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Leonid I. Groysman, Benjamin A. Emanuel, May A. Kim-Tenser, Gene Y. Sung, and William J. Mack

Induced hypothermia has been used for neuroprotection in cardiac and neurovascular procedures. Experimental and translational studies provide evidence for its utility in the treatment of ischemic cerebrovascular disease. Over the past decade, these principles have been applied to the clinical management of acute stroke. Varying induction methods, time windows, clinical indications, and adjuvant therapies have been studied. In this article the authors review the mechanisms and techniques for achieving therapeutic hypothermia in the setting of acute stroke, and they outline pertinent side effects and complications. The manuscript summarizes and examines the relevant clinical trials to date. Despite a reasonable amount of existing data, this review suggests that additional trials are warranted to define the optimal time window, temperature regimen, and precise clinical indications for induction of therapeutic hypothermia in the setting of acute stroke.

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Timothy Wen, Shuhan He, Frank Attenello, Steven Y. Cen, May Kim-Tenser, Peter Adamczyk, Arun P. Amar, Nerses Sanossian, and William J. Mack


As health care administrators focus on patient safety and cost-effectiveness, methodical assessment of quality outcome measures is critical. In 2008 the Centers for Medicare and Medicaid Services (CMS) published a series of “never events” that included 11 hospital-acquired conditions (HACs) for which related costs of treatment are not reimbursed. Cerebrovascular procedures (CVPs) are complex and are often performed in patients with significant medical comorbidities.


This study examines the impact of patient age and medical comorbidities on the occurrence of CMS-defined HACs, as well as the effect of these factors on the length of stay (LOS) and hospitalization charges in patients undergoing common CVPs.


The HACs occurred at a frequency of 0.49% (1.33% in the intracranial procedures and 0.33% in the carotid procedures). Falls/trauma (n = 4610, 72.3% HACs, 357 HACs per 100,000 CVPs) and catheter-associated urinary tract infections (n = 714, 11.2% HACs, 55 HACs per 100,000 CVPs) were the most common events. Age and the presence of ≥ 2 comorbidities were strong independent predictors of HACs (p < 0.0001). The occurrence of HACs negatively impacts both LOS and hospital costs. Patients with at least 1 HAC were 10 times more likely to have prolonged LOS (≥ 90th percentile) (p < 0.0001), and 8 times more likely to have high inpatient costs (≥ 90th percentile) (p < 0.0001) when adjusting for patient and hospital factors.


Improved quality protocols focused on individual patient characteristics might help to decrease the frequency of HACs in this high-risk population. These data suggest that risk adjustment according to underlying patient factors may be warranted when considering reimbursement for costs related to HACs in the setting of CVPs.

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Ben A. Strickland, Giuseppe Barisano, Aidin Abedi, Mark S. Shiroishi, Steven Cen, Benjamin Emanuel, Sebina Bulic, May Kim-Tenser, Peggy Nguyen, Steven L. Giannotta, William Mack, and Jonathan Russin


Aneurysmal subarachnoid hemorrhage (aSAH)–induced vasospasm is linked to increased inflammatory cell trafficking across a permeable blood-brain barrier (BBB). Elevations in serum levels of matrix metalloprotease 9 (MMP9), a BBB structural protein, have been implicated in the pathogenesis of vasospasm onset. Minocycline is a potent inhibitor of MMP9. The authors sought to detect an effect of minocycline on BBB permeability following aSAH.


Patients presenting within 24 hours of symptom onset with imaging confirmed aSAH (Fisher grade 3 or 4) were randomized to high-dose (10 mg/kg) minocycline or placebo. The primary outcome of interest was BBB permeability as quantitated by contrast signal intensity ratios in vascular regions of interest on postbleed day (PBD) 5 magnetic resonance permeability imaging. Secondary outcomes included serum MMP9 levels and radiographic and clinical evidence of vasospasm.


A total of 11 patients were randomized to minocycline (n = 6) or control (n = 5) groups. No adverse events or complications attributable to minocycline were reported. High-dose minocycline administration was associated with significantly lower permeability indices on imaging analysis (p < 0.01). There was no significant difference with respect to serum MMP9 levels between groups, although concentrations trended upward in both cohorts. Radiographic vasospasm was noted in 6 patients (minocycline = 3, control = 3), with only 1 patient developing symptoms of clinical vasospasm in the minocycline cohort. There was no difference between cohorts with respect to Lindegaard ratios, transcranial Doppler values, or onset of vasospasm.


Minocycline at high doses is well tolerated in the ruptured cerebral aneurysm population. Minocycline curtails breakdown of the BBB following aSAH as evidenced by lower permeability indices, though minocycline did not significantly alter serum MMP9 levels. Larger randomized clinical trials are needed to assess minocycline as a neuroprotectant against aSAH-induced vasospasm.

Clinical trial registration no.: NCT04876638 (