Imaging of peripheral vascular malformations - current concepts and future perspectives

Vascular Malformations belong to the spectrum of orphan diseases and can involve all segments of the vascular tree: arteries, capillaries, and veins, and similarly the lymphatic vasculature. The classification according to the International Society for the Study of Vascular Anomalies (ISSVA) is of major importance to guide proper treatment. Imaging plays a crucial role to classify vascular malformations according to their dominant vessel type, anatomical extension, and flow pattern. Several imaging concepts including color-coded Duplex ultrasound/contrast-enhanced ultrasound (CDUS/CEUS), 4D computed tomography angiography (CTA), magnetic resonance imaging (MRI) including dynamic contrast-enhanced MR-angiography (DCE-MRA), and conventional arterial and venous angiography are established in the current clinical routine. Besides the very heterogenous phenotypes of vascular malformations, molecular and genetic profiling has recently offered an advanced understanding of the pathogenesis and progression of these lesions. As distinct molecular subtypes may be suitable for targeted therapies, capturing certain patterns by means of molecular imaging could enhance non-invasive diagnostics of vascular malformations. This review provides an overview of subtype-specific imaging and established imaging modalities, as well as future perspectives of novel functional and molecular imaging approaches. We highlight recent pioneering imaging studies including thermography, positron emission tomography (PET), and multispectral optoacoustic tomography (MSOT), which have successfully targeted specific biomarkers of vascular malformations

Percutaneous Sclerotherapy of Venous Malformations of the Hand: A Multicenter Analysis

PURPOSE To evaluate the safety and outcome of percutaneous sclerotherapy for treating venous malformations (VMs) of the hand. MATERIALS AND METHODS A retrospective multicenter trial of 29 patients with VMs primarily affecting the hand, including wrist, carpus, and/or fingers, treated by 81 percutaneous image-guided sclerotherapies using ethanol gel and/or polidocanol was performed. Clinical and imaging findings were assessed to evaluate clinical response, lesion size reduction, and complication rates. Substratification analysis was performed with respect to the Puig's classification, the sclerosing agent, the injected volume of the sclerosant, and to previously performed treatments. RESULTS The mean number of procedures per patient was 2.8 (± 2.2). Last follow-up (mean = 9.2~months) revealed a partial relief of symptoms in 78.9% (15/19), while three patients (15.8%) presented symptom-free and one patient (5.3%) with no improvement. Post-treatment imaging revealed an overall objective response rate of 88.9%. Early post-procedural complications occurred after 5/81 sclerotherapies (6.2%) and were entirely resolved by conservative means. Type of VM (Puig's classification) as well as sclerosing agent had no impact on clinical response (p = 0.85, p = 0.11) or complication rates (p = 0.66, p = 0.69). The complication rates were not associated with the sclerosant volume injected (p = 0.76). In addition, no significant differences in clinical success (p = 0.11) or complication rates (p = 0.89) were detected when comparing patients with history of previous treatments compared to therapy-naive patients. CONCLUSION Percutaneous sclerotherapy is both safe and effective for treating VMs of the hand. Even patients with history of previous treatments benefit from further sclerotherapy showing similar low complication rates to therapy-naive patients. LEVEL OF EVIDENCE Level 4, Retrospective study

Pleuropulmonary pathologies in the early phase of acute pancreatitis correlate with disease severity

Background Respiratory failure worsens the outcome of acute pancreatitis (AP) and underlying factors might be early detectable. Aims To evaluate the prevalence and prognostic relevance of early pleuropulmonary pathologies and pre-existing chronic lung diseases (CLD) in AP patients. Methods Multicentre retrospective cohort study. Caudal sections of the thorax derived from abdominal contrast enhanced computed tomography (CECT) performed in the early phase of AP were assessed. Independent predictors of severe AP were identified by binary logistic regression analysis. A one-year survival analysis using Kaplan-Meier curves and log rank test was performed. Result 358 patients were analysed, finding pleuropulmonary pathologies in 81%. CECTs were performed with a median of 2 days (IQR 1-3) after admission. Multivariable analysis identified moderate to severe or bilateral pleural effusions (PEs) (OR = 4.16, 95%CI 2.05-8.45, p Conclusions Increasing awareness of the prognostic impact of large and bilateral PEs and pre-existing CLD could facilitate the identification of patients at high risk for severe AP in the early phase and thus improve their prognosis.Peer reviewe

Mean muscle attenuation correlates with severe acute pancreatitis unlike visceral adipose tissue and subcutaneous adipose tissue

Background: Acute pancreatitis (AP) is a frequent disorder with considerable morbidity and mortality. Obesity has previously been reported to influence disease severity. Objective The aim of this study was to investigate the association of adipose and muscle parameters with the severity grade of AP. Methods: In total 454 patients were recruited. The first contrast-enhanced computed tomography of each patient was reviewed for adipose and muscle tissue parameters at L3 level. Associations with disease severity were analysed through logistic regression analysis. The predictive capacity of the parameters was investigated using receiver operating characteristic (ROC) curves. Results: No distinct variation was found between the AP severity groups in either adipose tissue parameters (visceral adipose tissue and subcutaneous adipose tissue) or visceral muscle ratio. However, muscle mass and mean muscle attenuation differed significantly with p-values of 0.037 and 0.003 respectively. In multivariate analysis, low muscle attenuation was associated with severe AP with an odds ratio of 4.09 (95% confidence intervals: 1.61-10.36, p-value 0.003). No body parameter presented sufficient predictive capability in ROC-curve analysis. Conclusions: Our results demonstrate that a low muscle attenuation level is associated with an increased risk of severe AP. Future prospective studies will help identify the underlying mechanisms and characterise the influence of body composition parameters on AP.Peer reviewe

Image-guided embolization of arteriovenous malformations of the hand using Ethylene-vinyl Alcohol Copolymer

PURPOSEThis study aimed to evaluate the safety and outcome of image-guided embolization for treating arteriovenous malformations (AVMs) of the hand using ethylene-vinyl alcohol copolymer (EVOH).METHODSA retrospective, multicenter cohort of 15 patients with AVMs of the hand treated with 35 imageguided embolotherapies using EVOH was investigated. Clinical history, symptomatology, and imaging findings were assessed to evaluate clinical outcome (symptom-free, partial relief of pain, no improvement of pain, and clinical progression despite embolization), lesion devascularization (total, 100%; near-total, 90%-99%; substantial, 70%-90%; partial, 30%-70%; and failure, 0%-30%), and peri- and postprocedural complication rates (major complications classified according to CIRSE guidelines). Substratification analysis was performed with respect to the involvement of different anatomical compartments and the injected volume of the embolic agent.RESULTSPatients were treated for pain (93.3%), skin ulceration (46.7%), and local bleeding (33.3%). The mean number of embolotherapies was 2.3 (±1.1) in 3 patients, a planned surgical resection was conducted after embolization. Clinical outcome after a median follow-up of 18 months revealed an overall response of 11/15 patients (73.3%). Imaging at last follow-up revealed 70%- 99% reduced vascularization in 12/15 patients (80%) including 2 patients (13.3%) with a neartotal devascularization of 90%-99%. Peri- and postprocedural complications occurred in 8.5% and 31.5%, respectively, including 17.1% major complications, in 1 case requiring a previously unplanned resection. Involvement of the finger was associated with increased rates of persistent symptoms compared to the other groups (P=.049). No significant difference between the embolic agent volume injected and complication rates was found (P=.372).CONCLUSIONImage-guided embolization using EVOH-based liquid embolic agents is effective for treating AVMs of the hand in the mid-term

Multicentered analysis of percutaneous sclerotherapies in venous malformations of the face

ObjectivesTo evaluate the safety and outcome of image-guided sclerotherapy for treating venous malformations (VMs) of the face.Materials and methodsA multicenter cohort of 68 patients with VMs primarily affecting the face was retrospectively investigated. In total, 142 image-guided sclerotherapies were performed using gelified ethanol and/or polidocanol. Clinical and imaging findings were assessed to evaluate clinical response, lesion size reduction, and complication rates. Sub-analyses of complication rates depending on type and injected volume of the sclerosant as well as of pediatric versus adult patient groups were conducted.ResultsMean number of procedures per patient was 2.1 (±1.7) and mean follow-up consisted of 8.7 months (±6.8 months). Clinical response (n = 58) revealed a partial relief of symptoms in 70.7% (41/58), 13/58 patients (22.4%) presented symptom-free while only 4/58 patients (6.9%) reported no improvement. Post-treatment imaging (n = 52) revealed an overall objective response rate of 86.5% (45/52). The total complication rate was 10.6% (15/142) including 4.2% (7/142) major complications, mostly (14/15, 93.3%) resolved by conservative means. In one case, a mild facial palsy persisted over time. The complication rate in the gelified ethanol subgroup was significantly higher compared to polidocanol and to the combination of both sclerosants (23.5 vs. 6.0 vs. 8.3%, p = 0.01). No significant differences in complications between the pediatric and the adult subgroup were observed (12.1 vs. 9.2%, p = 0.57). Clinical response did not correlate with lesion size reduction on magnetic resonance imaging (MRI).ConclusionImage-guided sclerotherapy is effective for treating VMs of the face. Clinical response is not necessarily associated with size reduction on imaging. Despite the complex anatomy of this location, the procedures are safe for both adults and children

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

MASTREE+: Time-series of plant reproductive effort from six continents.

Significant gaps remain in understanding the response of plant reproduction to environmental change. This is partly because measuring reproduction in long-lived plants requires direct observation over many years and such datasets have rarely been made publicly available. Here we introduce MASTREE+, a data set that collates reproductive time-series data from across the globe and makes these data freely available to the community. MASTREE+ includes 73,828 georeferenced observations of annual reproduction (e.g. seed and fruit counts) in perennial plant populations worldwide. These observations consist of 5971 population-level time-series from 974 species in 66 countries. The mean and median time-series length is 12.4 and 10 years respectively, and the data set includes 1122 series that extend over at least two decades (≥20 years of observations). For a subset of well-studied species, MASTREE+ includes extensive replication of time-series across geographical and climatic gradients. Here we describe the open-access data set, available as a.csv file, and we introduce an associated web-based app for data exploration. MASTREE+ will provide the basis for improved understanding of the response of long-lived plant reproduction to environmental change. Additionally, MASTREE+ will enable investigation of the ecology and evolution of reproductive strategies in perennial plants, and the role of plant reproduction as a driver of ecosystem dynamics

Transarterial Coil Embolization of a Symptomatic Posttraumatic Plantar Pseudoaneurysm

Posttraumatic pseudoaneurysms of the lateral plantar artery are rare. We report the case of a 31-year-old woman with a painful pseudoaneurysm of the lateral plantar artery resulting from a deep plantar cut injury. The pseudoaneurysm was successfully treated by performing a transarterial “frontdoor-backdoor” coil embolization technique, which is a minimally invasive alternative to conventional ligature of the artery