Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial.

BACKGROUND: Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke. METHODS: In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0·9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants. FINDINGS: Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7·3%, 95% CI -16·6 to 2·1, lower limit of one-sided 95% CI -15·1%, crossing the non-inferiority margin of -12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy (risk difference -1·0%, 95% CI -4·8 to 2·7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [91%] of 201 vs 199 [96%] of 207, risk difference -5·1%, 95% CI -10·2 to 0·0, p=0·047). INTERPRETATION: Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients. FUNDING: Medtronic and University Hospital Bern.

Clipping Versus Coiling for Ruptured MCA Aneurysms Associated with Intracerebral Hematoma Requiring Surgical Evacuation.

BACKGROUND: Ruptured middle cerebral artery aneurysm (MCAa) can lead to intracerebral hematoma, and surgical evacuation can be performed in these cases. MCAa can be treated by clipping or before by endovascular therapy (EVT). Our objective was to compare the impact on the functional outcome of MCAa in patients with intracerebral hematoma requiring evacuation. METHODS: This is a multicenter, retrospective, cohort study with nine French neurosurgical units from January 1, 2013, to December 31, 2020. All participants were adult patients who required evacuation of an intracerebral hematoma. We looked for risk factors for poor outcomes by comparing the baseline characteristics and treatments performed by using the 6-month modified Rankin scale score. Poor outcomes were defined by an modified Rankin scale score of 3-6. RESULTS: A total of 162 patients were included. A total of 129 (79.6%) patients were treated by microsurgery, and 33 (20.4%) patients were treated by EVT. In multivariate analysis, factors associated with poor outcomes included hematoma volume, realization of a decompressive craniectomy, occurrence of procedure-related symptomatic cerebral ischemia, occurrence of delayed cerebral ischemia, and EVT. In the propensity score matching analysis (n = 33 per group), poor outcomes were observed in 30% of the patients in the clipping group versus 76% in the EVT group (P < 0.001). These differences may have been related to a longer delay between hospital admission and hematoma evacuation in the EVT group. CONCLUSIONS: In the specific subgroup of ruptured MCAa with intracerebral hematoma that requires surgical evacuation, clipping with concomitant hematoma evacuation could provide better functional outcomes than EVT followed by surgical evacuation.

Safety and effectiveness of the LVIS and LVIS Jr devices for the treatment of intracranial aneurysms: Final results of the LEPI multicenter cohort study.

BACKGROUND: The Low profile visualized intraluminal support (LVIS)/LVIS Jr is a self-expanding braiding stent for the treatment of intracranial aneurysm. This study is to determine the safety and effectiveness of the LVIS/LVIS Jr for the treatment of intracranial aneurysms in a real-world setting. METHODS: This prospective, observational, multicenter study enrolled patients with unruptured, ruptured and recanalized intracranial aneurysms treated with the LVIS stents, between February 2018 to December 2019. Primary endpoint was the cumulative morbidity and mortality rate (CMMR) assessed at 12 months follow-up (FU). RESULTS: A total of 130 patients were included (62.3 % women, mean age 55.9 ± 11.4) on an intention-to-treat basis. Four patients (3.1 %) had 2 target aneurysms; 134 total aneurysms were treated. The aneurysms were mainly located on the middle cerebral artery (41/134; 30.6 %) and the anterior communicating artery (31/134; 23.1 %). The CMMR at 1 year linked to the procedure and/or device was 4.6 % (6/130). The overall mortality was 1.5 % (2/130), none of these deaths adjudged as being linked to the procedure and/or device. All aneurysms (134/134, 100 %) were successfully treated with LVIS stent and/or other devices. At a mean FU of 16.8 months post-procedure, complete/nearly complete occlusion was achieved in 112 aneurysms (92.6 %), and only 3 patients (2.5 %) required aneurysm retreatment. CONCLUSION: This study provides evidence that the LVIS/LVIS Jr devices are safe and effective in the treatment of complex intracranial aneurysms, with very high rates of adequate occlusion at FU. These angiographic results are stable over time with an acceptable complication rate. TRIAL REGISTRATION: ClinicalTrial.gov under NCT03553771.

The Combination of MR Elastography and Proton Density Fat Fraction Improves Diagnosis of Nonalcoholic Steatohepatitis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide. It is subdivided into nonalcoholic fatty liver (NAFL) and the more aggressive form, nonalcoholic steatohepatitis (NASH), which carries a higher risk of developing fibrosis and cirrhosis. There is currently no reliable non-invasive method for differentiating NASH from NAFL. PURPOSE: To investigate the ability of magnetic resonance imaging (MRI)-based imaging biomarkers to diagnose NASH and moderate fibrosis as well as assess their repeatability. STUDY TYPE: Prospective. SUBJECTS: Sixty-eight participants (41% women) with biopsy-proven NAFLD (53 NASH and 15 NAFL). Thirty participants underwent a second MRI in order to assess repeatability. FIELD STRENGTH/SEQUENCE: 3.0 T; MR elastography (MRE) (a spin-echo echo-planar imaging [SE-EPI] sequence with motion-encoding gradients), MR proton density fat fraction (PDFF) and R2* mapping (a multi-echo three-dimensional gradient-echo sequence), T1 mapping (a single-point saturation-recovery technique), and diffusion-weighted imaging (SE-EPI sequence). ASSESSMENT: Quantitative MRI measurements were obtained and assessed alone and in combination with biochemical markers (cytokeratin-18 [CK18] M30, alanine transaminase [ALT], and aspartate transaminase [AST]) using logistic regression models. Models that could differentiate between NASH and NAFL and between moderate to advanced fibrosis (F2-4) and no or mild fibrosis (F0-1), based on the histopathological results, were identified. STATISTICAL TESTS: Independent samples t-test, Pearson's chi-squared test, area under the receiver operating characteristic curve (AUROC), Spearman's correlation, intra-individual coefficient of variation, and intraclass correlation coefficient (ICC). Statistical significance was set at P < 0.05. RESULTS: There was a significant difference between the NASH and NAFL groups with liver stiffness assessed with MRE, CK18 M30, and ALT, with an AUROC of 0.74, 0.76, and 0.70, respectively. Both MRE and PDFF contributed significantly to a bivariate model for diagnosing NASH (AUROC = 0.84). MRE could significantly differentiate between F2-4 and F0-1 (AUROC = 0.74). A model combining MRE with AST improved the diagnosis of F2-4 (AUROC = 0.83). The ICC for repeatability was 0.94 and 0.99 for MRE and PDFF, respectively. DATA CONCLUSION: MRE can potentially diagnose NASH and differentiate between fibrosis stages. Combining MRE with PDFF improves the diagnosis of NASH. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Peritumoral portal enhancement during transarterial chemoembolization: a potential prognostic factor for patients with hepatocellular carcinoma.

BACKGROUND: Tumor response and survival varies in patients treated with transarterial chemoembolization (TACE) for intermediate stage hepatocellular carcinoma (HCC) and may be associated with several factors. PURPOSE: To evaluate safety and efficacy of TACE in patients with intermediate stage HCC and to identify factors related to tumor response and survival. MATERIAL AND METHODS: Consecutive patients with HCC treated with TACE between September 2008 and September 2018 were retrospectively reviewed. RESULTS: In 87 patients (71 men; mean age = 68 ± 9 years), 327 TACE treatments were performed (mean = 3/patient; range = 1-12). Mean and median overall survival were 32 and 19 months, respectively. Survival rates at 30 days, one, three, and five years were 99%, 71%, 19%, and 8%, respectively. Objective response (OR) was seen in 84% and disease control (DC) was seen in 92% of the patients. Patients in whom peritumoral portal lipiodol enhancement (PPLE) was seen during TACE had better OR (97 vs. 73%; P = 0.007) and DC (100 vs. 85%; P = 0.024), and a reduced risk of death (hazard ratio [HR] = 0.52; 95% confidence interval = 0.32-0.86) compared to those without PPLE. Severe adverse events were rare (15%) and occurred more often in patients with a larger tumor size. CONCLUSIONS: TACE was effective and safe in patients with intermediate stage HCC. Patients with PPLE during TACE had better tumor response and longer survival than those without PPLE. Severe adverse events occurred more often in patients with larger tumors.

Benefit of mechanical thrombectomy in acute ischemic stroke related to calcified cerebral embolus.

PURPOSE: Mechanical thrombectomies (MT) in patients with large vessel occlusion (LVO) related to calcified cerebral embolus (CCE) have been reported, through small case series, being associated with low reperfusion rate and worse outcome, compared to regular MT. The purpose of the MASC (Mechanical Thrombectomy in Acute Ischemic Stroke Related to Calcified Cerebral Embolus) study was to evaluate the incidence of CCEs treated by MT and the effectiveness of MT in this indication. METHODS: The MASC study is a retrospective multicentric (n = 37) national study gathering the cases of adult patients who underwent MT for acute ischemic stroke with LVO related to a CCE in France from January 2015 to November 2019. Reperfusion rate (mTICI ≥ 2B), complication rate and 90-day mRS were systematically collected. We then conducted a systematic review by searching for articles in PubMed, Cochrane Library, Embase and Google Scholar from January 2015 to March 2020. A meta-analysis was performed to estimate clinical outcome at 90 days, reperfusion rate and complications. RESULTS: We gathered data from 35 patients. Reperfusion was obtained in 57% of the cases. Good clinical outcome was observed in 28% of the patients. The meta-analysis retrieved 136 patients. Reperfusion and good clinical outcome were obtained in 50% and 29% of the cases, respectively. CONCLUSION: The MASC study found worse angiographic and clinical outcomes compared to regular thrombectomies. Individual patient-based meta-analysis including the MASC findings shows a 50% reperfusion rate and a 29% of good clinical outcome.

Impact of Prior Antiplatelet Therapy on Outcomes After Endovascular Therapy for Acute Stroke: Endovascular Treatment in Ischemic Stroke Registry Results.

BACKGROUND AND PURPOSE: The influence of prior antiplatelet therapy (APT) uses on the outcomes of patients with acute ischemic stroke treated with endovascular therapy is unclear. We compared procedural and clinical outcomes of endovascular therapy in patients on APT or not before stroke onset. METHODS: We analyzed 2 groups from the ongoing prospective multicenter Endovascular Treatment in Ischemic Stroke registry in France: patients on prior APT (APT+) and patients without prior APT (APT-) treated by endovascular therapy, with and without intravenous thrombolysis. Multilevel mixed-effects logistic models including center as random effect were used to compare angiographic (rates of reperfusion at the end of procedure, procedural complications) and clinical (favorable and excellent outcome, 90-day all-cause mortality, and hemorrhagic complications) outcomes according to APT subgroups. Comparisons were adjusted for prespecified confounders (age, admission National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, intravenous thrombolysis, and time from onset to puncture), as well as for meaningful baseline between-group differences. RESULTS: A total of 2939 patients were analyzed, of whom 877 (29.8%) were on prior APT. Patients with prior APT were older, had more frequent vascular risk factors, cardioembolic stroke mechanism, and prestroke disability. Rates of complete reperfusion (37.9% in the APT- group versus 42.7 % in the APT+ group; aOR, 1.09 [95% CI, 0.88-1.34]; P=0.41) and periprocedural complication (16.9% versus 13.3%; aOR, 0.90 [95% CI, 0.7-1.2]; P=0.66) did not differ between the two groups. Symptomatic intracerebral hemorrhage (aOR, 0.93 [95% CI, 0.63-1.37]; P=0.73), 3 months favorable clinical outcome (modified Rankin Scale score of 0-2; aOR, 0.98 [95% CI, 0.77-1.25]; P=0.89), and mortality (aOR, 0.95 [95% CI, 0.72-1.26]; P=0.76) at 90 days did not differ between the groups. CONCLUSIONS: Prior APT does not influence angiographic and functional outcomes following endovascular therapy and should not be taken into account for acute revascularization strategies.

Portal vein embolization with n-butyl-cyanoacrylate before hepatectomy: a single-center retrospective analysis of 46 consecutive patients.

BACKGROUND: Preoperative portal vein embolization (PVE) is performed to induce hypertrophy of the future liver remnant enabling major liver resection in patients with various types of liver tumors. PURPOSE: To evaluate safety and effectiveness of PVE with n-butyl-cyanoacrylate (NBCA). MATERIAL AND METHODS: All consecutive patients referred to our hospital for PVE between July 2006 and July 2017 were retrospectively reviewed. Volumetry was performed on computed tomography images before and after PVE, segmenting the total liver volume and the future liver remnant (FLR), i.e. liver segments I-III. RESULTS: PVE was performed in 46 patients (18 women, 28 men; mean age = 61 years) using local anesthesia. The ipsilateral technique was used in 45 patients. Adverse events were rare. The mean FLR volume increase was 56%, the degree of hypertrophy was 9.7%, and the kinetic growth rate was 2.1%/week. The median ± SD period between PVE and liver surgery was 7 ± 3 weeks. Forty-two patients (91%) had surgery; liver resection was performed in 37 (80%) patients. Three patients (7%) developed transient liver failure after surgery. There was no 90-day post-PVE or postoperative mortality. CONCLUSION: PVE using NBCA through the ipsilateral approach in local anesthesia is safe and effective in inducing hypertrophy of the future liver remnant enabling surgery, and thereby increasing survival in patients with liver tumors.

Limitations and Possibilities of Transarterial Chemotherapeutic Treatment of Hepatocellular Carcinoma.

Because diagnostic tools for discriminating between hepatocellular carcinoma (HCC) and advanced cirrhosis are poor, HCC is often detected in a stage where transarterial chemoembolization (TACE) is the best treatment option, even though it provides a poor survival gain. Despite having been used worldwide for several decades, TACE still has many limitations. First, there is a vast heterogeneity in the cellular composition and metabolism of HCCs as well as in the patient population, which renders it difficult to identify patients who would benefit from TACE. Often the delivered drug does not penetrate sufficiently selectively and deeply into the tumour and the drug delivery system is not releasing the drug at an optimal clinical rate. In addition, therapeutic effectiveness is limited by the crosstalk between the tumour cells and components of the cirrhotic tumour microenvironment. To improve this widely used treatment of one of our most common and deadly cancers, we need to better understand the complex interactions between drug delivery, local pharmacology, tumour targeting mechanisms, liver pathophysiology, patient and tumour heterogeneity, and resistance mechanisms. This review provides a novel and important overview of clinical data and discusses the role of the tumour microenvironment and lymphatic system in the cirrhotic liver, its potential response to TACE, and current and possible novel DDSs for locoregional treatment.

Flow Diverters for Intracranial Aneurysms: The DIVERSION National Prospective Cohort Study.

Background and Purpose- Flow diverters are used for endovascular therapy of intracranial aneurysms. We did a nationwide prospective study to investigate the safety and effectiveness of flow diversion at 12 months. Methods- DIVERSION was a national prospective cohort study including all flow diverters placement between October 2012 and February 2014 in France. The primary end point was the event-free survival rate at 12 months, defined as the occurrence of morbidity (intracranial hemorrhage, ischemic stroke, noncerebral hemorrhage, or neurological deficit due to mass effect), retreatment, or death within 12 months post-treatment. A quality control was carried out on 100% of the collected data and of at least 10% of the included patients in each center, chosen at random. All reported serious events were adjudicated by an independent Data Safety and Monitoring Board. Satisfactory occlusion was defined as 3 or 4 on Kamran scale by an independent imaging core laboratory at 12 months. Results- We enrolled 398 patients harboring 477 intracranial aneurysms. At least 1 morbidity-mortality event was noted in 95 of 408 interventions representing an event-free survival rate of 75.7% (95% CI, 71.1-79.7). The rate of permanent-related serious events and mortality was 5.9% and 1.2% at 12 months, respectively. Multivariate analysis showed that high baseline blood pressure (hazard ratio, 2.54; 95% CI, 1.35-4.79; P=0.039), diabetes mellitus (hazard ratio, 3.70; 95% CI, 1.60-8.6; P=0.0022), and larger aneurysms (hazard ratio, 1.07; 95% CI, 1.04-1.11; P<0.0001) were associated with the occurrence of a neurological deficit. The satisfactory occlusion rate at 12 months was 79.9%, and the absence of high baseline blood pressure (odds ratio, 2.01; 95% CI, 1.12-3.71; P=0.0193) and postprocedural satisfactory occlusion (odds ratio, 2.75; 95% CI, 1.49-5.09; P=0.0012) were associated with a 12-month satisfactory occlusion. Conclusions- A satisfactory occlusion was achieved in almost 80% of cases after flow diverter treatment with a permanent-related serious event and mortality rates of 5.9% and 1.2% at 12 months, respectively.

Endovascular management of a giant petrous internal carotid artery aneurysm in a child. Case report and literature review.

BACKGROUND: Aneurysms of the petrosal segment of the internal carotid artery are rare in children and are usually found secondary to trauma and infection or can have a congenital origin. Management includes endovascular therapy, surgery, and in rare cases observation. DISCUSSION: Here, we report our experience with a giant petrous internal carotid artery aneurysm in a 16-year-old boy successfully managed endovascularly by parent artery occlusion.

Treatment of acute portomesenteric venous thrombosis with thrombectomy through a transjugular intrahepatic portosystemic shunt: a single-center experience.

Background Acute portomesenteric venous thrombosis (PMVT) is a potentially life-threatening condition and urgent treatment is required. Purpose To retrospectively evaluate the efficacy and safety of treating acute PMVT by the creation of a transjugular intrahepatic portosystemic shunt (TIPS) followed by thrombectomy. Material and Methods Six patients (all men, age range = 39-51 years) presenting with acute PMVT were treated with transjugular thrombectomy (TT) through a TIPS created in the same session. The intervention included iterated venography through the TIPS one to three times within the first week after diagnosis and repeated thrombectomy if needed (n = 5). Results Recanalization was successful with persistent blood flow through the main superior mesenteric vein, portal vein, and TIPS in all six patients. Five patients were treated primarily with thrombectomy through a TIPS with clinical improvement. The final patient was initially treated with surgical thrombectomy and bowel resection. TIPS and TT was performed two days after surgery due to re-thrombosis but the patient deteriorated and died of multi-organ failure. Procedure-related complications were transient hematuria (n = 3) and transient encephalopathy (n = 2). In-hospital time was <14 days in four of the five patients with primary TIPS and TT. No sign of re-thrombosis was noted during follow-up (mean = 18 months, range = 8-28 months). Conclusion Thrombectomy through a TIPS is feasible and can be effective in recanalization and symptom-relief in acute PMVT.

In Vivo Drug Delivery Performance of Lipiodol-Based Emulsion or Drug-Eluting Beads in Patients with Hepatocellular Carcinoma.

Doxorubicin (DOX) delivered in a lipiodol-based emulsion (LIPDOX) or in drug-eluting beads (DEBDOX) is used as palliative treatment in patients with intermediate-stage hepatocellular carcinoma (HCC). The primary objective of this study was to evaluate the in vivo delivery performance of DOX from LIPDOX or DEBDOX in HCC patients using the local and systemic pharmacokinetics of DOX and its main metabolite doxorubicinol (DOXol). Urinary excretion of DOX and DOXol and their short-term safety and antitumor effects were also evaluated. In this open, prospective, nonrandomized multicenter study, LIPDOX (n = 13) or DEBDOX (n = 12) were injected into the feeding arteries of the tumor. Local (vena cava/hepatic vein orifice) and systemic (peripheral vein) plasma concentrations of DOX and DOXol were determined in samples obtained up to 6 h and 7 days after treatment. Tumor response was assessed using computed tomography or magnetic resonance imaging. The Cmax and AUC0-24 h for DOX were 5.6-fold and 2.4-fold higher in LIPDOX vs DEBDOX recipients, respectively (p < 0.001). After 6 h, the respective mean proportions of the dose remaining in the liver or drug-delivery system (DDS) were 49% for LIPDOX and 88% for DEBDOX. LIPDOX releases DOX faster than DEBDOX in HCC patients and provides more extensive local and systemic exposure (AUC) to DOX and DOXol initially (0-7 days). DEBDOX formulation has a release and distribution of DOX that is more restricted and rate controlled than LIPDOX.

The number of unrecognized myocardial infarction scars detected at DE-MRI increases during a 5-year follow-up.

OBJECTIVES: In an elderly population, the prevalence of unrecognized myocardial infarction (UMI) scars found via late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging was more frequent than expected. This study investigated whether UMI scars detected with LGE-CMR at age 70 would be detectable at age 75 and whether the scar size changed over time. METHODS: From 248 participants that underwent LGE-CMR at age 70, 185 subjects underwent a follow-up scan at age 75. A myocardial infarction (MI) scar was defined as late enhancement involving the subendocardium. RESULTS: In the 185 subjects that underwent follow-up, 42 subjects had a UMI scar at age 70 and 61 subjects had a UMI scar at age 75. Thirty-seven (88 %) of the 42 UMI scars seen at age 70 were seen in the same myocardial segment at age 75. The size of UMI scars did not differ between age 70 and 75. CONCLUSIONS: The prevalence of UMI scars detected at LGE-CMR increases with age. During a 5-year follow-up, 88 % (37/42) of the UMI scars were visible in the same myocardial segment, reassuring that UMI scars are a consistent finding. The size of UMI scars detected during LGE-CMR did not change over time. KEY POINTS: • UMI scars detected by LGE-CMR are frequent in elderly. • The prevalence of UMI scars detected with LGE-CMR increases with age. • UMI scar size does not change over time.

Selective internal radiation therapy in patients with progressive neuroendocrine liver metastases.

PURPOSE: To evaluate the safety and efficacy of selective internal radiation therapy (SIRT) in patients with unresectable liver metastases from neuroendocrine tumours (NETLMs). METHODS: This retrospective study included 40 patients with progressive NETLMs (22 women, 18 men, mean age 61.6 years) who underwent SIRT with (90)Y-labelled resin microspheres. Tumour response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) on CT or MR images. Medical records were reviewed. RESULTS: In the 40 patients, 54 evaluable SIRT procedures were performed, 33 to the right liver lobe (mean activity 1.31 GBq), 13 to the left lobe (mean activity 0.85 GBq), and 8 to both lobes (mean activity 1.61 GBq). Late follow-up imaging (mean 20 months) was performed after 44 of the treatments. Objective tumour response and disease control rates were 54 % (29 of 54 treatments) and 94 % (51 treatments), respectively, at the early follow-up examination (mean 3 months) and 34 % (15 treatments) and 57 % (25 treatments), respectively at the late follow-up examination. Mean overall survival from the first SIRT was 34,8 months and survival rates at 1, 2, 3 and 5 years were 76 %, 59 %, 52 % and 35 % respectively. Adverse effects were generally mild and easily manageable, except in one patient who died from radiation-induced liver failure. Of the 45 patients, 18 (45 %) had received peptide receptor radionuclide therapy (PRRT) prior to SIRT. CONCLUSION: SIRT with (90)Y-labelled resin microspheres is a safe and effective treatment for patients with progressive NETLM, and also for those who have received prior PRRT.

Long-term prognosis of unrecognized myocardial infarction detected with cardiovascular magnetic resonance in an elderly population.

BACKGROUND: Individuals with unrecognized myocardial infarctions (UMIs) detected with cardiovascular magnetic resonance (CMR) constitute a recently defined group whose prognosis has not been fully evaluated. However, increasing evidence indicate that these individuals may be at considerable cardiovascular risk. The aim of the present study was to investigate the prognostic impact of CMR detected UMIs for major adverse cardiac events (MACE) in community living elderly individuals. METHODS: Late gadolinium enhancement CMR was performed in 248 randomly chosen 70-year-olds. Individuals with myocardial infarction (MI) scars, with or without a hospital diagnosis of MI were classified as recognized MI (RMI) or UMI, respectively. Medical records and death certificates were scrutinized. MACE was defined as cardiac death, non-fatal MI, a new diagnosis of angina pectoris, or symptom-driven coronary artery revascularization. RESULTS: During follow-up (mean 11 years) MACE occurred in 10 % (n = 18/182) of the individuals without MI scars, in 20 % (n = 11/55) of the individuals with UMI, and in 45 % (n = 5/11) of the individuals with RMI, with a significant difference between the UMI group and the group without MI scars (p = 0.045), and between the RMI group and the group without MI scars (p = 0.0004). Cardiac death and/or non-fatal MI occurred in 15, 5, and 3 of the individuals in the NoMI, UMI, and RMI group respectively. Hazards ratios for MACE adjusted for risk factors and sex were 2.55 (95 % CI 1.20-5.42; p = 0.015) for UMI and 3.28 (95 % CI1.16-9.22; p = 0.025) for RMI. CONCLUSIONS: The presence of a CMR detected UMI entailed a more than double risk for MACE in community living 70-year-old individuals.

Cardiac troponin I associated with the development of unrecognized myocardial infarctions detected with MRI.

BACKGROUND: Late enhancement MRI (LE-MRI) and cardiac troponin I (cTnI) are sensitive methods to detect subclinical myocardial injury. We sought to investigate the relation between plasma concentrations of cTnI measured with a high-sensitivity assay (hs-cTnI) and the development of unrecognized myocardial infarctions (UMIs) detected with LE-MRI. METHODS: After approval from the ethics committee and written informed consent were obtained, LE-MRI was performed on 248 randomly selected community-living 70-year-old volunteers and hs-cTnI was determined with a highly sensitive premarket assay. Five years later these individuals were invited to a second LE-MRI, and 176 of them (82 women, 94 men), who did not have a hospital diagnosis of MI, constitute the present study population. LE-MR images were analyzed by 2 radiologists independently and in a consensus reading, blinded to any information on previous disease or assessments. RESULTS: New or larger UMIs were detected in 37 participants during follow-up. Plasma concentrations of hs-cTnI at 70 years of age, which were mainly within what is considered to be the reference interval, were related to new or larger UMIs at 75 years of age with an odds ratio of 1.98 per 1 unit increase in ln-transformed cTnI (95% CI, 1.17-3.35; P = 0.010). Plasma concentrations of hs-cTnI at 70 years of age were associated with the volumes of the UMIs detected at 75 years of age (P = 0.028). CONCLUSIONS: hs-cTnI in 70-year-old community-living women and men was associated with the development of MRI-detected UMIs within 5 years.

Investigation of hepatobiliary disposition of doxorubicin following intrahepatic delivery of different dosage forms.

Unresectable, intermediate stage hepatocellular carcinoma (HCC) is often treated palliatively in humans by doxorubicin (DOX). The drug is administered either as a drug-emulsified-in-Lipiodol (DLIP) or as drug loaded into drug eluting beads (DEB), and both formulations are administered intrahepatically. However, several aspects of their in vivo performance in the liver are still not well-understood. In this study, DLIP and DEB were investigated regarding the local and systemic pharmacokinetics (PK) of DOX and its primary metabolite doxorubicinol (DOXol). An advanced PK-multisampling site acute in vivo pig model was used for simultaneous sampling in the portal, hepatic, and femoral veins and the bile duct. The study had a randomized, parallel design with four treatment groups (TI-TIV). TI (n = 4) was used as control and received an intravenous (i.v.) infusion of DOX as a solution. TII and TIII were given a local injection in the hepatic artery with DLIP (n = 4) or DEB (n = 4), respectively. TIV (n = 2) received local injections of DLIP in the hepatic artery and bile duct simultaneously. All samples were analyzed for concentrations of DOX and DOXol with UPLC-MS/MS. Compared to DLIP, the systemic exposure for DOX with DEB was reduced (p < 0.05), in agreement with a slower in vivo release. The approximated intracellular bioavailability of DOX during 6 h appeared to be lower for DEB than DLIP. Following i.v. infusion (55 min), DOX had a liver extraction of 41 (28-53)%, and the fraction of the dose eliminated in bile of DOX and DOXol was 20 (15-22)% and 4.2 (3.2-5.2)%, respectively. The AUCbile/AUCVP for DOX and DOXol was 640 (580-660) and 5000 (3900-5400), respectively. In conclusion, DLIP might initially deliver a higher hepatocellular concentration of DOX than DEB as a consequence of its higher in vivo release rate. Thus, DLIP delivery results in higher intracellular peak concentrations that might correlate with better anticancer effects, but also higher systemic drug exposure and safety issues.

Endovascular treatment of symptomatic vestibular aqueduct dehiscence as a result of jugular bulb abnormalities.

A new endovascular treatment consisting of stent-assisted coil implantation is described for jugular bulb abnormalities causing symptomatic vestibular aqueduct dehiscence. Three patients presenting with vertigo associated with pulsatile tinnitus or hearing loss were treated. This technique cured the vertigo and pulsatile tinnitus in all patients and preserved normal cerebral venous drainage with no side effects.