Membrane-bound Merkel cell polyomavirus middle T protein constitutively activates PLCγ1 signaling through Src-family kinases.

Merkel cell polyomavirus (MCV or MCPyV) is an alphapolyomavirus causing human Merkel cell carcinoma and encodes four tumor (T) antigen proteins: large T (LT), small tumor (sT), 57 kT, and middle T (MT)/alternate LT open reading frame proteins. We show that MCV MT is generated as multiple isoforms through internal methionine translational initiation that insert into membrane lipid rafts. The membrane-localized MCV MT oligomerizes and promiscuously binds to lipid raft-associated Src family kinases (SFKs). MCV MT-SFK interaction is mediated by a Src homology (SH) 3 recognition motif as determined by surface plasmon resonance, coimmunoprecipitation, and bimolecular fluorescence complementation assays. SFK recruitment by MT leads to tyrosine phosphorylation at a SH2 recognition motif (pMTY114), allowing interaction with phospholipase C gamma 1 (PLCγ1). The secondary recruitment of PLCγ1 to the SFK-MT membrane complex promotes PLCγ1 tyrosine phosphorylation on Y783 and activates the NF-κB inflammatory signaling pathway. Mutations at either the MCV MT SH2 or SH3 recognition sites abrogate PLCγ1-dependent activation of NF-κB signaling and increase viral replication after MCV genome transfection into 293 cells. These findings reveal a conserved viral targeting of the SFK-PLCγ1 pathway by both MCV and murine polyomavirus (MuPyV) MT proteins. The molecular steps in how SFK-PLCγ1 activation is achieved, however, differ between these two viruses.

Recent Advances in RNA-Targeted Cancer Therapy.

Ribonucleic acid (RNA) plays a pivotal role in gene regulation and protein biosynthesis. Interfering the physiological function of key RNAs to induce cell apoptosis holds great promise for cancer treatment. Many RNA-targeted anti-cancer strategies have emerged continuously. Among them, RNA interference (RNAi) has been recognized as a promising therapeutic modality for various disease treatments. Nevertheless, the primary obstacle in siRNA delivery-escaping the endosome and crossing the plasma membrane severely impedes its therapeutic potential. Thus far, a variety of nanosystems as well as carrier-free bioconjugation for siRNA delivery have been developed and employed to enhance the drug delivery and anti-tumor efficiency. Besides, the use of small molecules to target specific RNA structures and disrupt their function, along with the covalent modification of RNA, has also drawn tremendous attention recently owing to high therapeutic efficacy. In this review, we will provide an overview of recent progress in RNA-targeted cancer therapy including various siRNA delivery strategies, RNA-targeting small molecules, and newly emerged covalent RNA modification. Finally, challenges and future perspectives faced in this research field will be discussed.

Gadolinium Retention and Nephrotoxicity in a Mouse Model of Acute Ischemic Stroke: Linear Versus Macrocyclic Agents.

BACKGROUND: Gadolinium (Gd)-based contrast agents (GBCAs) have been widely used for acute ischemic stroke (AIS) patients. GBCAs or AIS alone may cause the adverse effects on kidney tissue, respectively. However, whether GBCAs and AIS would generate a synergistic negative effect remains undefined. PURPOSE: To evaluate synergistic negative effects of AIS and GBCAs on renal tissues in a mouse model of AIS, and to compare the differences of these negative effects between linear and macrocyclic GBCAs. STUDY TYPE: Animal study. ANIMAL MODEL: Seventy-two healthy mice underwent transient middle cerebral artery occlusion (tMCAO) and sham operation to establish AIS and sham model (N = 36/model). 5.0 mmol/kg GBCAs (gadopentetate or gadobutrol) or 250 µL saline were performed at 4.5 hours and 1 day after model establishing (N = 12/group). ASSESSMENT: Inductively coupled plasma mass spectrometry (ICP-MS) was performed to detect Gd concentrations. Serum biochemical analyzer was performed to measure the serum creatinine (Scr), uric acid (UA), and blood urea nitrogen (BUN). Pathological staining was performed to observe tubular injury, cell apoptosis, mesangial hyperplasia, and interstitial fibrosis. STATISTICAL TESTS: Two-way analysis of variances with post hoc Sidak's tests and independent-samples t-tests were performed. A P-value <0.05 was considered statistically significant. RESULTS: AIS groups showed higher Gd concentration than sham group on day 1 p.i. regardless of gadopentetate or gadobutrol used. Increased total Gd concentration was also found in AIS + gadopentetate group compared with the sham group on day 28 p.i. Significantly higher rates for renal dysfunction, higher tubular injury scores, and higher numbers of apoptotic cells on days 1 or 28 p.i. were found for AIS mice injected with GBCA. AIS + gadopentetate group displayed more severe renal damage than the AIS + gadobutrol group. DATA CONCLUSION: AIS and GBCAs may cause increased total Gd accumulation and nephrotoxicity in a mouse, especially linear GBCAs were used. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

Aneurysmal subarachnoid hemorrhage complicating spinal subarachnoid hematoma causing acute cauda equina syndrome: a case report.

BACKGROUND: Spinal subarachnoid hematoma (SSH) is a known but rare entity that can cause cauda equina compression. The occurrence of SSH associated with aneurysmal subarachnoid hemorrhage has rarely been described in the literature. CASE PRESENTATION: A 56-year-old woman presented with subarachnoid hemorrhage secondary to a ruptured middle cerebral artery aneurysm and was managed with coiling embolization without stent assistance. There was no history of either lumbar puncture or the use of anticoagulants. The patient developed severe lumbago radiating to bilateral legs nine days after the procedure. Subsequent magnetic resonance imaging demonstrated a SSH extending from L5 to S2 and wrapping around the cauda equina. The patient was treated with intravenous methylprednisolone (250 mg/day) for four consecutive days, followed by a taper of oral prednisolone (20 mg/day) until complete recovery. Magnetic resonance imaging at one month follow-up revealed complete resolution of the SSH. CONCLUSIONS: Here, we report a case of acute cauda equina syndrome caused by a SSH after aneurysmal subarachnoid hemorrhage, which will facilitate timely intervention of patients with this disorder.

Potential Approach to Quantifying the Volume of the Ischemic Core in Truncated Computed Tomography Perfusion Scans: A Preliminary Study.

OBJECTIVE: This study aimed to provide an alternative approach for quantifying the volume of the ischemic core (IC) if truncation of computed tomography perfusion (CTP) occurs in clinical practice. METHODS: Baseline CTP and follow-up diffusion-weighted imaging (DWI) data from 88 patients with stroke were retrospectively collected. CTP source images (CTPSI) from the unenhanced phase to the peak arterial phase (CTPSI-A) or the peak venous phase (CTPSI-V) were collected to simulate the truncation of CTP in the arterial or venous phases, respectively. The volume of IC on CTPSI-A (V CTPSI-A ) or CTPSI-V (V CTPSI-V ) was defined as the volume of the brain tissue with >65% reduction in attenuation compared with that of the normal tissue. The volume of IC on the baseline CTP (V CTP ) was defined as a relative cerebral blood flow of <30% of that in the normal tissue. The volume of the posttreatment infarct on the follow-up DWI (V DWI ) image was manually delineated and calculated. One-way analysis of variance, Bland-Altman plots, and Spearman correlation analyses were used for the statistical analysis. RESULTS: V CTPSI-A was significantly higher than V DWI ( P < 0.001); however, no significant difference was observed between V CTP and V DWI ( P = 0.073) or between V CTPSI-V and V DWI ( P > 0.999). The mean differences between V DWI and V CTPSI-V , V DWI and V CTP , and V DWI and V CTPSI-A were 1.70 mL (limits of agreement [LoA], -56.40 to 59.70), 8.30 mL (LoA, -40.70 to 57.30), and -68.10 mL (LoA, -180.90 to 44.70), respectively. Significant correlations were observed between V DWI and V CTP ( r = 0.68, P < 0.001) and between V DWI and V CTPSI-V ( r = 0.39, P < 0.001); however, no significant correlation was observed between V DWI and V CTPSI-A ( r = 0.20, P = 0.068). CONCLUSIONS: V CTPSI-V may be a promising method for quantifying the volume of the IC if truncation of CTP occurs.

Preoperative Contrast-Enhanced Ultrasound Predicts Microvascular Invasion in Hepatocellular Carcinoma as Accurately as Contrast-Enhanced MR.

OBJECTIVES: Both contrast-enhanced ultrasound (CEUS) and contrast-enhanced magnetic resonance (CEMR) are important imaging methods for hepatocellular carcinoma (HCC). This study aimed to establish a model using preoperative CEUS parameters to predict microvascular invasion (MVI) in HCC, and compare its predictive efficiency with that of CEMR model. METHODS: A total of 93 patients with HCC (39 cases in MVI positive group and 54 cases in MVI negative group) who underwent surgery in our hospital from January 2020 to June 2021 were retrospectively analyzed. Their clinical and imaging data were collected to establish CEUS and CEMR models for predicting MVI. The predictive efficiencies of both models were compared. RESULTS: By the univariate and multivariate regression analyses of patients' clinical information, preoperative CEUS static and dynamic images, we found that serrated edge and time to peak were independent predictors of MVI. The CEUS prediction model achieved a sensitivity of 92.3%, a specificity of 83.3%, and an accuracy of 84.6% (Az: 0.934). By analyzing the clinical and CEMR information, we found that tumor morphology, fast-in and fast-out, peritumoral enhancement, and capsule were independent predictors of MVI. The CEMR prediction model achieved a sensitivity of 97.4%, a specificity of 77.8%, and an accuracy of 83.2% (Az: 0.900). The combination of the two models achieved a sensitivity of 84.6%, a specificity of 87.0%, and an accuracy of 86.2% (Az: 0.884). There was no significant statistical difference in the areas under the ROC curve of the three models. CONCLUSION: The CEUS model and the CEMR model have similar predictive efficiencies for MVI of HCC. CEUS is also an effective method to predict MVI before operation.

High-throughput precision MRI assessment with integrated stack-ensemble deep learning can enhance the preoperative prediction of prostate cancer Gleason grade.

BACKGROUND: To develop and test a Prostate Imaging Stratification Risk (PRISK) tool for precisely assessing the International Society of Urological Pathology Gleason grade (ISUP-GG) of prostate cancer (PCa). METHODS: This study included 1442 patients with prostate biopsy from two centres (training, n = 672; internal test, n = 231 and external test, n = 539). PRISK is designed to classify ISUP-GG 0 (benign), ISUP-GG 1, ISUP-GG 2, ISUP-GG 3 and ISUP GG 4/5. Clinical indicators and high-throughput MRI features of PCa were integrated and modelled with hybrid stacked-ensemble learning algorithms. RESULTS: PRISK achieved a macro area-under-curve of 0.783, 0.798 and 0.762 for the classification of ISUP-GGs in training, internal and external test data. Permitting error ±1 in grading ISUP-GGs, the overall accuracy of PRISK is nearly comparable to invasive biopsy (train: 85.1% vs 88.7%; internal test: 85.1% vs 90.4%; external test: 90.4% vs 94.2%). PSA ≥ 20 ng/ml (odds ratio [OR], 1.58; p = 0.001) and PRISK ≥ GG 3 (OR, 1.45; p = 0.005) were two independent predictors of biochemical recurrence (BCR)-free survival, with a C-index of 0.76 (95% CI, 0.73-0.79) for BCR-free survival prediction. CONCLUSIONS: PRISK might offer a potential alternative to non-invasively assess ISUP-GG of PCa.

Gadolinium retention in the ischemic cerebrum: Implications for pain, neuron loss, and neurological deficits.

PURPOSE: To investigate the effects of gadolinium (Gd) retention of macrocyclic (gadobutrol) or linear (gadopentetate) Gd-based contrast agents (GBCAs) on neuron loss, neurological deficits, and sensory behavior in mice with or without stroke. METHODS: Ninety C57BL/6 mice underwent sham (n = 36) or transient middle cerebral artery occlusion (tMCAO) (n = 54) surgery and then received intraperitoneal injections of 5.0 mmol/kg gadobutrol, 5.0 mmol/kg gadopentetate or saline (10 ml/kg/administration) per day for 3 consecutive days. The Gd concentration in the ischemic cerebrum was quantified by inductively coupled plasma mass spectrometry on Day 1 and Day 28 after the last injection (post-injection, p. i.). Neuron loss, glia activation and neurological deficits were assessed on Day 1 and 28 p. i. Sensory behavior was also assessed on Day 28 p. i. RESULTS: Gd concentrations were higher in the brains of tMCAO mice than in those of sham mice on Days 1 p. i. of both GBCAs (gadobutrol, p &lt; 0.05; gadopentetate, p &lt; 0.001) and 28 p. i of gadopentetate. (p &lt; 0.001). Sham or tMCAO mice injected with GBCAs showed no significant difference in neuron loss, glia activation, neurological deficits, brain atrophy, or hippocampus-dependent memory (all p &gt; 0.05). Both gadobutrol and gadopentetate induced mechanical and heat hyperalgesia in sham mice (all p &lt; 0.05). However, mechanical hyperalgesia but rather heat hyperalgesia was found in tMCAO mice with the highest force tested (1.0 g) and statistically significant in both paws (right and left) with gadopentetate only (p &lt; 0.05). CONCLUSIONS: Neither gadobutrol nor gadopentetate worsened neuron loss, glia activation, brain atrophy, neurological deficits, or hippocampus-dependent memory after tMCAO. However, GBCA administration induced mechanical hyperalgesia in sham and tMCAO mice although in the same level, which may be an important consideration for patients with central post-stroke pain and those who are sensitive to pain and about to receive multiple GBCA administrations.

Does the presence of systemic artery-pulmonary circulation shunt during bronchial arterial embolization increase the recurrence of noncancer-related hemoptysis? A retrospective cohort study.

BACKGROUND: The presence of systemic artery-pulmonary circulation shunt (SPS) during the bronchial arterial embolization (BAE) procedure, has been inferred to be a potential risk factor for recurrence. The aim of this study is to reveal the impact of SPS on the recurrence of noncancer-related hemoptysis after BAE. METHODS: In this study, 134 patients with SPS (SPS-present group) and 192 patients without SPS (SPS-absent group) who underwent BAE for noncancer-related hemoptysis from January 2015 to December 2020 were compared. Four different Cox proportional hazards regression models were used to clarify the impact of SPSs on hemoptysis recurrence after BAE. RESULTS: During the median follow-up time of 39.8 months, recurrence occurred in 75 (23.0%) patients, including 51 (38.1%) in the SPS-present group and 24 (12.5%) in the SPS-absent group. The 1-month, 1-year, 2-year, 3-year and 5-year hemoptysis-free survival rates in the SPS-present and SPS-absent groups were 91.8%, 79.7%, 70.6%, 62.3%, and 52.6% and 97.9%, 94.7%, 89.0%, 87.1%, and 82.3%, respectively (P < 0.001). The adjusted hazard ratios of SPSs in the four models were 3.37 [95% confidence intervals (CI), 2.07-5.47, P < 0.001 in model 1], 1.96 (95% CI, 1.11-3.49, P = 0.021 in model 2), 2.29 (95% CI, 1.34-3.92, P = 0.002 in model 3), and 2.39 (95% CI, 1.44-3.97, P = 0.001 in model 4). CONCLUSIONS: The presence of SPS during BAE increases the recurrence probability of noncancer-related hemoptysis after BAE.

Predictors of ghost infarct core on baseline computed tomography perfusion in stroke patients with successful recanalization after mechanical thrombectomy.

OBJECTIVES: To assess the predictors of ghost infarct core (GIC) in stroke patients achieving successful recanalization after mechanical thrombectomy (MT), based on final infarct volume (FIV) calculated from follow-up diffusion-weighted imaging (DWI). METHODS: A total of 115 consecutive stroke patients who had undergone baseline computed tomography perfusion (CTP) scan, achieved successful recanalization after MT, and finished follow-up DWI evaluation were retrospectively enrolled. Ischemic core volume was automatically generated from baseline CTP, and FIV was determined manually based on follow-up DWI. Stroke-related risk factors and demographic, clinical, imaging, and procedural data were collected and assessed. Univariate and multivariate analyses were applied to identify the predictors of GIC. RESULTS: Of the 115 included patients (31 women and 84 men; median age, 66 years), 18 patients (15.7%) showed a GIC. The GIC group showed significantly shorter time interval from stroke onset to CTP scan and that from stroke onset to recanalization (both p < 0.001), but higher ischemic core volume (p < 0.001), hypoperfused area volume (p < 0.001), mismatch area volume (p = 0.006), and hypoperfusion ratio (p = 0.001) than the no-GIC group. In multivariate analysis, time interval from stroke onset to CTP scan (odds ratio [OR], 0.983; p = 0.005) and ischemic core volume (OR, 1.073; p < 0.001) were independently associated with the occurrence of GIC. CONCLUSIONS: In stroke patients achieving successful recanalization after MT, time interval from stroke onset to CTP and ischemic core volume are associated with the occurrence of GIC. Patients cannot be excluded from MT solely based on baseline CTP-derived ischemic core volume, especially for patients with a shorter onset time. KEY POINTS: • Ghost infarct core (GIC) was found in 15.7% of patients with acute ischemic stroke (AIS) in our study cohort. • GIC was associated with stroke onset time, volumetric parameters derived from CTP, and collateral status indicated by HIR. • Time interval from stroke onset to CTP scan and ischemic core volume were independent predictors of GIC.

Predictors of malignant middle cerebral artery infarction after endovascular thrombectomy: results of DIRECT-MT trial.

OBJECTIVES: Predictors of malignant middle cerebral artery infarction (mMCAi) in patients after intravenous thrombolysis were well documented, but the risk factors of mMCAi after endovascular thrombectomy (EVT) were not fully explored. Therefore, the present study aimed to investigate the predictors of mMCAi after EVT in stroke patients. METHODS: This was a secondary analysis of the DIRECT-MT trial. Patients who underwent EVT for the occlusions of MCA and/or intracranial internal carotid artery were analyzed. Primary outcome was the occurrence of mMCAi after EVT. Demographic, clinical, imaging, and treatment data were recorded, and multivariate logistic regression analysis was used to identify independent predictors. All of the candidate predictors were included, and forward elimination was applied to establish the most effective predictive model. Predictive ability and calibration of the model were assessed using the area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow test, respectively. RESULTS: Of 559 enrolled patients, 74 (13.2%) patients developed mMCAi. Predictors of mMCAi included unsuccessful reperfusion, higher serum glucose, lower Alberta Stroke Project Early Computed Tomography Change Score (ASPECTS), higher clot burden score (CBS), lower collateral score, and higher pass number of thrombectomy device. AUC of predictive model integrating all independent variables was 0.836. The Hosmer-Lemeshow test showed appropriate calibration (p = 0.859). CONCLUSIONS: Reperfusion, serum glucose, ASPECTS, CBS, collateral, and pass number of thrombectomy device were associated with the occurrence of mMCAi in stroke patients after EVT, while alteplase treatment was not. Our findings might facilitate the early identification and management of stroke patients at a high risk of mMCAi. KEY POINTS: • A total of 13.2% of stroke patients with large vessel occlusion of anterior circulation developed mMCAi after EVT. • The occurrence of mMCAi had a definite negative impact on the outcome for stroke patients. • Reperfusion, serum glucose, ASPECTS, CBS, collateral score, and the pass number of thrombectomy device were associated with the occurrence of mMCAi after EVT in stroke patients.

ASPECTS-based net water uptake outperforms target mismatch for outcome prediction in patients with acute ischemic stroke and late therapeutic window.

OBJECTIVE: To compare the prognostic value of net water uptake (NWU) and target mismatch (TM) on CT perfusion (CTP) in acute ischemic stroke (AIS) patients with late time window. METHODS: One hundred and nine consecutive AIS patients with anterior-circulation large vessel occlusion presenting within 6-24 h from onset/last seen well were enrolled. Automated Alberta Stroke Program Early CT Score-based NWU (ASPECTS-NWU) was calculated from admission CT. The correlation between ASPECTS-NWU and CTP parameters was assessed. Predictors for favorable outcome (modified Rankin Scale score ≤ 2) at 90 days were assessed using logistic regression analysis. The ability of outcome prediction between ASPECTS-NWU and TM (an ischemic core < 70 mL, a mismatch ratio ≥ 1.8, and an absolute difference ≥ 15 mL) was compared using receiver operating characteristic (ROC) curve. RESULTS: A higher level of ASPECTS-NWU was associated with a larger ischemic core (r = 0.66, p < 0.001) and a larger hypoperfusion volume (r = 0.38, p < 0.001). ASPECTS-NWU performed better than TM for outcome stratification (area under the curve [AUC], 0.738 vs 0.583, p = 0.004) and was the only independent neuroimaging marker associated with favorable outcomes compared with CTP parameters (odds ratio, 0.73; 95% confidence interval [CI] 0.62-0.87, p < 0.001). An outcome prediction model including ASPECTS-NWU and clinical variables (National Institutes of Health Stroke Scale scores and age) yielded an AUC of 0.828 (95% CI 0.744-0.893; sensitivity 65.4%; specificity 87.7%). CONCLUSION: ASPECTS-NWU performed better than TM for outcome prediction in AIS patients with late time window and might be an alternative imaging biomarker to CTP for patient selection. CLINICAL RELEVANCE STATEMENT: Automated Alberta Stroke Program Early CT Score-based net water uptake outperforms target mismatch on CT perfusion for the outcome prediction in patients with acute ischemic stroke and can be an alternative imaging biomarker for patient selection in late therapeutic window. KEY POINTS: • A higher ASPECTS-based net water uptake was associated with larger ischemic cores and hypoperfusion volumes on CT perfusion. • ASPECTS-based net water uptake outperformed target mismatch for outcome prediction in acute ischemic stroke with extended therapeutic window. • ASPECTS-based net water uptake can be an alternative biomarker to target mismatch for selecting acute ischemic stroke patients with late therapeutic window.

Diffusion-relaxation correlation spectrum imaging for predicting tumor consistency and gross total resection in patients with pituitary adenomas: a preliminary study.

OBJECTIVE: To evaluate the ability of diffusion-relaxation correlation spectrum imaging (DR-CSI) to predict the consistency and extent of resection (EOR) of pituitary adenomas (PAs). METHODS: Forty-four patients with PAs were prospectively enrolled. Tumor consistency was evaluated at surgery as either soft or hard, followed by histological assessment. In vivo DR-CSI was performed and spectra were segmented following to a peak-based strategy into four compartments, designated A (low ADC), B (mediate ADC, short T2), C (mediate ADC, long T2), and D (high ADC). The corresponding volume fractions ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]) along with the ADC and T2 values were calculated and assessed using univariable analysis for discrimination between hard and soft PAs. Predictors of EOR > 95% were analyzed using logistic regression model and receiver-operating-characteristic analysis. RESULTS: Tumor consistency was classified as soft (n = 28) or hard (n = 16). Hard PAs presented higher [Formula: see text] (p = 0.001) and lower [Formula: see text] (p = 0.013) than soft PAs, while no significant difference was found in other parameters. [Formula: see text] significantly correlated with the level of collagen content (r = 0.448, p = 0.002). Knosp grade (odds ratio [OR], 0.299; 95% confidence interval [CI], 0.124-0.716; p = 0.007) and [Formula: see text] (OR, 0.834, per 1% increase; 95% CI, 0.731-0.951; p = 0.007) were independently associated with EOR > 95%. A prediction model based on these variables yielded an AUC of 0.934 (sensitivity, 90.9%; specificity, 90.9%), outperforming the Knosp grade alone (AUC, 0.785; p < 0.05). CONCLUSION: DR-CSI may serve as a promising tool to predict the consistency and EOR of PAs. CLINICAL RELEVANCE STATEMENT: DR-CSI provides an imaging dimension for characterizing tissue microstructure of PAs and may serve as a promising tool to predict the tumor consistency and extent of resection in patients with PAs. KEY POINTS: • DR-CSI provides an imaging dimension for characterizing tissue microstructure of PAs by visualizing the volume fraction and corresponding spatial distribution of four compartments ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]). • [Formula: see text] correlated with the level of collagen content and may be the best DR-CSI parameter for discrimination between hard and soft PAs. • The combination of Knosp grade and [Formula: see text] achieved an AUC of 0.934 for predicting the total or near-total resection, outperforming the Knosp grade alone (AUC, 0.785).

Spatial accuracy of computed tomography perfusion to estimate the follow-up infarct on diffusion-weighted imaging after successful mechanical thrombectomy.

BACKGROUND: Volumetric accuracy of using computed tomography perfusion (CTP) to estimate the post-treatment infarct in stroke patients with successful recanalization after mechanical thrombectomy (MT) has been studied a lot, however the spatial accuracy and its influence factors has not been fully investigated. METHODS: This retrospective study reviewed the data from consecutive anterior large vessel occlusion (LVO) patients who had baseline CTP, successful recanalization after MT, and post-treatment diffusion-weighed imaging (DWI). Ischemic core on baseline CTP was estimated using relative cerebral blood flood (CBF) of < 30%. The infarct area was outlined manually on post-treatment DWI, and registered to CTP. Spatial agreement was assessed using the Dice similarity coefficient (DSC) and average Hausdorff distance. According to the median DSC, the study population was dichotomized into high and low Dice groups. Univariable and multivariable regression analyses were used to determine the factors independently associated with the spatial agreement. RESULTS: In 72 included patients, the median DSC was 0.26, and the median average Hausdorff distance was 1.77 mm. High Dice group showed significantly higher median ischemic core volume on baseline CTP (33.90 mL vs 3.40 mL, P < 0.001), lower proportion of moderate or severe leukoaraiosis [27.78% vs 52.78%, P = 0.031], and higher median infarct volume on follow-up DWI (51.17 mL vs 9.42 mL, P < 0.001) than low Dice group. Ischemic core volume on baseline CTP was found to be independently associated with the spatial agreement (OR, 1.092; P < 0.001). CONCLUSIONS: CTP could help to spatially locate the post-treatment infarct in anterior LVO patients who achieving successful recanalization after MT. Ischemic core volume on baseline CTP was independently associated with the spatial agreement.

Impact on etiology diagnosis by high-resolution vessel wall imaging in young adults with ischemic stroke or transient ischemic attack.

PURPOSE: The etiological features of stroke in young adults are different from those in older adults. We aimed to investigate the impact of high-resolution vessel wall imaging (HRVWI) on etiologic diagnosis in young adults with ischemic stroke or transient ischemic attack (TIA). METHODS: A total of 253 young adults (aged 18-45 years) who consecutively underwent HRVWI for clarifying stroke etiology were retrospectively recruited. Two experienced neurologists classified stroke etiology for each patient using Trial of Org 10,172 in Acute Stroke Treatment categories with and without the inclusion of HRVWI diagnosis. Multivariate logistic regression was performed to determine which etiologic category would be significantly impacted after including HRVWI. RESULTS: The etiologic classification was altered in 39.1% (99/253) of patients after including HRVWI in the conventional investigations. The proportion of patients classified as having stroke of undetermined etiology (SUE) and the proportion of patients classified as having small-artery occlusion (SAO) both significantly decreased (36.4 to 13.8% and 9.1 to 2.0%), whereas the proportion of patients classified as having large artery atherosclerosis (LAA) significantly increased (28.5 to 58.1%) (all P < 0.001). The inclusion of HRVWI had a significant diagnostic impact on young adults who were primarily classified as SAO (odds ratio [OR] 14.4, 95% confidence interval [CI] [2.9, 71.8], P < 0.001) or SUE (OR 8.3, 95% CI [2.2, 31.5], P < 0.01). CONCLUSIONS: HRVWI had a substantial impact on etiologic classification in young adults with ischemic stroke or TIA, particularly for those primarily classified as having SAO or SUE. This impact of HRVWI will be beneficial for therapeutic decision-making.

Subcortical infarcts on admission CTP predict poor outcome despite excellent reperfusion in delayed time windows.

PURPOSE: The effect of pretreatment infarct location on clinical outcome after successful mechanical thrombectomy is not understood. Our aim was to evaluate the association between computed tomography perfusion (CTP)-based ischemic core location and clinical outcome following excellent reperfusion in late time windows. METHODS: We retrospectively reviewed patients who underwent thrombectomy for acute anterior circulation large vessel occlusion in late time windows from October 2019 to June 2021 and enrolled 65 patients with visible ischemic core on admission CTP who had received excellent reperfusion (modified thrombolysis in cerebral infarction grade 2c/3). Poor outcome was defined as a modified Rankin scale score of 3-6 at 90 days. The ischemic core infarct territories were classified into the cortical and subcortical areas. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were used in this study. RESULTS: Of the 65 patients analyzed, 38 (58.5%) had a poor outcome. Multivariable logistic analysis showed that the subcortical infarcts (OR 11.75; 95% CI 1.79-77.32; P = 0.010) and their volume (OR 1.17; 95% CI 1.04-1.32; P = 0.011) were independently associated with poor outcome. The ROC curve indicated the capacity of the subcortical infarct involvement (areas under the curve (AUC) = 0.65; 95% CI, 0.53-0.77, P < 0.001) and subcortical infarct volume (AUC = 0.72; 95% CI, 0.60-0.83, P < 0.001) in predicting poor outcome accurately. CONCLUSION: Subcortical infarcts and their volume on admission CTP are associated with poor outcome after excellent reperfusion in late time windows, rather than cortical infarcts.

A nomogram for predicting thrombus composition in stroke patients with large vessel occlusion: combination of thrombus density and perviousness with clinical features.

PURPOSE: To establish a nomogram incorporating pretreatment imaging parameters and clinical characteristics for predicting the thrombus composition of acute ischemic stroke (AIS) with large vessel occlusion (LVO). METHODS: We retrospectively enrolled patients with occlusion of the Middle Cerebral Artery (MCA) who underwent Mechanical Thrombectomy (MT). Retrieved thrombi were stained with Hematoxylin and Eosin (H&E) and Martius Scarlet Blue (MSB). Thrombi are assigned to the Fibrin-rich or RBC-rich group based on the relative fractions of Red Blood Cells (RBC), fibrin, and platelet. The independent risk factors for Fibrin-rich clots were determined via univariate and multivariate logistic regression analysis and were then integrated to establish a nomogram. RESULTS: In total, 98 patients were included in this study. Patients with fibrin-rich clots had worse functional outcome [modified Rankin scale (mRS) 0-2, 34.7% vs 63.2%, p = 0.005], longer procedure time (76.8 min vs 50.8 min, p = 0.001), and increased maneuvers of MT (1.84 vs 1.46, p = 0.703) than those with RBC-rich clots. The independent risk factors for Fibrin-rich clots were lower perviousness measured by Non-Contrast Computer Tomography (NCCT) and CT Angiography (CTA), lower thrombus relative attenuation on NCCT, elevated Platelet-WBC ratio (PWR) of admission peripheral blood, and previous antithrombotic medication. The nomogram showed good discrimination with an area under the Receiver Operating Characteristic (ROC) curve (AUC) of 0.852 (95% CI: 0.778-0.926). The calibration curve and decision curve analysis also displayed satisfactory accuracy and clinical utility. CONCLUSION: This study has developed and internally validated an easy-to-use nomogram which can help predict clot composition and optimize therapeutic strategies for thrombectomy.

CT perfusion with increased temporal sampling interval to predict target mismatch status in patients with acute ischemic stroke.

PURPOSE: To evaluate the feasibility of using CT perfusion (CTP) with increased temporal sampling interval to predict the target mismatch status in acute ischemic stroke (AIS) patients with anterior circular large-vessel occlusion (LVO). METHODS: CTP with a sampling interval of 1.7 s (CTP1.7 s) was scanned in 77 AIS patients for pre-treatment evaluation. Simulated CTP data with sampling interval of 3.4 s (CTP3.4 s) or 5.1 s (CTP5.1 s) were reconstructed, respectively. Target mismatch was defined according to the EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) trial criteria, respectively. Pearson correlation analysis, Mann-Whitney U test, Bland-Altman analysis, and chi-square test were used for statistical analysis as appropriate. RESULTS: Significant correlations were found on the volume of ischemic core, hypo-perfused area, mismatch area, and ratio between CTP1.7 s and CTP3.4 s or CTP5.1 s (all p < 0.001). There was no significant difference on the volume of ischemic core, hypo-perfused area, mismatch area, and mismatch ratio between CTP1.7 s and CTP3.4 s or CTP5.1 s (all p > 0.05). Compared with CTP1.7 s, CTP3.4 s or CTP5.1 s showed comparable performance in predicting the target mismatch status in the AIS patients with LVO (both p > 0.05). CONCLUSIONS: CTPs with increased temporal sampling intervals that lead to reduced radiation doses are feasible and may provide comparable performance in predicting target mismatch status in AIS patients with LVO.

Survival prediction for patients with malignant biliary obstruction caused by pancreatic cancer undergoing biliary drainage: the COMBO-PaS model.

BACKGROUND: Patients with pancreatic cancer-caused biliary obstruction (PC-BO) have poor prognosis, but we lack of tools to predict survival for clinical decision-making. This study aims to establish a model for survival prediction among patients with PC-BO. METHODS: A total of 172 patients with PC-BO treated with percutaneous biliary drainage were randomly divided into a training group (n = 120) and a validation group (n = 52). The independent risk factors for overall survival were selected to develop a Cox model. The predictive performance of M stage, hepatic metastases, cancer antigen 199, and the Cox model was determined. Naples prognostic score (NPS), the prognostic nutritional index (PNI), and the controlling nutritional status (CONUT) for 1-month mortality risk were compared with the Cox model. RESULTS: The Cox model was developed based on total cholesterol, direct bilirubin, hepatic metastases, cancer antigen 199, stenosis type, and preprocedural infection (all P < 0.05), which named "COMBO-PaS." The COMBO-PaS model had the highest area under the curves (AUC) (0.801-0.933) comparing with other predictors (0.506-0.740) for 1-, 3-, and 6-month survival prediction. For 1-month mortality risk prediction, the COMBO-PaS model had the highest AUC of 0.829 comparing with NPS, PNI, and CONUT. CONCLUSION: The COMBO-PaS model was useful for survival prediction among patients with PC-BO.

Effect of Truncal-Type Occlusion Based on Multiphase or Single-Phase Computed Tomographic Angiography in Predicting Intracranial Atherosclerotic Stenosis-Related Acute Middle Cerebral Artery Occlusion.

OBJECTIVE: To investigate whether truncal-type occlusion based on multiphase computed tomographic angiography (mpCTA) was more effective for predicting intracranial atherosclerotic stenosis-related occlusion (ICAS-O) than occlusion type based on single-phase computed tomographic angiography (spCTA) in patients with acute ischemic stroke with large-vessel occlusion (AIS-LVO) in the middle cerebral artery (MCA). METHODS: Data were retrospectively collected from 72 patients with AIS-LVO in the MCA between January 2018 and December 2019. The occlusion types included truncal-type and branching-site occlusions. The association between ICAS-O and occlusion type based on the 2 computed tomographic angiography patterns was analyzed, and receiver operating characteristic curves were plotted for assessment. The areas under the curve were compared to determine the difference between the predictive powers of truncal-type occlusion based on mpCTA and spCTA. RESULTS: Among the 72 patients, 16 were classified as having ICAS-O and 56 as having embolisms. In univariate analysis, truncal-type occlusion was significantly associated with ICAS-O ( P < 0.001 for mpCTA and P = 0.001 for spCTA). After multivariable analysis, truncal-type occlusion based on both mpCTA and spCTA remained independently associated with ICAS-O ( P = 0.002 for mpCTA and P = 0.029 for spCTA). The areas under the curve were 0.821 for mpCTA and 0.683 for spCTA; this difference was statistically significant ( P = 0.024). CONCLUSIONS: In patients with AIS-LVO in the MCA, truncal-type occlusion based on mpCTA enables more accurate detection of ICAS-O than that based on spCTA.