Functional maturation and longitudinal imaging of intraportal neonatal porcine islet grafts in genetically diabetic pigs.

Allogeneic intraportal islet transplantation (ITx) has become an established treatment for patients with poorly controlled type 1 diabetes. However, the loss of viable beta-cell mass after transplantation remains a major challenge. Therefore, noninvasive imaging methods for long-term monitoring of the transplant fate are required. In this study, [68Ga]Ga-DOTA-exendin-4 positron emission tomography/computed tomography (PET/CT) was used for repeated monitoring of allogeneic neonatal porcine islets (NPI) after intraportal transplantation into immunosuppressed genetically diabetic pigs. NPI transplantation (3320-15,000 islet equivalents per kg body weight) led to a reduced need for exogenous insulin therapy and finally normalization of blood glucose levels in 3 out of 4 animals after 5 to 10 weeks. Longitudinal PET/CT measurements revealed a significant increase in standard uptake values in graft-bearing livers. Histologic analysis confirmed the presence of well-engrafted, mature islet clusters in the transplanted livers. Our study presents a novel large animal model for allogeneic intraportal ITx. A relatively small dose of NPIs was sufficient to normalize blood glucose levels in a clinically relevant diabetic pig model. [68Ga]Ga-DOTA-exendin-4 PET/CT proved to be efficacious for longitudinal monitoring of islet transplants. Thus, it could play a crucial role in optimizing ITx as a curative therapy for type 1 diabetes.

Clinical benefits of MRI-guided freehand biopsy of small focal liver lesions in comparison to CT guidance.

OBJECTIVES: To compare clinical success, procedure time, and complication rates between MRI-guided and CT-guided real-time biopsies of small focal liver lesions (FLL) < 20 mm. METHODS: A comparison of a prospectively collected MRI-guided cohort (n = 30) to a retrospectively collected CT-guided cohort (n = 147) was performed, in which patients underwent real-time biopsies of small FLL < 20 mm in a freehand technique. In both groups, clinical and periprocedural data, including clinical success, procedure time, and complication rates (classified according to CIRSE guidelines), were analyzed. Wilcoxon rank sum test, Pearson's chi-squared test, and Fisher's exact test were used for statistical analysis. Additionally, propensity score matching (PSM) was performed using the following criteria for direct matching: age, gender, presence of liver cirrhosis, liver lobe, lesion diameter, and skin-to-target distance. RESULTS: The median FLL diameter in the MRI-guided cohort was significantly smaller compared to CT guidance (p < 0.001; 11.0 mm vs. 16.3 mm), while the skin-to-target distance was significantly longer (p < 0.001; 90.0 mm vs. 74.0 mm). MRI-guided procedures revealed significantly higher clinical success compared to CT guidance (p = 0.021; 97% vs. 79%) as well as lower complication rates (p = 0.047; 0% vs. 13%). Total procedure time was significantly longer in the MRI-guided cohort (p < 0.001; 38 min vs. 28 min). After PSM (n = 24/n = 38), MRI-guided procedures still revealed significantly higher clinical success compared to CT guidance (p = 0.039; 96% vs. 74%). CONCLUSION: Despite the longer procedure time, freehand biopsy of small FLL < 20 mm under MR guidance can be considered superior to CT guidance because of its high clinical success and low complication rates. CLINICAL RELEVANCE STATEMENT: Biopsy of small liver lesions is challenging due to the size and conspicuity of the lesions on native images. MRI offers higher soft tissue contrast, which translates into a higher success of obtaining enough tissue material with MRI compared to CT-guided biopsies. KEY POINTS: • Image-guided biopsy of small focal liver lesions (FLL) is challenging due to inadequate visualization, leading to sampling errors and false-negative biopsies. • MRI-guided real-time biopsy of FLL < 20 mm revealed significantly higher clinical success (p = 0.021; 97% vs. 79%) and lower complication rates (p = 0.047; 0% vs. 13%) compared to CT guidance. • Although the procedure time is longer, MRI-guided biopsy can be considered superior for small FLL < 20 mm.

Outcome of bleomycin electrosclerotherapy of slow-flow malformations in adults and children.

OBJECTIVES: To evaluate the safety and clinical outcome of bleomycin electrosclerotherapy (BEST) for treating extracranial slow-flow malformations. METHODS: In this retrospective investigation of a multicenter cohort presenting symptomatic slow-flow malformations, patient records were analyzed with respect to procedural details and complications. A treatment-specific, patient-reported questionnaire was additionally evaluated, obtained 3-12 months after the last treatment, to assess the subjective outcomes, including mobility, aesthetic aspects, and pain, as well as the occurrence of postprocedural skin hyperpigmentation. All outcome parameters were compared according to patients' age. RESULTS: Overall, 325 BEST treatments were performed in 233 patients after intralesional and/or intravenous bleomycin injection. The total complication rate was 10.2% (33/325), including 29/352 (8.9%) major complications. Patient-reported mobility decreased in 10/133 (8.8%), was stable in 30/113 (26.5%), improved in 48/113 (42.5%), and was rated symptom-free in 25/113 (22.1%) patients. Aesthetic aspects were rated impaired compared to baseline in 19/113 (16.8%), stable in 21/133 (18.6%), improved in 62/113 (54.9%), and perfect in 11/133 (9.7%) patients. Postprocedural skin hyperpigmentation occurred in 78/113 (69%) patients, remaining unchanged in 24/78 (30.8%), reduced in 51/78 (65.5%), and completely resolved in 3/78 (3.8%) patients. The median VAS pain scale was 4.0 (0-10) preprocedural and 2.0 (0-9) postprocedural. Children/adolescents performed significantly better in all parameters compared to adults (≥ 16 years) (mobility, p = 0.011; aesthetic aspects, p < 0.001; pain, p < 0.001). CONCLUSIONS: BEST is effective for treating slow-flow vascular malformations, with few but potentially significant major complications. Regarding patient-reported outcomes, children seem to benefit better compared to older patients, suggesting that BEST should not be restricted to adults. CLINICAL RELEVANCE STATEMENT: Bleomycin electrosclerotherapy is a safe and effective approach and therapy should not be restricted to adults due to good clinical outcomes in children.

Efficacy and Safety of Local Liver Radioablation in Hepatocellular Carcinoma Lesions within and beyond Limits of Thermal Ablation.

INTRODUCTION: CT-guided interstitial brachytherapy (iBT) radiotherapy has been established in the treatment of liver tumors. With iBT, hepatocellular carcinoma (HCC) lesions can be treated beyond the limits of thermal ablation (i.e., size and location). However, a comprehensive analysis of the efficacy of iBT in patients within and beyond thermal ablation limits is lacking. MATERIALS AND METHODS: A total of 146 patients with 216 HCC lesions have been analyzed retrospectively. Clinical and imaging follow-up data has been collected. Lesions were evaluated in terms of suitability for thermal ablation or not. The correlation between local tumor control (LTC), time to progression (TTP), overall survival (OS), and clinical and imaging parameters have been evaluated using univariable and multivariable Cox regression analyses. RESULTS: LTC rates at 12 months, 24 months, and 36 months were 87%, 75%, and 73%, respectively. 65% of lesions (n = 141) were not suitable for radiofrequency ablation (RFA). The median TTP was 13 months, and the median OS was not reached (3-year OS rate: 70%). No significant difference in LTC, TTP, or OS regarding RFA suitability existed. However, in the overall multivariable analysis, lesion diameter >5 cm was significantly associated with lower LTC (HR: 3.65, CI [1.60-8.31], p = 0.002) and shorter TTP (HR: 2.08, CI [1.17-3.70], p = 0.013). Advanced BCLC stage, Child-Pugh Stage, and Hepatitis B were associated with shorter OS. CONCLUSION: iBT offers excellent LTC rates and OS in local HCC treatment regardless of the limits of thermal ablation, suggesting further evidence of its alternative role to thermal ablation in patients with early-stage HCC.

Cost-effectiveness of short-protocol emergency brain MRI after negative non-contrast CT for minor stroke detection.

OBJECTIVES: To investigate the cost-effectiveness of supplemental short-protocol brain MRI after negative non-contrast CT for the detection of minor strokes in emergency patients with mild and unspecific neurological symptoms. METHODS: The economic evaluation was centered around a prospective single-center diagnostic accuracy study validating the use of short-protocol brain MRI in the emergency setting. A decision-analytic Markov model distinguished the strategies "no additional imaging" and "additional short-protocol MRI" for evaluation. Minor stroke was assumed to be missed in the initial evaluation in 40% of patients without short-protocol MRI. Specialized post-stroke care with immediate secondary prophylaxis was assumed for patients with detected minor stroke. Utilities and quality-of-life measures were estimated as quality-adjusted life years (QALYs). Input parameters were obtained from the literature. The Markov model simulated a follow-up period of up to 30 years. Willingness to pay was set to $100,000 per QALY. Cost-effectiveness was calculated and deterministic and probabilistic sensitivity analysis was performed. RESULTS: Additional short-protocol MRI was the dominant strategy with overall costs of $26,304 (CT only: $27,109). Cumulative calculated effectiveness in the CT-only group was 14.25 QALYs (short-protocol MRI group: 14.31 QALYs). In the deterministic sensitivity analysis, additional short-protocol MRI remained the dominant strategy in all investigated ranges. Probabilistic sensitivity analysis results from the base case analysis were confirmed, and additional short-protocol MRI resulted in lower costs and higher effectiveness. CONCLUSION: Additional short-protocol MRI in emergency patients with mild and unspecific neurological symptoms enables timely secondary prophylaxis through detection of minor strokes, resulting in lower costs and higher cumulative QALYs. KEY POINTS: • Short-protocol brain MRI after negative head CT in selected emergency patients with mild and unspecific neurological symptoms allows for timely detection of minor strokes. • This strategy supports clinical decision-making with regard to immediate initiation of secondary prophylactic treatment, potentially preventing subsequent major strokes with associated high costs and reduced QALY. • According to the Markov model, additional short-protocol MRI remained the dominant strategy over wide variations of input parameters, even when assuming disproportionally high costs of the supplemental MRI scan.

Stent-graft placement for hepatic arterial bleeding: assessment of technical efficacy and clinical outcome in a tertiary care center.

BACKGROUND: To evaluate technical and clinical results of stent-graft (SG) placement for bleeding from the hepatic artery (HA). METHODS: All patients intended and treated with SG deployment for bleeding from the HA at single center from January 2012 to May 2020 were retrospectively identified, and procedural details, risk factors for rebleeding, SG occlusion and mortality were analyzed. RESULTS: Twenty-seven patients (mean age 68.8 ± 10.1) were identified, and 25 patients underwent 26 SG procedures. Twenty-four patients had recent surgery. The technical success rate was 92.8%. Three patients (3/25) had rebleeding (88% clinical success). Intensive-care need before the procedure (p = 0.013) and smaller stent-graft size (≤4 mm, p = 0.032) were related to clinical failure. Twenty-two patients had follow-up imaging. The SG maintained patency in 10 (45.4%) patients at the most recent imaging. Only placement of SG distal to the HA bifurcation (p = 0.012) was related to occlusion. The 30-day and in-hospital mortality rate after SG was 8% and 24%. In-hospital mortality was associated with the intraabdominal septic source (p = 0.010) and revision surgery (p = 0.001). CONCLUSION: Stent-grafts are effective in the emergent treatment of HA bleeding. Mortality is mainly related to the general condition of the patient, and stent-grafts offer time to treat underlying medical problems sufficiently.

Computed Tomography Perfusion Deficit Volumes Predict Functional Outcome in Patients With Basilar Artery Occlusion.

Background and Purpose: Basilar artery occlusion is associated with high morbidity and mortality. Optimal imaging and treatment strategy are still controversial and prognosis estimation challenging. We, therefore, aimed to determine the predictive value of computed tomography perfusion (CTP) parameters for functional outcome in patients with basilar artery occlusion in the context of endovascular treatment. Methods: Patients with basilar artery occlusion who underwent endovascular treatment were selected from a prospectively acquired cohort. Ischemic changes were assessed with the posterior-circulation Acute Stroke Prognosis Early Computed Tomography Score on noncontrast computed tomography, computed tomography angiography (CTA) source images, and CTP maps. Basilar artery on CTA score, posterior-circulation CTA score, and posterior-circulation collateral score were evaluated on CTA. Perfusion deficit volumes were quantified on CTP maps. Good functional outcome was defined as modified Rankin Scale score ≤3 at 90 days. Statistical analysis included binary logistic regressions and receiver operating characteristics analyses. Results: Among 49 patients who matched the inclusion criteria, 24 (49.0%) achieved a good outcome. In univariate analysis, age, National Institutes of Health Stroke Scale score on admission, posterior cerebral artery involvement, absence of or hypoplastic posterior communicating arteries, basilar artery on CTA score, posterior-circulation Acute Stroke Prognosis Early Computed Tomography Score, and perfusion deficit volumes on all CTP parameter maps presented significant association with functional outcome (P<0.05). In multivariate analyses, Basilar artery on CTA score, posterior-circulation Acute Stroke Prognosis Early Computed Tomography Score (odds ratio range, 1.31­2.10 [95% CI, 1.00­7.24]), and perfusion deficit volumes on all CTP maps (odds ratio range, 0.77­0.98 [95% CI, 0.63­1.00]) remained as independent outcome predictors. Cerebral blood flow deficit volume yielded the best performance for the classification of good clinical outcome with an area under the curve of 0.92 (95% CI, 0.84­0.99). Age and admission National Institutes of Health Stroke Scale had lower discriminatory power (area under the curve, <0.7). Conclusions: CTP imaging parameters contain prognostic information for functional outcome in patients with stroke due to basilar artery occlusion and may identify patients with higher risk of disability at an early stage of hospitalization.

Clinical and Imaging Parameters Associated With Hyperacute Infarction Growth in Large Vessel Occlusion Stroke.

Background and Purpose- Large vessel occlusion stroke leads to highly variable hyperacute infarction growth. Our aim was to identify clinical and imaging parameters associated with hyperacute infarction growth in patients with an large vessel occlusion stroke of the anterior circulation. Methods- Seven hundred twenty-two consecutive patients with acute stroke were prospectively included in our monocentric stroke registry between 2009 and 2017. We selected all patients with a large vessel occlusion stroke of the anterior circulation, documented times from symptom onset, and CT perfusion on admission for our analysis (N=178). Ischemic core volume was determined with CT perfusion using automated thresholds. Hyperacute infarction growth was defined as ischemic core volume divided by times from symptom onset, assuming linear progression during times from symptom onset to imaging on admission. For collateral assessment, the regional leptomeningeal collateral score (rLMC) was used. Clinical data included the National Institutes of Health Stroke Scale score on admission and cardiovascular risk factors. Regression analysis was performed to adjust for confounders. Results- Median ischemic core volume was 34.4 mL, and median hyperacute infarction growth was 0.27 mL/min. In regression analysis including age, sex, National Institutes of Health Stroke Scale, clot burden score, diabetes mellitus, smoking, hypercholesteremia, hypertension, Alberta Stroke Program Early CT Score, and rLMC scores, only the rLMC score had a significant, independent association with hyperacute infarction growth (adjusted ß=-0.35; P<0.001). Trichotomizing patients by rLMC scores yielded 65 patients with good (rLMC >15), 67 with intermediate (rLMC 11-15) and 46 with poor collaterals (rLMC <11) with an infarction growth of 0.17 mL/min, 0.26 mL/min, and 0.41 mL/min, respectively. Conclusions- Hyperacute infarction growth strongly depends on collaterals. In primary stroke centers, hyperacute infarction growth may be extrapolated to estimate the stroke progression during transfer times to thrombectomy centers and to support decisions on which patients to transfer.

Attenuation Changes in ASPECTS Regions: A Surrogate for CT Perfusion-based Ischemic Core in Acute Ischemic Stroke.

Background Recent studies have proven the effectiveness of thrombectomy up to 24 hours after stroke onset for patients with specific criteria at advanced CT or MRI. Clinical implementation of treatment in this extended time window remains a challenge, as many stroke centers do not routinely use advanced imaging. Purpose To determine whether automated cerebral x-ray attenuation measurements at noncontrast CT provide information on the presence of CT perfusion-defined ischemic core as applied in late time windows for thrombectomy. Materials and Methods In this retrospective study, patients with middle cerebral artery stroke due to proximal occlusion from 2009 to 2017 were included. All patients underwent noncontrast CT and CT perfusion. Automated software was used to calculate relative Hounsfield unit (rHU) values for Alberta Stroke Program Early CT Score (ASPECTS) regions on noncontrast CT images as the ratio of x-ray attenuation between ischemic versus non-ischemic hemispheres. Sensitivity, specificity, and diagnostic performance of rHU and composite rHU-ASPECTS, a score incorporating rHU from all regions, were analyzed for the classification of regional ischemic core and late time window thrombectomy criteria at CT perfusion. Results Data in a total of 200 patients were evaluated (105 women [mean age, 74 years ± 14 {standard deviation}] and 95 men [mean age, 76 years ± 14]). There were 121 patients in the validation cohort and 79 patients in the independent test cohort. Compared among all examined regions, rHU values yielded the best classification of ischemic core for the caudate nucleus, the lentiform nucleus, and the insula (with areas under the receiver operating characteristic curve [AUCs] ranging from 0.70 to 0.77; P < .001 for each). The composite rHU-ASPECTS score allowed classification of CT perfusion imaging selection criteria of ischemic core sizes of less than 70 mL and target mismatch of greater than 1.8 with AUCs of 0.80 (P = .001; 75% sensitivity and 83% specificity) in the test cohort and 0.74 (P < .001; 58% sensitivity and 82% specificity) in the validation cohort. Conclusion Noncontrast CT x-ray attenuation measurements identify Alberta Stroke Program Early CT Score regions classified as ischemic core at CT perfusion. This approach may serve as a selection criteria surrogate for thrombectomy in late time windows. © RSNA, 2019 Online supplemental material is available for this article.

Platelets Guide Leukocytes to Their Sites of Extravasation.

Effective immune responses require the directed migration of leukocytes from the vasculature to the site of injury or infection. How immune cells "find" their site of extravasation remains largely obscure. Here, we identified a previously unrecognized role of platelets as pathfinders guiding leukocytes to their exit points in the microvasculature: upon onset of inflammation, circulating platelets were found to immediately adhere at distinct sites in venular microvessels enabling these cellular blood components to capture neutrophils and, in turn, inflammatory monocytes via CD40-CD40L-dependent interactions. In this cellular crosstalk, ligation of PSGL-1 by P-selectin leads to ERK1/2 MAPK-dependent conformational changes of leukocyte integrins, which promote the successive extravasation of neutrophils and monocytes to the perivascular tissue. Conversely, blockade of this cellular partnership resulted in misguided, inefficient leukocyte responses. Our experimental data uncover a platelet-directed, spatiotemporally organized, multicellular crosstalk that is essential for effective trafficking of leukocytes to the site of inflammation.

Matrix metalloproteinases modulate ameboid-like migration of neutrophils through inflamed interstitial tissue.

In vitro studies suggest that leukocytes locomote in an ameboid fashion independently of pericellular proteolysis. Whether this motility pattern applies for leukocyte migration in inflamed tissue is still unknown. In vivo microscopy on the inflamed mouse cremaster muscle revealed that blockade of serine proteases or of matrix metalloproteinases (MMPs) significantly reduces intravascular accumulation and transmigration of neutrophils. Using a novel in vivo chemotaxis assay, perivenular microinjection of inflammatory mediators induced directional interstitial migration of neutrophils. Blockade of actin polymerization, but not of actomyosin contraction abolished neutrophil interstitial locomotion. Multiphoton laser scanning in vivo microscopy showed that the density of the interstitial collagen network increases in inflamed tissue, thereby providing physical guidance to infiltrating neutrophils. Although neutrophils locomote through the interstitium without pericellular collagen degradation, inhibition of MMPs, but not of serine proteases, diminished their polarization and interstitial locomotion. In this context, blockade of MMPs was found to modulate expression of adhesion/signaling molecules on neutrophils. Collectively, our data indicate that serine proteases are critical for neutrophil extravasation, whereas these enzymes are dispensable for neutrophil extravascular locomotion. By contrast, neutrophil interstitial migration strictly relies on actin polymerization and does not require the pericellular degradation of collagen fibers but is modulated by MMPs.

Tissue plasminogen activator promotes postischemic neutrophil recruitment via its proteolytic and nonproteolytic properties.

OBJECTIVE: Neutrophil infiltration of the postischemic tissue considerably contributes to organ dysfunction on ischemia/reperfusion injury. Beyond its established role in fibrinolysis, tissue-type plasminogen activator (tPA) has recently been implicated in nonfibrinolytic processes. The role of this serine protease in the recruitment process of neutrophils remains largely obscure. APPROACH AND RESULTS: Using in vivo microscopy on the postischemic cremaster muscle, neutrophil recruitment and microvascular leakage, but not fibrinogen deposition at the vessel wall, were significantly diminished in tPA(-/-) mice. Using cell transfer techniques, leukocyte and nonleukocyte tPA were found to mediate ischemia/reperfusion-elicited neutrophil responses. Intrascrotal but not intra-arterial application of recombinant tPA induced a dose-dependent increase in the recruitment of neutrophils, which was significantly higher compared with stimulation with a tPA mutant lacking catalytic activity. Whereas tPA-dependent transmigration of neutrophils was selectively reduced on the inhibition of plasmin or gelatinases, neutrophil intravascular adherence was significantly diminished on the blockade of mast cell activation or lipid mediator synthesis. Moreover, stimulation with tPA caused a significant elevation in the leakage of fluorescein isothiocyanate dextran to the perivascular tissue, which was completely abolished on neutrophil depletion. In vitro, tPA-elicited macromolecular leakage of endothelial cell layers was abrogated on the inhibition of its proteolytic activity. CONCLUSIONS: Endogenously released tPA promotes neutrophil transmigration to reperfused tissue via proteolytic activation of plasmin and gelatinases. As a consequence, tPA on transmigrating neutrophils disrupts endothelial junctions allowing circulating tPA to extravasate to the perivascular tissue, which, in turn, amplifies neutrophil recruitment through the activation of mast cells and release of lipid mediators.

C-C motif chemokine CCL3 and canonical neutrophil attractants promote neutrophil extravasation through common and distinct mechanisms.

Initial observations suggested that C-C motif chemokines exclusively mediate chemotaxis of mononuclear cells. In addition, recent studies also implicated these chemotactic cytokines in the recruitment of neutrophils. The underlying mechanisms remained largely unknown. Using in vivo microscopy on the mouse cremaster muscle, intravascular adherence and subsequent paracellular transmigration of neutrophils elicited by the chemokine (C-C motif) ligand 3 (CCL3, synonym MIP-1α) were significantly diminished in mice with a deficiency of the chemokine (C-C motif) receptor 1 (Ccr1(-/-)) or 5 (Ccr5(-/-)). Using cell-transfer techniques, neutrophil responses required leukocyte CCR1 and nonleukocyte CCR5. Furthermore, neutrophil extravasation elicited by CCL3 was almost completely abolished on inhibition of G protein-receptor coupling and PI3Kγ-dependent signaling, while neutrophil recruitment induced by the canonical neutrophil attractants chemokine (C-X-C motif) ligand 1 (CXCL1, synonym KC) or the lipid mediator platetelet-activating factor (PAF) was only partially reduced. Moreover, Ab blockade of ß(2) integrins, of α(4) integrins, or of their putative counter receptors ICAM-1 and VCAM-1 significantly attenuated CCL3-, CXCL1-, or PAF-elicited intravascular adherence and paracellular transmigration of neutrophils. These data indicate that the C-C motif chemokine CCL3 and canonical neutrophil attractants exhibit both common and distinct mechanisms for the regulation of intravascular adherence and transmigration of neutrophils.

Assessing regional hepatic function changes after hypertrophy induction by radioembolisation: comparison of gadoxetic acid-enhanced MRI and 99mTc-mebrofenin hepatobiliary scintigraphy.

BACKGROUND: To compare Gd-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and 99mTc-labelled mebrofenin hepatobiliary scintigraphy (HBS) as imaging-based liver function tests after unilateral radioembolisation (RE) in patients with primary or secondary liver malignancies. METHODS: Twenty-three patients with primary or secondary liver malignancies who underwent Gd-EOB-DTPA-enhanced MRI within a prospective study (REVoluTion) were evaluated. REVoluTion was a prospective open-label, non-randomised, therapy-optimising study of patients undergoing right-sided or sequential RE for contralateral liver hypertrophy at a single centre in Germany. MRI and hepatobiliary scintigraphy were performed before RE (baseline) and 6 weeks after (follow-up). This exploratory subanalysis compared liver enhancement on hepatobiliary phase MRI normalised to the spleen (liver-to-spleen ratio (LSR)) and the muscle (liver-to-muscle ratio (LMR)) with mebrofenin uptake on HBS for the total liver (TL) and separately for the right (RLL) and left liver lobe (LLL). RESULTS: Mebrofenin uptake at baseline and follow-up each correlated significantly with LSR and LMR on MRI for TL (≤ 0.013) and RLL (≤ 0.049). Regarding the LLL, mebrofenin uptake correlated significantly with LMR (baseline, p = 0.013; follow-up, p = 0.004), whereas with LSR, a borderline significant correlation was only seen at follow-up (p = 0.051; p = 0.046). CONCLUSION: LSRs and LMR correlate with mebrofenin uptake in HBS. This study indicates that Gd-EOB-DTPA-enhanced MRI and 99mTc-labelled mebrofenin HBS may equally be used to assess an increase in contralateral liver lobe function after right-sided RE. RELEVANCE STATEMENT: MRI may be a convenient and reliable method for assessing the future liver remnant facilitating treatment planning and monitoring of patients after RE-induced hypertrophy induction. KEY POINTS: • Both MRI and HBS can assess liver function after RE. • Liver enhancement on MRI correlates with mebrofenin uptake on HBS. • MRI might be a convenient alternative for estimating future liver remnants after hypertrophy induction.

Percutaneous transhepatic biliary drainage (PTBD) in patients with biliary leakage: Technical and clinical outcomes.

The purpose of this study is to evaluate the technical and clinical outcome of percutaneous transhepatic biliary drainage (PTBD) in patients with biliary leakage. All patients who underwent ultrasound-assisted PTBD between January 2017 and December 2021 due to biliary leakage with nondilated biliary systems were retrospectively evaluated for periprocedural characteristics, medical indications, technical success (successful placement of drainage catheter), clinical success (resolved leak without additional procedures), fluoroscopy time, procedure duration, and clinical outcomes. 74 patients with a mean age of 64.1 ± 15.1 years were identified. Surgery was the most common etiology of biliary leak with 93.2% of the cases. PTBD had a 91.8% (68/74) technical success rate and an 80.8% clinical success rate. The mean procedure and fluoroscopy duration were 43.5 and 18.6 minutes. Age > 65 years (P = .027) and left-sided drainage (P = .034) were significant risk factors of clinical failure. Procedure-related major complications were 2 bleedings from the liver and 1 bleeding from an intercostal artery (major complication rate 4%). PTBD is a feasible, safe, and effective treatment option in patients with biliary leakage with low complication rates.

Urokinase-type plasminogen activator promotes paracellular transmigration of neutrophils via Mac-1, but independently of urokinase-type plasminogen activator receptor.

BACKGROUND: Urokinase-type plasminogen activator (uPA) has recently been implicated in the pathogenesis of ischemia-reperfusion (I/R) injury. The underlying mechanisms remain largely unclear. METHODS AND RESULTS: Using in vivo microscopy on the mouse cremaster muscle, I/R-elicited firm adherence and transmigration of neutrophils were found to be significantly diminished in uPA-deficient mice and in mice treated with the uPA inhibitor WX-340, but not in uPA receptor (uPAR)-deficient mice. Interestingly, postischemic leukocyte responses were significantly reduced on blockade of the integrin CD11b/Mac-1, which also serves as uPAR receptor. Using a cell transfer technique, postischemic adherence and transmigration of wild-type leukocytes were significantly decreased in uPA-deficient animals, whereas uPA-deficient leukocytes exhibited a selectively reduced transmigration in wild-type animals. On I/R or stimulation with recombinant uPA, >90% of firmly adherent leukocytes colocalized with CD31-immunoreactive endothelial junctions as detected by in vivo fluorescence microscopy. In a model of hepatic I/R, treatment with WX-340 significantly attenuated postischemic neutrophil infiltration and tissue injury. CONCLUSIONS: Our data suggest that endothelial uPA promotes intravascular adherence, whereas leukocyte uPA facilitates the subsequent paracellular transmigration of neutrophils during I/R. This process is regulated via CD11b/Mac-1, and does not require uPAR. Pharmacological blockade of uPA interferes with these events and effectively attenuates postischemic tissue injury.

The Flashlight-Sign: A Novel B-Flow Based Ultrasound Finding for Detection of Intraluminal, Wall-Adherent, Floating Structures of the Abdominal Aorta and Peripheral Arteries.

This study aimed to evaluate the potential diagnostic value of a novel, sonographic, B-Flow (BFl)-based sign ("flashlight sign", FLS) for the detection of wall-adherent, floating arterial structures (WAFAS). The FLS, characterized by a fast moving, very bright, intraluminal signal, was detected in 28 patients with WAFAS. We divided this cohort into three subgroups according to the affected vascular segments: (1) peripheral arteries (n = 10); (2) native abdominal aorta (n = 8); and (3) abdominal aorta after endovascular aortic repair (EVAR; n = 10). Clinical characteristics were analyzed and BFl-findings were compared with contrast-enhanced ultrasound (CEUS) and computed tomography angiography (CTA). Seven patients (25%) suffered from arterial embolism downstream to the FLS (EVAR, n = 4; native abdominal aorta, n = 1; peripheral arteries, n = 2). WAFAS of the abdominal aorta (native or after EVAR), as indicated by the FLS, were visible by CEUS and CTA in 60% and 93.3%, respectively. Based on the largest cohort (to this point) of patients with WAFAS, we propose a clinically useful, BFl-based sonographic sign for the detection of these underrated arterial pathologies in the abdominal aorta and the peripheral arteries.

REDUCE - Indication catalogue based ordering of chest radiographs in intensive care units.

PURPOSE: To advance a transition towards an indication-based chest radiograph (CXR) ordering in intensive care units (ICUs) without compromising patient safety. MATERIALS AND METHODS: Single-center prospective cohort study with a retrospective reference group including 857 ICU patients. The routine group (n = 415) received CXRs at the discretion of the ICU physician, the restrictive group (n = 442) if specified by an indication catalogue. Documented data include number of CXRs per day and CXR radiation dose as primary outcomes, re-intubation and re-admission rates, hours of mechanical ventilation and ICU length of stay. RESULTS: CXR numbers were reduced in the restrictive group (964 CXRs in 2479 days vs. 1281 CXRs in 2318 days) and median radiation attributed to CXR per patient was significantly lowered in the restrictive group (0.068 vs. 0.076 Gy x cm2, P = 0.003). For patients staying ≥24 h, median number of CXRs per day was significantly reduced in the restrictive group (0.41 (IQR 0.21-0.61) vs. 0.55 (IQR 0.34-0.83), P < 0.001). Survival analysis proved non-inferiority. Secondary outcome parameters were not significantly different between the groups. CXR reduction was significant even for patients in most critical conditions. CONCLUSIONS: A substantial reduction of the number of CXRs on ICUs was feasible and safe using an indication catalogue thereby improving resource management. TRIAL REGISTRATION: DRKS00015621, German Clinical Trials Register.

CT after interhospital transfer in acute ischemic stroke: Imaging findings and impact of prior intravenous contrast administration.

Objectives: Large vessel occlusion (LVO) stroke patients routinely undergo interhospital transfer to endovascular thrombectomy capable centers. Imaging is often repeated with residual intravenous (IV) iodine contrast at post-transfer assessment. We determined imaging findings and the impact of residual contrast on secondary imaging. Anterior circulation LVO stroke patients were selected out of a consecutive cohort. Directly admitted patients were contrast naïve, and transferred patients had previously received IV iodine contrast for stroke assessment at the referring hospital. Two independent readers rated the visibility of residual contrast on non-contrast computed tomography (CT) after transfer and assessed the hyperdense vessel sign. Multivariate linear regression analysis was used to investigate the association of the Alberta Stroke Program Early CT score (ASPECTS) with prior contrast administration, time from symptom onset (TFSO), and CTP ischemic core volume in both directly admitted and transferred patients. Results: We included 161 patients, with 62 (39%) transferred and 99 (62%) directly admitted patients. Compared between these groups, transferred patients had a longer TFSO-to-imaging at our institution (median: 212 vs. 75 min, p < 0.001) and lower ASPECTS (median: 8 vs. 9, p < 0.001). Regression analysis presented an independent association of ASPECTS with prior contrast administration (ß = -0.25, p = 0.004) but not with TFSO (ß = -0.03, p = 0.65). Intergroup comparison between transferred and directly admitted patients pointed toward a stronger association between ASPECTS and CTP ischemic core volume in transferred patients (ß = -0.39 vs. ß = -0.58, p = 0.06). Detectability of the hyperdense vessel sign was substantially lower after transfer (66 vs. 10%, p < 0.001). Conclusion: Imaging alterations due to residual IV contrast are frequent in clinical practice and render the hyperdense vessel sign largely indetectable. Larger studies are needed to clarify the influence on the association between ASPECTS and ischemic core.

Image-Guided Embolotherapy of Arteriovenous Malformations of the Face.

PURPOSE: To evaluate the safety and outcome of image-guided embolotherapy of extracranial arteriovenous malformations (AVMs) primarily affecting the face. MATERIALS AND METHODS: A multicenter cohort of 28 patients presenting with AVMs primarily affecting the face was retrospectively investigated. Fifty image-guided embolotherapies were performed, mostly using ethylene-vinyl alcohol copolymer-based embolic agents. Clinical and imaging findings were assessed to evaluate response during follow-up (symptom-free, partial relief of symptoms, no improvement, and progression despite embolization), lesion devascularization (total, 100%; substantial, 76-99%; partial, 51-75%; failure, < 50%; and progression), and complication rates (classified according to the CIRSE guidelines). Sub-analyses regarding clinical outcome (n = 24) were performed comparing patients with (n = 12) or without (n = 12) subsequent surgical resection after embolotherapy. RESULTS: The median number of embolotherapy sessions was 2.0 (range, 1-4). Clinical outcome after a mean follow-up of 12.4 months (± 13.3; n = 24) revealed a therapy response in 21/24 patients (87.5%). Imaging showed total devascularization in 14/24 patients (58.3%), including the 12 patients with subsequent surgery and 2 additional patients with embolotherapy only. Substantial devascularization (76-99%) was assessed in 7/24 patients (29.2%), and partial devascularization (51-75%) in 3/24 patients (12.5%). Complications occurred during/after 12/50 procedures (24.0%), including 18.0% major complications. Patients with subsequent surgical resections were more often symptom-free at the last follow-up compared to the group having undergone embolotherapy only (p = 0.006). CONCLUSION: Image-guided embolotherapy is safe and effective for treating extracranial AVMs of the face. Subsequent surgical resections after embolization may substantially improve patients' clinical outcome, emphasizing the need for multimodal therapeutic concepts. LEVEL OF EVIDENCE: Level 4, Retrospective study.