Delayed hypersensitivity reaction to a dural repair substitute.

BACKGROUND: Modern neurosurgeons commonly rely on dural grafts to aid in obtaining watertight closures when the native dura itself cannot be approximated. CASE PRESENTATION: We present a patient who developed a symptomatic, delayed hypersensitivity reaction to a cellulose-based synthetic dural graft, which resolved after reoperation and removal of the graft. DISCUSSION: Dural grafts are a safe and common implant utilized in neurosurgery. Nevertheless, as with all implanted material, there is a chance for symptomatic immune reactions to occur. CONCLUSION: This type of response is exceedingly uncommon, but recognition of this rare presentation may help other providers recognize it in the future.

Neurosurgical management of vascular compression presenting as visual symptoms secondary to elongated styloid processes (Eagle syndrome).

BACKGROUND: Eagle syndrome (ES) was first described in 1937, to characterize elongation of the styloid process. It is rarely encountered by neurosurgeons but does present the potential for vascular sequelae and neurological complications. DEMONSTRATIVE CASES: We discuss three patients with uncommon presentations of neurovascular compromise with uncommon symptomatology, secondary to ES. Their management ranged from retrospective diagnoses following self-limited events, antiplatelet therapy, and endovascular and surgical interventions. DISCUSSION: While traumatic fractures, chiropractic manipulation, and history of prior neck surgery have been implicated as the etiologies for ES, congenital cases are common. The styloid process intimately interplays with adjacent neurovascular and nervous structures; its elongation can cause symptoms in 10% of patients. CONCLUSION: Awareness of this potentially dangerous but rare disease - more commonly seen by our otolaryngology colleagues - may help reduce diagnostic delays when an elongated styloid process is the cause, as surgery may be required.

Environmental and Occupational Exposures and Amyotrophic Lateral Sclerosis in New England.

BACKGROUND: Recent data provide support for the concept that potentially modifiable exposures are responsible for sporadic amyotrophic lateral sclerosis (ALS). OBJECTIVE: To evaluate environmental and occupational exposures as risk factors for sporadic ALS. METHODS: We performed a case-control study of ALS among residents of New England, USA. The analysis compared questionnaire responses from 295 patients with a confirmed ALS diagnosis to those of 225 controls without neurodegenerative illness. RESULTS: Self-reported job- or hobby-related exposure to one or more chemicals, such as pesticides, solvents, or heavy metals, increased the risk of ALS (adjusted OR 2.51; 95% CI 1.64-3.89). Industries with a higher toxicant exposure potential (construction, manufacturing, mechanical, military, or painting) were associated with an elevated occupational risk (adjusted OR 3.95; 95% CI 2.04-8.30). We also identified increases in the risk of ALS associated with frequent participation in water sports, particularly waterskiing (adjusted OR 3.89; 95% CI 1.97-8.44). Occupation and waterskiing both retained independent statistical significance in a composite model containing age, gender, and smoking status. CONCLUSIONS: Our study contributes to a growing body of literature implicating occupational- and hobby-related toxicant exposures in ALS etiology. These epidemiologic study results also provide motivation for future evaluation of water-body-related risk factors.

The Epidemiology of Amyotrophic Lateral Sclerosis in New Hampshire, USA, 2004-2007.

BACKGROUND/AIMS: Trends in disease incidence and mortality can provide clues to disease etiology. Previously, we described a town in New Hampshire (N.H.), USA, with 25 times the expected incidence rate of amyotrophic lateral sclerosis (ALS). This study aimed to describe the incidence and mortality of ALS across the state to assess rates relative to other states and industrialized nations. METHOD: A retrospective review of records from regional ALS centers, clinics and ALS organizations was conducted to obtain demographics and diagnostic details for patients diagnosed with ALS or primary lateral sclerosis in N.H. from January 2004 to December 2007. Data on mortality from review of death certificates were obtained for a similar time frame. RESULTS: We identified 113 N.H. residents diagnosed with ALS in 2004-2007, yielding an age-standardized incidence rate ranging from 1.3 to 2.2 per 100,000 of the population per year. During the same period, the standardized mortality rate per 100,000 varied from 2.6 to 3.5. ALS was more common among men (ratio 1.6:1), who were more likely than women to have an earlier age at onset (59 ± 14.2 vs. 65 ± 11.8 years, p = 0.01). CONCLUSION: While localized areas in N.H. with high ALS incidence rates have been reported previously, the overall incidence and mortality rates of ALS in N.H. are similar to those in other industrialized nations.

Multicenter early United States feasibility study and periprocedural safety of LVIS EVO for the treatment of unruptured intracranial aneurysms.

BACKGROUND: Stent development has focused recently on low-profile, self-expandable stents compatible with 0.0165 inch microcatheters. The LVIS EVO is the second-generation version of the Low-Profile Visualized Intraluminal Support (LVIS) with improved visibility and resheathability. The LVIS EVO underwent a limited premarket release (PMR) in December 2023. This study aims to report the early safety and feasibility experience with the LVIS EVO stent for the treatment of intracranial aneurysms in the United States (US). METHODS: This was a multicenter, retrospective, observational study evaluating patients who underwent treatment of an intracranial aneurysm with an LVIS EVO stent after the limited PMR. All physicians who had placed an LVIS EVO stent were asked to input their cases after institutional review board approval was obtained. The data were then sent to a single center for analysis. Any patient aged 18 years or older who underwent treatment of an intracranial aneurysm with a LVIS EVO stent in the US was included from the initial PMR in December 2023 until April 2024. Patient age (or ≤90 years old), sex, preoperative modified Rankin Scale (mRS), aneurysm location, aneurysm measurements, and information about preoperative antiplatelet management were all collected. Data on periprocedural complications, 30-day mortality, discharge mRS, and length of stay were also collected. RESULTS: Some 53 patients with 55 aneurysms underwent treatment with the LVIS EVO stent at 15 institutions. All aneurysms were unruptured. The most common location was the anterior communicating artery (35%) followed by the middle cerebral artery bifurcation (31%). All patients were on dual antiplatelet therapy. The average aneurysm size was 5.2 mm with a neck size of 3.7 mm. The smallest distal parent vessel size was 1.2 mm and 36% of stents were deployed in distal parent vessels <2 mm. All (100%) cases had successful deployment and the stent was repositioned in 10% of cases. A single stent was utilized in 91% of cases. Coils were placed in 48 cases (87.2%) and a microcatheter was jailed in 98% of those cases. Immediate Raymond Roy (RR) Class I occlusion was obtained in 33%, Class II in 22%, Class IIIa in 37%, and Class IIIb in 8% of cases. There were no delayed thromboembolic or hemorrhagic complications. CONCLUSIONS: The LVIS EVO is a braided, self-expanding, retrievable stent with enhanced visibility and smaller cell size. The drawn filled tube (DFT) technology results in improved visibility of the stent, allowing for more controlled stent positioning and visualization of vessel wall apposition. All cases in our series had complete neck coverage and good wall apposition. There were no thromboembolic or hemorrhagic complications.

Spatial analysis of amyotrophic lateral sclerosis in Northern New England, USA, 1997-2009.

INTRODUCTION: An environmental trigger of sporadic amyotrophic lateral sclerosis (ALS) is supported by geographic disparities in ALS incidence and development of the disease in conjugal couples. This study aims to investigate the incidence of ALS in the Northern New England states of New Hampshire (NH), Vermont (VT), and Maine (ME). METHODS: We reviewed medical records and community databases to identify dwelling addresses of 688 patients diagnosed with ALS in 1997-2009 in NH, VT, and ME. We used spatial analysis to identify clusters of census block groups with statistically significant high incidence. RESULTS: We identified 11 clusters of statistically significant high incidence, each containing 6 or more cases of ALS. These 11 clusters are grouped in 4 distinct regions. CONCLUSIONS: There appear to be areas of significant spatial clustering within Northern New England. Further analysis will be needed to confirm whether there is any correlation between these areas and potential environmental risk factors.

Artificial intelligence improves transfer times and ischemic stroke workflow metrics.

INTRODUCTION: Rapid initiation of mechanical thrombectomy (MT) for the treatment of large-vessel occlusion (LVO) critically improves patient outcomes. Artificial intelligence algorithms aid in the identification of LVOs and improve door to puncture times as well as patient transfer times. OBJECTIVES: We aimed to determine whether the implementation of an LVO detection algorithm that provides immediate active notification to the thrombectomy team provider's cell phone would improve ischemic stroke workflow at our institution and aid in patient transfer from outlying hospitals when compared to our prior system of passive computed tomography perfusion software analysis and radiologist interpretation and notification. METHODS: A retrospective review of our institutional thrombectomy registry was performed for all patients who underwent MT between January 2020 and March 2022. Demographic, radiographic, and stroke workflow metrics and notification times were collected. Transfer times and stroke metrics were compared pre- and post-implementation of the Viz.ai (Viz.ai, San Francisco, California, USA) smartphone application. RESULTS: Two hundred sixty-two patients underwent MT during the study period. Door-to-puncture time decreased 15 min (p = 0.009) after the implementation of Viz.ai at our Comprehensive Stroke Center. Transfer time from outside hospitals that implemented Viz.ai was reduced by 37 min (p = 0.04). There was no significant change in transfer time over the same time period in outlying hospitals that did not implement the Viz.ai software. CONCLUSION: Active notification of the neurosurgical team significantly reduces patient transfer time and initiation of MT.

Use of intravenous cangrelor in the treatment of ruptured and unruptured cerebral aneurysms: an updated single-center analysis and pooled analysis of current studies.

BACKGROUND: Intracranial stent placement for the treatment of cerebral aneurysms is increasingly utilized in both ruptured and unruptured scenarios. Intravenous (IV) cangrelor is a relatively new antiplatelet agent that was initially approved for coronary interventions. In addition to our institution, five other centers have published their results using IV cangrelor in neurointerventional procedures. This article combines the aneurysm treatment data from all prior studies to provide insight into the safety and efficacy of cangrelor for intracranial aneurysm treatment. METHODS: A prospectively maintained database was reviewed to identify all cases of IV cangrelor administration during aneurysm embolization. 20 additional patients were identified who had not been previously published. In addition, a literature search was performed to identify prior publications regarding cangrelor in neurointervention. The data from these were combined with our institutional results in a pooled-analysis. RESULTS: Overall, 85 patients who received IV cangrelor during aneurysm embolization were identified, including 46 ruptured and 39 unruptured cases. The asymptomatic and symptomatic intracranial hemorrhage rates were 4% (2/46) for ruptured cases and 2.6% (1/39) for unruptured cases. The rate of retroperitoneal hematoma and gastrointestinal bleeding was 0%. There were no incidents of intraprocedural thromboembolic complication or intraprocedural in-stent thrombosis in either cohort. One subject suffered an ischemic stroke at 24 hours secondary to in-stent thrombosis in a ruptured case. CONCLUSIONS: IV cangrelor during aneurysm embolization appears to be safe, with a symptomatic intracranial hemorrhage rate of 4% in ruptured cases and 2.6% in unruptured cases. More research is needed to determine the ideal dosing regimen.

Comparison of pipeline embolization device, flow re-direction endoluminal device and surpass flow diverters in the treatment of intracerebral aneurysms.

OBJECTIVES: The use of flow diversion for the treatment of intracranial aneurysms has gained broad acceptance. Three flow-diverting stents are approved by the Food and Drug Administration for use in the United States. We sought to compare the outcomes and safety profiles between the three devices at our institution. METHODS: A retrospective review of aneurysms treated with pipeline embolization device (PED), flow re-direction endoluminal device (FRED), and SURPASS was performed for aneurysms treated between 2018 and 2022 at our institution. RESULTS: The study cohort consisted of 142 patients. Precisely, 86 aneurysms were treated with a pipeline, 33 aneurysms were treated with FRED, and 23 aneurysms were treated with SURPASS. The 1-year complete occlusion rates were 59.4%, 60%, and 65%, respectively (0.91). Linear regression models found that only adjunctive coiling predicted aneurysm occlusion at 6 months (p = 0.02), but this effect was lost at 1 year and beyond. There was no significant difference in acute thrombotic or acute hemorrhagic complications between the three cohorts. There was a higher rate of delayed hemorrhagic complications in the SURPASS cohort (10%) compared to the PED (1.3%) and FRED (0%) cohorts (p = 0.04). There was also a higher rate of in-stent stenosis in the SURPASS cohort (20%) compared to the PED (5%) and FRED (3.1%) cohorts (p < 0.01). CONCLUSIONS: Treatment with PED, FRED, and SURPASS all resulted in similar complete occlusion rates at 6 months and 1 year. SURPASS was associated with higher in-stent stenosis as well as delayed hemorrhagic complications. Additional future studies evaluating the newest generation of flow-diverting stents with long-term follow-up will be necessary to make any definitive conclusions.

Drainage, Irrigation, and Fibrinolytic Therapy (DRIFT) for Adult Intraventricular Hemorrhage Associated with Primary Hypertensive Hemorrhages Using IRRAflow Self-Irrigating Catheter: A Report of Three Cases and Prior Historical Controls.

BACKGROUND: Spontaneous primary intracerebral hemorrhage (ICH) accounts for 10%-15% of strokes and is accompanied by ventricular involvement in 10%-30% of cases. Intraventricular hemorrhage (IVH) is a poor prognostic factor and the current treatment paradigm of external ventricular drainage requires frequent flushing and replacement. Given the documented high rate of failure standard EVD catheters, we sought to determine if the use of the IRRAflow system with the addition of alteplase would be beneficial in this patient population for the treatment of IVH associated with primary hypertensive ganglionic hemorrhages. METHODS: Three patients with ganglionic hemorrhages and IVH underwent treatment with the IRRAflow system at our institution from December 2022 to January 2023. A retrospective review was then performed of patients with primary hypertensive ganglionic hemorrhages and EVD placement at our institution from January 2021 to present day. RESULTS: Three patients underwent treatment with the IRRAflow system and continuous lavage of Tissue Plasminogen Activator (tPA). The IVH was efficiently cleared in all cases and the drains were removed within 8 days in all cases. No patients required replacement of the drain and there were no hemorrhagic complications noted. In our retrospective review, 28 patients were identified who underwent placement of a standard EVD for the treatment of primary hypertensive ganglionic hemorrhages. When patients who had early withdrawal of care were excluded, the average length of EVD treatment was 11.3 days and the EVD replacement rate was 24%. CONCLUSIONS: We demonstrate here that the use of the IRRAflow system for the treatment of primary hypertensive hemorrhages with IVH results in rapid clearance of the IVH without safety concerns. Compared to historical controls there was a decrease in EVD duration, EVD replacement and, ICU LOS.

The Enterprise stent still useful after all these years.

BACKGROUND: The Enterprise stent (Codman Neuro, Massachusetts, USA) received Food and Drug Administration (FDA) approval in 2007 for stent-assisted coiling (SAC). Since its introduction, newer stents and devices for aneurysm treatment have been developed resulting in a shift in the utilization of this stent from SAC to other off-label indications. OBJECTIVE: To describe our experience with the Enterprise stent being used for SAC and other off-label indications. METHODS: This is a multi-center retrospective review of the use of the Enterprise stent between 2018 and 2023. All patients in which the Enterprise stent was successfully deployed were included in the study. RESULTS: Our study cohort comprised of 194 patients, mostly females (n = 112, 57.7%), with a mean age of 63.2 years ± 14.3. The Enterprise stent was used for SAC in only 24 (12.4%) patients and was used for rescue stenting in stroke in 101 patients (52.1%), treatment of intracranial stenosis in 53 patients (27.3%), treatment of in-stent stenosis in 1 patient (0.5%), and for treatment of dissections in 15 patients (7.7%). From 2018 to 2023, the use of Enterprise stents for SAC significantly decreased (p < 0.0001) while the use of Enterprise stents for non-SAC purposes was insignificantly variable (p = 0.05). CONCLUSION: Our study shows that the Enterprise stent remains a reliable tool in neuroendovascular procedures, even if its original intended use has been supplanted by other devices.

Spatial clustering of amyotrophic lateral sclerosis and the potential role of BMAA.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative syndrome which has no known cause, except for a small proportion of cases which are genetically inherited. The development of ALS likely involves both genetic and environmental risk factors. Environmental risk factors implicated in ALS have included heavy metals, trauma, pesticides, electrical injuries, electromagnetic radiation and the cyanobacterial-derived neurotoxin beta-N-methylamino-L-alanine (BMAA). To investigate possible environmental risks, a number of epidemiological studies of ALS have been conducted. Some of these studies employ spatial analysis techniques that examine for spatial clusters of ALS and can help guide further research into identifying environmental exposures. Despite identifying geographical disparities in the distribution of ALS cases, these studies have not provided any clear associations with environmental factors. We review the literature on important studies of spatial clustering of ALS and explore the hypothesized link between the neurotoxin BMAA and ALS.

Comparison of hydrogel coils versus bare platinum coils for the treatment of anterior communicating artery aneurysms.

INTRODUCTION: While endovascular coiling has been shown to be a safe treatment option for intracranial aneurysms, there remains concern regarding increased recurrence and retreatment rates. Preliminary studies evaluating hydrogel coated coils have demonstrated decreased recurrence rates compared to bare metal coils. METHODS: A retrospective chart review was done on all patients with anterior communicating artery aneurysms (ACoAAs) treated with endovascular coiling between 2014 and 2018. Treatment groups were divided into hydrogel coated coils or bare metal coils. Patients were categorized into the hydrogel group when ≥ 70% of the coil length was hydrogel coated. RESULTS: Eighty-four ACoAAs were treated with coil embolization between 2014 and 2018. Postoperative imaging was available for 68 patients. Twenty-six patients were categorized into the hydrogel treatment group. Aneurysm recurrence was seen in 7.7% (2/26) of patients treated with hydrogel coated coils compared to 33.3% (14/42) of those treated with bare metal coils (P = 0.03). Subanalysis of patients with ruptured aneurysms revealed decreased recurrence rates in patients treated with hydrogel coated coils at 5.9% (1/17) compared to patients treated with bare metal coils at 39.4% (13/33) (P = 0.01). CONCLUSIONS: Hydrogel-coated coils may reduce recurrence rates in the treatment of both ruptured and unruptured ACoAAs.

Developing a fast-track discharge protocol for patients with cerebral aneurysms treated via neuroendovascular techniques.

INTRODUCTION: As we emerge from the current pandemic, hospitals, staff, and resources will need to continue to adjust to meet ongoing healthcare demands. Lessons learned during past shortages can be used to optimize peri-procedural protocols to safely improve the utilization of hospital resources. METHODS: Retrospective review of patients who underwent elective endovascular intracranial aneurysm treatment was performed. Multivariable logistic regression was used to identify factors associated with patients who were able to be discharged within 24 h of elective procedures. Rates of complications (particularly readmission) were determined. RESULTS: 330 patients underwent elective endovascular aneurysm treatment with 86 (26.1%) discharged within 24 h. Factors associated with earlier discharge included procedure years (2019-2021) and male sex. Patients were more likely to be discharged later (after 24 h) if they underwent stent-coil embolization or flow-diversion. There was no association between discharge timing and likelihood of readmission. DISCUSSION: Our review highlights the safety of earlier discharge and allowed us to prepare a fast-track protocol for same-day discharge in these patients. This protocol will be studied prospectively in the next phase of this study. As we gain more comfort with emerging, minimally invasive endovascular therapies, we hope to safely achieve same-day discharge on a protocolized and routine basis, reducing the demand of elective aneurysm treatments on our healthcare system. CONCLUSION: We retrospectively demonstrate that early discharge following elective aneurysm treatment is safe in our cohort and provide a fast-track pathway based on these findings for other centers developing similar protocols.

Outpatient management of chronic expanding subdural hematomas with endovascular embolization to minimize inpatient admissions during the COVID-19 viral pandemic.

Chronic subdural hematomas are complex collections that usually form after a trauma, particularly in elderly patients. This vulnerable population is at increased risk given the current viral pandemic. We share our experience in managing minimally symptomatic, enlarging subdural collections via middle meningeal embolization through the outpatient setting. This approach minimizes inpatient hospitalizations in hopes or reducing nosocomial spread (e.g., of COVID-19).

The Role of Gender in Neurosurgical Residency Applicants' Letters of Recommendation.

BACKGROUND: Letters of recommendation (LORs) are one of the most important components of the neurosurgical residency application. Studies in other fields and surgical subspecialties have found gender bias. OBJECTIVE: To determine whether neurosurgical LORs contain significant linguistic gendered differences. METHODS: We performed a retrospective review and linguistic analysis of all LORs submitted on behalf of applicants offered an interview invitation to a single neurosurgical residency program at an academic medical center between 2015-2016 and 2018-2019. RESULTS: A total of 599 letters from 156 applicants (120 males and 36 females) were included. Background demographics, including United States Medical Licensing Examination (USMLE) Step 1 score and publications, were not significantly different between applicants. Male faculty authored 93% of all letters. Female faculty were more likely to write letters for female applicants than male applicants (12.1% vs 5.5%, P < .001). Letters for women were significantly longer (334 words vs 277 words, P < .001). Overall, 1754 agentic terms and 854 communal terms were coded. Letters for men contained significantly fewer agentic terms (10.7 vs 13.1, per applicant, P < .01) and communal terms (5.2 vs 6.4, P < .034). This difference, however, is nonsignificant when word count was used as a covariate. Female applicants were more significantly likely to be labeled "Outstanding" (2.4 vs 1.6 mentions per applicant). CONCLUSION: Overall, there are more similarities than differences between genders in LORs for neurosurgical applicants. This finding is at odds with what has previously been reported in most other surgical specialties.

Characterization of antiplatelet response to low-dose cangrelor utilizing platelet function testing in neuroendovascular patients.

STUDY OBJECTIVES: The optimal antiplatelet therapy for emergent neuroendovascular stenting is uncertain. Cangrelor is an intravenous P2Y12 inhibitor that is an attractive option due its favorable pharmacokinetic profile and ease of measurability but optimal dosing remains unclear. The primary objective of this study is to characterize the dose response of low dose cangrelor (<2 mcg/kg/min) with the utilization of platelet function testing (PFT). DESIGN: A retrospective review of all patients treated with cangrelor for either procedural stenting or bridging was conducted between January 1st, 2019 and October 31st, 2020. Seventy-two patients met inclusion criteria. An in-depth analysis of dose response to low dose cangrelor based on PFT was performed. PATIENTS: Neuroendovascular patients treated with cangrelor. SETTING: Albany Medical Center Hospital. INTERVENTION AND MAIN RESULTS: Patients who underwent procedural stenting were given a bolus of 5 mcg/kg and an initial infusion rate of either 0.75 mcg/kg/min or 1 mcg/kg/min. Patients who were bridged with cangrelor were administered an initial infusion rate of 0.75 mcg/kg/min or 1 mcg/kg/min. Twelve patient's doses were titrated to achieve a platelet reactivity unit (PRU) between 50-150; three patient's doses were titrated multiple times. Based on initial PFT results, utilizing the 1 mcg/kg/min maintenance dose resulted in more patients being in the acceptable (10-180) and desired (50-150) PRU range than the 0.75 mcg/kg/min dose (47% vs 56% and 70% vs 80%, respectively). Final recorded PRU results showed that 64% of patients had PRUs in the optimal range (50-150) and 88% of patients had PRUs in the desire range (10-180). CONCLUSIONS: Utilizing low doses of cangrelor with platelet function testing is an option during emergent neuroendovascular stenting and bridging. Cangrelor demonstrates significant variability in response at low doses and exhibits a dose response relationship when PFT is utilized.

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.

Ecology of speciation in the genus Bacillus.

Microbial ecologists and systematists are challenged to discover the early ecological changes that drive the splitting of one bacterial population into two ecologically distinct populations. We have aimed to identify newly divergent lineages ("ecotypes") bearing the dynamic properties attributed to species, with the rationale that discovering their ecological differences would reveal the ecological dimensions of speciation. To this end, we have sampled bacteria from the Bacillus subtilis-Bacillus licheniformis clade from sites differing in solar exposure and soil texture within a Death Valley canyon. Within this clade, we hypothesized ecotype demarcations based on DNA sequence diversity, through analysis of the clade's evolutionary history by Ecotype Simulation (ES) and AdaptML. Ecotypes so demarcated were found to be significantly different in their associations with solar exposure and soil texture, suggesting that these and covarying environmental parameters are among the dimensions of ecological divergence for newly divergent Bacillus ecotypes. Fatty acid composition appeared to contribute to ecotype differences in temperature adaptation, since those ecotypes with more warm-adapting fatty acids were isolated more frequently from sites with greater solar exposure. The recognized species and subspecies of the B. subtilis-B. licheniformis clade were found to be nearly identical to the ecotypes demarcated by ES, with a few exceptions where a recognized taxon is split at most into three putative ecotypes. Nevertheless, the taxa recognized do not appear to encompass the full ecological diversity of the B. subtilis-B. licheniformis clade: ES and AdaptML identified several newly discovered clades as ecotypes that are distinct from any recognized taxon.