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Background and aims: Few data are available regarding the combination of biologics or small molecules in inflammatory bowel disease (IBD) patients. We report safety and efficacy of such combinations through a retrospective multicentre series.Methods: Combination therapy was defined as the concomitant use of two biologics or one biologic with a small molecule. Patient demographics, disease characteristics and types of combinations were recorded. Safety was evaluated according to the occurrence of serious infection, opportunistic infection, hospitalisation, lifethreatening event, worsening of IBD or immune-mediated inflammatory diseases (IMID), cancer and death. Efficacy was evaluated as the physician global assessment of the combination and comparison of clinical/endoscopic scores of IBD/IMID activity prior and during combination.Results: A total of 104 combinations were collected in 98 patients. Concomitant IMID were present in 41 patients. Reasons for starting combination therapy were active IBD (67%), active IMID or extra-intestinal manifestations (EIM) (22%), both (10%) and unclassified in 1. Median duration of combination was 8 months (interquartile range 5-16). During 122 patient-years of follow-up, 42 significant adverse events were observed, mostly related to uncontrolled IBD. There were 10 significant infections, 1 skin cancer and no death. IBD disease activity was clinically improved in 70% and IMID/EIM activity in 81% of the patients. Overall, combination was continued in 55% of the patients.Conclusions: Combination of biologics and small molecules in patients with IBD and IMID/EIM seems to be a promising therapeutic strategy but is also associated with a risk of opportunistic infections or infections leading to hospitalisation in 10%.

BackgroundElderly patients are at high risk for postoperative complications and increased mortality after hip fracture (HF) surgery due to frailty and co-morbidities. The prediction of postoperative outcome could be used for clinical decision making. A reliable score to predict postoperative mortality after HF surgery in this sub-population remains unavailable.MethodsA single-centre retrospective cohort study was performed in 782 patients who were operated on for HF. Receiver Operating Characteristic (ROC)-curves were used to analyse the performance of gender, age, neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) at admission (D0) as prognostic factors, alone or combined with the PreOperative Score to predict PostOperative Mortality (POSPOM) in univariate and multivariate linear regression models.ResultsNo correlation between gender, age, NLR D0 or CRP D0 and postoperative, intra-hospital mortality was found. The Area Under the ROC-curve (AUC) for age, male gender, NLR and CRP were 0.61 [95% confidence interval (CI) = 0.45–0.61], 0.56 [95% CI = 0.42–0.56], 0.47 [95% CI = 0.29–0.47] and 0.49 [95% CI = 0.31–0.49] respectively. Combination with the POSPOM score did not increase its discriminative capacity as neither age (AUC = 0.69, 95% CI = 0.54–0.69), gender (AUC = 0.72, 95% CI = 0.58–0.72), NLR D0 (AUC = 0.71, 95% CI = 0.56–0.71), nor the CRP D0 (AUC = 0.71, 95% CI = 0.58–0.71) improved the POSPOM performance.ConclusionsNeither age, gender, NLR D0 nor CRP D0 are suitable parameters to predict postoperative, intra-hospital mortality in elderly patients undergoing surgery for HF.

Most daily activities are bimanual and their efficient performance requires learning and retention of bimanual coordination. Despite in-depth knowledge of the various stages of motor skill learning in general, how new bimanual coordination control policies are established is still unclear. We designed a new cooperative bimanual task in which subjects had to move a cursor across a complex path (a circuit) as fast and as accurately as possible through coordinated bimanual movements. By looking at the transfer of the skill between different circuits and by looking at training with varying circuits, we identified two processes in early bimanual motor learning. Loss of performance due to the switch in circuit after 15 min of training amounted to 20%, which suggests that a significant portion of improvements in bimanual performance is specific to the used circuit (circuit-specific skill). In contrast, the loss of performance due to the switch in circuit was 5% after 4 min of training. This suggests that learning the new bimanual coordination control policy dominates early in the training and is independent of the used circuit. Finally, switching between two circuits throughout training did not affect the early stage of learning (i.e., the first few minutes), but did affect the later stage. Together, these results suggest that early bimanual motor skill learning includes two different processes. Learning the new bimanual coordination control policy predominates in the first minutes whereas circuit-specific skill improvements unfold later in parallel with further improvements in the bimanual coordination control policy.

Obesity is characterized by an excessive triacylglycerol accumulation in white adipocytes. Various mechanisms allowing the tight regulation of triacylglycerol storage and mobilization by lipid droplet-associated proteins as well as lipolytic enzymes have been identified. Increasing energy expenditure by inducing a mild uncoupling of mitochondria in adipocytes might represent a putative interesting anti-obesity strategy as it reduces the adipose tissue triacylglycerol content (limiting alterations caused by cell hypertrophy) by stimulating lipolysis through yet unknown mechanisms, limiting the adverse effects of adipocyte hypertrophy. Herein, the molecular mechanisms involved in lipolysis induced by a mild uncoupling of mitochondria in white 3T3-L1 adipocytes were characterized. Mitochondrial uncoupling-induced lipolysis was found to be independent from canonical pathways that involve lipolytic enzymes such as HSL and ATGL. Finally, enhanced lipolysis in response to mitochondrial uncoupling relies on a form of autophagy as lipid droplets are captured by endolysosomal vesicles. This new mechanism of triacylglycerol breakdown in adipocytes exposed to mild uncoupling provides new insights on the biology of adipocytes dealing with mitochondria forced to dissipate energy.