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To quantitatively evaluate blood-brain barrier (BBB) permeability in the perihaematomal region of spontaneous intracerebral haemorrhage (ICH) and investigate the association between the alterations in cerebral blood flow and BBB permeability around the haematoma.Spontaneous ICH patients underwent unenhanced computed tomography (CT) and CT perfusion (CTP) simultaneously. Haematoma volume was measured on CT. The values of cerebral haemodynamic parameters including cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and permeability-surface area product (PS) were measured in the perihaematomal region and the contralateral mirror region, and then relative values were calculated for statistical analysis. Linear regression was used to evaluate associations between BBB permeability and variables.A total of 87 ICH patients were included in this study. The focally elevated BBB permeability was observed in the perihaematomal region in ICH patients. Linear regression showed that reduced rCBF (β = -0.379, p=0.001) and increased rCBV (β = 0.412, p=0.000) correlated independently with increased relative PS (rPS) value in deep ICH, while only increased rCBV (β = 0.423, p=0.071) correlated to increased rPS value in patients with lobar ICH.BBB permeability is focally elevated in the region around the haematoma. Cerebral haemodynamic alterations are associated with increased BBB permeability. Cerebral hypoperfusion may aggravate BBB compromise, and a compensatory increase in CBV may lead to reperfusion injury on BBB.

Hydrotropes are small amphiphilic compounds that increase the aqueous solubility of hydrophobic molecules. Recent evidence suggests that adenosine triphosphate (ATP), which is the primary energy carrier in cells, also assumes hydrotropic properties to prevent the aggregation of hydrophobic proteins, but the mechanism of hydrotropy is unknown. Here, we compare the hydrotropic behavior of all four biological nucleoside triphosphates (NTPs) using molecular dynamics (MD) simulations. We launch all atom MD simulations of aqueous solutions of NTPs [ATP, guanosine triphosphate (GTP), cytidine triphosphate (CTP), and uridine triphosphate (UTP)] with pyrene, which acts both as a model hydrophobic compound and as a spectroscopic reporter for aggregation. GTP prevents pyrene aggregation effectively. Dissolution is not achieved in the presence of CTP and UTP. The higher stability of the base stacking in guanine is responsible for the higher hydrotropic efficiency of GTP. Consistent with the simulations, spectroscopic measurements also suggest that the hydrotropic activity of GTP is higher than ATP. Stacking of aromatic pyrene with the aromatic base of NTPs is a characteristic feature of this hydrotropic property. Both ATP and GTP also dissolve clusters of di- and tripeptides containing tryptophan but with equal potency. Importantly, the presence of aromatic amino acids is a necessary condition for the hydrotropic potency of ATP and GTP. Our results can have broad implications for hydrotrope design in the pharmaceutical industry, as well as the possibility of cells employing GTP as a hydrotrope to regulate the hydrophobic protein aggregation in membrane-less biological condensates.

Radiation dose associated with computed tomography (CT) perfusion (CTP) may discourage its use despite its added diagnostic benefit in quantifying ischemic lesion volume. Sparse-view CT reduces scan dose by acquiring fewer X-ray projections per gantry rotation but is contaminated by streaking artifacts using filtered back projection (FBP). We investigated the achievable dose reduction by sparse-view CTP with FBP without affecting CTP lesion volume estimations.Thirty-eight consecutive patients with acute ischemic stroke and CTP were included in this simulation study. CTP projection data was simulated by forward projecting original reconstructions with 984 views and adding Gaussian noise. Full-view (984 views) and sparse-view (492, 328, 246, and 164 views) CTP studies were simulated by FBP of simulated projection data. Cerebral blood flow (CBF) and time-to-maximum of the impulse residue function (Tmax) maps were generated by deconvolution for each simulated CTP study. Ischemic volumes were measured by CBF30% relative to the contralateral hemisphere and Tmax6 s. Volume accuracy was evaluated with respect to the full-view CTP study by the Friedman test with post hoc multiplicity-adjusted pairwise tests and Bland-Altman analysis.Friedman and multiplicity-adjusted pairwise tests indicated that 164-view CBF30%, 246- and 164-view Tmax6 s volumes were significantly different to full-view volumes (p0.001). Mean difference ± standard deviation (sparse minus full-view lesion volume) ranged from -1.0 ± 2.8 ml to -4.1 ± 11.7 ml for CBF30% and -2.9 ± 3.8 ml to -12.5 ± 19.9 ml for Tmax6 s from 492 to 164 views, respectively.By ischemic volume accuracy, our study indicates that sparse-view CTP may allow dose reduction by up to a factor of 3.

Melanoma is a malignant and metastatic form of skin cancer, which is not diagnosed in early stages of the disease. Nowadays, immunotherapy is changing the treatment landscape for metastatic melanoma. Placenta-specific1 (PLAC1) is a cancer-testis-placenta (CTP) antigen with differential expression in melanoma tissues. Here, we evaluated the potential of plac1 to induce anti-cancer immune responses as well as to prevent cancer development in a mouse model of melanoma.Two proteins containing full extracellular domain (ED) of mouse plac1+KDEL3 and full ED of mouse plac1+ tetanus toxin P2 and P30+ pan DR epitope (PADRE) ​+ ​KDEL3 were produced and injected in mice to evaluate their capacity to induce anti-cancer immune responses as well as their potential to prevent melanoma development. Induction of plac1-specific humoral and cellular responses as well as tumor-associated parameters were tested in a series of 36 mice.Sera of mice immunized with ED ​+ ​P2P30+PADRE ​+ ​KDEL3 contained antibodies able to react with surface plac1 in B16F10 ​cells. Both proteins induced proliferative cellular immune responses against B16F10 ​cells and plac1-specific cytotoxic T cells (CTL) and CD107a ​+ ​CTL responses, which was higher in mice immunized with ED ​+ ​P2P30+PADRE ​+ ​KDEL3. Splenocytes of mice vaccinated with ED ​+ ​P2P30+PADRE ​+ ​KDEL3 exerted a significant cytotoxicity against B16F10 ​cells. Vaccination with ED ​+ ​P2P30+PADRE ​+ ​KDEL3 significantly delayed B16F10-induced tumor onset, reduced tumor growth, and increased survival. Tumors induced by B16F10 expressed plac1 in vivo.Our results pave the way for development of effective melanoma preventive vaccine in humans, although further studies are needed.

The tripartite ParABS system mediates chromosome segregation in a wide range of bacteria. Dimeric ParB was proposed to nucleate on parS sites and spread to neighboring DNA. However, how properly distributed ParB dimers further compact chromosomal DNA into a higher-order nucleoprotein complex for partitioning remains poorly understood. Here, using a single-molecule approach, we show that tens of Bacillus subtilis ParB (Spo0J) proteins can stochastically multimerize on and stably bind to nonspecific DNA. The introduction of CTP promotes the formation and diffusion of the multimeric ParB along DNA, offering an opportunity for ParB proteins to further forgather and cluster. Intriguingly, ParB multimers can recognize parS motifs and are more inclined to remain immobile on them. Importantly, the ParB multimer features distinct capabilities of not only bridging two independent DNA molecules but also mediating their transportation, both of which are enhanced by the presence of either CTP or parS in the DNA. These findings shed new light on ParB dynamics in self-multimerization and DNA organization and help to better comprehend the assembly of the ParB-DNA partition complex.

Background and ObjectivesEndovascular thrombectomy (EVT) is effective for patients with large vessel occlusion (LVO) stroke with smaller volumes of CT perfusion (CTP)-defined ischemic core. However, the benefit of EVT is unclear in those with a core volume >70 mL. We aimed to compare outcomes of EVT and non-EVT patients with an ischemic core volume ≥70 mL, hypothesizing that there would be a benefit from EVT for fair outcome (3-month modified Rankin scale [mRS] 0–3) after stroke.MethodsA retrospective analysis of patients enrolled into a multicenter (Australia, China, and Canada) registry (2012–2020) who underwent CTP within 24 hours of stroke onset and had a baseline ischemic core volume ≥70 mL was performed. The primary outcome was the estimation of the association of EVT in patients with core volume ≥70 mL and within 70–100 and ≥100 mL subgroups with fair outcome.ResultsOf the 3,283 patients in the registry, 299 had CTP core volume ≥70 mL and 269 complete data (135 had core volume between 70 and 100 mL and 134 had core volume ≥100 mL). EVT was performed in 121 (45%) patients. EVT-treated patients were younger (median 69 vs 75 years; p = 0.011), had lower prestroke mRS, and smaller median core volumes (92 [79–116.5] mL vs 105.5 [85.75–138] mL, p = 0.004). EVT-treated patients had higher odds of achieving fair outcome in adjusted analysis (30% vs 13.9% in the non-EVT group; adjusted odds ratio [aOR] 2.1, 95% CI 1–4.2, p = 0.038). The benefit was seen predominantly in those with 70–100 mL core volume (71/135 [52.6%] EVT-treated), with 54.3% in the EVT-treated vs 21% in the non-EVT group achieving a fair outcome (aOR 2.5, 95% CI 1–6.2, p = 0.005). Of those with a core volume ≥100 mL, 50 of the 134 (37.3%) underwent EVT. Proportions of fair outcome were very low in both groups (8.1% vs 8.7%; p = 0.908).DiscussionWe found a positive association of EVT with the 3-month outcome after stroke in patients with a baseline CTP ischemic core volume 70–100 mL but not in those with core volume ≥100 mL. Randomized data to confirm these findings are required.Classification of EvidenceThis study provides Class III evidence that EVT is associated with better motor outcomes 3 months after CTP-defined ischemic stroke with a core volume of 70–100 mL.

The purpose of this study was to update trends, investigate sociodemographic disparities, and evaluate the impact on mortality of stroke neuroimaging across the United States from 2012 to 2019.Retrospective cohort study using CMS Medicare 5% Research Identifiable Files, representing consecutive ischemic stroke emergency department or hospitalized patients aged ≥65 years. A total of 85,547 stroke episodes with demographic and clinical information were analyzed using Cochran-Mantel-Haenszel tests and logistic regression. Outcome measures were neuroimaging (CT angiography [CTA], CT perfusion [CTP], MRI, MR angiography [MRA]) utilization, acute treatment (endovascular thrombectomy [EVT] and intravenous thrombolysis [IVT]), and mortality while in the hospital and at 30 days and 1 year post discharge.Significantly increasing utilization trends for CTA (250%), CTP (428%) and MRI (18%), and a decreasing trend for MRA (-33%) were observed from 2012 to 2019 (P.0001). Controlling for covariates in the logistic regression models, CTA and CTP were significantly associated with higher EVT and IVT utilization. Although CTA, MRI, and MRA were associated with lower mortality, CTP was associated with higher mortality post discharge. Less neuroimaging was performed in rural patients; older patients (≥80 years) had lower utilization of CTA, MRI, and MRA; female patients had lower rates of CTA; and Black patients had lower utilization of CTA and CTP.CTA and CTP utilization increased in the Medicare ischemic stroke population from 2012 to 2019 and both were associated with greater EVT and IVT use. However, disparities exist in neuroimaging utilization across all demographic groups, and further understanding of the root causes of these disparities will be crucial to achieving equity in stroke care.

Catalyst transfer polymerization (CTP) is widely applied to the synthesis of well-defined π-conjugated polymers. Unlike other polymerization reactions that can be performed in water (e.g., controlled radical polymerizations and ring-opening polymerizations), CTP has yet to be adapted for the modification of biopolymers. Here, we report the use of protein-palladium oxidative addition complexes (OACs) that enable catalyst transfer polymerization to furnish protein-polyarene conjugates. These polymerizations occur with electron-deficient monomers in aqueous buffers open to air at mild (≤37 °C) temperatures with full conversion of the protein OAC and an average polymer length of nine repeating units. Proteins with polyarene chains terminated with palladium OACs can be readily isolated. Direct evidence of protein-polyarene OAC formation was obtained using mass spectrometry, and all protein-polyarene chain ends were uniformly functionalized via C-S arylation to terminate the polymerization with a small molecule thiol or a cysteine-containing protein.

This study compared ischemic core and penumbra volumes obtained using different computed tomography perfusion (CTP) software and evaluated the predictive value of CTP and magnetic resonance imaging (MRI) results for 90-day outcomes.In total, 105 acute ischemic stroke patients who underwent endovascular treatment from January 2016 to December 2020 were included. Patients were divided into good and poor outcome groups by a modified Rankin Scale score. Computed tomography perfusion core and penumbra volumes were obtained using OleaSphere and Vitrea software to assess the volumetric relationship with MRI using the Spearman correlation test, intraclass correlation coefficient (ICC), and Bland-Altman plot. Three multivariable models were developed: baseline variables with MRI infarct volume, baseline variables with OleaSphere core volume, and baseline variables with Vitrea core volume. The area under the receiver operating characteristic curve of the 3 models was compared using the DeLong test.Median core volumes were 27.5, 26.9, and 31.1 mL for OleaSphere, Vitrea, and MRI, respectively. There was substantial correlation and excellent agreement between OleaSphere and MRI core volume ( ρ = 0.84, P0.001; ICC = 0.84) and Vitrea and MRI core volume ( ρ = 0.80, P0.001; ICC = 0.83). The areas under curve for MRI volume, OleaSphere, and Vitrea were 0.86, 0.84, and 0.83, respectively. There were no significant differences ( P = 0.18) between the predictive value of the 3 models.Computed tomography perfusion core volumes showed substantial correlation and excellent agreement with MRI. There was no significant difference in the predictive value of the 3 models, suggesting that core volumes measured using CTP software can predict patient prognosis.

Cirrhosis is the 11th leading cause of death worldwide. Because of the limitations of liver transplantation, cell- and granulocyte colony-stimulating factor (G-CSF)-based therapies are considered potential treatment methods. This work analyzes the effectiveness of cell- and G-CSF-based therapies by network meta-analysis.A literature search was performed in four databases from inception to September 10, 2021. Registered randomized controlled trials (RCTs) evaluating cell-based therapies and/or G-CSF-based therapies for cirrhosis patients were included. Traditional and network meta-analyses were analyzed in terms of survival, model for end-stage liver disease (MELD) score, Child-Turcotte-Pugh (CTP) score, alanine aminotransferase levels and aspartate aminotransferase levels.Twenty-four studies were included in this analysis. The results showed that G-CSF-based therapies (odds ratio [OR], 2.38, 95% confidence interval [CI], 1.49-3.79, P0.01) and cell-based therapies (OR, 1.54, 95% CI, 1.00-2.40, P = 0.048) improved the transplantation-free survival rate compared with standard medical treatment. Network analysis results showed that G-CSF combined with erythropoietin (EPO) and growth hormone (GH) had a therapeutic advantage, and cell-based therapy with mononuclear cell (MNC) hepatic artery injection and intravenous mesenchymal stem cells (MSCs) combined with G-CSF also had a relative advantage in terms of survival outcome. For the MELD score, G-CSF plus GH and MSC portal vein injection had relative advantages. G-CSF plus GH and G-CSF plus EPO had advantages in terms of CTP scores. The included strategies demonstrated no obvious improvement in liver injury indicators.Cell-based therapy has potential therapeutic effects for liver cirrhosis. Among cell-based therapies, intravenous MSCs and hepatic artery injection of MNCs have advantageous therapeutic effects. The use of G-CSF was also noted in regimens that improved survival outcomes. However, more well-designed, large-scale RCTs are needed to confirm this conclusion.

Delayed cerebral ischemia (DCI) is a devastating complication of aneurysmal subarachnoid hemorrhage (aSAH). We aim to investigate the efficacy of early CT perfusion (CTP) parameters for predicting DCI in patients with aSAH. The search was conducted in five databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and China Biology Medicine database). Studies were reviewed by two independent authors, and the included studies were assessed for methodological quality. Fifteen studies with 882 participants were included for the final analysis. The meta-analysis of quantitative parameters showed that mean transit time represented the most valuable predictor when the calculation of the mean value was uniformed (MD 0.30 s, 95% CI: 0.10 to 0.49 s, P = 0.003). Semi-quantitative parameters using relative values or index scores were also widely used to minimize undue variations derived from patients, operators, machines, and software. Studies also demonstrated that these relative parameters had better predictive accuracy than corresponding absolute parameters. Perfusion thresholds in each study were incomparable, and the results warranted further validation. The best threshold for the prediction was 0.9 using the relative cerebral blood flow parameter (sensitivity 97% and specificity 89%). We conclude that CTP in the early phase is a promising tool for predicting DCI in aSAH patients. However, the parameters require standardization. Future studies with prospective, multi-centered design and large sample size are needed to validate the thresholds and optimize the parameters.

Background: The optimal imaging paradigm for endovascular thrombectomy (EVT) patient selection in early time window (0–6 hours) treated acute ischemic stroke patients remains uncertain. We aimed to compare post-EVT outcomes between patients who underwent prerandomization basic (noncontrast computed tomography [CT], CT angiography only) versus additional advanced imaging (computed tomography perfusion [CTP] imaging) and to determine the association of performance of prerandomization CTP imaging with clinical outcomes. Methods: The HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) pooled patient-level data from randomized controlled trials comparing EVT with usual care for acute ischemic stroke due to anterior circulation large vessel occlusion. Good functional outcome, defined as modified Rankin Scale score 0 to 2 at 90 days, was compared between randomized patients with and without CTP baseline imaging. Univariable and multivariable binary logistic regression analysis was performed to determine the association of baseline CTP imaging and good functional outcome. Results: We analyzed 1348 patients 610 (45.3%) of whom underwent CTP prerandomization. The benefit of EVT compared with best medical management was maintained irrespective of the baseline imaging paradigm (90-day modified Rankin Scale score 0–2 in EVT versus control patients: with CTP: 46.0% (137/298) versus 28.9% (88/305), without CTP: 44.1% (162/367) versus 27.3% (100/366). Performance of CTP baseline imaging compared with baseline noncontrast CT and CT angiography only yielded similar rates of good outcome (odds ratio, 1.05 [95% CI, 0.82–1.33], adjusted odds ratio, 1.04, [95% CI, 0.80–1.35]). Conclusions: Rates of good functional outcome were similar among patients in whom CTP was or was not performed, and EVT treatment effect in the 0- to 6-hour time window was similar in patients with and without baseline CTP imaging.

Objectives To compare single parameter thresholding with multivariable probabilistic classification of ischemic stroke regions in the analysis of computed tomography perfusion (CTP) parameter maps. Methods Patients were included from two multicenter trials and were divided into two groups based on their modified arterial occlusive lesion grade. CTP parameter maps were generated with three methods—a commercial method (ISP), block-circulant singular value decomposition (bSVD), and non-linear regression (NLR). Follow-up non-contrast CT defined the follow-up infarct region. Conventional thresholds for individual parameter maps were established with a receiver operating characteristic curve analysis. Probabilistic classification was carried out with a logistic regression model combining the available CTP parameters into a single probability. Results A total of 225 CTP data sets were included, divided into a group of 166 patients with successful recanalization and 59 with persistent occlusion. The precision and recall of the CTP parameters were lower individually than when combined into a probability. The median difference [interquartile range] in mL between the estimated and follow-up infarct volume was 29/23/23 [52/50/52] (ISP/bSVD/NLR) for conventional thresholding and was 4/6/11 [31/25/30] (ISP/bSVD/NLR) for the probabilistic classification. Conclusions Multivariable probability maps outperform thresholded CTP parameter maps in estimating the infarct lesion as observed on follow-up non-contrast CT. A multivariable probabilistic approach may harmonize the classification of ischemic stroke regions. Key Points • Combining CTP parameters with a logistic regression model increases the precision and recall in estimating ischemic stroke regions. • Volumes following from a probabilistic analysis predict follow-up infarct volumes better than volumes following from a threshold-based analysis. • A multivariable probabilistic approach may harmonize the classification of ischemic stroke regions.

In the absence of an automated software analysis, the role of computed tomography perfusion (CTP) in a real time clinical practice is not well established. We evaluated the clinical significance of a widely accessible and simple visual grading scale of CTP in the anterior circulation of acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT).The single center consecutive CT investigations of AIS patients treated with MT in the anterior circulation have been evaluated retrospectively. ASPECT score and collateral circulation evaluation based on the Maas score were determined. Time to peak parametric maps, derived from CTP, were graded into four categories, from least to most favorable. The primary endpoint was functional outcome evaluated as modified Rankin Scale (mRS) ≤ 2 at 90 days after MT.We included 318 patients in the analysis; 142 (45%) patients had mRS ≤ 2 after 90 days, mortality rate was 24%. Higher CTP and Maas score were significantly correlated with better clinical outcome (Pearson χWe demonstrated that both visually graded CTP and collateral circulation grade strongly correlated with the clinical outcome of MT in the anterior circulation of AIS patients. Importantly, CTP correlated with the clinical outcome independent of the collateral circulation.

BACKGROUND AND PURPOSE: Contrast curve truncation in CTP protocols may introduce errors. We sought to identify risk factors and design a protocol to avoid truncation while limiting radiation. MATERIALS AND METHODS: In an initial fixed-timing cohort, patients underwent a 65-second CTP with 2-second delay postcontrast injection. Multivariable analysis identified factors associated with truncation. A later case-specific cohort underwent either the original protocol or a low cardiac output protocol with a 7-second delay and 75-second scanning window, with selection determined by CTA test-dose enhancement upswing delay. Time-density curves were assessed for truncation and compared between the 2 groups, and the radiation dose was evaluated. RESULTS: From September 2017 through May 2018, one hundred fifty-three patients underwent the standard fixed-timing protocol. Age (OR, 1.82/10-year increase; P = .019), reduced left ventricle ejection fraction (OR, 9.23; P = .001), and hypertension (OR, 0.32; P = .06) were independently associated with truncation in an exploratory multivariable model. From May 2018 through April 2019, one hundred fifty-seven patients underwent either the standard (72 patients) or low cardiac output protocol (85 patients). The fixed-timing cohort had 15 truncations (9.8%) versus 4 in the case-specific cohort (2.5%; P = .009). If the low cardiac output protocol were applied to those with >10.6% predicted risk of truncation based on age, left ventricle ejection fraction, and hypertension, the number of truncations would have decreased from 15 to 4 in the fixed-timing cohort. CONCLUSIONS: Older age, left ventricle ejection fraction, and the absence of hypertension increase the risk of time-density curve truncation. However, a CTA test-dose-directed case-specific protocol can reduce truncation to ensure accurate data while mitigating radiation dose increases.

Evaluation of cerebral perfusion is important for treatment selection in patients with acute large vessel occlusion (LVO). To assess ischemic core and tissue at risk more accurately, we developed a deep learning model named U-net using computed tomography perfusion (CTP) images. A total of 110 acute ischemic stroke patients undergoing endovascular treatment with major reperfusion (≥ 80%) or minimal reperfusion (≤ 20%) were included. Using baseline CTP, we developed two U-net models: one model in major reperfusion group to identify infarct core; the other in minimal reperfusion group to identify tissue at risk. The performance of fixed-thresholding methods was compared with that of U-net models. In the major reperfusion group, the model estimated infarct core with a Dice score coefficient (DSC) of 0.61 and an area under the curve (AUC) of 0.92, while fixed-thresholding methods had a DSC of 0.52. In the minimal reperfusion group, the model estimated tissue at risk with a DSC of 0.67 and an AUC of 0.93, while fixed-thresholding methods had a DSC of 0.51. In both groups, excellent volumetric consistency (intraclass correlation coefficient was 0.951 in major reperfusion and 0.746 in minimal reperfusion) was achieved between the estimated lesion and the actual lesion volume. Thus, in patients with anterior LVO, the CTP-based U-net models were able to identify infarct core and tissue at risk on baseline CTP superior to fixed-thresholding methods, providing individualized prediction of final lesion in patients with different reperfusion patterns.

BackgroundIn patients with stroke, current guidelines recommend non-invasive vascular imaging to identify intracranial vessel occlusions (VO) that may benefit from endovascular treatment (EVT). However, VO can be missed in CT angiography (CTA) readings. We aim to evaluate the impact of consistently including CT perfusion (CTP) in admission stroke imaging protocols.MethodsFrom April to October 2020 all patients admitted with a suspected acute ischemic stroke underwent urgent non-contrast CT, CTA and CTP and were treated accordingly. Hypoperfusion areas defined by time-to-maximum of the tissue residue function (Tmax) >6 s, congruent with the clinical symptoms and a vascular territory, were considered VO (CTP-VO). In addition, two experienced neuroradiologists blinded to CTP but not to clinical symptoms retrospectively evaluated non-contrast CT and CTA to identify intracranial VO (CTA-VO).ResultsOf the 338 patients included in the analysis, 157 (46.5%) presented with CTP-VO (median Tmax >6s: 73 (29–127) mL). CTA-VO was identified in 83 (24.5%) of the cases. Overall CTA-VO sensitivity for the detection of CTP-VO was 50.3% and specificity was 97.8%. Higher hypoperfusion volume was associated with increased CTA-VO detection (OR 1.03; 95% CI 1.02 to 1.04). EVT was performed in 103 patients (30.5%; Tmax >6s: 102 (63–160) mL), representing 65.6% of all CTP-VO. Overall CTA-VO sensitivity for the detection of EVT-VO was 69.9% and specificity was 95.3%. Among patients who received EVT, the rate of false negative CTA-VO was 30.1% (Tmax >6s: 69 (46–99.5) mL).ConclusionSystematically including CTP in acute stroke admission imaging protocols may increase the diagnosis of VO and rate of EVT.

Cognitive deficits are known to be related to most forms of psychopathology. Here, we perform local genetic correlation analysis as a means of identifying independent segments of the genome that show biologically interpretable pleiotropic associations between cognitive dimensions and psychopathology. We identify collective segments of the genome, which we call “meta-loci”, showing differential pleiotropic patterns for psychopathology relative to either cognitive task performance (CTP) or performance on a non-cognitive factor (NCF) derived from educational attainment. We observe that neurodevelopmental gene sets expressed during the prenatal-early childhood period predominate in CTP-relevant meta-loci, while post-natal gene sets are more involved in NCF-relevant meta-loci. Further, we demonstrate that neurodevelopmental gene sets are dissociable across CTP meta-loci with respect to their spatial distribution across the brain. Additionally, we find that GABA-ergic, cholinergic, and glutamatergic genes drive pleiotropic relationships within dissociable meta-loci.

The Freiburg index of post-TIPS survival (FIPS) score was recently demonstrated to improve prediction of post-TIPS mortality relative to existing standards. As this score was derived from a German cohort over an extended time period, it is unclear if performance will translate well to other settings. This study aimed to externally validate the FIPS score in a large Veterans Affairs (VA) cohort over two separate eras of TIPS-related care. This was a retrospective cohort study of patients with cirrhosis who underwent TIPS placement in the VA from 2008 to 2020. Cox regression models for post-TIPS survival were constructed using FIPS, MELD, MELD-Na, or CTP scores as predictors. Discrimination (Harrell’s C) and calibration (joint tests of calibration curve slope and intercept) were evaluated for each score. A stratified analysis was performed for time periods between 2008–2013 and 2014–2020. The cohort of 1,274 patients was 97.3% male with mean age 60.9 years and mean MELD-Na 14. The FIPS score demonstrated the highest overall discrimination versus MELD, MELD-Na, and CTP (0.634 vs. 0.585, 0.626, 0.612, respectively). However, in the modern treatment era (2014–2020), the FIPS score performed similarly to MELD-Na. Additionally, the FIPS score demonstrated poor calibration at one-month and six-month post-TIPS timepoints (joint p = 0.04 and 0.004, respectively). MELD, MELD-Na, and CTP were well-calibrated at each timepoint (each joint p > 0.05). The FIPS score performed similarly to MELD-Na in the modern TIPS treatment era and demonstrated regions of poor calibration. Future models derived with contemporary data may improve prediction of post-TIPS mortality.

Background: Direct oral anticoagulants (DOACs) remain mostly investigational in patients with moderate to severe hepatic cirrhosis, yet are often selected over traditional anticoagulants including warfarin and enoxaparin in this setting. Objective: To determine the safety and efficacy of DOACs in patients with moderate to severe hepatic cirrhosis as compared with traditional anticoagulation. Methods: This was a retrospective, single-center cohort study evaluating inpatients and outpatients who were prescribed a DOAC, warfarin, or enoxaparin for therapeutic anticoagulation with Child-Turcotte-Pugh (CTP) B or C status at the time that the prescription was written. Included patients were followed until first bleeding or thromboembolic event, or until discontinuation of anticoagulation therapy. Data were collected by manual chart review. The primary outcomes included both bleeding events and thromboembolic events in the DOAC population as compared with traditional anticoagulation. Results: A total of 101 patients were included in the study, 69 treated with DOAC therapy and 32 with traditional anticoagulation. Bleeding events occurred in 36% of patients in the DOAC group and 22% of patients in the traditional group ( P = 0.149). In both groups, bleeds were most commonly gastrointestinal. Thromboembolic events occurred in 4% of the DOAC population and no patients in the traditional population ( P = 0.55). No fatal bleeding or thromboembolic events occurred. Conclusion and Relevance: DOACs do not appear to be more harmful than traditional anticoagulation in patients with CTP B or C status. These results support the use of DOACs in patients with CTP B or C hepatic cirrhosis when considering safety, efficacy, and convenience.

Flavins play a central role in metabolism as molecules that catalyze a wide range of redox reactions in living organisms. Several variations in flavin biosynthesis exist among the domains of life, and their analysis has revealed many new structural and mechanistic insights till date. The cytidine triphosphate (CTP)-dependent riboflavin kinase in archaea is one such example. Unlike most kinases that use adenosine triphosphate, archaeal riboflavin kinases utilize CTP to phosphorylate riboflavin and produce flavin mononucleotide. In this study, we present the characterization of a new mesophilic archaeal CTP-utilizing riboflavin kinase homologue from Methanococcus maripaludis (MmpRibK), which is linked closely in sequence to the previously characterized thermophilic Methanocaldococcus jannaschii homologue. We reconstitute the activity of MmpRibK, determine its kinetic parameters and molecular factors that contribute to its unique properties, and finally establish the residues that improve its thermostability using computation and a series of experiments. Our work advances the molecular understanding of flavin biosynthesis in archaea by the characterization of the first mesophilic CTP-dependent riboflavin kinase. Finally, it validates the role of salt bridges and rigidifying amino acid residues in imparting thermostability to this unique structural fold that characterizes archaeal riboflavin kinase enzymes, with implications in enzyme engineering and biotechnological applications.

The novel coronavirus SARS-CoV-2 is the causative agent of the COVID-19 outbreak that is affecting the entire planet. As the pandemic is still spreading worldwide, with multiple mutations of the virus, it is of interest and of help to employ computational methods for identifying potential inhibitors of the enzymes responsible for viral replication. Attractive antiviral nucleotide analogue RNA-dependent RNA polymerase (RdRp) chain terminator inhibitors are investigated with this purpose. This study, based on molecular dynamics (MD) simulations, addresses the important aspects of the incorporation of an endogenously synthesized nucleoside triphosphate, ddhCTP, in comparison with the natural nucleobase cytidine triphosphate (CTP) in RdRp. The ddhCTP species is the product of the viperin antiviral protein as part of the innate immune response. The absence of the ribose 3'-OH in ddhCTP could have important implications in its inhibitory mechanism of RdRp. We built an in silico model of the RNA strand embedded in RdRp using experimental methods, starting from the cryo-electron microscopy structure and exploiting the information obtained by spectrometry on the RNA sequence. We determined that the model was stable during the MD simulation time. The obtained results provide deeper insights into the incorporation of nucleoside triphosphates, whose molecular mechanism by the RdRp active site still remains elusive.

Myocardial computed tomography perfusion (CTP) imaging is a noninvasive method for detecting myocardial ischemia. This study aimed to compare the diagnostic performance of dynamic and static adenosine-stress CTPs for detecting hemodynamically significant coronary stenosis. We prospectively enrolled 42 patients (mean age, 59.7 ± 8.8 years; 31 males) with ≥40% coronary artery stenosis. All patients underwent dynamic CTP for adenosine stress. The static CTP was simulated by choosing the seventh dynamic dataset after the initiation of the contrast injection. Diagnostic performance was compared with invasive fractional flow reserve (FFR)0.8 as the reference. Of the 125 coronary vessels in 42 patients, 20 (16.0%) in 16 (38.1%) patients were categorized as hemodynamically significant. Dynamic and static CTP yielded similar diagnostic accuracy (90.4% vs 88.8% using visual analysis, P = .558; 77.6% vs 80.8% using quantitative analysis, P = .534; 78.4% vs 82.4% using combined visual and quantitative analyses, P = .426). The diagnostic accuracy of combined coronary computed tomography angiography (CCTA) and dynamic CTP (89.6% using visual analysis, P = .011; 88.8% using quantitative analysis, P = .018; 89.6% using combined visual and quantitative analyses, P = .011) and that of combined CCTA and static CTP (88.8% using visual analysis, P = .018; 90.4% using quantitative analysis, P = .006; 91.2% using combined visual and quantitative analyses, P = .003) were significantly higher than that of CCTA alone (77.6%). Dynamic CTP and static CTP showed similar diagnostic performance in the detection of hemodynamically significant stenosis.

Molnupiravir is an orally available antiviral drug candidate currently in phase III trials for the treatment of patients with COVID-19. Molnupiravir increases the frequency of viral RNA mutations and impairs SARS-CoV-2 replication in animal models and in humans. Here, we establish the molecular mechanisms underlying molnupiravir-induced RNA mutagenesis by the viral RNA-dependent RNA polymerase (RdRp). Biochemical assays show that the RdRp uses the active form of molnupiravir, β-d-N4-hydroxycytidine (NHC) triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RdRp uses the resulting RNA as a template, NHC directs incorporation of either G or A, leading to mutated RNA products. Structural analysis of RdRp–RNA complexes that contain mutagenesis products shows that NHC can form stable base pairs with either G or A in the RdRp active center, explaining how the polymerase escapes proofreading and synthesizes mutated RNA. This two-step mutagenesis mechanism probably applies to various viral polymerases and can explain the broad-spectrum antiviral activity of molnupiravir., Quantitative biochemical assays and high-resolution cryo-EM analysis reveal how the COVID-19 antiviral drug candidate molnupiravir causes lethal viral mutagenesis by the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2.

Summary Cereal grain endosperms are an important source of human nutrition. Nuclear division in early endosperm development plays a major role in determining seed size; however, this development is not well understood. We identified the rice mutant endospermless 2 (enl2), which shows defects in the early stages of endosperm development. These phenotypes arise from mutations in OsCTPS1 that encodes a cytidine triphosphate synthase (CTPS). Both wild‐type and mutant endosperms were normal at 8 h after pollination (HAP). In contrast, at 24 HAP, enl2 endosperm had approximately 10–16 clumped nuclei while wild‐type nuclei had increased in number and migrated to the endosperm periphery. Staining of microtubules in endosperm at 24 HAP revealed that wild‐type nuclei were evenly distributed by microtubules while the enl2‐2 nuclei were tightly packed due to their reduction in microtubule association. In addition, OsCTPS1 interacts with tubulins; thus, these observations suggest that OsCTPS1 may be involved in microtubule formation. OsCTPS1 transiently formed macromolecular structures in the endosperm during early developmental stages, further supporting the idea that OsCTPS1 may function as a structural component during endosperm development. Finally, overexpression of OsCTPS1 increased seed weight by promoting endosperm nuclear division, suggesting that this trait could be used to increase grain yield.

CTP synthase (CTPS) can form filamentous structures termed cytoophidia in cells from all three domains of life. In order to study the mesoscale structure of cytoophidia, we perform fluorescence recovery after photobleaching (FRAP) and stimulated emission depletion (STED) microscopy in human cells. By using EGFP dimeric tag, as a tool to explore the physical properties of cytoophidia, we find that cytoophidia are dynamic and reticular. The reticular structure of CTPS cytoophidia may provide space for other components such as IMPDH. In addition, we observe CTPS granules with tentacles.

To determine whether the monocyte-to-lymphocyte ratio (MLR), as a systemic inflammation index, predicts malnutrition risk during the early stages of cirrhosis.We conducted a single-center prospective cohort study, enrolling patients from June 2016 to September 2020. The patients underwent malnutrition risk assessments upon admission. The patients were classified into five clinical stages according to portal hypertension. The malnutrition risk was scored using the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) and validated by the Nutritional Risk Screening 2002 (NRS-2002) or Liver Disease Undernutrition Screening Tool (LDUST). Routine clinical laboratory measurements were performed to calculate the MLR, Child-Turcotte-Pugh (CTP) class, and model for end-stage liver disease (MELD) score. The patients were followed up for 2 years.Among the 154 patients with cirrhosis, 60 had compensated cirrhosis and 94 had decompensated cirrhosis. The optimal cutoff value of the MLR,0.4, was effective in predicting malnutrition related to death or liver transplantation. Those with a high malnutrition risk defined by the NRS-2002 or RFH-NPT had a higher MLR than those with a low malnutrition risk. For patients with class A CTP cirrhosis or a MELD score of10, an MLR cutoff of0.4 significantly distinguished more patients with a low malnutrition risk than those with a high malnutrition risk. Both the RFH-NPT score and MLR increased significantly across the decompensated cirrhosis substages. Interestingly, the MLR exhibited a positive correlation with the RFH-NPT score until varices appeared, but the correlation was the highest at the substage of a history of variceal bleeding (r = 0.714, P = 0.009). Multivariable analysis demonstrated that an MLR of0.4 was an independent factor for malnutrition risk by screening with the RFH-NPT, and this was confirmed using the LDUST and NRS-2002.Immune-related inflammatory dysfunction predicts malnutrition risk during the early stages of cirrhosis.

The Charlotte Large artery occlusion Endovascular therapy Outcome Score (CLEOS) and Totaled Health Risks in Vascular Events (THRIVE) predict functional outcomes after anterior circulation endovascular thrombectomy (EVT). We evaluated the performance of CLEOS and THRIVE in patients presenting with an acute basilar artery occlusion (BAO) treated with EVT.We conducted a retrospective analysis of a health system's stroke registry. Patients presenting with an acute BAO treated with EVT and evaluated with pre-thrombectomy CT perfusion (CTP) from January 2017 to December 2021 were included. CLEOS = (5 × age) + (10 × National Institutes of Health Stroke Scale [NIHSS]) + Glucose - (150 × CTP cerebral blood volume index) and THRIVE (0-9 points) = age 60-79 years, 1 point; age ≥ 80 years, 2 points; NIHSS 11-20, 2 points; NIHSS ≥ 21, 4 points; hypertension, diabetes mellitus, atrial fibrillation, 1 point each. Multivariable logistic regression was performed for the ability of CLEOS and THRIVE to predict the primary outcome, modified Rankin Scale score 3-6.Fifty-seven patients had mean age 66.6 (± 14.9) years and median NIHSS 15.5 (5-24). In the multivariable regression analysis, increased CLEOS was associated with significantly higher odds of a poor functional outcome (odds ratio [OR] = 1.0011, 95% confidence interval [CI]: 1.0003-1.0019, p = .008), whereas THRIVE was not (OR = 1.0326, 95% CI: 0.9478-1.1250, p = .466). CLEOS gt; 503 best predicted poor outcomes.A higher CLEOS score was associated with elevated odds of a poor 90-day functional outcome in our cohort of acute BAO patients treated with EVT.

Background and objective Computed tomography perfusion (CTP) is widely used in the evaluation of acute ischemic stroke patients for endovascular thrombectomy (EVT). The stability of CTP core estimation is suboptimal and varies between software packages. We aimed to quantify the volumetric and spatial agreement between the CTP ischemic core and follow-up infarct for four ischemic core estimation approaches using syngo.via. Methods We included successfully reperfused, EVT-treated patients with baseline CTP and 24h follow-up diffusion weighted magnetic resonance imaging (DWI) (November 2017–September 2020). Data were processed with syngo.via VB40 using four core estimation approaches based on: cerebral blood volume (CBV) Results In 59 patients, median estimated CTP core volumes for four core estimation approaches ranged from 12–39 mL. Median 24h follow-up DWI infarct volume was 11 mL. The intraclass correlation coefficient (ICC) showed moderate–good volumetric agreement for all approaches (range 0.61–0.76). Median Dice was low for all approaches (range 0.16–0.21). CTP core overestimation >10mL occurred least frequent (14/59 [24%] patients) using the CBV-based core estimation approach with smoothing filter. Conclusions In successfully reperfused patients who underwent EVT, syngo.via CTP ischemic core estimation showed moderate volumetric and spatial agreement with the follow-up infarct on DWI. In patients with complete reperfusion after EVT, the volumetric agreement was excellent. A CTP core estimation approach based on CBV

Liquid–liquid phase separation is a fundamental biophysical process to organize eukaryotic and prokaryotic cytosols. While many biomolecular condensates are formed in the vicinity of, or even on lipid membranes, little is known about the interaction of protein condensates and lipid bilayers. In this study, we characterize the recently unknown phase behavior of the bacterial nucleoid occlusion protein Noc. We find that, similarly to other ParB-like proteins, CTP binding tightly regulates Noc’s propensity to phase separate. As CTP-binding and hydrolysis also allows Noc to bind and spread on membranes, we furthermore establish Noc condensates as model system to investigate how lipid membranes can influence protein condensation and vice versa. Last, we show that Noc condensates can recruit FtsZ to the membrane, while this does not happen in the non-phase separated state. These findings suggest a new model of Noc mediated nucleoid occlusion, with membrane-mediated liquid–liquid phase separation as underlying principle of complex formation and regulation thereof.

The application of cerebral perfusion imaging has demonstrated significant assessment benefits and an ability to establish an appropriate triage of patients with acute ischemic stroke (AIS) and large artery occlusion (LAO) in the extended time window. Computed tomography perfusion (CTP) and magnetic resonance imaging (MRI) are routinely used to determine the ischemic core, as well as the tissue at risk, to aid in therapeutic decision-making. However, the time required to transport patients to imaging extends the door-to-reperfusion time. C-arm cone-beam CT (CBCT) is a novel tomography technology that combines 2D radiography and 3D CT imaging based on the digital subtraction angiography platform. In comparison with CT or MRI perfusion techniques, CBCT combined with catheterized angiogram or therapy can serve as a "one-stop-shop" for the diagnosis and treatment of AIS, and greatly reduce the door to reperfusion time. Here, we review the current evidence on the efficacy and theoretical basis of CBCT, as well as other perfusion techniques, with the purpose to assist clinicians to establish an effective and repaid workflow for patients with AIS and LAO in clinical practice.

CTP synthase (CTPS), a metabolic enzyme responsible for the de novo synthesis of CTP, can form filamentous structures termed cytoophidia, which are evolutionarily conserved from bacteria to humans. Here we used Schizosaccharomyces pombe to study the cytoophidium assembly regulation by ubiquitination. We tested the CTP synthase’s capacity to be epigenetically modified by ubiquitin or be affected by the ubiquitination state of the cell, showed that CTPS is immunoprecipitated with ubiquitin, and that ubiquitination is important for the maintenance of the CTPS filamentous structure in fission yeast. We have identified proteins which are in complex with CTPS, including specific ubiquitination regulators which significantly affect CTPS filamentation, and mapped probable ubiquitination targets on CTPS. Furthermore, we discovered that a cohort of deubiquitinating enzymes is significant for the regulation of cytoophidium morphology. Our study provides a framework for the analysis of the effects that ubiquitination and deubiquitination have on the formation of CTPS filaments.

Spontaneous ascitic fluid infection (SAI) is common in cirrhotic patients leading to significant morbidity and mortality. Third-generation cephalosporins are currently recommended as first-line therapy. This is a retrospective observational study that aims to determine bacterial etiology, susceptibility patterns of SAI, and its correlation with model for end-stage liver disease-sodium (MELD-Na) and Child-Turcotte-Pugh (CTP) score.The present study was conducted on 274 consecutive cases admitted in Bombay Hospital and Medical Research Centre, Mumbai, India. Cases of cirrhosis (irrespective of etiology) with ascites between the ages of 18-85 years were included in this study. Ascitic fluid of every patient was aspirated under all aseptic measures and was sent for biochemical, culture, and cytological analysis.Of the 274 patients studied, 34 (12.4%) patients were diagnosed to have SAI. Culture-negative neutrocytic ascites (CNNA) was present in 27 patients, spontaneous bacterial peritonitis (SBP) was present in six patients, and monomicrobial bacteriascites was seen in one patient. Mean age of patients enrolled was 56.05 ± 2.47 years. Eighty-two percent were males and 18% were females. Alcohol (45.45%) was the leading cause of cirrhosis followed by nonalcoholic steatohepatitis (NASH) related cirrhosis (26.47.7%) and hepatitis C virus (HCV) related cirrhosis (11.46%) and cryptogenic cirrhosis (8.82%). Average MELD-Na score was 25 and the CTP class C was most common. Klebsiella pneumoniae was the most commonly isolated organism followed by Escherichia coli. The various factors that predispose to development of SBP include low ascitic fluid protein concentration, a high level of serum bilirubin, deranged serum creatinine, high Child-Pugh score, and high MELD-Na score.Ascitic fluid analysis remains the single most important test for identifying and assessing a course of SBP. Early diagnosis and treatment will reduce the mortality rate in these patients.

A non-contrast cranial computer tomography (ncCT) is often employed for the diagnosis of the early stage of the ischemic stroke. However, the number of false negatives is high. More accurate results are obtained by an MRI. However, the MRI is not available in every hospital. Moreover, even if it is available in the clinic for the routine tests, emergency often does not have it. Therefore, this paper proposes an end-to-end framework for detection and segmentation of the brain infarct on the ncCT. The computer tomography perfusion (CTp) is used as the ground truth. The proposed ensemble model employs three deep convolution neural networks (CNNs) to process three end-to-end feature maps and a hand-craft features characterized by specific contra-lateral features. To improve the accuracy of the detected infarct area, the spatial dependencies between neighboring slices are employed at the postprocessing step. The numerical experiments have been performed on 18 ncCT-CTp paired stroke cases (804 image-pairs). The leave-one-out approach is applied for evaluating the proposed method. The model achieves 91.16% accuracy, 65.15% precision, 77.44% recall, 69.97% F1 score, and 0.4536 IoU.

N-acetylglucosamine (GlcNAc) is a key component of glycans such as glycoprotein and the cell wall. GlcNAc kinase is an enzyme that transfers a phosphate onto GlcNAc to generate GlcNAc-6-phosphate, which can be a precursor for glycan synthesis. GlcNAc kinases have been found in a broad range of organisms, including pathogenic yeast, human and bacteria. However, this enzyme has never been discovered in Saccharomyces cerevisiae, a eukaryotic model. In this study, the first GlcNAc kinase from S. cerevisiae was identified and named Ngk1. The Km values of Ngk1 for GlcNAc and glucose were 0.11 mM and 71 mM, respectively, suggesting that Ngk1 possesses a high affinity for GlcNAc, unlike hexokinases. Ngk1 showed the GlcNAc phosphorylation activity with various nucleoside triphosphates, namely ATP, CTP, GTP, ITP, and UTP, as phosphoryl donors. Ngk1 is phylogenetically distant from known enzymes, as the amino acid sequence identity with others is only about 20% or less. The physiological role of Ngk1 in S. cerevisiae is also discussed.

Objective To investigate the impact of N-terminal pro-B-type natriuretic peptide (NT-proBNP) on CTP infarct core volume and poor 90-day functional outcomes in acute ischemic stroke (AIS). Methods A total of 403 hospitalized patients with AIS in the Stroke Center of the First Hospital Affiliated to Soochow University were enrolled from March 2018 to January 2021. The association between NT-proBNP and clinical outcomes in acute ischemic patients was assessed by logistic regression and adjusted for confounding factors. Also, subgroup analyses were conducted based on treatment decisions. Results NT-proBNP was positively correlated with CTP ischemic volume (p p p p = 0.002). This phenomenon was persistent after adjusted for age, sex, and body mass index in model 2 (p = 0.011), adjusted for SBP, current smoking, family history of stroke, hypertension, and diabetes mellitus in model 3 (p p = 0.027). A high NT-proBNP was associated with a high 90-days mRS score among the total population, IV rt-PA, and standardized treatment groups, but not in IV rt-PA + EVT, EVT, and EVT/IV rt-PA + EVT groups. Conclusion Elevated NT-proBNP levels reveal large CTP infarct core volume and poor 90-day functional outcome in AIS. NT-pro BNP is an independent risk factor for functional outcomes.

Funding Information: This project was granted funding for 2019 and 2020 by the Helsinki University Hospital governmental subsidiary funds for clinical research (Y1249NEUR1), the Maire Taponen foundation, and the South Karelian Medical Association Publisher Copyright: © 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Objectives: Current guidelines for recanalization treatment are based on the time elapsed between symptom onset and treatment and visualization of existing penumbra in computed tomography perfusion (CTP) imaging. The time window for treatment options relies on linear growth of infarction although individual infarct growth rate may vary. We aimed to test how accurately the estimated follow-up infarct volume (eFIV) can be approximated by using a linear growth model based on CTP baseline imaging. If eFIV did not fall within the margins of +/− 19% of the follow-up infarct volume (FIV) measured at 24 h from non-enhanced computed tomography images, the results would imply that the infarct growth is not linear. Materials and Methods: All consecutive endovascularly treated (EVT) patients from 11/2015 to 9/2019 at the Helsinki University Hospital with large vessel occlusion (LVO), CTP imaging, and known time of symptom onset were included. Infarct growth rate was assumed to be linear and calculated by dividing the ischemic core volume (CTPcore) by the time from symptom onset to baseline imaging. eFIV was calculated by multiplying the infarct growth rate with the time from baseline imaging to recanalization or in case of futile recanalization to follow-up imaging at 24 h, limited to the penumbra. Collateral flow was estimated by calculating hypoperfusion intensity ratio (HIR). Results: Of 5234 patients, 48 had LVO, EVT, CTP imaging, and known time of symptom onset. In 40/48 patients (87%), infarct growth was not linear. HIR did not differ between patients with linear and nonlinear growth (p >.05). As expected, in over half of the patients with successful recanalization eFIV exceeded FIV. Conclusions: Infarct growth was not linear in most patients and thus time elapsed from symptom onset and CTPcore appear to be insufficient parameters for clinical decision-making in EVT candidates.