Lower plasma insulin levels during overnight closed-loop in school children with type 1 diabetes: Potential advantage? A randomized cross-over trial.

BACKGROUND: Studies have shown that overnight closed-loop insulin delivery can improve glucose control and reduce the risk of hypoglycemia and hence may improve metabolic outcomes and reduce burden for children with type 1 diabetes and their families. However, research so far has not reported insulin levels while comparing closed-loop to open-loop insulin delivery in children. Therefore, in this study we obtained glucose levels as well as plasma insulin levels in children with type 1 diabetes to evaluate the efficacy of a model-based closed-loop algorithm compared to an open-loop administration. METHODS: Fifteen children with type 1 diabetes, 6-12 years, participated in this open-label single center study. We used a randomized cross over design in which we compared overnight closed-loop insulin delivery with sensor augmented pump therapy for two nights in both the hospital and at home (i.e., 1 night in-patient stay and at home per treatment condition). Only during the in-patient stay, hourly plasma insulin and blood glucose levels were assessed and are reported in this paper. RESULTS: Results of paired sample t-tests revealed that although plasma insulin levels were significantly lower during the closed-loop than in the open-loop (Mean difference 36.51 pmol/l; t(13) = 2.13, p = .03, effect size d = 0.57), blood glucose levels did not vary between conditions (mean difference 0.76 mmol/l; t(13) = 1.24, p = .12, d = 0.37). The administered dose of insulin was significantly lower during the closed-loop compared with the open-loop (mean difference 0.10 UI; t(12) = 2.45, p = .02, d = 0.68). CONCLUSIONS: Lower insulin doses were delivered in the closed-loop, resulting in lower plasma insulin levels, whereby glucose levels were not affected negatively. This suggests that the closed-loop administration is better targeted and hence could be more effective

Unbiased single cell spatial analysis localises inflammatory clusters of immature neutrophils-CD8 T cells to alveolar progenitor cells in fatal COVID-19 lungs

Single cell spatial interrogation of the immune-structural interactions in COVID -19 lungs is challenging, mainly because of the marked cellular infiltrate and architecturally distorted microstructure. To address this, we developed a suite of mathematical tools to search for statistically significant co-locations amongst immune and structural cells identified using 37-plex imaging mass cytometry. This unbiased method revealed a cellular map interleaved with an inflammatory network of immature neutrophils, cytotoxic CD8 T cells, megakaryocytes and monocytes co-located with regenerating alveolar progenitors and endothelium. Of note, a highly active cluster of immature neutrophils and cytotoxic CD8 T cells, was found spatially linked with alveolar progenitor cells, and temporally with the diffuse alveolar damage stage. These findings provide new insights into how immune cells interact in the lungs of severe COVID-19 disease. We provide our pipeline [Spatial Omics Oxford Pipeline (SpOOx)] and visual-analytical tool, Multi-Dimensional Viewer (MDV) software, as a resource for spatial analysis

Lower plasma insulin levels during overnight closed-loop in school children with type 1 diabetes: Potential advantage? A randomized cross-over trial.

BackgroundStudies have shown that overnight closed-loop insulin delivery can improve glucose control and reduce the risk of hypoglycemia and hence may improve metabolic outcomes and reduce burden for children with type 1 diabetes and their families. However, research so far has not reported insulin levels while comparing closed-loop to open-loop insulin delivery in children. Therefore, in this study we obtained glucose levels as well as plasma insulin levels in children with type 1 diabetes to evaluate the efficacy of a model-based closed-loop algorithm compared to an open-loop administration.MethodsFifteen children with type 1 diabetes, 6-12 years, participated in this open-label single center study. We used a randomized cross over design in which we compared overnight closed-loop insulin delivery with sensor augmented pump therapy for two nights in both the hospital and at home (i.e., 1 night in-patient stay and at home per treatment condition). Only during the in-patient stay, hourly plasma insulin and blood glucose levels were assessed and are reported in this paper.ResultsResults of paired sample t-tests revealed that although plasma insulin levels were significantly lower during the closed-loop than in the open-loop (Mean difference 36.51 pmol/l; t(13) = 2.13, p = .03, effect size d = 0.57), blood glucose levels did not vary between conditions (mean difference 0.76 mmol/l; t(13) = 1.24, p = .12, d = 0.37). The administered dose of insulin was significantly lower during the closed-loop compared with the open-loop (mean difference 0.10 UI; t(12) = 2.45, p = .02, d = 0.68).ConclusionsLower insulin doses were delivered in the closed-loop, resulting in lower plasma insulin levels, whereby glucose levels were not affected negatively. This suggests that the closed-loop administration is better targeted and hence could be more effective

Does the site of bleeding matter? A stratified analysis on location of TIMI-graded bleedings and their impact on 12-month outcome in patients with ST-segment elevation myocardial infarction.

While bleeding in patients with STEMI undergoing primary percutaneous coronary intervention (pPCI) is known to be associated with poor outcomes, the differential prognostic impact of access-site related versus non access-site related bleedings is unknown. We aimed to assess the relative impact of access-site related bleeding, as compared to non access-site related, on 12-month clinical outcome in patients undergoing intervention for STEMI. METHODS AND RESULTS: Thirty-day bleeding endpoints, stratified into access-site versus non access-site, were examined according to the TIMI scale in 744 patients with STEMI enrolled in the MULTISTRATEGY trial. TIMI major or minor bleeding complications occurred in 56 (7.5%) patients within 30 days, 46% had an access-site related bleed and 34% required blood transfusion. Bleeding severity and the need for transfusion were equally distributed between site access- versus non-site access-related bleeds. After adjustment, patients with any TIMI rated bleed were more likely to die or develop recurrent MI within 12 months (HR 2.1 [95% CI: 1.13-3.8]; p=0.02). This ratio was entirely driven by non-site access-related bleeds (adjusted HR: 2.66 [95% CI: 1.21-5.8]; p=0.007), whereas site-access bleeds were not associated with worse outcomes (HR: 0.74 [95% CI: 0.16-3.4]; p=0.70). CONCLUSIONS: While bleeds of any TIMI severity within 30 days were independently associated with worse cardiovascular outcomes at 12 months, thus confirming previous analyses, this relationship was entirely driven in our study by non access-site related haemorrhagic events. Investigation on whether the site of bleeding complications may preferentially impact cardiovascular outcomes is warranted

Comparison of angioplasty with infusion of tirofiban or abciximab and with implantation of sirolimus-eluting or uncoated stents for acute myocardial infarction: the MULTISTRATEGY randomized trial.

Abciximab infusion and uncoated-stent implantation is a complementary treatment strategy to reduce major adverse cardiac events in patients undergoing angioplasty for ST-segment elevation myocardial infarction (STEMI). It is uncertain whether there may be similar benefits in replacing abciximab with high-dose bolus tirofiban. Similarly, the use of drug-eluting stents in this patient population is currently discouraged because of conflicting results on efficacy reported in randomized trials and safety concerns reported by registries.To evaluate the effect of high-dose bolus tirofiban and of sirolimus-eluting stents as compared with abciximab infusion and uncoated-stent implantation in patients with STEMI undergoing percutaneous coronary intervention.An open-label, 2 x 2 factorial trial of 745 patients presenting with STEMI or new left bundle-branch block at 16 referral centers in Italy, Spain, and Argentina between October 2004 and April 2007.High-dose bolus tirofiban vs abciximab infusion and sirolimus-eluting stent vs uncoated stent implantation.For drug comparison, at least 50\% ST-segment elevation resolution at 90 minutes postintervention with a prespecified noninferiority margin of 9\% difference (relative risk, 0.89); for stent comparison, the rate of major adverse cardiac events, defined as the composite of death from any cause, reinfarction, and clinically driven target-vessel revascularization within 8 months.ST-segment resolution occurred in 302 of 361 patients (83.6\%) who had received abciximab infusion and 308 of 361 (85.3\%) who had received tirofiban infusion (relative risk, 1.020; 97.5\% confidence interval, 0.958-1.086; P < .001 for noninferiority). Ischemic and hemorrhagic outcomes were similar in the tirofiban and abciximab groups. At 8 months, major adverse cardiac events occurred in 54 patients (14.5\%) with uncoated stents and 29 (7.8\%) with sirolimus stents (P = .004), predominantly reflecting a reduction of revascularization rates (10.2\% vs 3.2\%). The incidence of stent thrombosis was similar in the 2 stent groups.In patients with STEMI undergoing percutaneous coronary intervention, compared with abciximab, tirofiban therapy was associated with noninferior resolution of ST-segment elevation at 90 minutes following coronary intervention, whereas sirolimus-eluting stent implantation was associated with a significantly lower risk of major adverse cardiac events than uncoated stents within 8 months after intervention.clinicaltrials.gov Identifier: NCT00229515