of the most clinically efficient hypoabsorptive bariatric procedures, namely Roux-en-Y gastric bypass (RYGB), biliopancreatic diversion with duodenal switch (BPD-DS) and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S). METHODS: Diet-induced obese (DIO) male Wistar rats were divided into seven groups. In addition to the groups subjected to RYGB, BPD-DS and SADI-S, the following four control groups were included: SHAM-operated rats fed a high-fat diet (SHAM HF), SHAM fed a low-fat diet (SHAM LF), SHAM HF-pair-weighed to BPD-DS (SHAM HF-PW) and sleeve-gastrectomy (SG) rats. Body weight, food intake, glucose tolerance, insulin sensitivity/resistance, and L-cell secretion were assessed. The gut microbiota (16 S ribosomal RNA gene sequencing) as well as the fecal and cæcal contents of short-chain fatty acids (SCFAs) were also analyzed prior to, and after the surgeries. RESULTS: The present study demonstrates the beneficial effect of RYGB, BPD-DS and SADI-S on fat mass gain and glucose metabolism in DIO rats. These benefits were proportional to the effect of the surgeries on food digestibility (BPD-DS > SADI-S > RYGB). Notably, hypoabsorptive surgeries led to consonant microbial signatures characterized by decreased abundance of the Ruminococcaceae (Oscillospira and Ruminococcus), Oscillospiraceae (Oscillibacter) and Christensenellaceae, and increased abundance of the Clostridiaceae (Clostridium), Sutterellaceae (Sutterella) and Enterobacteriaceae. The gut bacteria following hypoabsorptive surgeries were associated with higher fecal levels of propionate, butyrate, isobutyrate and isovalerate. Increases in the fecal SCFAs were in turn positively and strongly correlated with the levels of peptide tyrosine-tyrosine (PYY) and with the beneficial effects of the surgery. CONCLUSION: The present study emphasizes the consistency with which the three major hypoabsorptive bariatric procedures RYGB, BPD-DS and SADI-S create a gut microbial environment capable of producing a SCFA profile favorable to the secretion of PYY and to beneficial metabolic effects.

Molecular remodeling of adipose tissue is associated with metabolic recovery after weight loss surgery.

BACKGROUND: Bariatric surgery is an effective therapy for individuals with severe obesity to achieve sustainable weight loss and to reduce comorbidities. Examining the molecular signature of subcutaneous adipose tissue (SAT) following different types of bariatric surgery may help in gaining further insight into their distinct metabolic impact. RESULTS: Subjects undergoing biliopancreatic diversion with duodenal switch (BPD-DS) showed a significantly higher percentage of total weight loss than those undergoing gastric bypass or sleeve gastrectomy (RYGB + SG) (41.7 ± 4.6 vs 28.2 ± 6.8%; p = 0.00005). Individuals losing more weight were also significantly more prone to achieve both type 2 diabetes and dyslipidemia remission (OR = 0.75; 95%CI = 0.51-0.91; p = 0.03). Whole transcriptome and methylome profiling showed that bariatric surgery induced a profound molecular remodeling of SAT at 12 months postoperative, mainly through gene down-regulation and hypermethylation. The extent of changes observed was greater following BPD-DS, with 61.1% and 49.8% of up- and down-regulated genes, as well as 85.7% and 70.4% of hyper- and hypomethylated genes being exclusive to this procedure, and mostly associated with a marked decrease of immune and inflammatory responses. Weight loss was strongly associated with genes being simultaneously differentially expressed and methylated in BPD-DS, with the strongest association being observed for GPD1L (r2 = 0.83; p = 1.4 × 10-6). CONCLUSIONS: Present findings point to the greater SAT molecular remodeling following BPD-DS as potentially linked with higher metabolic remission rates. These results will contribute to a better understanding of the metabolic pathways involved in the response to bariatric surgery and will eventually lead to the development of gene targets for the treatment of obesity. Trial registration ClinicalTrials.gov NCT02390973.

Spontaneous neural activity changes after bariatric surgery: A resting-state fMRI study.

BACKGROUND: Metabolic disorders associated with obesity could lead to alterations in brain structure and function. Whether these changes can be reversed after weight loss is unclear. Bariatric surgery provides a unique opportunity to address these questions because it induces marked weight loss and metabolic improvements which in turn may impact the brain in a longitudinal fashion. Previous studies found widespread changes in grey matter (GM) and white matter (WM) after bariatric surgery. However, findings regarding changes in spontaneous neural activity following surgery, as assessed with the fractional amplitude of low frequency fluctuations (fALFF) and regional homogeneity of neural activity (ReHo), are scarce and heterogenous. In this study, we used a longitudinal design to examine the changes in spontaneous neural activity after bariatric surgery (comparing pre- to post-surgery), and to determine whether these changes are related to cardiometabolic variables. METHODS: The study included 57 participants with severe obesity (mean BMI=43.1 ± 4.3 kg/m2) who underwent sleeve gastrectomy (SG), biliopancreatic diversion with duodenal switch (BPD), or Roux-en-Y gastric bypass (RYGB), scanned prior to bariatric surgery and at follow-up visits of 4 months (N = 36), 12 months (N = 29), and 24 months (N = 14) after surgery. We examined fALFF and ReHo measures across 1022 cortical and subcortical regions (based on combined Schaeffer-Xiao parcellations) using a linear mixed effect model. Voxel-based morphometry (VBM) based on T1-weighted images was also used to measure GM density in the same regions. We also used an independent sample from the Human Connectome Project (HCP) to assess regional differences between individuals who had normal-weight (N = 46) or severe obesity (N = 46). RESULTS: We found a global increase in the fALFF signal with greater increase within dorsolateral prefrontal cortex, precuneus, inferior temporal gyrus, and visual cortex. This effect was more significant 4 months after surgery. The increase within dorsolateral prefrontal cortex, temporal gyrus, and visual cortex was more limited after 12 months and only present in the visual cortex after 24 months. These increases in neural activity measured by fALFF were also significantly associated with the increase in GM density following surgery. Furthermore, the increase in neural activity was significantly related to post-surgery weight loss and improvement in cardiometabolic variables, such as blood pressure. In the independent HCP sample, normal-weight participants had higher global and regional fALFF signals, mainly in dorsolateral/medial frontal cortex, precuneus and middle/inferior temporal gyrus compared to the obese participants. These BMI-related differences in fALFF were associated with the increase in fALFF 4 months post-surgery especially in regions involved in control, default mode and dorsal attention networks. CONCLUSIONS: Bariatric surgery-induced weight loss and improvement in metabolic factors are associated with widespread global and regional increases in neural activity, as measured by fALFF signal. These findings alongside the higher fALFF signal in normal-weight participants compared to participants with severe obesity in an independent dataset suggest an early recovery in the neural activity signal level after the surgery.

Cholecalciferol Supplementation Does Not Prevent the Development of Metabolic Syndrome or Enhance the Beneficial Effects of Omega-3 Fatty Acids in Obese Mice.

BACKGROUND: Cholecalciferol (D3) may improve inflammation, and thus provide protection from cardiometabolic diseases (CMD), although controversy remains. Omega-3 fatty acids (ω-3FA) may also prevent the development of CMD, but the combined effects of ω-3FA and D3 are not fully understood. OBJECTIVES: We determined the chronic independent and combined effects of D3 and ω-3FA on body weight, glucose homeostasis, and markers of inflammation in obese mice. METHODS: We gave 8-week-old male C57BL/6J mice, which had been fed a high-fat, high-sucrose (HF) diet (65.5% kcal fat, 19.8% kcal carbohydrate, and 14% kcal protein) for 12 weeks, either a standard D3 dose (+SD3; 1400 IU D3/kg diet) or a high D3 dose (+HD3; 15,000 IU D3/kg diet). We fed 1 +SD3 group and 1 +HD3 group with 4.36% (w/w) fish oil (+ω-3FA; 44% eicosapentaenoic acid, 25% docosahexaenoic acid), and fed the other 2 groups with corn oil [+omega-6 fatty acids (ω-6FA)]. A fifth group was fed a low-fat (LF; 15.5% kcal) diet. LF and HF+ω-6+SD3 differences were tested by a Student's t-test and HF treatment differences were tested by a 2-way ANOVA. RESULTS: D3 supplementation in the +HD3 groups did not significantly increase plasma total 25-hydroxyvitamin D and 25-hydroxyvitamin D3 [25(OH)D3] versus the +SD3 groups, but it increased 3-epi-25-hydroxyvitamin D3 levels by 3.4 ng/mL in the HF+ω-6+HD3 group and 4.0 ng/mL in the HF+ω-3+HD3 group, representing 30% and 70%, respectively, of the total 25(OH)D3 increase. Energy expenditure increased in those mice fed diets +ω-3FA, by 3.9% in the HF+ω-3+SD3 group and 7.4% in the HF+ω-3+HD3 group, but it did not translate into lower body weight. The glucose tolerance curves of the HF+ω-3+SD3 and HF+ω-3+HD3 groups were improved by 11% and 17%, respectively, as compared to the respective +ω-6FA groups. D3 supplementation, within the ω-3FA groups, altered the gut microbiota by increasing the abundance of S24-7 and Lachnospiraceae taxa compared to the standard dose, while within the ω-6FA groups, D3 supplementation did not modulate specific taxa. CONCLUSIONS: Overall, D3 supplementation does not prevent CMD or enhance the beneficial effects of ω-3FA in vitamin D-sufficient obese mice.

Factors associated with discharge destination following inpatient functional rehabilitation in patients with traumatic spinal cord injury.

STUDY DESIGN: Retrospective review of data from a prospective database of a Level 1 trauma center. OBJECTIVES: This project aims to identify factors collected during the acute and rehabilitative care following a traumatic spinal cord injury (TSCI) associated with success and failure to return home after inpatient intensive functional rehabilitation (IFR). SETTING: Level 1 trauma center specialized in TSCI care in Montreal, Canada. METHODS: All eligible patients from our prospective database were separated into two groups according to discharge destination following IFR. Clinical variables collected during the acute and rehabilitative care as well as demographic variables were compared between patients who managed to return home (Group 1) and those who were discharged elsewhere (Group 2). Multivariable regression analyses were conducted with variables that were significant at the univariate level. RESULTS: Out of the 193 patients included, 22 (11%) failed to return home following IFR. Six variables were associated with failure to return home at the univariate level: longer acute length of stay (LOS), longer rehabilitation LOS, living alone, higher neurological level of injury, having comorbidities, and having a pressure injury (PI) during acute care. Three variables remained significant at the multivariate level: living alone, increasing acute LOS and presenting a high cervical (C1-C4) neurological level of injury. CONCLUSIONS: It is important that acute care clinicians recognize the aforementioned factors early after TSCI in order to optimize patients for community reintegration.

Are early clinical manifestations of spasticity associated with long-term functional outcome following spinal cord injury? A retrospective study.

STUDY DESIGN: Retrospective study of a prospective cohort of patients with traumatic spinal cord injury (SCI). OBJECTIVES: Determine the relationship between the occurrence of early spasticity, defined as the development of signs and/or symptoms of spasticity during the hospitalization in traumatology, and the functional outcome 6-12 months following a SCI. Secondly, to determine the specific impact of early clonus, velocity-dependent hypertonia and/or muscle spasms on the functional outcome at the same timepoint. SETTING: Single trauma center specialized in SCI care. METHODS: One hundred sixty-two patients sustaining an acute traumatic SCI were included in the analyses. Comparative analysis was performed to describe the characteristics of patients with early spasticity. Correlations were performed to determine the relationship between the clinical signs of spasticity and the Spinal Cord Independence Measure (SCIM) scores collected 6-12 months after SCI. RESULTS: 51.9% of the cohort developed clinical signs of spasticity during the hospitalization in traumatology (29.7 days) following SCI. These showed a significantly lower total SCIM score and subscores compared to individuals without early spasticity at follow-up (p < 0.05). After adjusting for confounding factors, the occurrence of early spasms was only clinical sign of spasticity significantly associated with a decreased mobility at follow-up (r = -0.17, p = 0.04). CONCLUSIONS: The development of signs and symptoms of spasticity, in particular the occurrence of spasms in the first month following the injury may be associated with decreased functional outcome and mobility. Early assessment of spasticity following SCI is thus recommended.

An evaluation of the representativeness of a national spinal cord injury registry: a population-based cohort study.

STUDY DESIGN: Population-based cohort study for the western part of Quebec. OBJECTIVES: To determine the impact of declining to participate in a national spinal cord injury (SCI) registry on patient outcomes and continuum of care. SETTING: Level-1 trauma center specialized in SCI care in Montreal, Canada. METHODS: This cohort study compared the outcomes of 444 patients who were enrolled in the Rick Hansen SCI registry and 140 patients who refused. Logistic regression analyses were performed to assess the association between voluntary participation and the outcomes, while adjusting for confounding factors. The main outcomes were: attendance to follow-up 6- to 12-month post injury, 1-year mortality, and the occurrence of pressure injury during acute care. RESULTS: Declining to be enrolled in the registry was a significant predictor of lower attendance to specialized follow-up (adjusted odds ratio [OR] 0.04, 95% confidence interval [CI] 0.02-0.08). It was also associated with a higher 1-year mortality rate (OR 12.50, CI 4.50-33.30) and higher occurrence of pressure injury (OR 2.56, CI 1.56-4.17). CONCLUSIONS: This study sheds invaluable insight on individuals that researchers and clinicians are usually blind to in SCI cohort studies. This study suggests that decline to participate in a registry during the care hospitalization may be associated with worsened health, poorer outcomes, and reduced follow-up to specialized care. Declining the enrollment to voluntary registry could represent a potential prognostic factor for future research.

Clinical judgment is a cornerstone for validating and using clinical prediction rules: a head-to-head study on ambulation outcomes for spinal cord injured patients.

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: Clinical prediction rules (CPRs) are an effervescent topic in the medical literature. Recovering ambulation after a traumatic spinal cord injury (tSCI) is a priority for patients and multiple CPRs have been proposed for predicting ambulation outcomes. Our objective is to confront clinical judgment to an established CPR developed for patients with tSCI. SETTINGS: Level one trauma center specialized in tSCI and its affiliated rehabilitation center. METHOD: In this retrospective comparative study, six physicians had to predict the ambulation outcome of 68 patients after a tSCI based on information from the acute hospitalization. Ambulation was also predicted according to the CPR of van Middendorp (CPR-vM). The success rate of the CPR-vM and clinicians to predict ambulation was compared using criteria of 5% for defining clinical significance, and a level of statistical significance of 0.05 for bilateral McNemar tests. RESULTS: There was no statistical difference between the overall performance of physicians (success rate of 79%) and of the CPR-vM (81%) for predicting ambulation. The differences between the CPR-vM and physicians varied clinically and significantly with the level of experience, clinical setting, and field of expertise. CONCLUSION: Confronting CPRs with the judgment of a group of clinicians should be an integral part of the design and validation of CPRs. Head-to-head comparison of CPRs with clinicians is also a cornerstone for defining the optimal strategy for translation into the clinical practice, and for defining which clinician and specific clinical context would benefit from using the CPR.

Neuroanatomical changes in white and grey matter after sleeve gastrectomy.

BACKGROUND: MRI studies show that obese adults have reduced grey matter (GM) and white matter (WM) tissue density as well as altered WM integrity. Bariatric surgery can lead to substantial weight loss and improvements in metabolic parameters, but it remains to be examined if it induces structural brain changes. The aim of this study was to characterize GM and WM density changes measured with MRI in a longitudinal setting following sleeve gastrectomy, and to determine whether any changes are related to inflammation and cardiometabolic blood markers. METHODS: 29 participants with obesity (age: 45.9 â€‹± â€‹7.8 years) scheduled to undergo sleeve gastrectomy were recruited. High-resolution T1-weighted anatomical images were acquired 1 month prior to as well as 4 and 12 months after surgery. GM and WM densities were quantified using voxel-based morphometry (VBM). Circulating lipid profile, glucose, insulin and inflammatory markers (interleukin-6, C-reactive protein and lipopolysaccharide-binding protein) were measured at each time point. A linear mixed effect model was used to compare brain changes before and after SG, controlling for age, sex, initial BMI and diabetic status. To assess the associations between changes in adiposity, metabolism and inflammation and changes in GM or WM density, the mean GM and WM densities were extracted across all the participants using atlas-derived regions of interest, and linear mixed-effect models were used. RESULTS: As expected, weight, BMI, waist circumference and neck circumference significantly decreased after SG compared with baseline (p â€‹< â€‹0.001 for all). A widespread increase in WM density was observed after surgery, particularly in the cerebellum, brain stem, cerebellar peduncle, cingulum, corpus callosum and corona radiata (p â€‹< â€‹0.05, after FDR correction). Significant increases in GM density were observed 4 months after SG compared to baseline in several brain regions such as the bilateral occipital cortex, temporal cortex, postcentral gyrus, cerebellum, hippocampus and insula as well as right fusiform gyrus, right parahippocampal gyrus, right lingual gyrus and right amygdala. These GM and WM increases were more pronounced and widespread after 12 months and were significantly associated with post-operative weight loss and the improvement of metabolic alterations. A linear mixed-effect model also showed associations between post-operative reductions in lipopolysaccharide-binding protein, a marker of inflammation, and increased WM density. To confirm our results, we tested whether the peak of each significant region showed BMI-related differences in an independent dataset (Human Connectome Project). We matched a group of individuals who were severely obese with a group of individuals who were lean for age, sex and ethnicity. Severe obesity was associated with reduced WM density in the brain stem and cerebellar peduncle as well as reduced GM density in cerebellum, regions that significantly changed after surgery (p â€‹< â€‹0.01 for all clusters). CONCLUSIONS: Bariatric surgery-induced weight loss and improvement in metabolic alterations is associated with widespread increases in WM and GM densities. These post-operative changes overlapped with baseline brain differences between participants who were severely obese and those who were normal-weight in a separate dataset, which may suggest a recovery of WM and GM alterations after bariatric surgery.

Morphological features of thoracolumbar burst fractures associated with neurological outcome in thoracolumbar traumatic spinal cord injury.

PURPOSE: To identify specific morphological characteristics in thoracolumbar burst fractures associated with neurological outcome after severe traumatic spinal cord injury (TSCI). METHODS: We retrospectively analyzed the clinical and radiological (CT scan morphological characteristics) data of 25 consecutive patients admitted for TSCI secondary to a burst fracture at levels from T11 to L2 between 2010 and 2017 in single level-1 trauma center. We included severe TSCI, defined as American Spinal Injury Association Impairment Scale (AIS) grade A, B or C. RESULTS: Among the 25 patients with severe TSCI, 14 were AIS A, 5 were AIS B, and 6 were AIS C upon initial preoperative neurological evaluation. The AIS grade and the burden of associated injuries (Injury Severity Score, ISS) were the only clinical factors significantly associated with poor neurological recovery. The trauma level of energy was not associated with neurological outcome. Several fractures parameters were independently related to neurological recovery: the postero-inferior corner translation, presence of retropulsed fragment comminution and complete lamina fracture. The magnitude of sagittal kyphosis angle, vertebral kyphosis index and vertebral body comminution were not associated with the neurological outcome. CONCLUSIONS: Morphological features of the bony structures involving the spinal canal in thoracolumbar burst fractures with severe TSCI are associated with the chronic neurological outcome and could provide more insight than the AIS clinical grading. The fracture pattern may better reflect the actual level of energy transferred to the spinal cord than distinguishing between low- and high-energy trauma.

Patterns and predictors of functional recovery from the subacute to the chronic phase following a traumatic spinal cord injury: a prospective study.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: To determine the extent of functional recovery between 6 and 12 months following a traumatic spinal cord injury (TSCI) and to identify individuals achieving a small clinical functional improvement during this period. SETTING: A single level-1 trauma center specialized in SCI care. METHODS: A cohort of 125 patients sustaining TSCI was studied. The Spinal Cord Independence Measure (SCIM) version III at 6 and 12 months post injury was used as the main outcome measure. RESULTS: The observed functional improvement for the final cohort did not reach a clinically significant level between 6 and 12 months post injury. However, 30.4% of individuals achieved this level (≥4 points in the SCIM-III total score). This group showed a higher proportion of motor-complete TSCI (AIS grade A or B) and showed a tendency toward older age and higher trauma severity. Longer duration of intensive functional rehabilitation was the single factor associated with reaching a small clinically important improvement in the SCIM-III total score. CONCLUSIONS: Functional status between 6 and 12 months following a TSCI may be considered clinically similar, regardless of the level of injury. However, 30% may reach a small clinical functional improvement in the subacute to chronic phase following TSCI, particularly individuals sustaining severe deficits and older age, which may highlight the importance of functional compensation during this period for these patients.

The use of classification and regression tree analysis to identify the optimal surgical timing for improving neurological outcomes following motor-complete thoracolumbar traumatic spinal cord injury.

STUDY DESIGN: Observational cohort study. OBJECTIVES: To identify the optimal surgical timing for improving neurological outcomes in patients that sustained a motor-complete traumatic spinal cord injury (TSCI) secondary to a thoracolumbar injury. SETTING: Level 1 trauma center specialized in TSCI care. METHODS: We prospectively analyzed clinical data of 35 patients admitted for motor-complete TSCI secondary to a thoracolumbar injury. We quantified neurological recovery with three different outcomes: the improvement of at least one grade on the American Spinal Injury Association Impairment Scale (AIS), of at least one neurological level of injury (NLI), and of at least 10-points on the motor score (MS). Classification and regression tree analysis was used to identify outcome predictors and to provide cutoff values of surgical timing associated with recovery. RESULTS: The proportion of the patients improving by at least one AIS grade was higher in the group undergoing early surgery within 25.7 h of the TSCI (46% vs 0%). The proportion of patients that improved by at least one NLI was also higher in the group undergoing early surgery within 21.5 h of the TSCI (71% vs 18%). Lastly, 25% of the AIS grade A patients undergoing early surgery within 25.6 h of the TSCI improved 10 MS points or more as compared with 0% in the other group. CONCLUSIONS: Earlier surgery was effective in improving neurological outcome in motor-complete TSCI at the thoracolumbar levels. Performing surgery within 21.5 h from the traumatic event in these patients increases the likelihood of improving the neurological recovery. SPONSORSHIP: This study was supported by the Fonds de Recherche du Québec-Santé (FRQS), Department of the Army-United States Army Medical Research Acquisition Activity, Rick Hansen Spinal Cord Injury Registry and Medtronic research chair in spinal trauma at Université de Montréal.

The relevance of MRI for predicting neurological recovery following cervical traumatic spinal cord injury.

STUDY DESIGN: Retrospective cohort study of 82 patients with cervical traumatic spinal cord injury (TSCI). OBJECTIVES: Determine the relevance of preoperative MRI to predict neurological recovery following cervical TSCI. SETTING: Level I trauma center specialized in TSCI. METHODS: The following three MRI parameters were assessed: presence of an intramedullary hemorrhage, intramedullary lesion length and maximal compression of the spinal cord compression (MSCC). Analyses were performed to assess the relationship between MRI parameters and three neurological outcomes: ASIA motor score (AMS), improvement by at least one ASIA impairment scale (AIS) grade (conversion of AIS grade), and reaching AIS grade D or E. RESULTS: Predicting AMS based on initial AIS grade and intramedullary hemorrhage resulted in a validation R-squared of 0.662, and of 0.636 when using only the initial AIS grade. Predicting conversion of AIS grade based on initial AIS grade, intramedullary hemorrhage and lesion length resulted in a validation c-index of 0.704, and of 0.727 when using only the initial AIS grade. Predicting the likelihood of a follow-up AIS grade D or E based on initial AIS grade and intramedullary hemorrhage in a validation c-index of 0.903, and of 0.873 when using only the initial AIS grade. CONCLUSIONS: Intramedullary hemorrhage and lesion length assessed from preoperative MRI were predictors of the neurological recovery following cervical TSCI. However, the clinical benefit of these MRI parameters to predict the neurological recovery remains limited when the initial AIS grade is available, confirming that the initial neurological status remains the most important predictor of the neurological outcome.

Interscapular brown adipose tissue denervation does not promote the oxidative activity of inguinal white adipose tissue in male mice.

Brown adipose tissue (BAT) thermogenesis is a key controller of energy metabolism. In response to cold or other adrenergic stimuli, brown adipocytes increase their substrate uptake and oxidative activity while uncoupling ATP synthesis from the mitochondrial respiratory chain activity. Brown adipocytes are found in classic depots such as in the interscapular BAT (iBAT). They can also develop in white adipose tissue (WAT), such as in the inguinal WAT (iWAT), where their presence has been associated with metabolic improvements. We previously reported that the induction of oxidative metabolism in iWAT is low compared with that of iBAT, even after sustained adrenergic stimulation. One explanation to this apparent lack of thermogenic ability of iWAT is the presence of an active iBAT, which may prevent the full activation of iWAT. In this study, we evaluated whether iBAT denervation-induced browning of white fat enhanced the thermogenic activity of iWAT following cold acclimation, under beta-3 adrenergic stimulation (CL 316,243). Following a bilateral denervation of iBAT, we assessed energy balance, evaluated the oxidative activity of iBAT and iWAT using 11C-acetate, and quantified the dynamic glucose uptake of those tissues using 2-deoxy-2-[18F]- fluoro-d-glucose. Our results indicate that despite portraying marked browning and mildly enhanced glucose uptake, iWAT of cold-adapted mice does not exhibit significant oxidative activity following beta-3 adrenergic stimulation in the absence of a functional iBAT. The present results suggest that iWAT is not readily recruitable as a thermogenic organ even when functional iBAT is lacking.