Association of CT-DSA vascular assessment and perioperative outcomes in metastatic spinal surgery.

INTRODUCTION: Computed tomography-digital subtraction angiography (CT-DSA) is a radiological method for assessing spinal metastatic tumor vascularity. The study aimed to investigate the association between CT-DSA results and perioperative outcomes in spinal metastatic surgery. MATERIAL AND METHODS: Patients who underwent spinal metastatic operations with preoperative CT-DSA examinations at any time between January 2018 to December 2022. CT-DSA was classified into five grades ranging from grade 0 to grade 4. Grades 3 and 4 were indicative of hypervascularity. We analyzed the perioperative outcomes of intraoperative blood loss amount, massive hemorrhage (≥2500 ml) occurrence, blood transfusion status, operation time, hospital stay duration, and 30-day and 60-day mortality rates. Logistic regression analyses were conducted to identify factors affecting the likelihood of massive hemorrhage in conjunction with CT-DSA. RESULTS: Data from 212 operations involving 209 patients were analyzed. In total, 30, 36, 66, 56, and 24 operations had CT-DSA grades from grade 0 to grade 4, respectively. Eighty (38 %) studies were indicative of hypervascularity. CT-DSA grade was positively correlated with the amount of operative blood loss, the occurrence of massive hemorrhage, and the amount of blood in blood transfusion (p < 0.05). However, CT-DSA grades was not significantly associated with operation duration or mortality rate. A multivariable analysis indicated that factors such as hemoglobulin, hypervascular pathology, and spinal instability neoplastic scores were positively correlated with CT-DSA grade. CT-DSA grade (odds ratio: 2.37, p = 0.02), spinal metastatic invasiveness index, and tumor size (≥50 mL) were found to be independent predictors in a multivariable logistic regression analysis where factors associated with massive hemorrhage were included. Hypervascular pathology type was not significantly associated with the likelihood of hemorrhage in the univariable and multivariable analyses. CONCLUSIONS: CT-DSA serves as an effective tool for assessing vascularity, and is associated with intra-operative blood loss and likelihood of experiencing massive hemorrhage. The predictive capability of CT-DSA surpasses that of traditional histopathology classifications, making it a useful method for preoperative planning in spinal metastatic surgeries.

Diagnostic performance of computed tomography-digital subtraction angiography and conventional magnetic resonance imaging for evaluating the vascularity of osseous spinal tumors.

BACKGROUND AND PURPOSE: Patients with hypervascular spinal tumors may have severe blood loss during tumor resection, which increases the risks of perioperative morbidity and mortality. However, the preoperative evaluation of tumor vascularity may be challenging; moreover, the reliability of the data obtained in conventional preoperative noninvasive imaging is debatable. In this study, we compared conventional magnetic resonance imaging (MRI) and subtraction computed tomography angiography (CTA) in terms of their performance in vascularity evaluation. The catheter digital subtraction angiography (DSA) technique was used as a reference standard. METHODS: This study included 123 consecutive patients with spinal tumor who underwent subtraction CTA, catheter DSA, and subsequent surgery between October 2015 and October 2021. Data regarding qualitative and semiquantitative subtraction CTA parameters and conventional MRI signs were collected for comparison with tumor vascularity graded through catheter DSA. The diagnostic performance of qualitative CTA, quantitative CTA, and conventional MRI in assessing spinal tumor vascularity was analyzed. RESULTS: Qualitative subtraction CTA was the best noninvasive imaging modality in terms of diagnostic performance (area under the receiver operating characteristic curve [AUROC], 0.95). Quantitative CTA was relatively inferior (AUROC, 0.87). MRI results had low reliability (AUROC, 0.51 to 0.59). Intratumoral hemorrhage and prominent foraminal venous plexus were found to be the specific signs for hypervascularity (specificity 93.2%). CONCLUSIONS: Qualitative subtraction CTA offers the highest diagnostic value in evaluating spinal tumor vascularity, compared to quantitative CTA and MRI. Although conventional MRI may not be a reliable approach, certain MRI signs may have high specificity, which may be crucial for assessing spinal tumor vascularity.

Associations of diabetes status and glucose measures with outcomes after endovascular therapy in patients with acute ischemic stroke: an analysis of the nationwide TREAT-AIS registry.

Background: Hyperglycemia affects the outcomes of endovascular therapy (EVT) for acute ischemic stroke (AIS). This study compares the predictive ability of diabetes status and glucose measures on EVT outcomes using nationwide registry data. Methods: The study included 1,097 AIS patients who underwent EVT from the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke. The variables analyzed included diabetes status, admission glucose, glycated hemoglobin (HbA1c), admission glucose-to-HbA1c ratio (GAR), and outcomes such as 90-day poor functional outcome (modified Rankin Scale score ≥ 2) and symptomatic intracranial hemorrhage (SICH). Multivariable analyses investigated the independent effects of diabetes status and glucose measures on outcomes. A receiver operating characteristic (ROC) analysis was performed to compare their predictive abilities. Results: The multivariable analysis showed that individuals with known diabetes had a higher likelihood of poor functional outcomes (odds ratios [ORs] 2.10 to 2.58) and SICH (ORs 3.28 to 4.30) compared to those without diabetes. Higher quartiles of admission glucose and GAR were associated with poor functional outcomes and SICH. Higher quartiles of HbA1c were significantly associated with poor functional outcomes. However, patients in the second HbA1c quartile (5.6-5.8%) showed a non-significant tendency toward good functional outcomes compared to those in the lowest quartile (<5.6%). The ROC analysis indicated that diabetes status and admission glucose had higher predictive abilities for poor functional outcomes, while admission glucose and GAR were better predictors for SICH. Conclusion: In AIS patients undergoing EVT, diabetes status, admission glucose, and GAR were associated with 90-day poor functional outcomes and SICH. Admission glucose was likely the most suitable glucose measure for predicting outcomes after EVT.

The Clinical Outcome of Carotid Blowout Syndrome Showing Non-bleeding Angiography.

OBJECTIVE: Patient with carotid blowout syndrome (CBS) may demonstrated non-bleeding digital subtraction angiography (DSA) without identifying pseudoaneurysm or contrast extravasation. Our objective is to evaluate the clinical outcomes for this specific subset of patients. MATERIALS AND METHODS: A retrospective observational study was conducted on 172 CBS patients who received DSA for evaluation of transarterial embolization (TAE) between 2005 and 2022, of whom 19 patients had non-bleeding DSA and did not undergo TAE. RESULTS: The age (55.2 ± 7.3 vs. 54.8 ± 11.1), male sex (17/19 vs. 135/153), tumor size (5.6 ± 2.4 vs. 5.2 ± 2.2), cancer locations were similar (P > 0.05) between both groups; except for there were more pseudoaneurysm/active bleeding (85.6% vs. 0%) and less vascular irregularity (14.4% vs. 94.7%) in the TAE group (P < 0.001). In the multivariable Cox regression model adjusting for age, sex, and tumor size, non-bleeding DSA group was independently associated with recurrent bleeding compared to TAE group (adjusted hazard ratio = 3.5, 95% confidence interval: 1.9-6.4, P < 0.001). Furthermore, the presence of vascular irregularity was associated with segmental recurrent bleeding (adjusted HR = 8.0, 95% CI 2.7-23.3, P < 0.001). CONCLUSION: Patient showing non-bleeding DSA thus not having TAE had higher risk of recurrent bleeding, compared to patient who received TAE. Level of Evidence Level 4, Case Series.

Validation of the Lung Immune Prognostic Index (LIPI) as a prognostic biomarker in metastatic renal cell carcinoma.

BACKGROUND: The Lung Immune Prognostic Index (LIPI) is associated with immune checkpoint inhibitors (ICI) outcomes across different solid tumors, particularly in non-small cell lung cancer. Data regarding the prognostic and/or predictive role of LIPI in metastatic renal cell carcinoma (mRCC) are still scarce. The aim of this study was to evaluate whether LIPI could be predictive of survival in mRCC patients. METHODS: We used patient level data from three different prospective studies (NIVOREN trial: nivolumab; TORAVA trial: VEGF/VEGFR-targeted therapy (TT); CheckMate 214: nivolumab-ipilimumab vs sunitinib). LIPI was calculated based on a derived neutrophils/(leukocyte-neutrophil) ratio > 3 and lactate-dehydrogenase >upper limit of normal, classifying patients into three groups (LIPI good, 0 factors;LIPI intermediate (int), 1 factor;LIPI poor, 2 factors) and/or into two groups (LIPI good, 0 factors;LIPI int/poor, 1-2 factors) according to trial sample size. Primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: In the Nivolumab dataset (n = 619), LIPI was significantly associated with OS (LIPI-good 30.1 vs 13.8 months in the LIPI int/poor; HR= 0.47) and PFS (HR=0.74). In the VEGF/VEGFR-TT dataset (n = 159), only a correlation with PFS was observed. In the CheckMate214 dataset (n = 1084), LIPI was significantly associated with OS (nivolumab-ipilimumab OS LIPI good vs int/poor: HR=0.55, p < 0.0001; sunitinib: OS LIPI good vs int/poor: 0.38, p < 0.0001) in both treatment groups in univariate and multivariate analysis. CONCLUSIONS: Pretreatment-LIPI correlated with worse survival outcomes in mRCC treated with either ICI or antiangiogenic therapy, confirming LIPI's prognostic role in mRCC irrespective of systemic treatment used.

Prevalence and clinical features of carotid artery web in patients undergoing endovascular thrombectomy for acute ischemic stroke.

PURPOSE: Carotid artery web (CaW) is a rare focal fibromuscular dysplasia that can lead to embolic strokes with large vessel occlusion. This condition can be effectively treated with endovascular thrombectomy (EVT). Our study aims to assess the prevalence of CaW among patients with acute ischemic stroke (AIS) who underwent EVT and to compare the clinical characteristics of CaW with other carotid artery pathologies. METHODS: We enrolled consecutive patients with AIS who underwent EVT at a single medical center and two regional teaching hospitals in Taiwan from September 2014 to December 2021. We compared CaW with carotid dissection (CaD) and carotid large artery atherosclerosis (CaLAA) in terms of patient demographics and thrombus histological findings. RESULTS: Of the 576 AIS patients who underwent EVT, four (mean age: 50 years) were diagnosed with CaW, resulting in a prevalence of 0.69%. Among these four patients, three experienced successful reperfusion after EVT and achieved functional independence (defined as a modified Rankin Scale score ≤2) three months post-stroke. Importantly, none of the CaW patients suffered a recurrent stroke within one year. Patients with CaW were younger than those with CaD or CaLAA, and exhibited fewer vascular risk factors. Additionally, CaW was associated with distal occlusion sites. The thrombus composition in CaW patients was similar to that in CaD patients. CONCLUSIONS: In conclusion, CaW is a rare finding among Asian patients with carotid artery disease who undergo for AIS. It is more prevalent in younger patients with a limited number of vascular risk factors.

Imaging Characteristics and Interpretation Strategy for Renal Hyperparathyroidism: A Retrospective 4-Dimensional Computed Tomography Study.

OBJECTIVE: Parathyroidectomy treats uncontrolled renal hyperparathyroidism (RHPT), requiring identification of all glands. Three types of enhancement are proposed. Type A lesions have higher arterial phase attenuation than the thyroid, type B lesions lack higher arterial phase attenuation but have lower venous phase attenuation, and type C lesions have neither higher arterial phase attenuation nor lower venous phase attenuation than the thyroid. We aimed to outline the image features of problematic parathyroid glands in RHPT and propose a 4-dimensional computed tomography (4DCT) interpretation algorithm. METHODS: This retrospective study involved data collection from patients with RHPT who underwent preoperative 4DCT for parathyroidectomy between January and November 2022. Pathologically confirmed parathyroid lesions were retrospectively identified on 4DCT according to the location and size described in the surgical notes. The attenuation of parathyroid lesions and the thyroid glands was assessed in 3 phases, and demographic data of the patients were collected. RESULTS: Ninety-seven pathology-proven parathyroid glands from 27 patients were obtained, with 86 retrospectively detected on 4DCT. In the arterial phase, the attenuation of parathyroid lesions in RHPT did not exceed that of the thyroid gland (P < .001). In the venous phase, parathyroid lesions demonstrated lower attenuation than the thyroid gland (P < .001). A total of 81 parathyroid lesions (94.2%) exhibited type B patterns. CONCLUSION: Unlike primary hyperparathyroidism, lesions in RHPT exhibited more type B enhancement, making them less readily identifiable in the arterial phase. Therefore, we propose a distinct imaging interpretation strategy to locate these problematic glands more efficiently.

Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry.

BACKGROUND: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase). METHODS: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis. RESULTS: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata. CONCLUSIONS: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.

The Extent of Tumor Invasion and Therapeutic Embolization Are Associated with Recurrent Hemorrhage in Patients with External Carotid Artery Blowout Syndrome.

PURPOSE: To explore the optimal strategies of therapeutic embolization for patients with carotid blowout syndrome in the external carotid artery (ECA), who may also present with arterial tumor invasion or necrosis extending to the internal carotid artery (ICA) or common carotid artery (CCA). MATERIALS AND METHODS: The study included 110 patients with ECA blowout between 2005 and 2022. Antecedent cross-sectional imaging features were examined, including tumor size, extent of arterial invasion, and air-containing necrosis. Patients were divided into Groups 1 (n = 53, simultaneous ICA/CCA invasion + ECA therapeutic embolization), 2 (n = 18, simultaneous ICA/CCA invasion + ECA-ICA/CCA therapeutic embolization), and 3 (n = 39, no ICA/CCA invasion + ECA therapeutic embolization). Kaplan-Meier and multivariable Cox regression analyses were performed to evaluate associations of clinical, imaging, and therapeutic embolization characteristics with recurrent bleeding. RESULTS: Multivariable Cox regression revealed that Group 1 was independently associated with a higher risk of recurrent bleeding than that in Group 2 (adjusted hazard ratio, 6.3; 95% CI, 1.7‒23.4; P = .005) and Group 3 (adjusted hazard ratio, 3.8; 95% CI, 1.8‒8.3; P = .001). In the subgroup with simultaneous ICA/CCA invasion, air-containing necrosis around the ICA/CCA was independently associated with recurrent bleeding after therapeutic embolization of the ECA (adjusted hazard ratio, 5.0; 95% CI, 1.8‒13.6; P = .002). CONCLUSIONS: In patients with ECA blowout treated with therapeutic embolization, there was a lower risk of recurrent bleeding when the extents of arterial invasion and therapeutic embolization were concordant. Air-containing necrosis around the ICA/CCA was associated with recurrent bleeding, so extensive therapeutic embolization to the ICA/CCA should be evaluated in such patients.

Association of Ferroptosis with Severity and Outcomes in Acute Ischemic Stroke Patients Undergoing Endovascular Thrombectomy: A Case-control Study.

Ferroptosis, an iron-dependent form of cell death, is characterized by intracellular accumulation of iron and reactive oxygen species-induced lipid peroxidation. Animal experiments have shown the important roles of ferroptosis in ischemic stroke, but the evidence in human stroke is insufficient. This prospective study evaluated the associations between plasma ferroptosis biomarkers at hyperacute stage and long-term outcomes in patients with acute ischemic stroke undergoing endovascular thrombectomy (EVT). The plasma samples were collected immediately before and after EVT (T1 and T2) and at 24 h (T3) for the 126 stroke patients and once for the 50 stroke-free control subjects. Compared with controls, stroke patients had higher 4-hydroxynonenal (4-HNE) levels at T1 and T2 while lower homocysteine and soluble transferrin receptor (sTfR) levels at T3. In stroke patients, higher National Institutes of Health Stroke Scale scores at admission were correlated with higher 4-HNE and lower sTfR levels. Lower Alberta Stroke Program Early CT (ASPECT) scores and larger infarct core volumes on CT perfusion before EVT were correlated with higher 4-HNE and homocysteine levels. After adjusting for significant parameters, homocysteine levels at T2 were significantly associated with poor functional outcome and mortality at 3 months. In the receiver operating characteristic (ROC) models, adding homocysteine levels at T2 and hemoglobin levels to the reference model for predicting poor functional outcome significantly increased the area under the ROC curve. In summary, this study provides evidence that ferroptosis is associated with stroke severity and outcomes in patients with acute ischemic stroke undergoing EVT.

Association of temporalis muscle thickness with functional outcomes in patients undergoing endovascular thrombectomy.

INTRODUCTION: Temporalis muscle thickness (TMT) is a surrogate marker for sarcopenia. This study investigated the association of TMT with clinical outcomes in patients receiving endovascular thrombectomy (EVT) for stroke involving acute large vessel occlusion (LVO). MATERIAL AND METHODS: We enrolled consecutive patients who had undergone EVT between September 2014 and December 2021 at three thrombectomy-capable institutes. TMT was measured through preprocedural computerized tomography angiography. The clinical variables affecting TMT were investigated. The associations between TMT and clinical functional outcomes, defined using the modified Rankin scale, were also studied. RESULTS: A total of 657 patients were included (mean age: 72.0 ± 12.7 years; male: 52.1%). The mean TMT was 6.35 ± 1.84 mm. Younger age, male sex, higher body mass index, and premorbid functional independence were associated with larger TMT in both univariate and multivariate linear regression (P <.05). Ordinal logistic regression revealed that TMT was associated with better clinical outcomes at 90 days (Ptrend = 0.047); multivariate logistic regression indicated that larger TMT was an independent predictor (adjusted odds ratio: 1.14, 95% confidence interval: 1.03-1.27, P = 0.02) of favorable functional independence (modified Rankin scale score: 0-2). The effect was stronger in older patients (≥80 years) than younger patients, as revealed by interaction modeling analysis (Pinteraction = 0.06). CONCLUSION: TMT is associated with age, sex, body mass index, and premorbid functional status. Larger TMT is associated with better outcomes after EVT. The effects of TMT are more pronounced in older adults, indicating that sarcopenia may have influence on stroke outcomes.

Effect of using G-FAST to recognize emergent large vessel occlusion: A city-wide community experience.

BACKGROUND/PURPOSE: A prehospital bypass strategy was suggested for large vessel occlusion. This study aimed to evaluate the effect of a bypass strategy using the gaze-face-arm-speech-time test (G-FAST) implemented in a metropolitan community. METHODS: Pre-notified patients with positive Cincinnati Prehospital Stroke Scale and symptom onset <3 h from July 2016 to December 2017 (pre-intervention period) and those with positive G-FAST and symptom onset <6 h from July 2019 to December 2020 (intervention period) were included. Patients aged <20 years and those with missing in-hospital data were excluded. The primary outcomes were the rates of receiving endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT). The secondary outcomes were total prehospital time, door-to-computed tomography (CT) time, door-to-needle (DTN) time, and door-to-puncture (DTP) time. RESULTS: We included 802 and 695 pre-notified patients from the pre-intervention and intervention periods, respectively. The characteristics of the patients in the two periods were similar. In the primary outcomes, pre-notified patients during the intervention period showed higher rates of receiving EVT (4.49% vs. 15.25%, p < 0.001) and IVT (15.34% vs. 21.58%, p = 0.002). In the secondary outcomes, pre-notified patients during intervention period had longer total prehospital time (mean 23.38 vs 25.23 min, p < 0.001), longer door-to-CT time (median 10 vs 11 min, p < 0.001), longer DTN time (median 53 vs 54.5 min, p < 0.001) but shorter DTP time (median 141 vs 139.5 min, p < 0.001). CONCLUSION: The prehospital bypass strategy with G-FAST showed benefits for stroke patients.

Efficacy of preoperative embolization for metastatic spinal tumor surgery using angiographic vascularity assessment.

OBJECTIVES: Preoperative embolization (PE) for metastatic spinal tumors is a method of minimizing intraoperative blood loss during aggressive surgery. This study specified angiographic standards and investigated the influence of these and other factors on blood loss in patients with spinal metastases and various pathologies. METHODS: The cohort comprised 126 consecutive patients receiving PE from 2015 to 2021. Their clinical, surgical, and angiographic characteristics were reviewed. Standard angiographic grading was used for vascularity assessment. Degree of embolization was divided into complete (≥ 90%), near complete (67 to < 90%), and partial (< 67%). Logistic regression analysis was used to investigate factors predictive of massive blood loss (> 2500 mL). A proportional odds model was used to assess factors predictive of the degree of embolization. RESULTS: Mean intraoperative blood loss was 1676 mL. Among the patients, 62 had hypervascular tumors and 64 had nonhypervascular tumors, according to the angiographic classification. Intraoperative blood loss differed significantly with embolization degree, both overall (p < 0.001) and in the hypervascular and nonhypervascular groups (p = 0.01 and 0.03). Angiographic hypervascularity, spinal metastasis invasiveness index, and embolization degree were significant predictors of massive blood loss in univariate analysis, but only embolization degree was significant in multivariate analysis. Only the presence of the radiculomedullary artery at the target level was significant in both the univariate and multivariate analyses for embolization degree. CONCLUSIONS: In addition to pathological classification, angiographic vascularity assessment is valuable. Although complete embolization is a reasonable goal, it is challenging to achieve in cases of visible radiculomedullary artery. KEY POINTS: • Angiography has a supplementary role in vascularity assessment for spinal metastatic surgery. • Better embolization degree is associated with less intraoperative blood loss in both angiographic hypervascular and nonhypervascular groups. • Presence of radiculomedullary artery in the target level causes worse embolization outcome.

Investigating sphingolipids as biomarkers for the outcomes of acute ischemic stroke patients receiving endovascular treatment.

BACKGROUND: Long-chain ceramides are associated with the mechanisms and clinical outcomes of acute ischemic stroke (AIS). This study aimed to investigate the plasma ceramides and sphingosine-1-phosphate in AIS patients undergoing endovascular thrombectomy (EVT) and their associations with outcomes. METHODS: Plasma samples were collected from 75 AIS patients who underwent EVT before (T1), immediately after (T2), and 24 h after (T3) the procedures and 19 controls that were matched with age, sex, and co-morbidities. The levels of ceramides with different fatty acyl chain lengths and sphingosine-1-phosphate were measured by UHPLC-ESI-MS/MS. A poor outcome was defined as a modified Rankin Scale score of 3-6 at 3 months after stroke. RESULTS: The plasma levels of long-chain ceramides Cer (d18:1/16:0) at all three time points, Cer (d18:1/18:0) at T1 and T3, and Cer (d18:1/20:0) at T1 and very-long-chain ceramide Cer (d18:1/24:1) at T1 were significantly higher in AIS patients than those in the controls. In contrast, the plasma levels of sphingosine-1-phosphate in AIS patients were significantly lower than those in the controls at all three time points. Among the AIS patients, 34 (45.3%) had poor functional outcomes at 3 months poststroke. Multivariable analysis showed that higher levels of Cer (d18:1/16:0) and Cer (d18:1/18:0) at all three time points, Cer (d18:1/20:0) at T1 and T2, and Cer (d18:1/24:0) at T2 remained significantly associated with poor functional outcomes after adjustment for potential confounding factors. CONCLUSION: Plasma ceramides were elevated early in AIS patients with acute large artery occlusion. Furthermore, Cer (d18:1/16:0) and Cer (d18:1/18:0) could be early prognostic indicators for AIS patients undergoing EVT.

Serum amyloid A predicts poor functional outcome in patients with ischemic stroke receiving endovascular thrombectomy: a case control study.

BACKGROUND: Post-stroke inflammation contributes to poor outcomes, but its impact on patients with stroke receiving endovascular thrombectomy (EVT) remains unknown. METHODS: We enrolled adult patients with stroke who received EVT, with blood sampling immediately before (T1) and after EVT (T2), and at 24 hours after EVT (T3). Non-stroke controls and patients with non-EVT stroke were also enrolled. The medical information, image findings and levels of serum amyloid A (SAA) and C-reactive protein (CRP) were analyzed to clarify the association with poor functional outcome (modified Rankin Scale 4-6) at 3 months after stroke. RESULTS: A total of 93 patients with stroke receiving EVT, 51 non-stroke controls, and 64 with non-EVT stroke were enrolled in this study. The SAA and CRP levels at T1 to T3 in patients with stroke receiving EVT were higher compared with those in controls (all p<0.001), and their levels at T3 were significantly higher than those at T1 (both p<0.0001) while similar to those in patients with non-EVT stroke. The SAA levels at the three time points were significantly associated with poor functional outcome (p=0.003 to 0.009). Furthermore, adding SAA level at T3 significantly improved the basic prediction model for 3-month poor functional outcome by receiver operating characteristic (ROC) analysis (areas under ROC curves from 0.803 to 0.878, p=0.03). CONCLUSIONS: Our findings demonstrate that plasma levels of SAA at an early stage are significant predictors for poor functional outcomes at 3 months in patients with stroke receiving EVT, indicating the substantial role of systemic inflammation in shaping stroke outcomes following EVT.

Outcome of endovascular thrombectomy in patients with end-stage renal disease undergoing dialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) are often excluded from clinical trials of endovascular thrombectomy (EVT). This study investigated the outcome in these patients. METHODS: From September 2014 to July 2021, all patients undergoing EVT for anterior circulation stroke in two stroke centers in Taiwan were included. They were divided into no renal dysfunction (non-RD, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2), RD (eGFR <60 mL/min/1.73 m2 but no dialysis), and ESRD undergoing dialysis (ESRD-dialysis). The clinical features and outcomes were compared. RESULTS: Of 482 patients included, there were 20 ESRD-dialysis, 110 RD, and 352 non-RD patients. The Alberta Stroke Program Early CT Score (ASPECTS), National Institutes of Health Stroke Scale (NIHSS), use of intravenous thrombolysis, EVT-related time metrics, and successful recanalization rates were comparable among the three groups. However, the ESRD-dialysis patients had more symptomatic intracerebral hemorrhage (ICH, 15% vs 3.6% vs 3.7%), more contrast-induced encephalopathy (15% vs 1.8% vs 0.9%), and a higher mortality at 90 days (35% vs 18% vs 11%) than the other groups. Multivariable analysis revealed that ESRD-dialysis was associated with a less favorable outcome (OR 0.21, 95% CI 0.04 to 0.77) and more severe disability or mortality (modified Rankin Scale 5 or 6; OR 13.1, 95% CI 3.93 to 48.1) at 90 days. In the ESRD-dialysis group, the patients with premorbid functional dependence had a significantly higher mortality than those without (75% vs 8.3%; P=0.004). CONCLUSION: ESRD-dialysis patients were associated with symptomatic ICH and less favorable outcome at 90 days. Patients with premorbid functional dependency had an excessively high mortality.

Long-term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma.

BACKGROUND: Patients with advanced renal cell carcinoma with sarcomatoid features (sRCC) have a poor prognosis and limited therapeutic options. First-line nivolumab plus ipilimumab (NIVO+IPI) provided efficacy benefits over sunitinib (SUN) in patients with intermediate/poor-risk sRCC at 42 months minimum follow-up in the phase 3 CheckMate 214 trial. In this exploratory post hoc analysis, we report clinical efficacy of NIVO+IPI in sRCC after a minimum follow-up of 5 years. METHODS: In CheckMate 214, patients with clear cell advanced RCC were randomized to NIVO 3 mg/kg plus IPI 1 mg/kg every 3 weeks (four doses), then NIVO 3 mg/kg every 2 weeks versus SUN 50 mg once daily (4 weeks; 6-week cycles). Randomized patients with sRCC were identified via independent central pathology review of archival tumor tissue or histological classification per local pathology report. Overall survival (OS), as well as progression-free survival (PFS) and objective response rate (ORR) per independent radiology review using Response Evaluation Criteria in Solid Tumors V.1.1, were evaluated in all International Metastatic Renal Cell Carcinoma Database Consortium intermediate/poor-risk sRCC patients and by baseline tumor PD-L1 expression level (≥1% vs <1%). Safety outcomes are reported using descriptive statistics. RESULTS: In total, 139 patients with intermediate/poor-risk sRCC were identified (NIVO+IPI, n=74; SUN, n=65). At 5 years minimum follow-up, more patients remained on treatment with NIVO+IPI versus SUN (12% vs zero). Efficacy benefits with NIVO+IPI versus SUN were maintained with median OS of 48.6 vs 14.2 months (HR 0.46), median PFS of 26.5 vs 5.5 months (HR 0.50), and ORR 60.8% vs 23.1%. In addition, median duration of response was longer (not reached vs 25.1 months), and more patients had complete responses (23.0% vs 6.2%) with NIVO+IPI versus SUN, respectively. Efficacy was better with NIVO+IPI versus SUN regardless of tumor PD-L1 expression, but the magnitude of OS, PFS, and ORR benefits with NIVO+IPI was greater for sRCC patients with tumor PD-L1 ≥1%. No new safety signals emerged in either arm with longer follow-up. CONCLUSIONS: Among patients with intermediate/poor-risk sRCC, NIVO+IPI maintained long-term survival benefits and demonstrated durable and deep responses over SUN at minimum follow-up of 5 years, supporting NIVO+IPI as a preferred first-line therapy in this population. TRIAL REGISTRATION NUMBER: NCT02231749.

FRACTION-RCC: nivolumab plus ipilimumab for advanced renal cell carcinoma after progression on immuno-oncology therapy.

BACKGROUND: The role and sequencing of combination immuno-oncology (IO) therapy following progression on or after first-line IO therapy has not been well-established. The Fast Real-time Assessment of Combination Therapies in Immuno-ONcology (FRACTION) program is an open-label, phase 2 platform trial designed to evaluate multiple IO combinations in patients with advanced renal cell carcinoma (aRCC) who progressed during or after prior IO therapy. Here, we describe the results for patients treated with nivolumab plus ipilimumab. For enrollment in track 2 (reported here), patients with histologically confirmed clear cell aRCC, Karnofsky performance status ≥70%, and life expectancy ≥3 months who had previously progressed after IO (anti-programmed death 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4)) therapy were eligible. Previous treatment with anti-CTLA-4 therapy plus anti-PD-1/PD-L1 therapy precluded eligibility for enrollment in the nivolumab plus ipilimumab arm. Patients were treated with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses, followed by nivolumab 480 mg every 4 weeks for up to 2 years or until progression, toxicity, or protocol-specified discontinuation. The primary outcome measures were objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) rate at 24 weeks. Secondary outcomes were safety and tolerability up to 2 years. Overall survival (OS) was a tertiary/exploratory endpoint. Overall, 46 patients were included with a median follow-up of 33.8 months. The ORR was 17.4% (95% CI, 7.8 to 31.4) with eight (17.4%) patients achieving partial response. Stable disease was achieved in 19 (41.3%) patients, while 14 (30.4%) had progressive disease. Median DOR (range) was 16.4 (2.1+ to 27.0+) months. The PFS rate at 24 weeks was 43.2%, and median OS was 23.8 (95% CI, 13.2 to not reached) months. Grade 3-4 immune-mediated adverse events were reported in seven (15.2%) patients. No treatment-related deaths were reported. Patients with aRCC treated with nivolumab plus ipilimumab may derive durable clinical benefit after progression on previous IO therapies, including heavily pretreated patients, with a manageable safety profile that was consistent with previously published safety outcomes. These outcomes contribute to the knowledge of optimal sequencing of IO therapies for patients with aRCC with high unmet needs. TRIAL REGISTRATION NUMBER: NCT02996110.

A Proposed Algorithm for Managing Cerebral Proliferative Angiopathy.

OBJECTIVE: Cerebral proliferative angiopathy (CPA) is a rare disease, characterized by a large vascular nidus, diffuse angiogenesis, and intermingled normal brain tissue. Conservative treatment, endovascular intervention, indirect revascularization, and radiotherapy have been applied to treat this disease. However, some cases deteriorate even after non-conservative treatment, and there has been no standard of treatment for this disease so far. In order to build a better treatment strategy, we review literature, present our case and propose an algorithm for managing CPA. METHODS: Following the PRISMA principle, we systemically reviewed literature discussing CPA. A case successfully managed with multi-modal treatment is also illustrated. RESULTS: A total of 23 articles with 74 cases of CPA were found. Thirty-three patients received single-modal management. These 33 cases include 24 receiving endovascular intervention, 7 receiving indirect revascularization, and 2 receiving radiotherapy. Three of the 33 patients deteriorated clinically, and 1 expired. We present a 6-year-old boy with left hemispheric CPA receiving indirect revascularization, followed by 2 consecutive courses of stereotactic radiosurgery targeting arteriovenous shunts in the left basal ganglia and arteriovenous shunts around the olfactory groove. In the follow-up period of more than 4 years, good collateral formation, improved perilesional perfusion, CPA shrinkage, and symptom relief were all achieved. CONCLUSIONS: Based on our literature review and case, we propose an algorithm for the management of CPA and emphasize that multi-modal treatment is necessary for most CPA cases.

Conditional survival and long-term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma.

BACKGROUND: Conditional survival estimates provide critical prognostic information for patients with advanced renal cell carcinoma (aRCC). Efficacy, safety, and conditional survival outcomes were assessed in CheckMate 214 (ClinicalTrials.gov identifier NCT02231749) with a minimum follow-up of 5 years. METHODS: Patients with untreated aRCC were randomized to receive nivolumab (NIVO) (3 mg/kg) plus ipilimumab (IPI) (1 mg/kg) every 3 weeks for 4 cycles, then either NIVO monotherapy or sunitinib (SUN) (50 mg) daily (four 6-week cycles). Efficacy was assessed in intent-to-treat, International Metastatic Renal Cell Carcinoma Database Consortium intermediate-risk/poor-risk, and favorable-risk populations. Conditional survival outcomes (the probability of remaining alive, progression free, or in response 2 years beyond a specified landmark) were analyzed. RESULTS: The median follow-up was 67.7 months; overall survival (median, 55.7 vs 38.4 months; hazard ratio, 0.72), progression-free survival (median, 12.3 vs 12.3 months; hazard ratio, 0.86), and objective response (39.3% vs 32.4%) benefits were maintained with NIVO+IPI versus SUN, respectively, in intent-to-treat patients (N = 550 vs 546). Point estimates for 2-year conditional overall survival beyond the 3-year landmark were higher with NIVO+IPI versus SUN (intent-to-treat patients, 81% vs 72%; intermediate-risk/poor-risk patients, 79% vs 72%; favorable-risk patients, 85% vs 72%). Conditional progression-free survival and response point estimates were also higher beyond 3 years with NIVO+IPI. Point estimates for conditional overall survival were higher or remained steady at each subsequent year of survival with NIVO+IPI in patients stratified by tumor programmed death ligand 1 expression, grade ≥3 immune-mediated adverse event experience, body mass index, and age. CONCLUSIONS: Durable clinical benefits were observed with NIVO+IPI versus SUN at 5 years, the longest phase 3 follow-up for a first-line checkpoint inhibitor-based combination in patients with aRCC. Conditional estimates indicate that most patients who remained alive or in response with NIVO+IPI at 3 years remained so at 5 years.