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.

Additive value of transarterial embolization to systemic sirolimus treatment in kaposiform hemangioendothelioma.

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor in children, which can be accompanied by life-threatening thrombocytopenia, referred to as Kasabach-Merritt phenomenon (KMP). The mTOR inhibitor sirolimus is emerging as targeted therapy in KHE. As the sirolimus effect on KHE occurs only after several weeks, we aimed to evaluate whether additional transarterial embolization is of benefit for children with KHE and KMP. Seventeen patients with KHE and KMP acquired from 11 hospitals in Germany were retrospectively divided into two cohorts. Children being treated with adjunct transarterial embolization and systemic sirolimus, and those being treated with sirolimus without additional embolization. Bleeding grade as defined by WHO was determined for all patients. Response of the primary tumor at 6 and 12 months assessed by magnetic resonance imaging (MRI), time to response of KMP defined as thrombocyte increase >150 × 103 /µL, as well as rebound rates of both after cessation of sirolimus were compared. N = 8 patients had undergone additive embolization to systemic sirolimus therapy, sirolimus in this group was started after a mean of 6.5 ± 3 days following embolization. N = 9 patients were identified who had received sirolimus without additional embolization. Adjunct embolization induced a more rapid resolution of KMP within a median of 7 days vs 3 months; however, tumor response as well as rebound rates were similar between both groups. Additive embolization may be of value for a more rapid rescue of consumptive coagulopathy in children with KHE and KMP compared to systemic sirolimus only.

Fluoroscopy-guided endoscopic sclerotherapy: a novel hybrid approach for symptomatic rectosigmoidal venous malformation (with video).

BACKGROUND AND AIMS: Recommendations for the treatment of lower GI bleeding do not include bleeding from venous malformations (VMs). The aim of this study was to delineate the usefulness of a novel hybrid intervention (fluoroscopy-guided endoscopic sclerotherapy) for the treatment of symptomatic VMs in the rectosigmoidal colon with bleeding. METHODS: The magnetic resonance images of 421 patients with VM, referred to multicenter vascular anomaly centers from 2009 to 2017, were analyzed retrospectively. Treatment was performed for all patients who experienced bleeding from rectosigmoidal VMs using fluoroscopy-guided endoscopic sclerotherapy with polidocanol foam as a novel approach. RESULTS: A total of 27 patients displayed VM in the rectosigmoidal area. Eleven of these presented with acute or previous bleeding and received treatment. Active bleeding was observed in 8 patients (72.7%), whereas 3 patients (27.3%) had signs of previous bleeding. Six of the 11 patients had anemia (54.5%). There were no adverse events within 24 hours of the intervention. In a 2-year follow-up period, only 1 patient (9.1%) presented with recurrent bleeding after 13 months and was successfully treated again with fluoroscopy-guided endoscopic sclerotherapy. CONCLUSIONS: Fluoroscopy-guided endoscopic sclerotherapy was shown to be a safe and effective treatment of symptomatic VMs of the rectosigmoidal area. Thus, fluoroscopy-guided endoscopic sclerotherapy should be considered for patients with bleeding from VMs of the rectosigmoid after a comprehensive workup and interdisciplinary case discussion.

Safety and Effectiveness of Ethylene Vinyl Alcohol Copolymer Embolization of Peripheral High-Flow Arteriovenous Malformations: Results of a Prospective Study.

PURPOSE: To prospectively evaluate the efficacy and safety of a new ethylene vinyl alcohol (EVOH) copolymer-based embolic agent in the treatment of symptomatic peripheral arteriovenous malformations (AVMs). MATERIALS AND METHODS: This prospective single-center study evaluated EVOH embolization with 3 different formulations of EVOH (Squid Peri 12 cP, 18 cP, and 34 cP; BALT Germany GmbH, Düsseldorf, Germany) in patients with symptomatic AVMs. Between April 2018 and October 2019, 36 embolization procedures in 21 patients (3 males and 18 females; mean age, 34.7 years) were performed (inclusion criteria: symptomatic peripheral AVM, ≥14 years of age, and elective embolization). Symptoms, technical aspects (transarterial, transvenous, or percutaneous approach; plug or balloon occlusion), clinical and technical success (defined as the improvement of symptoms and complete angiographic eradication of the AVM nidus), adverse events, and short-term outcomes were assessed. RESULTS: The mean volume of the embolic agent used per session was 3.4 mL of EVOH 34 cP (standard deviation [SD], ± 5.4), 6.2 mL ± 8.1 of EVOH 18 cP, and 4.6 mL ± 10.1 of EVOH 12 cP. Angiographic success was achieved in 18 patients (85.7%). The mean follow-up was 190 days (range, 90-538 days; median, 182 days). In the follow-up assessment, findings of magnetic resonance imaging showed that 19 patients (90.5%) had a persistent state of devascularization compared with postinterventional angiography. Amelioration or complete elimination of pain was achieved in 90.0% of the patients. One patient experienced a major adverse event; minor adverse events developed in 2 patients. CONCLUSIONS: In this study, EVOH appeared to be a safe and effective embolic agent in peripheral AVMs and had a low rate of adverse events in a limited number of patients.

A lack of red blood cell swelling in five elasmobranch fishes following air exposure and exhaustive exercise.

In teleost fishes, catecholamine-induced increases in the activity of cation exchangers compensate for decreases in hemoglobin oxygen affinity and maximum blood oxygen carrying capacity caused by decreases in plasma pH (i.e., metabolic acidosis). The resultant red blood cell (RBC) swelling has been documented in sandbar (Carcharhinus plumbeus) and epaulette (Hemiscyllium ocellatum) sharks following capture by rod-and-reel or after a 1.5 h exposure to anoxia (respectively), although the underlying mechanisms remain unknown. To determine if RBC swelling could be documented in other elasmobranch fishes, we collected blood samples from clearnose skate (Rostroraja eglanteria), blacktip reef shark (Carcharhinus melanopterus), and sicklefin lemon shark (Negaprion acutidens) subjected to exhaustive exercise or air exposure (or both) and measured hematocrit, hemoglobin concentration, RBC count, RBC volume, and mean corpuscular hemoglobin content. We did likewise with sandbar and epaulette sharks to further explore the mechanisms driving swelling when present. We could not document RBC swelling in any species; although hematocrit increased in all species (presumably due to RBC ejection from the spleen or fluid shifts out of the vascular compartment) except epaulette shark. Our results indicate RBC swelling and associated ion shifts in elasmobranch fishes is not inducible by exercise or hypoxia, thus implying this response maybe of lesser importance for maintaining oxygen delivery during acute acidosis than in teleost fishes.

Superior clinical results and higher satisfaction after customized compared with conventional TKA.

Investigation of functional outcome and patient`s satisfaction after implantation of a customized versus conventional TKA. In 31 consecutively enrolled patients with primary gonarthrosis, 33 customized TKA (custTKA) and in 31 patients, a conventional TKA (convTKA) was implanted. Perioperative and postoperative management were identical. Radio- graphic evaluation, ROM, KSS (Knee society score) and WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) were performed and patients satisfaction was evaluated after 3 and 12 months. Groups were comparable for age, sex, body mass index and extension/flexion. After 92 days average flexion in the convTKA group was significantly higher (119 vs. 113 degrees; unpaired t-test). At 375 days, mean flexion in both groups was 120 degrees. There was a significant higher number of outliers of neutral mechanical axis for convTKA patients (11 vs. 3; Chi-squared test). After 92 days there was no difference for KSS (convTKA: 160, custTKA: 167) but significant better results for WOMAC (19 vs. 40) in the custTKA group (unpaired t-test, p= 0.02). In addition, significantly better KSS (181 vs. 156) and WOMAC (99 vs. 42) were found for the custTKA group at 375 days (unpaired t-test, p= 0.002 and 0.001). Patients with the custTKA implant reported significant higher fulfillment of their expectations regarding function and knee strength. In the present study, the patients with a custTKA implant showed significantly superior short-term clinical results and fulfillment of their expectations regarding knee function.

Levels of agreement between cardiac magnetic resonance and conductance catheter measurements of right ventricular volumes after pulmonary artery banding.

BACKGROUND: Pressure-volume analysis is the gold standard for quantifying pump function of the right ventricle (RV); however, volume measurements based on a conductive catheter may be imprecise. The reference method for volume assessment is cardiac magnetic resonance (CMR). PURPOSE: To determine the levels of agreement between RV volume measurements obtained by cine CMR, phase-contrast CMR (PC CMR), and a conductance catheter in an animal model. MATERIAL AND METHODS: CMR was performed in 20 sheep three months after pulmonary artery banding. Ejection fraction (EF), end-diastolic (EDV), end-systolic (ESV), and stroke volumes (SV) were obtained by cine CMR and conductance catheter. RESULTS: Statistically significant differences between cine CMR and conductance catheter derived volume measurements were found for EDV (P < 0.001), ESV (P < 0.05), and SV (P < 0.05). Bland-Altman analysis showed very poor agreement between the two methods: EDV, bias 36.27 mL, agreement of limits 1.96-70.57 mL; ESV, bias 15.33 mL, agreement of limits -6.89-37.55 mL; and SV, bias 20.69 mL, agreement of limits 8.01-49.10 mL. Good agreement was found for SV between cine CMR and PC CMR (bias -7.0 mL, agreement of limits -24.01-9.98 mL), while SV derived from PC CMR measurements showed poor agreement with conductance catheter (bias 27.76 mL, agreement of limits -3.84-59.26 mL). CONCLUSION: Poor agreement between the conductance catheter and CMR RV volume measurements was found. PC CMR and cine CMR measurements of SV agreed well.

Projections of climate-driven changes in tuna vertical habitat based on species-specific differences in blood oxygen affinity.

Oxygen concentrations are hypothesized to decrease in many areas of the ocean as a result of anthropogenically driven climate change, resulting in habitat compression for pelagic animals. The oxygen partial pressure, pO2 , at which blood is 50% saturated (P50 ) is a measure of blood oxygen affinity and a gauge of the tolerance of animals for low ambient oxygen. Tuna species display a wide range of blood oxygen affinities (i.e., P50 values) and therefore may be differentially impacted by habitat compression as they make extensive vertical movements to forage on subdaily time scales. To project the effects of end-of-the-century climate change on tuna habitat, we calculate tuna P50 depths (i.e., the vertical position in the water column at which ambient pO2 is equal to species-specific blood P50 values) from 21st century Earth System Model (ESM) projections included in the fifth phase of the Climate Model Intercomparison Project (CMIP5). Overall, we project P50 depths to shoal, indicating likely habitat compression for tuna species due to climate change. Tunas that will be most impacted by shoaling are Pacific and southern bluefin tunas-habitat compression is projected for the entire geographic range of Pacific bluefin tuna and for the spawning region of southern bluefin tuna. Vertical shifts in P50 depths will potentially influence resource partitioning among Pacific bluefin, bigeye, yellowfin, and skipjack tunas in the northern subtropical and eastern tropical Pacific Ocean, the Arabian Sea, and the Bay of Bengal. By establishing linkages between tuna physiology and environmental conditions, we provide a mechanistic basis to project the effects of anthropogenic climate change on tuna habitats.

Spectral sensitivity, luminous sensitivity, and temporal resolution of the visual systems in three sympatric temperate coastal shark species.

We used electroretinography (ERG) to determine spectral and luminous sensitivities, and the temporal resolution (flicker fusion frequency, FFF) in three sympatric (but phylogenetically distant) coastal shark species: Carcharhinus plumbeus (sandbar shark), Mustelus canis (smooth dogfish), and Squalus acanthias (spiny dogfish). Spectral sensitivities were similar (range ~400-600 nm, peak sensitivity ~470 nm), with a high likelihood of rod/cone dichromacy enhancing contrast discrimination. Spiny dogfish were significantly less light sensitive than the other species, whereas their FFF was ~19 Hz at maximum intensities; a value equal to that of sandbar shark and significantly above that of smooth dogfish (~9-12 Hz). This occurred even though experiments on spiny dogfish were conducted at 12 versus 25 °C and 20 °C for experiments on sandbar shark and smooth dogfish, respectively. Although spiny dogfish have a rod-dominated retina (rod:cone ratio 50:1), their visual system appears to have evolved for a relatively high temporal resolution (i.e., high FFF) through a short integration time, with the requisite concomitant reduction in luminous sensitivity. Our results suggest adaptive plasticity in the temporal resolution of elasmobranch visual systems which reflects the importance of the ability to track moving objects such as mates, predators, or prey.

Potential for electropositive metal to reduce the interactions of Atlantic sturgeon with fishing gear.

Atlantic sturgeon (Acipenser oxyrhynchus) populations have been declared either endangered or threatened under the U.S. Endangered Species Act. Effective measures to repel sturgeon from fishing gear would be beneficial to both fish and fishers because they could reduce both fishery-associated mortality and the need for seasonal and area closures of specific fisheries. Some chondrostean fishes (e.g., sturgeons and paddlefishes) can detect weak electric field gradients (possibly as low as 5 Μv/cm) due to arrays of electroreceptors (ampullae of Lorenzini) on their snout and gill covers. Weak electric fields, such as those produced by electropositive metals (typically mixtures of the lanthanide elements), could therefore potentially be used as a deterrent. To test this idea, we recorded the behavioral responses of juvenile Atlantic sturgeon (31-43 cm fork length) to electropositive metal (primarily a mixture of the lanthanide elements neodymium and praseodymium) both in the presence and absence of food stimuli. Trials were conducted in an approximately 2.5 m diameter × 0.3 m deep tank, and fish behaviors were recorded with an overhead digital video camera. Video records were subsequently digitized (x, y coordinate system), the distance between the fish and the electropositive metal calculated, and data summarized by compiling frequency distributions with 5-cm bins. Juvenile sturgeon showed clear avoidance of electropositive metal but only when food was present. On the basis of our results, we conclude that the electropositive metals, or other sources of weak electric fields, may eventually be used to reduce the interactions of Atlantic sturgeon with fishing gear, but further investigation is needed.

Temperature, hypoxia, and mycobacteriosis: effects on adult striped bass Morone saxatilis metabolic performance.

Mycobacteriosis, a chronic bacterial disease of fishes, is prevalent in adult striped bass from Chesapeake Bay (USA). Although environmental factors may play a role in disease expression, the interaction between the disease and environmental stress remains unexplored. We therefore examined the individual and interactive effects of elevated temperature, hypoxia, and mycobacteriosis on the metabolism of wild-caught adult striped bass from Chesapeake Bay using respirometry. Because the spleen is the primary target organ of mycobacteriosis in striped bass, we hypothesized that the disease interferes with the ability of fish to increase their hematocrit in the face of increasing oxygen demands. We determined standard metabolic rate (SMR), maximum metabolic rate under normoxia (MMRN), critical oxygen saturation (S(crit)), and MMR under hypoxia (3 mg O(2) l-1: MMR(H)) for healthy and visibly diseased fish (i.e. exhibiting skin lesions indicative of mycobacteriosis). Measurements were taken at a temperature within the preferred thermal range (20°C) and at an elevated temperature (28°C) considered stressful to striped bass. In addition, we calculated aerobic scope (AS(N) = MMR(N) - SMR, AS(H) = MMR(H) - SMR) and factorial scope (FS(N) = MMR(N) SMR-1, FS(H) = MMR(H) SMR-1). SMR increased with increasing temperature, and hypoxia reduced MMR, AS, and FS. Mycobacteriosis alone did not affect either MMR(N) or MMR(H). However, elevated temperature affected the ability of diseased striped bass to tolerate hypoxia (S(crit)). Overall, our data indicate that striped bass performance under hypoxia is impaired, and that elevated water temperatures, hypoxia, and severe mycobacteriosis together reduce aerobic scope more than any of these stressors acting alone. We conclude that the scope for activity of diseased striped bass in warm hypoxic waters is significantly compromised.

Extracranial Vascular Anomalies Driven by RAS/MAPK Variants: Spectrum and Genotype-Phenotype Correlations.

BACKGROUND: We aimed to correlate alterations in the rat sarcoma virus (RAS)/mitogen-activated protein kinase pathway in vascular anomalies to the clinical phenotype for improved patient and treatment stratification. METHODS AND RESULTS: This retrospective multicenter cohort study included 29 patients with extracranial vascular anomalies containing mosaic pathogenic variants (PVs) in genes of the RAS/mitogen-activated protein kinase pathway. Tissue samples were collected during invasive treatment or clinically indicated biopsies. PVs were detected by the targeted sequencing of panels of genes known to be associated with vascular anomalies, performed using DNA from affected tissue. Subgroup analyses were performed according to the affected genes with regard to phenotypic characteristics in a descriptive manner. Twenty-five vascular malformations, 3 vascular tumors, and 1 patient with both a vascular malformation and vascular tumor presented the following distribution of PVs in genes: Kirsten rat sarcoma viral oncogene (n=10), neuroblastoma ras viral oncogene homolog (n=1), Harvey rat sarcoma viral oncogene homolog (n=5), V-Raf murine sarcoma viral oncogene homolog B (n=8), and mitogen-activated protein kinase kinase 1 (n=5). Patients with RAS PVs had advanced disease stages according to the Schobinger classification (stage 3-4: RAS, 9/13 versus non-RAS, 3/11) and more frequent progression after treatment (RAS, 10/13 versus non-RAS, 2/11). Lesions with Kirsten rat sarcoma viral oncogene PVs infiltrated more tissue layers compared with the other PVs including other RAS PVs (multiple tissue layers: Kirsten rat sarcoma viral oncogene, 8/10 versus other PVs, 6/19). CONCLUSIONS: This comparison of patients with various PVs in genes of the RAS/MAPK pathway provides potential associations with certain morphological and clinical phenotypes. RAS variants were associated with more aggressive phenotypes, generating preliminary data and hypothesis for future larger studies.

Individualized treatment of congenital vascular malformations of the tongue.

BACKGROUND/OBJECTIVE: Oral malformations of the tongue are exceedingly rare. The aim of this study was to evaluate the effectiveness of individualized treatment for patients with vascular malformations of the tongue. METHODS: This retrospective study is based on a consecutive local registry at a tertiary care Interdisciplinary Center for Vascular Anomalies. Patients with vascular malformations of the tongue were included. Indications for therapy of the vascular malformation were macroglossia with the impossibility to close the mouth, bleeding, recurrent infection and dysphagia. Size regression of the malformation (volume measurement) and symptom improvement were investigated. RESULTS: Out of 971 consecutive patients with vascular malformations, 16 patients suffered from a vascular malformation of the tongue. Twelve patients had slow-flow malformations and 4 fast-flow malformations. Indications for interventions were bleeding (4/16, 25%), macroglossia (6/16, 37.5%), and recurrent infections (4/16, 25%). For two patients (2/16, 12.5%), there was no indication for intervention due to absence of symptoms. Four patients received sclerotherapy, 7 patients Bleomycin-electrosclerotherapy (BEST) and 3 patients embolization. Median follow-up was 16 months (IQR 7-35.5). In all patients, symptoms had decreased after two interventions at a median (IQR 1-3.75). Volume reduction of the malformation of the tongue was 13.3% (from median 27.9 cm3 to median 24.2 cm3, p = 0.0039), and even more pronounced when considering only patients with BEST (from 86 cm3 to 59.1 cm3, p = 0.001). CONCLUSION: Symptoms of vascular malformations of the tongue are improved after a median of two interventions with significantly increased volume reduction after Bleomycin-electrosclerotherapy.

Ultra-short echo time (UTE) MR imaging: A brief review on technical considerations and clinical applications.

BACKGROUND: With the availability of MRI sequences with ultrashort echo times (UTE sequences), a signal can be gained from tissue, which was formerly only indirectly accessible. While already extensively employed in various research settings, the widespread transition of UTE imaging to clinical practice is just starting. METHODS: Based on a systematic literature search as well as knowledge gained through annual participation in conferences dedicated to advances in MRI, this review aims to give a brief overview of technical considerations and challenges of UTE imaging and summarizes the major areas of application of UTE imaging. RESULTS: UTE is already employed in clinical practice for structural lung imaging as well as the characterization of tissue composition and its alterations in selected musculoskeletal, cardiovascular, or neurodegenerative diseases. In specific contexts it can replace CT examinations with ionizing radiation and is especially attractive for pediatric patients and longitudinal monitoring of disease progression and treatment. CONCLUSION: UTE imaging provides an interesting and very valuable tool for various clinical purposes and promises a multitude of new insights into tissue properties. While some challenges remain, ongoing adoption in the clinical routine can be expected, as UTE approaches provide a new contrast and capture a signal in tissue formerly invisible on MR imaging. KEY POINTS: · UTE imaging gains relevance in clinical settings. · UTE imaging is employed for the characterization of tissue composition and its alterations in selected musculoskeletal, cardiovascular, or neurodegenerative diseases. · UTE imaging is employed in the clinical routine for structural lung imaging. · UTE imaging promises a multitude of new insights into tissue properties.

No association of malignant B-cell non-Hodgkin lymphomas with ipsilateral SARS-CoV-2 vaccination.

PURPOSE: SARS-CoV-2 vaccines cause acute ipsilateral lymph node swelling in an important proportion of vaccines. Thus far, no malignant lymphadenopathies have been reported in temporal context to vaccination in the ipsilateral draining lymph node areas. EXPERIMENTAL DESIGN: Prompted by two cases with unilateral axillary lymphomas that occurred ipsilaterally to prior SARS-CoV-2 vaccination, we systematically retrieved all B-cell non-Hodgkin lymphomas at two German University Medical Centers diagnosed before and after introduction of SARS-CoV-2 vaccines in Germany. Available lymphoma tissue (n=19) was subjected to next-generation immunosequencing of the IGH locus. Malignant clonotypes were mined in the CoVabDab database and published data sets from 342 uninfected individuals, 55 individuals 28 days after anti-SARS-CoV-2 vaccination and 139 individuals with acute COVID-19 together encompassing over 1 million CDR3 sequences in total. RESULTS: Of 313 newly diagnosed cases in the two centers and observation periods, 27 unilateral manifestations in the defined deltoid draining regions were identified. The majority thereof were diffuse large B-cell lymphomas (18 of 27 cases). Eleven unilateral cases were diagnosed in the era of SARS-CoV-2 vaccination and 16 in the control period before introduction of such vaccines. Of the 11 unilateral lymphomas that occurred during the vaccination period, ten had received a SARS-CoV-2 vaccine prior to lymphoma diagnosis. These cases were further evaluated. While left-sided were more frequent than right-sided lymphomas (19 vs 8 cases), no statistically significant association of vaccination site and laterality of the lymphoma manifestation was found. The unilateral lymphomas showed a normal range of B-cell receptors typically found in these lymphoma subtypes with no evidence for anti-SARS-CoV-2 sequences in the malignant clonotype. CONCLUSIONS: Together, we found no evidence that the current SARS-CoV-2 vaccines could serve as a trigger for lymphomagenesis in the draining lymph node areas of the deltoid region used for vaccination.

Clinical Outcome and Quality of Life of Multimodal Treatment of Extracranial Arteriovenous Malformations: The APOLLON Study Protocol.

PURPOSE: Arteriovenous malformations (AVMs) as rare diseases are diagnostically and therapeutically challenging. Due to the limited evidence regarding treatment outcome, prospective data are needed on how different treatment regimens affect outcome. The aims of this prospective trial are to determine effectiveness, safety, and clinical outcome of multimodal treatment in patients with extracranial AVMs. MATERIALS AND METHODS: After clinical and magnetic resonance imaging (MRI)-based diagnosis and informed consent, 146 patients (> 4 years and < 70 years) undergoing multimodal therapy in tertiary care vascular anomalies centers will be included in this prospective observational trial. Treatment options include conservative management, medical therapy, minimally invasive image-guided procedures (embolization, sclerotherapy) and surgery as well as combinations of the latter. The primary outcome is the patient-reported QoL 6 months after completion of treatment using the short form-36 health survey version 2 (SF-36v2) and the corresponding short form-10 health survey (SF-10) for children. In addition, clinical presentation (physician-reported signs), MRI imaging (radiological assessment of devascularization), recurrence rate, and therapeutic safety will be analyzed. Further follow-up will be performed after 12, 24, and 36 months. Moreover, liquid biopsies are being obtained from peripheral blood at multiple time points to investigate potential biomarkers for therapy response and disease progression. DISCUSSION: The APOLLON trial is a prospective, multicenter, observational open-label trial with unequal study groups to generate prospective evidence for multimodal treatment of AVMs. A multicenter design with the potential to assess larger populations will provide an increased understanding of multimodal therapy outcome in this orphan disease. TRIAL REGISTRATION: German Clinical Trials Register (identification number: DRKS00021019) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021019 .

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

PURPOSE This 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). METHODS A 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. RESULTS Patients 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). CONCLUSION Image-guided embolization using EVOH-based liquid embolic agents is effective for treating AVMs of the hand in the mid-term.

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.

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. RESULTS: 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<0.001) and pre-existing CLD (OR = 2.93, 95%CI 1.17-7.32, p = 0.022) as independent predictors of severe AP. Log rank test showed a significantly worse one-year survival in patients with bilateral compared to unilateral PEs in a subgroup. 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.