Notes

Picking flagship varieties to fix a bio-diversity efficiency predicament.
To determine if chronic motor deficits secondary to traumatic brain injury (TBI) can be improved by implantation of allogeneic modified bone marrow-derived mesenchymal stromal/stem cells (SB623).

This 6-month interim analysis of the 1-year double-blind, randomized, surgical sham-controlled, phase 2 STEMTRA trial (NCT02416492) evaluated safety and efficacy of the stereotactic intracranial implantation of SB623 in patients with stable chronic motor deficits secondary to TBI. Patients in this multi-center trial (N = 63) underwent randomization in a 1111 ratio to 2.5 × 10
, 5.0 × 10
, 10 × 10
SB623 cells or control. Safety was assessed in patients who underwent surgery (N = 61), and efficacy in the modified intent-to-treat population of randomized patients who underwent surgery (N = 61; SB623 = 46, control = 15).

The primary efficacy endpoint of significant improvement from baseline of Fugl-Meyer Motor Scale score at 6 months for SB623-treated patients was achieved. SB623-treated patients improved by (LS mean [SE]) +8.3 (1.4) vs +2.3 (2.5) for control at 6 months, the LS mean difference was 6.0 (95% CI 0.3-11.8);
= 0.040. Secondary efficacy endpoints improved from baseline, but were not statistically significant vs control at 6 months. There were no dose-limiting toxicities or deaths, and 100% of SB623-treated patients experienced treatment-emergent adverse events vs 93.3% of control patients (
= 0.25).

SB623 cell implantation appeared to be safe and well tolerated, and patients implanted with SB623 experienced significant improvement from baseline motor status at 6 months compared to controls.

This study provides Class I evidence that implantation of SB623 was well tolerated and associated with improvement in motor status.
This study provides Class I evidence that implantation of SB623 was well tolerated and associated with improvement in motor status.
To investigate the association between EVT start time in acute ischemic stroke (AIS) and mid-term functional outcome.

This retrospective cohort study included all AIS cases treated with EVT from two stroke center registries from January 2012 to December 2018. The primary outcome was the score on the modified Rankin Scale (mRS) and the utility-weighted mRS (uw-mRS) at 90 days. A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention at a given EVT start time would lead to lower scores on the mRS (shift analysis).

One thousand five hundred fifty-eight cases were equally allotted into twelve EVT-start-time periods. The primary outcome favored EVT start times in the morning at 0800-1020 and 1020-1134 (common odds ratio (OR), 0.53; 95% confidence interval (CI), 0.38 to 0.75; P<0.001; OR, 0.62; 95% CI, 0.44 to 0.87; P=0.006, respectively), while it disfavored EVT start times at the end of the working day at 1555-1715 and 1855-2055 (OR, 1.47; 95% CI, 1.03 to 2.09; P=0.034; OR, 1.49; 95% CI, 1.03 to 2.15; P=0.033). Symptom onset-to-EVT start time was significantly higher and use of IV t-PA significantly lower between 1020-1134 (P<0.004 and P=0.012, respectively).

EVT for AIS in the morning leads to better mid-term functional outcome, while EVT at the end of the work day leads to poorer mid-term functional outcome. Neither difference in baseline factors, standard workflow and technical efficacy metrics could be identified as potential mediators of this effect.
EVT for AIS in the morning leads to better mid-term functional outcome, while EVT at the end of the work day leads to poorer mid-term functional outcome. Neither difference in baseline factors, standard workflow and technical efficacy metrics could be identified as potential mediators of this effect.
Nemaline myopathy (NM) is a rare neuromuscular condition with clinical and genetic heterogeneity. To establish disease natural history, we performed a cross-sectional study of NM, complemented by longitudinal assessment and exploration of pilot outcome measures.

Fifty-seven individuals with NM were recruited at 2 family workshops, including 16 examined at both time points. Participants were evaluated by clinical history and physical examination. Functional outcome measures included the Motor Function Measure (MFM), pulmonary function tests (PFTs), myometry, goniometry, and bulbar assessments.

The most common clinical classification was typical congenital (54%), whereas 42% had more severe presentations. Fifty-eight percent of individuals needed mechanical support, with 26% requiring wheelchair, tracheostomy, and feeding tube. The MFM scale was performed in 44 of 57 participants and showed reduced scores in most with little floor/ceiling effect. Of the 27 individuals completing PFTs, abnormal values wereomising outcome measures for future clinical trials.
To compare efficacy and safety of dulaglutide at doses of 3.0 and 4.5 mg versus 1.5 mg in patients with type 2 diabetes inadequately controlled with metformin.

Patients were randomly assigned to once-weekly dulaglutide 1.5 mg, 3.0 mg, or 4.5 mg for 52 weeks. The primary objective was determining superiority of dulaglutide 3.0 mg and/or 4.5 mg over 1.5 mg in HbA
reduction at 36 weeks. Secondary superiority objectives included change in body weight. Two estimands addressed efficacy objectives treatment regimen (regardless of treatment discontinuation or rescue medication) and efficacy (on treatment without rescue medication) in all randomly assigned patients.

Mean baseline HbA
and BMI in randomly assigned patients (
= 1,842) was 8.6% (70 mmol/mol) and 34.2 kg/m
, respectively. At 36 weeks, dulaglutide 4.5 mg provided superior HbA
reductions compared with 1.5 mg (treatment-regimen estimand -1.77 vs. -1.54% [-19.4 vs. -16.8 mmol/mol], estimated treatment difference [ETD] -0.24% (-2.6 mmol/mol),
glutide 1.5 mg to 3.0 mg or 4.5 mg provided clinically relevant, dose-related reductions in HbA1c and body weight with a similar safety profile.
To demonstrate the performance and safety of a bihormonal (insulin and glucagon) artificial pancreas (AP) in adults with type 1 diabetes.

In this outpatient, randomized, crossover trial, 2-week fully closed loop glucose control (AP therapy) was compared with 2-week open loop control (patient's normal insulin pump therapy with a glucose sensor if they had one).

A total of 23 patients were included in the analysis. CX-5461 Time in range (70-180 mg/dL [3.9-10 mmol/L]) was significantly higher during closed loop (median 86.6% of time [interquartile range 84.9-88.5]) compared with open loop (53.9% [49.7-67.2];
< 0.0001).

Compared with insulin pump therapy, the bihormonal AP provided superior glucose control, without meal or exercise announcements, and was safe in adults with type 1 diabetes.
Compared with insulin pump therapy, the bihormonal AP provided superior glucose control, without meal or exercise announcements, and was safe in adults with type 1 diabetes.
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