Burden of comorbidities: Osteoporotic vertebral fracture during non-small cell lung cancer - the BONE study.

INTRODUCTION: Immunotherapy and targeted therapy have extended life expectancy in non-small cell lung cancer (NSCLC) patients, shifting it into a chronic condition with comorbidities, including osteoporosis. This study aims to evaluate the prevalence and incidence of osteoporotic vertebral fracture (OPVF) during NSCLC follow-up, identify risk factors of OPVF, and determine the impact on overall survival (OS). METHODS: We performed a longitudinal single-center retrospective cohort study involving patients with histologically proven NSCLC of any stage. Chest-abdomen-pelvis computed tomography (CAP CT) at diagnosis and during follow-up were double-blind reviewed to determine OPVF site, count, type, time to incident OPVF, and trabecular volumetric bone density (TVBD). An institutional expert committee adjudicated discrepancies. Binary logistic regression was used to predict the occurrence of incident OPVF. OS was calculated using the Kaplan-Meier method. RESULTS: We included 289 patients with a median follow-up of 29.7 months. OPVF prevalence was 10.7% at inclusion and 23.2% at the end of follow-up. Cumulative incidence was 12.5%, with an incidence rate of 4 per 100 patient-years. Median time to incident OPVF was 13 months (IQR: 6.7-21.2). Seven of the 36 patients with incident OPVF received denosumab or bisphosphonates. In multivariable analysis, independent risk factors for incident OPVF were BMI < 19 kg/m2 (OR: 5.62, 95%CI 1.84-17.20, p = 0.002), lower TVBD (OR: 0.982 per HU, 95%CI 0.97-0.99, p = 0.001) and corticosteroid use (OR: 4.77, 95%CI: 1.76-12.89, p = 0.001). OPVF was not significantly associated with OS. CONCLUSIONS: Osteoporosis should be screened for in NSCLC patients. Thoracic oncologists must broaden the use of steroid-induced osteoporosis recommendations.

Beyond activity patterns: The complex process of activity management among individuals with chronic musculoskeletal pain after an orthopaedic trauma.

CONTEXT: Individuals must change the way they perform activities in response to chronic pain. In the literature, three activity patterns are commonly described: avoidance, pacing, and persistence. Many studies have explored these activity patterns. However, little research has delved into the factors that lead people to adopt a particular activity behaviour. This study aimed to explore the relationship that people with chronic musculoskeletal pain have with activity and highlight the factors underlying their practices. METHODS: The qualitative study was conducted by researchers in the social sciences, physiotherapy, psychology, and rehabilitation medicine. Observations of vocational workshops and semi-structured interviews were conducted with 33 persons undergoing rehabilitation for chronic musculoskeletal pain after an accident. RESULTS: Patients' declarations and actions show that any one patient will alternate between activity patterns: the same person may adopt a strategy of avoidance, pacing or persistence depending on the context, the importance of the activity, personal objectives, and representations of self, pain, and activity. The decision to engage in a particular behaviour is based on a process of self-negotiation weighted by the circumstances, the nature of the activity, the importance attached to it, and the individual's perceived ability. CONCLUSION: Our study emphasized the complexity of physical, social, and contextual factors that intervene in the relationship toward activity. Rather than favouring pacing, the therapist's role in rehabilitation might be to reinforce the reflexive process and the patient's adaptability in approaching the activity, to foster the capacity to find flexible solutions. SIGNIFICANCE: Patients choose an activity pattern (avoidance, pacing, persistence) according to the challenges they face in their daily lives. Context, representations of self and activity, as well as goals sought influence these choices. Some patients report having learned to adapt their activity management strategies. Therefore, therapeutic approaches in the rehabilitation context could focus on these adaptive capacities to offer patients optimal pain and activity management and develop their ability to use different strategies according to the circumstance.

Working Together and Being Physically Active Are Not Enough to Advise Uniformly and Adequately Low Back Pain Patients: A Cross-Sectional Study.

The profession of the health-care providers (HCPs) influences their recommendations to the patients. Conversely, interdisciplinarity seeks to challenge such differences, so that the patient receives one single and consistent therapeutic message. Some studies also suggest associations between HCPs life habits and recommendations. Our hypotheses were (1) that despite interdisciplinary work, the profession remains a predictor of recommendations and (2) that HCPs who are more physically active recommend more activity. Three clinical vignettes were presented to a group of experts of low back pain (LBP) (guidelines), and 20 physicians, 22 physiotherapists, and 23 nurses to assess how they evaluate the symptoms and pathologies of LBP patients and how much work and physical activity they recommend. Physical activity was assessed with accelerometers and questionnaires. Some interprofessional differences remained present within an interdisciplinary team. The nurses were more restrictive and further away from the guidelines. The physicians were the most in line with them. The physiotherapists recommend as much physical activity, but less work activity than the physicians. The level of physical activity of the HCPs is not associated with their recommendations. To ensure a clear and unique message, educational actions may be undertaken to promote the biopsychosocial model and clarify the guidelines.

[How much pain is acceptable in rehabilitation?]. / Quelle douleur est supportable en rééducation?

Active therapies are well-accepted during a rehabilitation process or for the treatment of pain. However they may often cause additional pain that can reduce patient compliance. Mechanisms that control the effect of pain on muscle strength are so far poorly understood. It is of prime importance for the clinician to assess the impact of pain during rehabilitation, and especially the soreness induced by the therapies. Although this problem is recognized, it is often minimized by therapists. If the point of view of the patients is usually pretty close from the one of the therapist, it may differ on some points and this may lead to misunderstandings. In order to adjust the treatment and explanations, it is necessary to have a good assessment of the impact of pain on the lives of the patients. This is compulsory in order to get a better adhesion to the treatment.

Brown adipocyte progenitor population is modified in obese and diabetic skeletal muscle.

Brown adipose tissue mitochondria express the unique thermogenic uncoupling protein-1. Recently, brown adipocyte progenitors have been identified in the CD34+ cell population of human skeletal muscle. The aims of this study were firstly to determine if obesity and diabetes have altered amounts of muscle brown adipocyte progenitors and, secondly, to establish if the latter are correlated with clinical parameters of obesity and diabetes. Body mass index (BMI), plasma glucose, insulin, cholesterol and triglycerides as well as homeostasis model assessment were measured in lean (n=10), obese (n=18) and obese-diabetic (n=15) subjects and muscle biopsies were taken from the rectus abdominus. CD34 being also expressed on endothelial cells, we measured CD31, another endothelial marker, and expressed the brown adipocyte progenitors, as the CD34/CD31 mRNA ratio. The latter was significantly reduced in the obese vs lean subjects suggesting a smaller pool of brown adipocyte progenitors. More strikingly, for lean and obese subjects negative correlations were observed between the CD34/CD31 mRNA ratios and BMI, fasting insulin levels and homeostasis model assessment. These correlations highlight the potential physiological relevance of the muscle CD34/CD31 mRNA ratio.

Differentiation and characterization in primary culture of white adipose tissue brown adipocyte-like cells.

BACKGROUND: Rodent brown adipose tissue (BAT) is considered the main effector of adaptative thermogenesis as it contains a unique mitochondrial uncoupling protein, termed as uncoupling protein-1 (UCP1). The emergence of ectopic brown adipocytes in the white adipose tissue (WAT), called recruitment, might play an important role in the prevention of obesity. The recruitment phenomenon has until now been investigated mostly in vivo. OBJECTIVES: This study is an attempt to mimic in vitro the recruitment phenomenon. It consisted in culturing the stroma vascular fractions of mouse BAT and WAT in a brown adipocyte differentiation medium. The multilocular cells obtained, referred to as BAT(B) and WAT(B) adipocytes, respectively, were compared. RESULTS: The BAT(B) and WAT(B) adipocytes were morphologically different. The expressions of UCP1, peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), leptin and resistin mRNAs were low in WAT(B) adipocytes as compared with those in BAT(B) adipocytes. The expressions of UCP1 and PGC-1alpha proteins were, however, much higher in WAT(B) adipocytes, amounting 51% and 36% of those in BAT(B) adipocytes. The patterns of expression of UCP1, PGC-1alpha and leptin in the BAT(B) and in WAT(B) adipocytes were different with a higher relative expression of PGC-1alpha in the latter. Rosiglitazone increased UCP1 mRNA expression 4.5-fold in the BAT(B) and significantly more, 7.9-fold, in the WAT(B) adipocytes. Retinoic acid and triiodothyronine increased UCP1 mRNA expression in the BAT(B) adipocytes 1.6- and 2-fold, respectively but, surprisingly, slightly decreased UCP1 mRNA expression in the WAT(B) adipocytes. CONCLUSIONS: The study suggests that the nature and possibly the origin of WAT brown adipocytes is different from that of BAT brown adipocytes. It proposes an in vitro approach that could prove very useful to better characterize the WAT brown adipocyte-like cells.

Exercise in the fasted state facilitates fibre type-specific intramyocellular lipid breakdown and stimulates glycogen resynthesis in humans.

The effects were compared of exercise in the fasted state and exercise with a high rate of carbohydrate intake on intramyocellular triglyceride (IMTG) and glycogen content of human muscle. Using a randomized crossover study design, nine young healthy volunteers participated in two experimental sessions with an interval of 3 weeks. In each session subjects performed 2 h of constant-load bicycle exercise ( approximately 75% ), followed by 4 h of controlled recovery. On one occasion they exercised after an overnight fast (F), and on the other (CHO) they received carbohydrates before ( approximately 150 g) and during (1 g (kg bw)(-1) h(-1)) exercise. In both conditions, subjects ingested 5 g carbohydrates per kg body weight during recovery. Fibre type-specific relative IMTG content was determined by Oil red O staining in needle biopsies from m. vastus lateralis before, immediately after and 4 h after exercise. During F but not during CHO, the exercise bout decreased IMTG content in type I fibres from 18 +/- 2% to 6 +/- 2% (P = 0.007) area lipid staining. Conversely, during recovery, IMTG in type I fibres decreased from 15 +/- 2% to 10 +/- 2% in CHO, but did not change in F. Neither exercise nor recovery changed IMTG in type IIa fibres in any experimental condition. Exercise-induced net glycogen breakdown was similar in F and CHO. However, compared with CHO (11.0 +/- 7.8 mmol kg(-1) h(-1)), mean rate of postexercise muscle glycogen resynthesis was 3-fold greater in F (32.9 +/- 2.7 mmol kg(-1) h(-1), P = 0.01). Furthermore, oral glucose loading during recovery increased plasma insulin markedly more in F (+46.80 microU ml(-1)) than in CHO (+14.63 microU ml(-1), P = 0.02). We conclude that IMTG breakdown during prolonged submaximal exercise in the fasted state takes place predominantly in type I fibres and that this breakdown is prevented in the CHO-fed state. Furthermore, facilitated glucose-induced insulin secretion may contribute to enhanced muscle glycogen resynthesis following exercise in the fasted state.

UCP3 protein expression is lower in type I, IIa and IIx muscle fiber types of endurance-trained compared to untrained subjects.

Uncoupling protein 3 (UCP3) is a muscle mitochondrial protein believed to uncouple the respiratory chain, producing heat and reducing aerobic ATP production. Our aim was to quantify and compare the UCP3 protein levels in type I, IIa and IIx skeletal muscle fibers of endurance-trained (Tr) and healthy untrained (UTr) individuals. UCP3 protein content was quantified using Western blot and immunofluorescence. Skeletal muscle fiber type was determined by both an enzymatic ATPase stain and immunofluorescence. UCP3 protein expression measured in skeletal muscle biopsies was 46% lower ( P=0.01) in the Tr compared to the UTr group. UCP3 protein expression in the different muscle fibers was expressed as follows; IIx>IIa>I in the fibers for both groups ( P<0.0167) but was lower in all fiber types of the Tr when compared to the UTr subjects ( P<0.001). Our results show that training status did not change the skeletal muscle fiber hierarchical UCP3 protein expression in the different fiber types. However, it affected UCP3 content more in type I and type IIa than in the type IIx muscle fibers. We suggest that this decrease may be in relation to the relative improvement in the antioxidant defense systems of the skeletal muscle fibers and that it might, as a consequence, participate in the training induced improvement in mechanical efficiency.

Hemostatic markers in patients at risk of cerebral ischemia.

BACKGROUND: Increased levels of markers of hemostasis may assist in the determination of the extent of carotid occlusive disease and the identification of neurologically intact individuals at increased risk of ischemic events. METHODS: We conducted a prospective study of 304 subjects, including 82 with a recent (< or =7 days) transient ischemic attack (TIA), 157 asymptomatic individuals with a cervical bruit, and 65 control subjects. Baseline evaluation included a neurological assessment, ECG, cervical ultrasonography, and cerebral CT and/or MRI. Levels of markers of coagulation and fibrinolytic activity were also determined. Results were analyzed in relation to the degree of carotid disease and the subsequent occurrence of cerebral and cardiac ischemic events. RESULTS: Over a mean follow-up period of 2.8 years (SD, 1.3 years), 114 ischemic events occurred. Survival analyses showed that prothrombin fragment 1.2 (F(1.2)) was a predictor of time to cerebral and cardiac ischemic events in the combined TIA and asymptomatic bruit group (relative risk [RR], 1.46; 95% CI, 1.18 to 1.81) as well as in the asymptomatic bruit group separately (RR, 1.70; 95% CI, 1.14 to 2.53). In the TIA group, both F(1.2) (RR, 2.36; 95% CI, 1.19 to 4.68) and severe (> or =80%) carotid stenosis (RR, 3.53; 95% CI, 1.19 to 10.51) were predictive of time to ischemic stroke, myocardial infarction, or vascular death. CONCLUSIONS: In patients with TIAs and in asymptomatic individuals with cervical bruits, F(1.2) levels were found to be independent predictors of subsequent cerebral and cardiac ischemic events. Our results are consistent with an active role of the coagulation system through upregulation of thrombin in carotid disease progression and in the pathogenesis of ischemic events in patients at risk.