Early and late infarct growth rate in ischemic stroke patients after successful endovascular treatment in early time window: correlation of imaging and clinical factors with clinical outcome.

Background: The prospective study assessed infarct growth rate (IGR) in acute ischemic stroke (AIS) with large vessel occlusion (LVO) after recanalization in early time window. Early IGR (EIGR) and late IGR (LIGR) were correlated with imaging and clinical data; we searched for outcome predictors. Methods: We included 71 consecutive patients. Subjects underwent computed tomography perfusion (CTP) for ischemic core volume assessment at 99.0 minutes (median) from stroke onset, recanalization was performed at 78.0 minutes (median) from CTP. Final infarct volume (FIV) was measured on 24±2 hours imaging follow-up. EIGR was calculated as the core volume/time between stroke onset and CTP; LIGR was calculated as FIV/time between CTP and imaging follow-up. Twenty-two subjects were assessed as poor outcome, 49 as good outcome. Group differences were tested by Mann-Whitney test and χ2 test. Bayesian logistic regression models were used to predict clinical outcome, Pearson correlations for the log-transformed predictors. Results: Subjects with poor outcome were older, median age 78.0 [interquartile range (IQR): 71.8, 83.8] versus 68.0 (IQR: 57.0, 73.0) years; 95% confidence interval (CI): 6.00 to 16.00; P<0.001. Their stroke severity scale was higher, median 19.0 (IQR: 16.0, 20.0) versus 15.5 (IQR: 10.8, 18.0); 95% CI: 1.00 to 6.00; P<0.001. They had higher EIGR, median 23.9 (IQR: 6.4, 104.0) versus 6.7 (IQR: 1.7, 13.0) mL/h; 95% CI: 3.26 to 53.68; P=0.002; and larger core, median 52.5 (IQR: 13.1, 148.5) versus 10.0 (IQR: 1.4, 20.0) mL; 95% CI: 11.00 to 81.00; P<0.001. In subjects with poor outcome, infarct growth continued after thrombectomy with LIGR 2.0 (IQR: 1.2, 9.7) versus 0.3 (IQR: 0.0, 0.7) mL/h; 95% CI: 1.10 to 6.10; P<0.001; resulting in larger FIV, median 186.5 (IQR: 49.3, 280.8) versus 18.5 (IQR: 8.0, 34.0) mL; 95% CI: 55.30 to 214.00; P<0.001. Strong correlations among predictors were found e.g., core and EIGR (r=0.942), LIGR and FIV (r=0.779), core and FIV (r=0.761). Clinical outcome was best predicted using data from later measurements as FIV and LIGR. Conclusions: Data from later measurements were more predictive, there was no major benefit to use growth over volume data.

CT Brain Perfusion in the Prediction of Final Infarct Volume: A Prospective Study of Different Software Settings for Acute Ischemic Core Calculation.

CT perfusion (CTP) is used for the evaluation of brain tissue viability in patients with acute ischemic stroke (AIS). We studied the accuracy of three different syngo.via software (SW) settings for acute ischemic core estimation in predicting the final infarct volume (FIV). The ischemic core was defined as follows: Setting A: an area with cerebral blood flow (CBF) < 30% compared to the contralateral healthy hemisphere. Setting B: CBF < 20% compared to contralateral hemisphere. Setting C: area of cerebral blood volume (CBV) < 1.2 mL/100 mL. We studied 47 AIS patients (aged 68 ± 11.2 years) with large vessel occlusion in the anterior circulation, treated in the early time window (up to 6 h), who underwent technically successful endovascular thrombectomy (EVT). FIV was measured on MRI performed 24 ± 2 h after EVT. In general, all three settings correlated with each other; however, the absolute agreement between acute ischemic core volume on CTP and FIV on MRI was poor; intraclass correlation for all three settings was between 0.64 and 0.69, root mean square error of the individual observations was between 58.9 and 66.0. Our results suggest that using CTP syngo.via SW for prediction of FIV in AIS patients in the early time window is not appropriate.

FOXF1 as an Immunohistochemical Marker of Hilar Cholangiocarcinoma or Metastatic Pancreatic Ductal Adenocarcinoma. Single Institution Experience.

Cholangiocarcinoma (CCA) is a liver malignancy associated with a poor prognosis. Its main subtypes are peripheral/intrahepatic and hilar/extrahepatic CCA. Several molecular, morphological and clinical similarities between hilar/extrahepatic CCA and pancreatic ductal adenocarcinoma (PDAC) have been described. FOXF1 is a transcription factor which has been described to have prognostic significance in various tumors and it is involved in the development of bile ducts. The aim of this study is to determine occurrence of nuclear expression of FOXF1 in both subtypes of CCA and metastatic PDAC and assess its potential usefulness as a diagnostic marker. Secondary aims were to investigate the use of C-reactive protein (CRP) immunohistochemistry for diagnosing intrahepatic peripheral CCA and the significance of histological features in CCA subtypes. 32 archive specimens of CCA, combined hepatocellular carcinoma-CCA (HCC-CCA) and liver metastasis of PDAC were stained by FOXF1 and CRP immunohistochemistry and evaluated to determine histological pattern. The CCAs were classified radiologically into peripheral/intrahepatic and hilar subtype. Using Fisher exact test, we identified nuclear FOXF1 as a fairly specific (87%) but insensitive (65%) marker of hilar and extrahepatic CCA and metastatic PDAC (p = 0.005). CRP immunohistochemistry was characterized by a high sensitivity and specificity, of 79% and 88%, respectively (p = 0.001). We did not identify any histomorphological features associated with either types of CCA or metastatic PDAC. As a conclusion of novel finding, FOXF1 immunohistochemistry may be regarded as a specific but insensitive marker of hilar/extrahepatic CCA and metastatic PDAC and it may help distinguish them from peripheral CCA.

Is limited-coverage CT perfusion helpful in treatment decision-making in patients with acute ischemic stroke?

BACKGROUND: The initial core infarct volume predicts treatment outcome in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). According to the literature, CT perfusion (CTP) is able to evaluate cerebral parenchymal viability and assess the initial core in AIS. We prospectively studied whether limited-coverage CTP with automated core calculation correlates with the final infarct volume on follow-up non-enhanced CT (NECT) in patients successfully treated by mechanical thrombectomy. METHODS: We enrolled 31 stroke patients (20 women aged 74.4±12.9 years and 11 men aged 66±15.4 years; median initial NIHSS score 15.5) with occlusion of the medial cerebral artery and/or the internal carotid artery that were treated by successful mechanical thrombectomy. CTP performed in a 38.6 mm slab at the level of basal ganglia was included in the CT stroke protocol, but was not used to determine indication for mechanical thrombectomy. The infarction core volume based on CTP was automatically calculated using dedicated software with a threshold defined as cerebral blood flow <30% of the value in the contralateral healthy hemisphere. The final infarction volume was measured on 24-hour follow-up NECT in the same slab with respect to CTP. Pearson and Spearman correlation coefficients and robust linear regression were used for comparison of both volumes, P values <0.05 were considered as statistically significant. RESULTS: The median time from stroke onset to CT was 77 minutes (range, 31-284 minutes), and the median time from CT to vessel recanalization was 95 minutes (range, 55-215 minutes). The mean CTP-calculated core infarct volume was 24.3±19.2 mL (median 19 mL, range 1-79 mL), while the mean final infarct volume was 21.5±39.5 mL (median 8 mL; range 0-210 mL). Only a weak relationship was found between the CTP-calculated core and final infarct volume [Pr(29) =0.32, P=0.078; rho =0.40, P=0.028]. Regression analysis showed CTP significantly overestimated lower volumes. CONCLUSIONS: In our prospective study, the infarction core calculated using limited-coverage CTP only weakly correlated with the final infarction volume measured on 24-hour follow-up NECT; moreover, CTP significantly overestimated lower volumes. Our results do not support the use of limited-coverage CTP for guiding treatment recommendations in patients with AIS.

Durable Response to Brentuximab Vedotin-Based Chemotherapy in Refractory Hodgkin Lymphoma with Central Nervous System (CNS) Involvement.

BACKGROUND CNS involvement in Hodgkin lymphoma is rare. Despite various treatment options, median overall survival is only 13 months after diagnosis of CNS involvement in relapsed/refractory HL. CASE REPORT A 29-year-old woman with classical HL (mixed cellularity) in clinical stage IIB was treated with multilineage chemotherapy and radiotherapy without achieving a sustained complete remission. Systemic and CNS progression of HL occurred at the age of 32 years and the patient received 2 cycles of brentuximab vedotin with bendamustine alternating with 2 cycles of high-dose methotrexate-based treatment and achieved partial remission. She then underwent autologous stem cell transplantation followed by brentuximab vedotin consolidation. The disease progressed and the patient died 6 months after the last dose of brentuximab vedotin. CONCLUSIONS We demonstrated a durable response to brentuximab vedotin-based chemotherapy in a patient with refractory Hodgkin lymphoma with CNS involvement. Prognosis of these patients is poor and new treatment options are needed.

Gadoxetate disodium, a modern hepatospecific MRI contrast agent: Indirect signs for gadolinium deposition in the brain structures with signal intensity increase after intravenous application.

BACKGROUND: Gadolinium brain deposits after intravenous application of gadolinium-based contrast agents (GBCA) have been recently reported. AIM: We focused selectively on gadoxetate disodium, a hepatospecific linear GBCA. There are currently only a few studies in peer-reviewed literature focused selectively on gadoxetate disodium with conflicting results. MATERIALS AND METHODS: Twenty patients (mean age 55.5 ± 14.0 years) after previous repeated administrations of gadoxetate disodium (mean 2.6 ± 1.5) for liver diagnostic process were included. All patients had normal renal and liver functions, an intact blood-brain barrier, and did not receive any other GBCA. They underwent 26 brain magnetic resonance imaging (MRI) with T1WI axial scans for signal intensity (SI) evaluation. The SI changes were measured in globus pallidus (GP), dentate nucleus (DN), pons (Po), and thalamus (Th) and SI ratios (DN/Po, GP/Po, GP/Th, Th/Po) were calculated. The control group consisted of 10 healthy volunteers (mean age 54.8 ± 12.1 years) with no prior GBCA applications. STATISTICAL ANALYSIS: Robust linear regression was used to test the effect of number of applications on the SI ratios. RESULTS: The significant effect of number of gadoxetate previous applications on DN/Po SI ratio was found. On an average, the DN/Po ratio increased by 0.36 percentage points [P = 0.042, 95% CI (0.03, 0.69)]. Other SI ratios were not significantly affected. CONCLUSIONS: Repeated administrations of hepatospecific gadoxetate disodium leads to a statistically significant increase in the SI values in DN in patients with normal renal and liver functions, and with an intact blood-brain barrier, probably due to gadolinium deposition.

Hypophysitis and other autoimmune complications related to immune checkpoints inhibitors´ treatment: Spectrum of imaging appearances.

OBJECTIVES: Immune checkpoints inhibitors (ICI) represent a new therapy option for the treatment of several advanced tumors. However, this therapy has been linked to a spectrum of ICI related autoimmune (AI) adverse events. Some may be life threatening and their diagnosis is tricky. The aim of our study was to describe various imaging appearances of ICI related secondary hypophysitis and other coincidental AI diseases. MATERIAL AND METHODS: We included 28 patients (19 females, 9 men, mean aged 58±13 years), who were consecutively treated mostly for advanced stage melanoma by different ICI. All their CT/MRI records and clinical data were reviewed. RESULTS: We found 5 (18%) cases of endocrinology proven secondary hypophysitis; 2 cases of panhypopituitarism and 3 cases of central hypocortisolism. Four cases were MRI positive, 1 case was MRI negative. Three cases were accompanied by other AI diseases: 1 by hemorrhagic colitis and mesenterial lymphadenitis, 1 by AI pancreatitis and 1 by pneumonitis. On MRI pituitary gland was swollen in 3 cases, twice enhanced non-homogenously, once homogenously; infundibular enlargement was present in 2 cases. Those 3 cases reacted to glucocorticoid therapy by hypophyseal shrinkage. In 1 case of MRI positive hypophysitis, the pituitary gland was not enlarged, slightly nonhomogeneous with peripheral contour enhancement; no reaction to glucocorticoids was mentioned. CONCLUSION: Secondary hypophysitis is probably more common ICI related adverse event than reported in the literature. Its MRI appearance is variable. Most of our cases were in coincidence with other AI ICI related events that affected their clinical manifestations.

Gadolinium contrast agents - are they really safe?

Gadolinium-based contrast agents (GBCA) are used worldwide for enhanced MRI examinations, including heart and vessels. Gadolinium is a highly toxic heavy metal. If used in GBCA it must be tightly bound to ligands. The configuration of ligands influences the stability of the GBCA and two types of chelates have been used. Macrocyclic chelates offer better protection and binding of gadolinium ion than linear chelates with a flexible open chain - gadolinium could be more easily released from the latter ones. GBCAs are excreted from the body mostly by the kidneys, which is of importance in chronic kidney disease.Two states are related to gadolinium: nephrogenic systemic fibrosis (NSF) and gadolinium body storage. NSF is a severe and debilitating disease, directly connected to gadolinium toxicity, proven after the use of linear chelates. Due to strict recommendations of radiology societies, NSF was practically eradicated. Gadolinium deposition was observed especially in bones and in some brain areas: in dentate nucleus and in globus pallidus, even years after the GBCA administration. The form of the storage (chelated or free), as well as their clinical impact, are not clear, but first observations of "gadolinium deposition disease" have been reported.