Neutrophil-Lymphocyte ratio is associated with poor clinical outcome after mechanical thrombectomy in stroke in patients with COVID-19.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is emerging as an important biomarker of acute physiologic stress in a myriad of medical conditions, and is a confirmed poor prognostic indicator in COVID-19. OBJECTIVE: We sought to describe the role of NLR in predicting poor outcome in COVID-19 patients undergoing mechanical thrombectomy for acute ischemic stroke. METHODS: We analyzed NLR in COVID-19 patients with large vessel occlusion (LVO) strokes enrolled into an international 12-center retrospective study of laboratory-confirmed COVID-19, consecutively admitted between March 1, 2020 and May 1, 2020. Increased NLR was defined as ≥7.2. Logistic regression models were generated. RESULTS: Incidence of LVO stroke was 38/6698 (.57%). Mean age of patients was 62 years (range 27-87), and mortality rate was 30%. Age, sex, and ethnicity were not predictive of mortality. Elevated NLR and poor vessel recanalization (Thrombolysis in Cerebral Infarction (TICI) score of 1 or 2a) synergistically predicted poor outcome (likelihood ratio 11.65, p = .003). Patients with NLR > 7.2 were 6.8 times more likely to die (OR 6.8, CI95% 1.2-38.6, p = .03) and almost 8 times more likely to require prolonged invasive mechanical ventilation (OR 7.8, CI95% 1.2-52.4, p = .03). In a multivariate analysis, NLR > 7.2 predicted poor outcome even when controlling for the effect of low TICI score on poor outcome (NLR p = .043, TICI p = .070). CONCLUSIONS: We show elevated NLR in LVO patients with COVID-19 portends significantly worse outcomes and increased mortality regardless of recanalization status. Severe neuro-inflammatory stress response related to COVID-19 may negate the potential benefits of successful thrombectomy.

Cangrelor dose titration using platelet function testing during cerebrovascular stent placement.

BACKGROUND: Optimal antiplatelet inhibition is vital during cerebrovascular stenting procedures, yet no standardized recommendation exists for antithrombotic therapy in these scenarios. Cangrelor is an intravenous P2Y12 inhibitor with a favorable pharmacokinetic profile for use during neuroendovascular stenting. METHODS: A retrospective review of all neuroendovascular patients who underwent stenting between 1 January 2019 and 22 March 2020 and were treated with cangrelor was conducted. Thirty-seven patients met inclusion criteria. RESULTS: All patients were administered a bolus of 5 mcg/kg of cangrelor followed by a maintenance infusion. Antiplatelet effects of cangrelor were monitored using platelet reactivity units (PRU). Based on the initial PRU, seven patients' doses were adjusted with subsequent PRUs in or near the goal range of 50-150. One patient experienced an acute intraprocedural occlusion likely related to a subtherapeutic PRU which subsequently resolved with cangrelor dose adjustment and intra-arterial tirofiban administration, and one patient experienced a post-procedure stent occlusion which required a thrombectomy and intra-arterial tirofiban administration. No hemorrhagic complications occurred. DISCUSSION: Cangrelor utilization during neuroendovascular stenting with maintenance doses of <2 mcg/kg/min with dose adjustments based on platelet function testing has not been previously described. Cangrelor presents many advantages compared to standard therapy in patients undergoing stent placement related to its pharmacokinetic profile, rapid onset of action, ease of transition to oral P2Y12 antiplatelet agents, and measurability. CONCLUSION: Cangrelor is a promising alternative to currently available therapies, especially in patients with a high hemorrhagic risk.

Incidence, Characteristics and Outcomes of Large Vessel Stroke in COVID-19 Cohort: An International Multicenter Study.

BACKGROUND: While there are reports of acute ischemic stroke (AIS) in coronavirus disease 2019 (COVID-19) patients, the overall incidence of AIS and clinical characteristics of large vessel occlusion (LVO) remain unclear. OBJECTIVE: To attempt to establish incidence of AIS in COVID-19 patients in an international cohort. METHODS: A cross-sectional retrospective, multicenter study of consecutive patients admitted with AIS and COVID-19 was undertaken from March 1 to May 1, 2020 at 12 stroke centers from 4 countries. Out of those 12 centers, 9 centers admitted all types of strokes and data from those were used to calculate the incidence rate of AIS. Three centers exclusively transferred LVO stroke (LVOs) patients and were excluded only for the purposes of calculating the incidence of AIS. Detailed data were collected on consecutive LVOs in hospitalized patients who underwent mechanical thrombectomy (MT) across all 12 centers. RESULTS: Out of 6698 COVID-19 patients admitted to 9 stroke centers, the incidence of stroke was found to be 1.3% (interquartile range [IQR] 0.75%-1.7%). The median age of LVOs patients was 51 yr (IQR 50-75 yr), and in the US centers, African Americans comprised 28% of patients. Out of 66 LVOs, 10 patients (16%) were less than 50 yr of age. Among the LVOs eligible for MT, the average time from symptom onset to presentation was 558 min (IQR 82-695 min). A total of 21 (50%) patients were either discharged to home or discharged to acute rehabilitation facilities. CONCLUSION: LVO was predominant in patients with AIS and COVID-19 across 2 continents, occurring at a significantly younger age and affecting African Americans disproportionately in the USA.

Simultaneous revascularization of the occluded internal carotid artery using the Solitaire as a workhorse wire during acute ischemic stroke intervention.

INTRODUCTION: Tandem lesions involving a large vessel occlusion intracranially with concomitant cervical carotid critical stenosis or occlusion are a common presentation of acute ischemic stroke. These lesions are both challenging and time-consuming but can be extremely beneficial for patients when successful. We present a technique utilizing the pusher wire of the stent retriever used for intracranial thrombectomy as the workhorse wire for carotid intervention using a monorail system to perform cervical carotid angioplasty. METHODS: We reviewed four successive patients who presented with a tandem occlusion and underwent thrombectomy and simultaneous carotid artery intervention using this technique. RESULTS: All four patients had radiographically successful intracranial thrombectomy and cervical carotid revascularization. Time from groin puncture to intracranial stent retriever deployment was 63 min on average. Then, using the pusher wire as a monorail workhorse, time from stent retriever deployment to carotid angioplasty was on average 6 min. DISCUSSION: This technique allows for cervical carotid revascularization to begin during the recommended 5-min wait time after stent retriever deployment, allowing for rapid near-simultaneous revascularization across both lesions. This technique has been reported briefly in the past for management of a cervical dissection. There is continued debate regarding the management of tandem occlusions, as to which lesion should be managed first. CONCLUSION: As the management paradigms of tandem occlusions continue to evolve, this technique may improve outcomes by expediting endovascular intervention. Using the stent retriever wire provides a method of expediting the management of the proximal lesion after addressing the more distal intracranial occlusion first.

Contrast enhancement of chronic subdural hematomas after embolization of the middle meningeal artery.

Chronic subdural hematomas are a common neurosurgical presentation. They are difficult to treat, and current interventions - namely surgical evacuation - are not without complications or recurrences. Embolization of the middle meningeal artery is a promising new treatment option for this pathology. We have noted an interesting phenomenon in our patients following endovascular embolization, which is that the subdural hematoma is stained with contrast following the procedure. This ties into the basic physiology of chronic subdurals, which parasitize the middle meningeal artery during the process of membrane formation and neovascularization, which has previously been reported.

Pokeweed antiviral protein depurinates the sarcin/ricin loop of the rRNA prior to binding of aminoacyl-tRNA to the ribosomal A-site.

Ribosome-inactivating proteins, such as the pokeweed antiviral protein (PAP), inhibit translation by depurinating the conserved sarcin/ricin loop of the large ribosomal RNA. Depurinated ribosomes are unable to bind elongation factor 2, and, thus, the translocation step of the elongation cycle is inhibited. Though the consequences of depurination are well characterized, the ribosome conformation required for depurination to take place has not been described. In this report, we correlate biochemical and genetic data to conclude that pokeweed antiviral protein depurinates the sarcin/ricin loop when the A-site of the ribosomal peptidyl-transferase center is unoccupied. We show that prior incubation of ribosomes with puromycin, an analog of the 3'-terminus of aminoacyl-tRNA, inhibits both binding and depurination by PAP in a concentration-dependent manner. Expression of PAP in the yeast strain mak8-1 results in little depurination unless the cells are lysed, a process that would promote loss of aminoacyl-tRNA from the ribosome. The mak8-1 strain is known to exhibit a higher affinity for aminoacyl-tRNA compared with wild-type cells, and therefore, its ribosomes are more resistant to PAP in vivo. These data contribute to the mechanism of action of pokeweed antiviral protein; specifically, they have uncovered the ribosomal conformation required for depurination that leads to subsequent translation inhibition.