Tenecteplase With Concomitant Anticoagulation for Acute Respiratory Failure in Patients With COVID-19: A Randomized Controlled Trial.

Background Pulmonary thrombosis and thromboembolism play a significant role in the physiologic derangements seen in COVID-19 acute respiratory failure. The effect of thrombolysis with tenecteplase on patient outcomes is unknown. Methods We conducted a randomized, controlled, double-blind, phase II trial comparing tenecteplase versus placebo in patients with COVID-19 acute respiratory failure (NCT04505592). Patients with COVID-19 acute respiratory failure were randomized to tenecteplase 0.25 mg/kg or placebo in a 2:1 proportion. Both groups received therapeutic heparin for at least 72 hours. Results Thirteen patients were included in the trial. Eight patients were randomized to tenecteplase and five were randomized to placebo. At 28 days, 63% (n = 5) of patients assigned to the treatment group were alive and free from respiratory failure compared to 40% (n = 2) in the placebo arm (p = 0.43). Mortality at 28 days was 25% (n = 2) in the treatment arm and 20% (n = 1) in the control arm (p = 1.0). No patients in the treatment arm developed renal failure by 28 days compared to 60% (n = 3) in the placebo arm (p = 0.07). Major bleeding occurred in 25% (n = 2) of the treatment arm and 20% (n = 1) in the placebo arm; however, no patients in either arm experienced intracranial hemorrhage. Conclusions Tenecteplase with concomitant heparin may improve patient outcomes in patients with COVID-19 respiratory failure. As this study was limited by a small sample size, larger confirmatory studies are needed.

The profile of blunt traumatic infratentorial cranial bleed types.

Infratentorial traumatic intracranial bleeds (ICBs) are rare and the distribution of subtypes is unknown. To characterize this distribution the National Trauma Data Bank (NTDB) 2014 was queried for adults with single type infratentorial ICB, n = 1,821: subdural hemorrhage (SDH), subarachnoid hemorrhage (SAH), epidural hemorrhage (EDH), and intraparenchymal hemorrhage (IPH). Comparisons were made between the groups with statistical significance determined using chi squared and t-tests. SDH occurred in 29% of patients, mostly in elderly on anti-coagulants (13%) after a fall (77%), 42% of them underwent craniotomy, their mortality was the lowest (4%). SAH was the most common (56%) occurring mostly from traffic related injuries (27%). Furthermore, 9% of them had a severe head injury Glasgow Coma Scale ≤8 (GCS), but had the lowest Injury Severity Score (ISS, median 8) as well as a short hospital length of stay, 5.1 ±â€¯6.2 days. These patients were most likely to be discharged to home (64%). They had the lowest mortality (4%). EDH was the least common ICB (5%), occurred in younger patients (median age 49 years), and it had the highest percentage of associated injuries (13%). EDH patients presented with the poorest neurological status (26% GCS ≤8, ISS median 25) and were operated on more than any other ICB type (55%). EDH was the highest mortality (9%) ICB type and had a low discharge to home rate (58%). IPH was uncommon (10%). Infratentorial bleeds types have different clinical courses, and outcomes. Understanding these differences can be useful in managing these patients.

The profile of blunt traumatic supratentorial cranial bleed types.

The characteristics of blunt traumatic supratentorial cranial bleed (STCB) types have not been directly compared. The National Trauma Data Bank (NTDB) 2014 was queried for adults with an isolated single STCB n = 57,278. Patients were grouped by STCB categories: subdural (SDH), subarachnoid (SAH), epidural (EDH), intraparenchymal (IPH), and intraventricular hemorrhage (IVH). Frequency, demographics, clinical characteristics, procedures, and outcomes were compared among groups. SDH was the most common STCB (53%) and occurred mostly in elderly patients after a fall (78%), 30% underwent craniotomy and their mortality was 7%. SAH occurred in 32% of patients and carried the lowest mortality (3%). SAH were least likely to have a severe brain injury (7%), and had the lowest Injury Severity Score (ISS, median 8) and complication rate (1%), as well as the shortest hospital length of stay (HLOS, 4.6 ±â€¯6.4 days). EDH was uncommon (2%), occurred in younger patients (median 35 years), and had the highest percentage of traffic related injuries (28%). While EDH patients presented with the poorest neurological status (16% Glasgow Coma Scale ≤ 8, ISS median 18) and were operated on more than any other STCB type (51%), their mortality was lower (4%) and they had the highest discharge to home rate (71%). IVH was the least common (2%), but most lethal (9%) STCB type. These patients had the highest HLOS and intensive care unit LOS, and the lowest craniotomy rate (21%). STCB types have different clinical course, and outcomes. Understanding these differences can be useful in managing patients with STB.

Dynamic corticostriatal activity biases social bonding in monogamous female prairie voles.

Adult pair bonding involves dramatic changes in the perception and valuation of another individual. One key change is that partners come to reliably activate the brain's reward system, although the precise neural mechanisms by which partners become rewarding during sociosexual interactions leading to a bond remain unclear. Here we show, using a prairie vole (Microtus ochrogaster) model of social bonding, how a functional circuit from the medial prefrontal cortex to nucleus accumbens is dynamically modulated to enhance females' affiliative behaviour towards a partner. Individual variation in the strength of this functional connectivity, particularly after the first mating encounter, predicts how quickly animals begin affiliative huddling with their partner. Rhythmically activating this circuit in a social context without mating biases later preference towards a partner, indicating that this circuit's activity is not just correlated with how quickly animals become affiliative but causally accelerates it. These results provide the first dynamic view of corticostriatal activity during bond formation, revealing how social interactions can recruit brain reward systems to drive changes in affiliative behaviour.