A prolonged run-in period of standard subcutaneous microdialysis ameliorates quality of interstitial glucose signal in patients after major cardiac surgery

We evaluated a standard subcutaneous microdialysis technique for glucose monitoring in two critically ill patient populations and tested whether a prolonged run-in period improves the quality of the interstitial glucose signal. 20 surgical patients after major cardiac surgery (APACHE II score: 10.1 ± 3.2) and 10 medical patients with severe sepsis (APACHE II score: 31.1 ± 4.3) were included in this investigation. A microdialysis catheter was inserted in the subcutaneous adipose tissue of the abdominal region. Interstitial fluid and arterial blood were sampled in hourly intervals to analyse glucose concentrations. Subcutaneous adipose tissue glucose was prospectively calibrated to reference arterial blood either at hour 1 or at hour 6. Median absolute relative difference of glucose (MARD), calibrated at hour 6 (6.2 (2.6; 12.4) %) versus hour 1 (9.9 (4.2; 17.9) %) after catheter insertion indicated a significant improvement in signal quality in patients after major cardiac surgery (p < 0.001). Prolonged run-in period revealed no significant improvement in patients with severe sepsis, but the number of extreme deviations from the blood plasma values could be reduced. Improved concurrence of glucose readings via a 6-hour run-in period could only be achieved in patients after major cardiac surgery

Quantitative analysis of the anterolateral ossification mass in diffuse idiopathic skeletal hyperostosis of the thoracic spine

Diffuse idiopathic skeletal hyperostosis (DISH) is a systemic condition leading to ossification of spinal ligaments and has been shown to behave similarly to ankylosing spondylitis (AS) often leading to unstable hyperextension fractures. Currently, no quantitative data are available on the spatial relationship between the bridging anterolateral ossification mass (ALOM) and the vertebral body/intervertebral disc to explain the propensity in DISH to fracture through the vertebral body instead of through the intervertebral disc as more often seen in AS. Furthermore, no reasonable explanation is available for the typical flowing wax morphology observed in DISH. In the current study, a quantitative analysis of computed tomography (CT) data from human cadaveric specimens with DISH was performed to better understand the newly formed osseous structures and fracture biomechanics. Additionally, the results were verified using computed tomography angiography data from ten patients with DISH and ten controls. Transverse CT images were analyzed to obtain ALOM area and centroid angle relative to the anteroposterior axis; intervertebral disc and adjacent cranial and caudal levels. The ALOM area at the mid-vertebral body level averaged 57.9 ± 50.0 mm2; at the mid-intervertebral disc space level it averaged 246.4 ± 95.9 mm2. The mean ALOM area at the adjacent level caudal to the mid-vertebral body level was 169.6 ± 81.3 mm2; at the adjacent cranial level, it was 161.7 ± 78.2 mm2. The main finding was the significant difference between mean ALOM area at the mid-vertebral body level and other three levels (p < 0.0001). The subsequent verification study showed the presence of vertebral segmental arteries at the mid-vertebral body level in nearly all images irrespective of the presence of DISH. A larger area of ALOM seemed associated with increased counter-clockwise rotation (away from the aorta) of the centroid relative to the anteroposterior axis. The results from the present study suggest a predisposition for fractures through the vertebral body and a role for the arterial system in the inhibition of soft tissue ossification

A biodegradable antibiotic delivery system based on poly-(trimethylene carbonate) for the treatment of osteomyelitis

Background and purpose Many investigations on biodegradable materials acting as an antibiotic carrier for local drug delivery are based on poly(lactide). However, the use of poly(lactide) implants in bone has been disputed because of poor bone regeneration at the site of implantation. Poly(trimethylene carbonate) (PTMC) is an enzymatically degradable polymer that does not produce acidic degradation products. We explored the suitability of PTMC as an antibiotic releasing polymer for the local treatment of osteomyelitis

Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Behavioral Patterns and Associations with Glucose Control During 12-Week Randomized Free-Living Clinical Trial of Day and Night Hybrid Closed-Loop Insulin Delivery in Adults with Type 1 Diabetes

$\textbf{Objectives}$: We evaluated patterns of meal intake, insulin bolus delivery, and fingerstick glucose measurements during hybrid closed-loop and sensor-augmented pump (SAP) therapy, including associations with glucose control. $\textbf{Methods}$: Data were retrospectively analyzed from pump-treated adults with type 1 diabetes who underwent, in random order, 12 weeks free-living closed-loop (n = 32) and 12 weeks SAP (n = 33) periods. We quantified daily patterns of main meals, snacks, prandial insulin boluses, correction boluses, and fingerstick glucose measurements by analyzing data recorded on the study glucometer and on study insulin pump. $\textbf{Results}$: We analyzed 1942 closed-loop days and 2530 SAP days. The total number of insulin boluses was reduced during closed-loop versus SAP periods by mean 1.0 per day (95% confidence interval 0.6–1.4, P < 0.001) mainly because of a reduced number of correction boluses by mean 0.7 per day (0.4–1.0, P < 0.001). Other behavioral patterns were unchanged. The carbohydrate content of snacks but not the number of snacks was positively correlated with (1) glycemic variability as measured by standard deviation of sensor glucose (closed-loop P < 0.05; SAP P < 0.01), (2) mean sensor glucose (P < 0.05), and (3) postintervention HbA1c (P < 0.05). Behavioral patterns explained 47% of between-subject variance in glucose variability during SAP period and 30%–33% of variance of means sensor glucose and postintervention HbA1c. $\textbf{Conclusion}$: Fewer correction boluses are delivered during closed-loop period. The size of snacks appears to worsen glucose control possibly because of carbohydrate-rich content of snacks. Modifiable behavioral patterns may be important determinants of glucose control.We acknowledge support by the staff at the Addenbrooke's Wellcome Trust Clinical Research Facility. Josephine Hayes (University of Cambridge) provided administrative support. Karen Whitehead (University of Cambridge) provided laboratory support. We acknowledge support by the staff at Profil Institut, Krisztina Schmitz-Grozs provided support as a research physician, Martina Haase supported the study as an insulin pump expert, and Maren Luebkert, Kirstin Kuschma, and Elke Przetak provided administrative, coordinating, and documentation support. Barbara Semlitsch and Markus Schauer (both from Medical University of Graz) supported the study as insulin pump experts. Funding was by Seventh Framework Programme of the European Union (ICT FP7-247138). Additional support for the Artificial Pancreas work was by JDRF, National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome Strategic Award (100574/Z/12/Z), EC Horizon 2020 (H2020-SC1-731560), NIDDK (DP3DK112176 and 1UC4DK108520-01), Efficacy and Mechanism Evaluation Programme of National Institute for Health Research (14/23/09), and Helmsley Trust (Nos. 2016PG-T1D045 and 2016PG-T1D046). Abbott Diabetes Care supplied discounted continuous glucose monitoring devices, sensors, and communication protocol to facilitate real-time connectivity

Bolusing frequency and amount impacts glucose control during hybrid closed-loop.

AIM: To compare bolus insulin delivery patterns during closed-loop home studies in adults with suboptimally [HbA1c 58-86 mmol/mol (7.5%-10%)] and well-controlled [58 mmol/mol (< 7.5%)] Type 1 diabetes. METHODS: Retrospective analysis of daytime and night-time insulin delivery during home use of closed-loop over 4 weeks. Daytime and night-time controller effort, defined as amount of insulin delivered by closed-loop relative to usual basal insulin delivery, and daytime bolus effort, defined as total bolus insulin delivery relative to total daytime insulin delivery were compared between both cohorts. Correlation analysis was performed between individual bolus behaviour (bolus effort and frequency) and daytime controller efforts, and proportion of time spent within and below sensor glucose target range. RESULTS: Individuals with suboptimally controlled Type 1 diabetes had significantly lower bolus effort (P = 0.038) and daily bolus frequency (P < 0.001) compared with those with well-controlled diabetes. Controller effort during both daytime (P = 0.007) and night-time (P = 0.005) were significantly higher for those with suboptimally controlled Type 1 diabetes. Time when glucose was within the target range (3.9-10.0 mmol/L) during daytime correlated positively with bolus effort (r = 0.37, P = 0.016) and bolus frequency (r = 0.33, P = 0.037). Time when glucose was below the target range during daytime was comparable in both groups (P = 0.36), and did not correlate significantly with bolus effort (r = 0.28, P = 0.066) or bolus frequency (r = -0.21, P = 0.19). CONCLUSION: More frequent bolusing and higher proportion of insulin delivered as bolus during hybrid closed-loop use correlated positively with time glucose was in target range. This emphasises the need for user input and educational support to benefit from this novel therapeutic modality.Seventh Framework Programme of the European Union (ICT FP7- 247138). Additional support for the Artificial Pancreas work by JDRF, National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome Strategic Award (100574/Z/12/Z), EC Horizon 2020 (H2020-SC1-731560), NIDDK (DP3DK112176 and 1UC4DK108520-01), Efficacy and Mechanism Evaluation Programme of National Institute for Health Research (14/23/09) and Helmsley Trust (2016PG-T1D045 and #2016PG-T1D046)

24-h sheltering behaviour of individually kept horses during Swedish summer weather

Provision of shelter for horses kept on summer pasture is rarely considered in welfare guidelines, perhaps because the benefits of shelter in warm conditions are poorly documented scientifically. For cattle, shade is a valued resource during summer and can mitigate the adverse effects of warm weather on well-being and performance. We found in a previous study that horses utilized shelters frequently in summer. A shelter with a roof and closed on three sides (shelter A) was preferred and can reduce insect pressure whereas a shelter with roof and open on three sides was not utilized. However, shelter A restricts the all-round view of a horse, which may be important for horses as flight animals. Therefore, we studied whether a shelter with roof, where only the upper half of the rear wall was closed (shelter B), would be utilized while maintaining insect protection properties and satisfying the horses’ sense for security. A third shelter was offered with walls but no roof (shelter C) to evaluate whether the roof itself is an important feature from the horse’s perspective. Eight Warmblood horses were tested each for 2 days, kept individually for 24 h in two paddocks with access to shelters A and B, or shelters A and C, respectively. Shelter use was recorded continuously during the night (1800–2400 h, 0200–0600 h) and the following day (0900–1600 h), and insect defensive behaviour (e.g., tail swish) in instantaneous scan samples at 5-min intervals during daytime

Faster insulin action is associated with improved glycaemic outcomes during closed-loop insulin delivery and sensor-augmented pump therapy in adults with type 1 diabetes

We aimed to evaluate the relationship between insulin pharmacodynamics and glycaemic outcomes during closed-loop insulin delivery and sensor-augmented pump therapy. We retrospectively analysed data from a multicentre randomized control trial involving 32 adults with type 1 diabetes receiving day-and-night closed-loop insulin delivery and sensor-augmented pump therapy over 12 weeks. We estimated time-to-peak insulin action (t$_{max,IA}$) and insulin sensitivity (_Ix}) during both interventions, and correlated these with demographic factors and glycaemic outcomes. During both interventions, t$_{max,IA}$ was positively correlated with pre- and post-intervention HbA1c (r = 0.50-0.52, P  < .01) and mean glucose (r = 0.45-0.62, P  < .05), and inversely correlated with time sensor glucose, which was in target range 3.9 to 10 mmol/L (r = -0.64 to -0.47, P  < .05). Increased body mass index was associated with higher t$_{max,I}$ and lower S I (both P  < .05). During closed-loop insulin delivery, t$_{max, IA}$, was positively correlated with glucose variability ( P  < .05). Faster insulin action is associated with improved glycaemic control during closed-loop insulin delivery and sensor-augmented pump therapy.Seventh Framework Programme of the European Union (ICT FP7- 247138). Additional support for the Artificial Pancreas work by JDRF, National Institute for Health Research Cambridge Biomed ical Research Centre and Wellcome Strategic Award (100574/Z/12/Z). Abbott Diabetes Care supplied discounted continuous glucose-monitoring devices, sensors, and communication protocol to facilitate real-time connectivity