Neutrophil-to-Lymphocyte Ratios and Infections after Traumatic Brain Injury: Associations with Hospital Resource Utilization and Long-Term Outcome.

Traumatic brain injury (TBI) induces immune dysfunction that can be captured clinically by an increase in the neutrophil-to-lymphocyte ratio (NLR). However, few studies have characterized the temporal dynamics of NLR post-TBI and its relationship with hospital-acquired infections (HAI), resource utilization, or outcome. We assessed NLR and HAI over the first 21 days post-injury in adults with moderate-to-severe TBI (n = 196) using group-based trajectory (TRAJ), changepoint, and mixed-effects multivariable regression analysis to characterize temporal dynamics. We identified two groups with unique NLR profiles: a high (n = 67) versus a low (n = 129) TRAJ group. High NLR TRAJ had higher rates (76.12% vs. 55.04%, p = 0.004) and earlier time to infection (p = 0.003). In changepoint-derived day 0-5 and 6-20 epochs, low lymphocyte TRAJ, early in recovery, resulted in more frequent HAIs (p = 0.042), subsequently increasing later NLR levels (p ≤ 0.0001). Both high NLR TRAJ and HAIs increased hospital length of stay (LOS) and days on ventilation (p ≤ 0.05 all), while only high NLR TRAJ significantly increased odds of unfavorable six-month outcome as measured by the Glasgow Outcome Scale (GOS) (p = 0.046) in multivariable regression. These findings provide insight into the temporal dynamics and interrelatedness of immune factors which collectively impact susceptibility to infection and greater hospital resource utilization, as well as influence recovery.

Portable Neuromonitoring Device Detects Large Vessel Occlusion in Suspected Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Early detection of large vessel occlusion (LVO) stroke optimizes endovascular therapy and improves outcomes. Clinical stroke severity scales used for LVO identification have variable accuracy. We investigated a portable LVO-detection device (PLD), using electroencephalography and somatosensory-evoked potentials, to identify LVO stroke. METHODS: We obtained PLD data in suspected patients with stroke enrolled prospectively via a convenience sample in 8 emergency departments within 24 hours of symptom onset. LVO discriminative signals were integrated into a binary classifier. The National Institutes of Health Stroke Scale was documented, and 4 prehospital stroke scales were retrospectively calculated. We compared PLD and scale performance to diagnostic neuroimaging. RESULTS: Of 109 patients, there were 25 LVO (23%), 38 non-LVO ischemic (35%), 14 hemorrhages (13%), and 32 stroke mimics (29%). The PLD had higher sensitivity (80% [95% CI, 74-85]) and similar specificity (80% [95% CI, 77-83]) to all prehospital scales at their predetermined high probability LVO thresholds. The PLD had high discrimination for LVO (C-statistic=0.88). CONCLUSIONS: The PLD identifies LVO with superior accuracy compared with prehospital stroke scales in emergency department suspected stroke. Future studies need to validate the PLD's potential as an LVO triage aid in prehospital undifferentiated stroke populations.

Asymmetric hydroformylation-initiated tandem sequences for syntheses of (+)-patulolide C, (-)-pyrenophorol, (+)-decarestrictine L, and (+)-prelog djerassi lactone.

Four different Rh-catalyzed asymmetric hydroformylation (AHF) tandem reactions have been developed in the context of the total syntheses of (+)-patulolide C, (-)-pyrenophorol, (+)-decarestrictine L, and (+)-Prelog-Djerassi lactone. A total synthesis of (+)-patulolide C has been accomplished in three steps utilizing a Rh(I)-catalyzed Z-selective anti-Markovnikov hydroacetoxylation of a known alkyne to give a Z-enol acetate with excellent selectivity. An AHF/intramolecular Wittig olefination cascade was utilized to set the C4-hydroxyl stereochemistry, E-olefin geometry, and form the macrolactone. In addition, both (-)-pyrenophorol and (+)-decarestrictine L have been synthesized from the enantiomeric (4R)- and (4S)-4-(tert-butyldimethylsiloxy)-1-pentyne in five and four steps, respectively. These syntheses feature Ru(II)-catalyzed Z-selective anti-Markovnikov hydroacetoxylation of terminal alkynes followed by AHF/Wittig olefination sequences to rapidly establish functionality and stereogenicity. A synthesis of (+)-Prelog-Djerassi lactone was accomplished in three isolations from the known 1-vinyl-4-methyl-2,6,7-trioxabicyclo[2.2.2]octane ortho ester. An AHF/crotylation tandem sequence has been developed to set the C2-C4 stereochemistry. An asymmetric hydrogenation was employed to set the C6 stereochemistry, resulting in an especially efficient enantioselective synthesis from achiral starting material. In summary, these syntheses have greatly improved efficiency in terms of atom-economy, catalytic stereoselective transformations, inexpensive reagents, step-counts, and overall yield when compared with previous synthetic attempts.