Microsurgical Resection of Brainstem Cavernous Malformations in Older Adults: A Multicenter, 30-Year Experience.

BACKGROUND AND OBJECTIVES: Microsurgical resection is the only curative intervention for symptomatic brainstem cavernous malformations (BSCMs), but the management of these lesions in older adults (≥65 years) is not well described. This study sought to address this gap by examining the safety and efficacy of BSCM resection in a cohort of older adults. METHODS: Records of patients who underwent BSCM resection over a 30-year period were reviewed retrospectively. Baseline characteristics and outcomes were compared between older (≥65 years) and younger (<65 years) patients. RESULTS: Of 550 patients with BSCM who met inclusion criteria, 41 (7.5%) were older than 65 years. Midbrain (43.9% vs 26.1%) and medullary lesions (19.5% vs 13.6%) were more common in the older cohort than in the younger cohort (P = .01). Components of the Lawton BSCM grading system (ie, lesion size, crossing axial midpoint, developmental venous anomaly, and timing of hemorrhage) were not significantly different between cohorts (P ≥ .11). Mean (SD) Elixhauser comorbidity score was significantly higher in older patients (1.86 [1.06]) than in younger patients (0.66 [0.95]; P < .001). Older patients were significantly more likely than younger patients to have poor outcomes at final follow-up (28.9% vs 13.8%, P = .01; mean follow-up duration, 28.7 [39.1] months). However, regarding relative neurological outcome (preoperative modified Rankin Scale to final modified Rankin Scale), rate of worsening was not significantly different between older and younger patients (23.7% vs 14.9%, P = .15). CONCLUSION: BSCMs can be safely resected in older patients, and when each patient's unique health status and life expectancy are taken into account, these patients can have outcomes similar to younger patients.

Sex differences in patients with and without high-risk factors associated with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Controversy remains regarding the appropriate screening for intracranial aneurysms or for the treatment of aneurysmal subarachnoid hemorrhage (aSAH) for patients without known high-risk factors for rupture. This study aimed to assess how sex affects both aSAH presentation and outcomes for aSAH treatment. METHOD: A retrospective cohort study was conducted of all patients treated at a single institution for an aSAH during a 12-year period (August 1, 2007-July 31, 2019). An analysis of women with and without high-risk factors was performed, including a propensity adjustment for a poor neurologic outcome (modified Rankin Scale [mRS] score > 2) at follow-up. RESULTS: Data from 1014 patients were analyzed (69% [n = 703] women). Women were significantly older than men (mean ± SD, 56.6 ± 14.1 years vs 53.4 ± 14.2 years, p < 0.001). A significantly lower percentage of women than men had a history of tobacco use (36.6% [n = 257] vs 46% [n = 143], p = 0.005). A significantly higher percentage of women than men had no high-risk factors for aSAH (10% [n = 70] vs 5% [n = 16], p = 0.01). The percentage of women with an mRS score > 2 at the last follow-up was significantly lower among those without high-risk factors (34%, 24/70) versus those with high-risk factors (53%, 334/633) (p = 0.004). Subsequent propensity-adjusted analysis (adjusted for age, Hunt and Hess grade, and Fisher grade) found no statistically significant difference in the odds of a poor outcome for women with or without high-risk factors for aSAH (OR = 0.7, 95% CI = 0.4-1.2, p = 0.18). CONCLUSIONS: A higher percentage of women versus men with aSAH had no known high-risk factors for rupture, supporting more aggressive screening and management of women with unruptured aneurysms.

Modafinil Therapy and Mental Status Following Aneurysmal Subarachnoid Hemorrhage: Comprehensive Stroke Center Analysis.

BACKGROUND: Disorders of consciousness impair early recovery after aneurysmal subarachnoid hemorrhage (aSAH). Modafinil, a wakefulness-promoting agent, is efficacious for treating fatigue in stroke survivors, but data pertaining to its use in the acute setting are scarce. This study sought to assess the effects of modafinil use on mental status after aSAH. METHODS: Modafinil timing and dosage, neurological examination, intubation status, and physical and occupational therapy participation were documented. Repeated-measures paired tests were used for a before-after analysis of modafinil recipients. Propensity score matching (1:1 nearest neighbor) for modafinil and no-modafinil cohorts was used to compare outcomes. RESULTS: Modafinil (100-200 mg/day) was administered to 21% (88/422) of aSAH patients for a median (IQR) duration of 10.5 (4-16) days and initiated 14 (7-17) days after aSAH. Improvement in mentation (alertness, orientation, or Glasgow Coma Scale score) was documented in 87.5% (77/88) of modafinil recipients within 72 hours and 86.4% (76/88) at discharge. Of 37 intubated patients, 10 (27%) were extubated within 72 hours after modafinil initiation. Physical and occupational therapy teams noted increased alertness or participation in 47 of 56 modafinil patients (83.9%). After propensity score matching for baseline covariates, the modafinil cohort had a greater mean (SD) change in Glasgow Coma Scale score than the no-modafinil cohort at discharge (2.2 [4.0] vs. -0.2 [6.32], P = 0.003). CONCLUSIONS: A temporal relationship with improvement in mental status was noted for most patients administered modafinil after aSAH. These findings, a favorable adverse-effect profile, and implications for goals-of-care decisions favor a low threshold for modafinil initiation in aSAH patients in the acute-care setting.

Flow diversion for basilar quadrifurcation aneurysms.

BACKGROUND: Flow-diverting devices (FDDs), such as the Pipeline Embolization Device, have been gaining traction for treating challenging posterior circulation aneurysms. Few previous studies have focused on using FDDs to treat aneurysms of the basilar quadrifurcation. METHODS: We retrospectively reviewed the use of FDDs to treat patients with basilar quadrifurcation aneurysms. Patients were assessed for aneurysm type, previous aneurysm treatment, technical success, periprocedural complications, and long-term aneurysm occlusion. RESULTS: 34 patients were assessed; aneurysms of the basilar apex (n=23) or superior cerebellar artery (SCA) (n=7), or both (n=1), and posterior cerebral artery (PCA) (n=3). The mean (SD) largest aneurysm dimension was 8.7 (6.1) mm (range 1.9-30.8 mm). 14 aneurysms were previously surgically clipped or endovascularly coiled. All aneurysms had a saccular morphology. Complete or near-complete occlusion was achieved in 30 of 34 patients (88%) at final angiographic follow-up, a mean (SD) of 6.6 (5.4) months (range 0-19 months) postoperatively. No patient experienced postoperative symptomatic occlusions of the SCA or PCA; 4 patients developed asymptomatic posterior communicating artery occlusions; 28 patients (82%) experienced no complications; whereas 3 (9%) experienced major complications and 3 (9%) experienced minor complications; and 1 patient died as a result of subarachnoid hemorrhage. CONCLUSION: Flow diversion may be a safe and effective option to treat basilar quadrifurcation aneurysms. Previously treated basilar quadrifurcation aneurysms with recurrence or residual lesion may benefit from additional treatment with an FDD. Further prospective studies should be directed toward validating these findings.

Occipital Artery to Middle Cerebral Artery Direct Bypass: A Salvage Revascularization Technique for Ischemic Moyamoya Disease.

OBJECTIVE: The main treatment for moyamoya disease (MMD) is revascularization surgery. Most bypasses use the superficial temporal artery (STA) as the donor vessel. However, even if the STA-middle cerebral artery (MCA) bypass is functioning, the affected hemisphere can continue to be symptomatically malperfused. We sought to assess the efficacy of salvage direct revascularization surgery using the occipital artery (OA) as a donor vessel in patients with ischemic MMD who experience continued cerebral malperfusion despite previous successful STA-MCA bypass. METHODS: We retrospectively analyzed the cerebrovascular databases of 2 surgeons and described patients in whom the OA was used as the donor vessel for direct revascularization. RESULTS: Seven patients were included (5 women). Previous STA-MCA bypasses were direct (n = 2), indirect (n = 3), or combined/multiple (n = 2). The mean (SD) interval between STA-MCA and OA-MCA procedures was 29.2 (13.1) months. Despite an intact STA-MCA bypass in all 7 cases, all 7 patients had recurrent symptoms and demonstrated residual impaired cerebral perfusion. All 7 patients underwent successful OA-MCA direct revascularization. Follow-up perfusion imaging was obtained for 6 of 7 patients. All 6 of these patients demonstrated improved cerebral blood flow to the revascularized hemispheres. All 7 patients demonstrated clinical improvement. CONCLUSIONS: Patients with ischemic MMD who have continued symptoms and cerebral malperfusion despite previous successful STA-MCA bypass present a challenging clinical scenario. Our series highlights the potential utility of the OA-MCA direct bypass as a salvage therapy for these patients.

Pentobarbital coma for management of intracranial hypertension following traumatic brain injury: Lack of early response to treatment portends poor outcomes.

INTRODUCTION: Traumatic brain injury (TBI) results in the death of over 50,000 and the permanent disability of 80,000 individuals annually in the United States. Much of the permanent disability is the result of secondary brain injury from intracranial hypertension (ICH). Pentobarbital coma is often instituted following the failure of osmotic interventions and sedation to control intracranial pressure (ICP). The goal of this study was to evaluate the efficacy of pentobarbital coma with respect to ICP management and long-term functional outcome. METHODS: Traumatic brain injury patients who underwent pentobarbital coma at a level 1 trauma center between 2014 and 2021 were identified. Patient demographics, injury characteristics, Glasgow Coma Scale (GCS) scores, intracranial pressures (ICPs), and outcomes were obtained from the trauma registry as well as inpatient and outpatient medical records. The proportion of ICPs below 20 for each hospitalized patient-day was calculated. The primary outcome measured was GCS score at the last follow-up visit. RESULTS: 25 patients were identified, and the majority were male (n â€‹= â€‹23, 92%) with an average age of 30.0 years â€‹± â€‹12.9 and median injury severity score of 30 (21.5-33.5). ICPs were monitored for all patients with a median of 464 (326-1034) measurements. The average hospital stay was 16.9 days â€‹± â€‹11.5 and intensive care stay was 16.9 â€‹± â€‹10.8 days. 9 (36.0%) patients survived to hospital discharge. Mean follow-up time in months was 36.9 â€‹± â€‹28.0 (min-max 3-80). 7 of the 9 surviving patients presented as GCS 15 on follow-up and the remaining were both GCS 9. Patients presenting at last follow-up with GCS 15 had a significantly higher proportion of controlled ICPs throughout their hospitalization compared to patients who expired or with follow-up GCS <15 (GCS 15: 88% â€‹± â€‹10% vs. GCS <15 or dead: 68% â€‹± â€‹22%, P â€‹= â€‹0.006). A comparison of the daily proportion of controlled ICPs by group revealed negligible differences prior to pentobarbital initiation. Groups diverged nearly immediately upon pentobarbital coma initiation with a higher proportion of controlled ICPs for patients with follow-up GCS of 15. CONCLUSION: Patients that do not have an immediate response to pentobarbital coma therapy for ICH universally had poor outcomes. Alternative therapy or earlier palliation should be considered for such patients. In contrast, patients whose ICPs responded quickly to pentobarbital had excellent long-term outcomes.

Association between external ventricular drain removal or replacement and prophylactic anticoagulation in patients with aneurysmal subarachnoid hemorrhage: a propensity-adjusted analysis.

BACKGROUND: Withholding prophylactic anticoagulation from patients with aneurysmal subarachnoid hemorrhage (aSAH) before external ventricular drain (EVD) removal or replacement remains controversial. This study analyzed whether prophylactic anticoagulation was associated with hemorrhagic complications related to EVD removal. METHOD: All aSAH patients treated from January 1, 2014, to July 31, 2019, with an EVD placed were retrospectively analyzed. Patients were compared based on the number of prophylactic anticoagulant doses withheld for EVD removal (> 1 vs. ≤ 1). The primary outcome analyzed was deep venous thrombosis (DVT) or pulmonary embolism (PE) after EVD removal. A propensity-adjusted logistic-regression analysis was performed for confounding variables. RESULTS: A total of 271 patients were analyzed. For EVD removal, > 1 dose was withheld from 116 (42.8%) patients. Six (2.2%) patients had a hemorrhage associated with EVD removal, and 17 (6.3%) patients had a DVT or PE. No significant difference in EVD-related hemorrhage after EVD removal was found between patients with > 1 versus ≤ 1 dose of anticoagulant withheld (4 of 116 [3.5%] vs. 2 of 155 [1.3%]; p = 0.41) or between those with no doses withheld compared to ≥ 1 dose withheld (1 of 100 [1.0%] vs. 5 of 171 [2.9%]; p = 0.32). After adjustment, withholding > 1 dose of anticoagulant versus ≤ 1 dose was associated with the occurrence of DVT or PE (OR 4.8; 95% CI, 1.5-15.7; p = 0.009). CONCLUSIONS: In aSAH patients with EVDs, withholding > 1 dose of prophylactic anticoagulant for EVD removal was associated with an increased risk of DVT or PE and no reduction in catheter removal-associated hemorrhage.

Technique for Validation of Intraoperative Navigation in Minimally Invasive Spine Surgery.

BACKGROUND: Intraoperative 3-dimensional navigation is an enabling technology that has quickly become a commonplace in minimally invasive spine surgery (MISS). It provides a useful adjunct for percutaneous pedicle screw fixation. Although navigation is associated with many benefits, including improvement in overall screw accuracy, navigation errors can lead to misplaced instrumentation and potential complications or revision surgery. It is difficult to confirm navigation accuracy without a distant reference point. OBJECTIVE: To describe a simple technique for validating navigation accuracy in the operating room during MISS. METHODS: The operating room is set up in a standard fashion for MISS with intraoperative cross-sectional imaging available. A 16-gauge needle is placed within the bone of the spinous process before intraoperative cross-sectional imaging. The entry level is chosen such that the space between the reference array and the needle encompasses the surgical construct. Before placing each pedicle screw, accuracy is verified by placing the navigation probe over the needle. RESULTS: This technique has identified navigation inaccuracy and led to repeat cross-sectional imaging. No screws have been misplaced in the senior author's cases since adopting this technique, and there have been no complications attributable to the technique. CONCLUSION: Navigation inaccuracy is an inherent risk in MISS, but the described technique may mitigate this risk by providing a stable reference point.

Propensity-adjusted analysis of ultra-early aneurysmal subarachnoid hemorrhage treatment and patient outcomes.

BACKGROUND: Optimal definitive treatment timing for patients with aneurysmal subarachnoid hemorrhage (aSAH) remains controversial. We compared outcomes for aSAH patients with ultra-early treatment versus later treatment at a single large center. METHOD: Patients who received definitive open surgical or endovascular treatment for aSAH between January 1, 2014, and July 31, 2019, were included. Ultra-early treatment was defined as occurring within 24 h from aneurysm rupture. The primary outcome was poor neurologic outcome (modified Rankin Scale score > 2). Propensity adjustment was performed for age, sex, Charlson Comorbidity Index, Hunt and Hess grade, Fisher grade, aneurysm treatment type, aneurysm type, size, and anterior location. RESULTS: Of the 1013 patients (mean [SD] age, 56 [14] years; 702 [69%] women, 311 [31%] men) included, 94 (9%) had ultra-early treatment. Compared with the non-ultra-early cohort, the ultra-early treatment cohort had a significantly lower percentage of saccular aneurysms (53 of 94 [56%] vs 746 of 919 [81%], P <0 .001), greater frequency of open surgical treatment (72 of 94 [77%] vs 523 of 919 [57%], P <0 .001), and greater percentage of men (38 of 94 [40%] vs 273 of 919 [30%], P = .04). After adjustment, ultra-early treatment was not associated with neurologic outcome in those with at least 180-day follow-up (OR = 0.86), the occurrence of delayed cerebral ischemia (OR = 0.87), or length of stay (exp(ß), 0.13) (P ≥ 0.60). CONCLUSIONS: In a large, single-center cohort of aSAH patients, ultra-early treatment was not associated with better neurologic outcome, fewer cases of delayed cerebral ischemia, or shorter length of stay.

Relationship between cerebral vasospasm vascular territory and functional outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Vasospasm following aneurysmal subarachnoid hemorrhage (SAH) contributes significant morbidity and mortality after brain aneurysm rupture. However, the association between vascular territory of vasospasm and clinical outcome has not been studied. We present a hypothesis-generating study to determine whether the location of vasospasm within the intracranial circulation is associated with functional outcome after SAH. METHODS: A retrospective analysis of a prospective, intention-to-treat trial for aneurysmal SAH was performed to supplement trial outcomes with in-hospital angiographic imaging and treatment variables regarding vasospasm. The location of vasospasm and the position on the vessel (distal vs proximal) were evaluated. Modified Rankin scale (mRS) outcomes were assessed at discharge and 6 months, and predictive models were constructed. RESULTS: A total of 406 patients were included, 341 with follow-up data at 6 months. At discharge, left-sided vasospasm was associated with poor outcome (odds ratio (OR), 2.37; 95% CI, 1.25 to 4.66; P=0.01). At 6 months, anterior cerebral artery (ACA) vasospasm (OR, 3.87; 95% CI, 1.29 to 11.88; P=0.02) and basilar artery (BA) vasospasm (OR, 6.22; 95% CI, 1.54 to 27.11; P=0.01) were associated with poor outcome after adjustment. A model predicting 6-month mRS score and incorporating vasospasm variables achieved an area under the curve of 0.85 and a net improvement in reclassification of 13.2% (P<0.01) compared with a previously validated predictive model for aneurysmal SAH. CONCLUSIONS: In aneurysmal SAH, left-sided vasospasm is associated with worse discharge functional status. At 6 months, both ACA and BA vasospasm are associated with unfavorable functional status.

Incidence and Prediction of Chronic Depression Following Aneurysmal Subarachnoid Hemorrhage: A Single-Center 17-Year Experience.

OBJECTIVE: The incidence and risk factors for chronic depression after aneurysmal subarachnoid hemorrhage (aSAH) are described. METHODS: Patients with aSAH treated at a single institution (January 1, 2003-December 31, 2019) and a modified Rankin Scale score ≤3 at follow-up who were evaluated for chronic depression were analyzed. Chronic depression was defined using a depression screening questionnaire as ≥5 positive answers for symptoms lasting >2 weeks. A predictive model was designed for the primary outcome of depression. RESULTS: Among 1419 patients with aSAH, 460 patients were analyzed; 130 (28%) had major depressive disorder. Mean follow-up was >6 years. Higher depression rates were associated with tobacco smoking (odds ratio [OR] = 2.64, P < 0.001), illicit drug use (OR = 2.35, P = 0.007), alcohol use disorder (1.92, P = 0.04), chronic obstructive pulmonary disease (COPD) (OR=2.68, P = 0.03), and vasospasm requiring angioplasty (OR=2.09, P = 0.048). The predictive model included tobacco smoking, illicit drug use, liver disease, COPD, diabetes, nonsaccular aneurysm type, anterior communicating artery or anterior cerebral artery aneurysm location, refractory spasm requiring angioplasty, and a modified Rankin Scale score at discharge of >1 (P ≤ 0.03). The model performed with appropriate goodness of fit and an area under the receiver operator curve of 0.70 for depression. Individual independent predictors of depression were tobacco smoking, COPD, diabetes, and nonsaccular aneurysm. CONCLUSIONS: A substantial percentage of patients had symptoms of depression on follow-up. The proposed predictive model for depression may be a useful clinical tool to identify patients at high risk for developing depression who warrant early screening and evaluation.

Retained radial catheters associated with variant radial anatomy in neurointerventional procedures.

BACKGROUND: Transradial artery access (TRA) for neurointerventional procedures is gaining widespread acceptance. However, complications that were previously rare may arise as TRA procedures increase. Here we report a series of retained catheter cases with a literature review. METHODS: All patients who underwent a neurointerventional procedure during a 23-month period at a single institution were retrospectively reviewed for a retained catheter in TRA cases. In cases of retained catheters, imaging was reviewed for anatomical variances in the radial artery, and clinical and demographic case details were analyzed. RESULTS: A total of 1386 nondiagnostic neurointerventional procedures were performed during the study period, 631 (46%) initially via TRA. The 631 TRA cases were performed for aneurysm embolization (n=221, 35%), mechanical thrombectomy (n=116, 18%), carotid stent/angioplasty (n=40, 6%), arteriovenous malformation embolization (n=38, 6%), and other reasons (n=216, 34%). Thirty-nine (6%) TRA procedures crossed over to femoral access, most commonly because the artery of interest could not be catheterized (26/39, 67%). A retained catheter was identified in five cases (1%), and one (0.2%) patient had an entrapped catheter that was recovered. All six patients with a retained or entrapped catheter had aberrant radial anatomy. CONCLUSION: Retained catheters for neurointerventional procedures performed via TRA are rare. However, this complication may be associated with variant radial anatomy. With the increased use of TRA for neurointerventional procedures, awareness of anatomical abnormalities that may lead to a retained catheter is necessary. We propose a simple protocol to avoid catheter entrapment, including in emergent situations such as TRA for stroke thrombectomy.

Single-Position Anterior and Lateral Lumbar Fusion in the Supine Position: A Novel Technique for Multilevel Arthrodesis.

OBJECTIVE: Anterior lumbar interbody fusion (ALIF) and lateral lumbar interbody fusion are common techniques that typically require staged procedures when performed in combination. Interest is emerging in single-position surgery to increase operative efficiency. We report a novel surgical technique, supine extended reach lateral fusion, to perform ALIF and lateral lumbar interbody fusion with the patient in a single supine position. METHODS: A man in his fifties presented with degenerative levoscoliosis, spondylolisthesis, sagittal plane deformity, and progressive low back pain. He was offered L3-S1 anterolateral fusion. RESULTS: With the patient supine, a left abdominal paramedian incision was performed to gain anterior retroperitoneal access, and standard L5-S1 and L4-5 ALIFs were performed. The anterior incision was used for direct visualization, retraction, and bimanual dissection. A left lateral incision was then made to perform an L3-4 lateral lumbar interbody fusion. He subsequently underwent a second-stage L3-S1 posterior percutaneous fixation. The patient tolerated the procedures well, without complications. His postoperative radiograph findings confirmed acceptable implant positioning. He was discharged home in stable condition and was doing well at follow-up. CONCLUSIONS: This case description is the first report of the supine extended reach technique, which allows incorporation of anterior and lateral fusion constructs at adjacent levels without changing patient positioning. Many surgeons believe the ALIF to be the most powerful technique for achieving lordosis, and this technique enables concomitant lateral access in a supine position. It can also be used as an alternative strategy when anterior access to the disc space is unobtainable. Further clinical investigation of this technique is warranted.

Vertebrobasilar dissecting aneurysms: microsurgical management in 42 patients.

OBJECTIVE: Vertebrobasilar dissecting (VBD) aneurysms are rare, and patients with these aneurysms often present with thromboembolic infarcts or subarachnoid hemorrhage (SAH). The morphological nature of VBD aneurysms often precludes conventional clip reconstruction or coil placement and encourages parent artery exclusion or endovascular stenting. Treatment considerations include aneurysm location along the vertebral artery (VA), the involvement of the posterior inferior cerebellar artery (PICA), and collateral blood flow. Outcomes after endovascular treatment have been well described in the neurosurgical literature, but microsurgical outcomes have not been detailed. Patient outcomes from a large, single-surgeon, consecutive series of microsurgically managed VBD aneurysms are presented, and 3 illustrative case examples are provided. METHODS: The medical records of patients with dissecting aneurysms affecting the intracranial VA (V4), basilar artery, and PICA that were treated microsurgically over a 19-year period were reviewed. Patient demographics, aneurysm characteristics, surgical procedures, and clinical outcomes (according to modified Rankin Scale [mRS] scores at last follow-up) were analyzed. RESULTS: Forty-two patients with 42 VBD aneurysms were identified. Twenty-six aneurysms (62%) involved the PICA, 14 (33%) were distinct from the PICA origin on the V4 segment of the VA, and 2 (5%) were located at the vertebrobasilar junction. Thirty-four patients (81%) presented with SAH with a mean Hunt and Hess grade of 3.2 at presentation. Six (14%) of the 42 patients had been previously treated using endovascular techniques. Nineteen aneurysms (45%) underwent clip wrapping, 17 (40%) were treated with bypass trapping, and 6 (14%) underwent parent artery sacrifice. The complete aneurysm obliteration rate was 95% (n = 40), and the surgical complication rate was 7% (n = 3). The 8 patients with unruptured VBD aneurysms were significantly more likely to be discharged home (n = 6, 75%) compared with 34 patients with ruptured aneurysms (n = 9, 27%; p = 0.01). Good outcomes (mRS score ≤ 2) were observed in 20 patients (48%). Eight patients (19%) died. CONCLUSIONS: These data demonstrate that patients with VBD aneurysms often present after a rupture in poor neurological condition, but favorable results can be achieved with open microsurgical repair in almost half of such cases. Microsurgery remains a viable treatment option, with the choice between bypass trapping and clip wrapping largely dictated by the specific location of the aneurysm and its relationship to the PICA.

Simultaneous detection of genotype and phenotype enables rapid and accurate antibiotic susceptibility determination.

Multidrug resistant organisms are a serious threat to human health1,2. Fast, accurate antibiotic susceptibility testing (AST) is a critical need in addressing escalating antibiotic resistance, since delays in identifying multidrug resistant organisms increase mortality3,4 and use of broad-spectrum antibiotics, further selecting for resistant organisms. Yet current growth-based AST assays, such as broth microdilution5, require several days before informing key clinical decisions. Rapid AST would transform the care of patients with infection while ensuring that our antibiotic arsenal is deployed as efficiently as possible. Growth-based assays are fundamentally constrained in speed by doubling time of the pathogen, and genotypic assays are limited by the ever-growing diversity and complexity of bacterial antibiotic resistance mechanisms. Here we describe a rapid assay for combined genotypic and phenotypic AST through RNA detection, GoPhAST-R, that classifies strains with 94-99% accuracy by coupling machine learning analysis of early antibiotic-induced transcriptional changes with simultaneous detection of key genetic resistance determinants to increase accuracy of resistance detection, facilitate molecular epidemiology and enable early detection of emerging resistance mechanisms. This two-pronged approach provides phenotypic AST 24-36 h faster than standard workflows, with <4 h assay time on a pilot instrument for hybridization-based multiplexed RNA detection implemented directly from positive blood cultures.

Adverse events after clipping of unruptured intracranial aneurysms: the NSQIP unruptured aneurysm scale.

OBJECTIVE: The complex decision analysis of unruptured intracranial aneurysms entails weighing the benefits of aneurysm repair against operative risk. The goal of the present analysis was to build and validate a predictive scale that identifies patients with the greatest odds of a postsurgical adverse event. METHODS: Data on patients who underwent surgical clipping of an unruptured aneurysm were extracted from the prospective National Surgical Quality Improvement Program registry (NSQIP; 2007-2014); NSQIP does not systematically collect data on patients undergoing intracranial endovascular intervention. Multivariable logistic regression evaluated predictors of any 30-day adverse event; variables screened included patient demographics, comorbidities, functional status, preoperative laboratory values, aneurysm location/complexity, and operative time. A predictive scale was constructed based on statistically significant independent predictors, which was validated using both NSQIP (2015-2016) and the Nationwide Inpatient Sample (NIS; 2002-2011). RESULTS: The NSQIP unruptured aneurysm scale was proposed: 1 point was assigned for a bleeding disorder; 2 points for age 51-60 years, cardiac disease, diabetes mellitus, morbid obesity, anemia (hematocrit < 36%), operative time 240-330 minutes; 3 points for leukocytosis (white blood cell count > 12,000/µL) and operative time > 330 minutes; and 4 points for age > 60 years. An increased score was predictive of postoperative stroke or coma (NSQIP: p = 0.002, C-statistic = 0.70; NIS: p < 0.001, C-statistic = 0.61), a medical complication (NSQIP: p = 0.01, C-statistic = 0.71; NIS: p < 0.001, C-statistic = 0.64), and a nonroutine discharge (NSQIP: p < 0.001, C-statistic = 0.75; NIS: p < 0.001, C-statistic = 0.66) in both validation populations. Greater score was also predictive of increased odds of any adverse event, a major complication, and an extended hospitalization in both validation populations (p ≤ 0.03). CONCLUSIONS: The NSQIP unruptured aneurysm scale may augment the risk stratification of patients undergoing microsurgical clipping of unruptured cerebral aneurysms.

A Genome-Wide Analysis of the Penumbral Volume in Inbred Mice following Middle Cerebral Artery Occlusion.

Following ischemic stroke, the penumbra, at-risk neural tissue surrounding the core infarct, survives for a variable period of time before progressing to infarction. We investigated genetic determinants of the size of penumbra in mice subjected to middle cerebral artery occlusion (MCAO) using a genome-wide approach. 449 male mice from 33 inbred strains underwent MCAO for 6 hours (215 mice) or 24 hours (234 mice). A genome-wide association study using genetic data from the Mouse HapMap project was performed to examine the effects of genetic variants on the penumbra ratio, defined as the ratio of the infarct volume after 6 hours to the infarct volume after 24 hours of MCAO. Efficient mixed model analysis was used to account for strain interrelatedness. Penumbra ratio differed significantly by strain (F = 2.7, P < 0.001) and was associated with 18 significant SNPs, including 6 protein coding genes. We have identified 6 candidate genes for penumbra ratio: Clint1, Nbea, Smtnl2, Rin3, Dclk1, and Slc24a4.

The Timing of Tracheostomy and Outcomes After Aneurysmal Subarachnoid Hemorrhage: A Nationwide Inpatient Sample Analysis.

BACKGROUND: The goal of this study was to investigate the association of tracheostomy timing with outcomes after aneurysmal subarachnoid hemorrhage (SAH) in a national population. METHODS: Poor-grade aneurysmal SAH patients were extracted from the Nationwide Inpatient Sample (2002-2011). Multivariable linear regression was used to analyze predictors of tracheostomy timing and multivariable logistic regression was used to evaluate the association of timing of intervention with mortality, complications, and discharge to institutional care. Covariates included patient demographics, comorbidities, severity of subarachnoid hemorrhage (measured using the NIS-SAH severity scale), hospital characteristics, and other complications and length of stay. RESULTS: The median time to tracheostomy among 1380 poor-grade SAH admissions was 11 (interquartile range: 7-15) days after intubation. The mean number of days from intubation to tracheostomy in SAH patients at the hospital (p < 0.001) was the strongest predictor of tracheostomy timing for a patient, while comorbidities and SAH severity were not significant predictors. Mortality, neurologic complications, and discharge disposition did not differ significantly by tracheostomy time. However, later tracheostomy (when evaluated continuously) was associated with greater odds of pulmonary complications (p = 0.004), venous thromboembolism (p = 0.04), and pneumonia (p = 0.02), as well as a longer hospitalization (p < 0.001). Subgroup analysis only found these associations between tracheostomy timing and medical complications in patients with moderately poor grade (NIS-SAH severity scale 7-9), while there were no significant differences by timing of intervention in very poor-grade patients (NIS-SAH severity scale > 9). CONCLUSIONS: In this analysis of a large, national data set, variation in hospital practices was the strongest predictor of tracheostomy timing for an individual. In patients with moderately poor grade, later tracheostomy was independently associated with pulmonary complications, venous thromboembolism, pneumonia, and a longer hospitalization, but not with mortality, neurological complications, or discharge disposition. However, tracheostomy timing was not significantly associated with outcomes in very poor-grade patients.