Hemorrhage control prior to shock onset is increasingly recognized as a time-critical intervention. Although tourniquets (TQs) have been demonstrated to save lives, less is known about the physiologic parameters underlying successful TQ application beyond palpation of distal pulses. The current study directly visualized distal arterial occlusion via ultrasonography and measured associated pressure and contact force.

Fifteen tactical officers participated as live models for the study. Arterial occlusion was performed using a standard adult blood pressure (BP) cuff and a Combat Application Tourniquet Generation 7 (CAT7) TQ, applied sequentially to the left mid-bicep. Arterial flow cessation was determined by radial artery palpation and brachial artery pulsed wave doppler ultrasound (US) evaluation. Steady state maximal generated force was measured using a thin-film force sensor.

The mean (95% CI) systolic blood pressure (SBP) required to occlude palpable distal pulse was 112.9mmHg (109-117); contact force was 23.8N [Newton] (22.0-25.6). Arterial flow was visible via US in 100% of subjects despite lack of palpable pulse. The mean (95% CI) SBP and contact force to eliminate US flow were 132mmHg (127-137) and 27.7N (25.1-30.3). The mean (95% CI) number of windlass turns to eliminate a palpable pulse was 1.3 (1.0-1.6) while 1.6 (1.2-1.9) turns were required to eliminate US flow.

Loss of distal radial pulse does not indicate lack of arterial flow distal to upper extremity TQ. On average, an additional one-quarter windlass turn was required to eliminate distal flow. Blood pressure and force measurements derived in this study may provide data to guide future TQ designs and inexpensive, physiologically accurate TQ training models.

Ketamine is a rapidly-acting antidepressant treatment with robust response rates. Previous studies have reported that serial ketamine therapy modulates resting state functional connectivity in several large-scale networks, though it remains unknown whether variations in brain structure, function, and connectivity impact subsequent treatment success. We used a data-driven approach to determine whether pretreatment multimodal neuroimaging measures predict changes along symptom dimensions of depression following serial ketamine infusion.

Patients with depression (n = 60) received structural, resting state functional, and diffusion MRI scans before treatment. Depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HDRS-17), the Inventory of Depressive Symptomatology (IDS-C), and the Rumination Response Scale (RRS) before and 24 h after patients received four (0.5 mg/kg) infusions of racemic ketamine over 2 weeks. Nineteen unaffected controls were assessed at similar timepoints. Random forest regression models predicted symptom changes using pretreatment multimodal neuroimaging and demographic measures.

Two HDRS-17 subscales, the HDRS-6 and core mood and anhedonia (CMA) symptoms, and the RRS: reflection (RRSR) scale were predicted significantly with 19, 27, and 1% variance explained, respectively. Increased right medial prefrontal cortex/anterior cingulate and posterior insula (PoI) and lower kurtosis of the superior longitudinal fasciculus predicted reduced HDRS-6 and CMA symptoms following treatment. RRSR change was predicted by global connectivity of the left posterior cingulate, left insula, and right superior parietal lobule.

Our findings support that connectivity of the anterior default mode network and PoI may serve as potential biomarkers of antidepressant outcomes for core depressive symptoms.

Subanesthetic ketamine infusion therapy can produce fast-acting antidepressant effects in patients with major depression. How single and repeated ketamine treatment modulates the whole-brain functional connectome to affect clinical outcomes remains uncharacterized.

Data-driven whole brain functional connectivity (FC) analysis was used to identify the functional connections modified by ketamine treatment in patients with major depressive disorder (MDD). MDD patients (N = 61, mean age = 38, 19 women) completed baseline resting-state (RS) functional magnetic resonance imaging and depression symptom scales. Of these patients, n = 48 and n = 51, completed the same assessments 24 h after receiving one and four 0.5 mg/kg intravenous ketamine infusions. Healthy controls (HC) (n = 40, 24 women) completed baseline assessments with no intervention. Analysis of RS FC addressed effects of diagnosis, time, and remitter status.

Significant differences (p < 0.05, corrected) in RS FC were observed between HC and MDD at baseline in the somatomotor network and between association and default mode networks. These disruptions in FC in MDD patients trended toward control patterns with ketamine treatment. Furthermore, following serial ketamine infusions, significant decreases in FC were observed between the cerebellum and salience network (SN) (p < 0.05, corrected). Patient remitters showed increased FC between the cerebellum and the striatum prior to treatment that decreased following treatment, whereas non-remitters showed the opposite pattern.

Results support that ketamine treatment leads to neurofunctional plasticity between distinct neural networks that are shown as disrupted in MDD patients. Cortico-striatal-cerebellar loops that encompass the SN could be a potential biomarker for ketamine treatment.