High incidence of deep vein thrombosis during the treatment of pseudoaneurysms - a retrospective nonrandomized study.

Background: Pseudoaneurysms (PSAs) are concerning complications after arterial invasive interventions. Therapeutic options include manual ultrasound-assisted compression, pressure dressings, surgical intervention and thrombin injection. Compression of neighboring veins is obvious. However, the incidence of deep vein thrombosis (DVT) in patients with PSA has not previously been investigated. Patients and methods: In this retrospective, nonrandomized study 238 patients with PSA were analyzed from 2013 to 2018. In 149 patients, all of the parameters were complete for participating. PSAs were treated according to the local standard therapy with either ultrasound-guided compression followed by compression bandage or thrombin injection. Treatment success was evaluated 24 hours later, and the venous system was examined for the presence of DVT. Results: Peripheral DVT was found in 25.4% patients after ultrasound-assisted compression and subsequent pressure bandages, but only 6.4% of patients had DVT after thrombin injection (p = 0.013). Lower leg veins, particularly veins of the crural muscles, were primarily affected. Significantly more PSAs were successfully treated without the occurrence of DVT in the thrombin injection group compared to the compression group (93.6 vs. 69.0%; p = 0.001). Conclusions: Our study revealed that the use of thrombin injections resulted in a significantly lower rate of postinterventional DVT and a higher total number of successfully treated PSAs compared to compression therapy.

The immunological landscape of peripheral blood in glioblastoma patients and immunological consequences of age and dexamethasone treatment.

Background: Glioblastomas manipulate the immune system both locally and systemically, yet, glioblastoma-associated changes in peripheral blood immune composition are poorly studied. Age and dexamethasone administration in glioblastoma patients have been hypothesized to limit the effectiveness of immunotherapy, but their effects remain unclear. We compared peripheral blood immune composition in patients with different types of brain tumor to determine the influence of age, dexamethasone treatment, and tumor volume. Methods: High-dimensional mass cytometry was used to characterise peripheral blood mononuclear cells of 169 patients with glioblastoma, lower grade astrocytoma, metastases and meningioma. We used blood from medically-refractory epilepsy patients and healthy controls as control groups. Immune phenotyping was performed using FlowSOM and t-SNE analysis in R followed by supervised annotation of the resulting clusters. We conducted multiple linear regression analysis between intracranial pathology and cell type abundance, corrected for clinical variables. We tested correlations between cell type abundance and survival with Cox-regression analyses. Results: Glioblastoma patients had significantly fewer naive CD4+ T cells, but higher percentages of mature NK cells than controls. Decreases of naive CD8+ T cells and alternative monocytes and an increase of memory B cells in glioblastoma patients were influenced by age and dexamethasone treatment, and only memory B cells by tumor volume. Progression free survival was associated with percentages of CD4+ regulatory T cells and double negative T cells. Conclusion: High-dimensional mass cytometry of peripheral blood in patients with different types of intracranial tumor provides insight into the relation between intracranial pathology and peripheral immune status. Wide immunosuppression associated with age and pre-operative dexamethasone treatment provide further evidence for their deleterious effects on treatment with immunotherapy.

Proteomic Profiling of Advanced Melanoma Patients to Predict Therapeutic Response to Anti-PD-1 Therapy.

PURPOSE: Despite high clinical need, there are no biomarkers that accurately predict the response of patients with metastatic melanoma to anti-PD-1 therapy. EXPERIMENTAL DESIGN: In this multicenter study, we applied protein depletion and enrichment methods prior to various proteomic techniques to analyze a serum discovery cohort (n = 56) and three independent serum validation cohorts (n = 80, n = 12, n = 17). Further validation analyses by literature and survival analysis followed. RESULTS: We identified several significantly regulated proteins as well as biological processes such as neutrophil degranulation, cell-substrate adhesion, and extracellular matrix organization. Analysis of the three independent serum validation cohorts confirmed the significant differences between responders (R) and nonresponders (NR) observed in the initial discovery cohort. In addition, literature-based validation highlighted 30 markers overlapping with previously published signatures. Survival analysis using the TCGA database showed that overexpression of 17 of the markers we identified correlated with lower overall survival in patients with melanoma. CONCLUSIONS: Ultimately, this multilayered serum analysis led to a potential marker signature with 10 key markers significantly altered in at least two independent serum cohorts: CRP, LYVE1, SAA2, C1RL, CFHR3, LBP, LDHB, S100A8, S100A9, and SAA1, which will serve as the basis for further investigation. In addition to patient serum, we analyzed primary melanoma tumor cells from NR and found a potential marker signature with four key markers: LAMC1, PXDN, SERPINE1, and VCAN.

PI3K Signaling in Dendritic Cells Aggravates DSS-Induced Colitis.

Aberrant innate immune responses to the gut microbiota are causally involved in the pathogenesis of inflammatory bowel diseases (IBD). The exact triggers and main signaling pathways activating innate immune cells and how they modulate adaptive immunity in IBD is still not completely understood. Here, we report that the PI3K/PTEN signaling pathway in dendritic cells enhances IL-6 production in a model of DSS-induced colitis. This results in exacerbated Th1 cell responses and increased mortality in DC-specific PTEN knockout (PTENΔDC) animals. Depletion of the gut microbiota using antibiotics as well as blocking IL-6R signaling rescued mortality in PTENΔDC mice, whereas adoptive transfer of Flt3L-derived PTEN-/- DCs into WT recipients exacerbated DSS-induced colitis and increased mortality. Taken together, we show that the PI3K signaling pathway in dendritic cells contributes to disease pathology by promoting IL-6 mediated Th1 responses.

Pseudoaneurysm.

Pseudoaneurysms (PSAs) are commonly known as complications associated with invasive interventions. Because of the pulsatile in- and outflow of blood through the neck of PSAs, they tend to grow and, in the worse cases, can rupture. Therapeutic options are compression therapy, using a compression bandage and ultrasound-guided compression, and thrombin injection. Manual ultrasound-guided compression is widely performed and is successful in most cases. In general, it is combined with a subsequently applied compression bandage. Thrombin injection is a more difficult technique, but it has a higher success rate. This article gives an overview of the characteristics of PSAs, their diagnostic characteristics and the therapeutic methods used to treat them. Complications associated with compression or thrombin injection are also explained in detail.

Pseudoaneurysmen (PSA) gehören neben den Hämatomen zu den häufigsten Komplikationen nach endovaskulären Eingriffen. Durch die Verbindung zum arteriellen Gefäßsystem kommt es zu einem pulsierenden Bluteinstrom, wodurch das PSA an Größe zunimmt und im schlimmsten Fall rupturieren kann. Therapeutische Maßnahmen sind die manuelle ultraschallgestützte Kompression, der Druckverband, die operative Sanierung und die Thrombininjektion. Die manuelle ultraschallgestützte Kompression ist fast in jedem Fall einsetzbar und in der überwiegenden Mehrheit auch erfolgreich. In der Regel wird sie mit der nachfolgenden Anlage eines Druckverbands kombiniert. Die Thrombininjektion ist technisch anspruchsvoller als die alleinige Kompression, zeigt allerdings eine bessere Erfolgsrate. Dieser Artikel gibt eine Übersicht über die Charakteristika von Pseudoaneurysmen, deren Diagnostik und die genannten Therapieverfahren. Auch Komplikationen, welche im Zusammenhang mit der Kompression bzw. Thrombininjektion stehen, werden näher erläutert.

Sauna exposure immediately prior to short-term heat acclimation accelerates phenotypic adaptation in females.

OBJECTIVES: Investigate whether a sauna exposure prior to short-term heat acclimation (HA) accelerates phenotypic adaptation in females. DESIGN: Randomised, repeated measures, cross-over trial. METHODS: Nine females performed two 5-d HA interventions (controlled hyperthermia Tre≥38.5°C), separated by 7-wk, during the follicular phase of the menstrual cycle confirmed by plasma concentrations of 17-ß estradiol and progesterone. Prior to each 90-min HA session participants sat for 20-min in either a temperate environment (20°C, 40% RH; HAtemp) wearing shorts and sports bra or a hot environment (50°C, 30% RH) wearing a sauna suit to replicate sauna conditions (HAsauna). Participants performed a running heat tolerance test (RHTT) 24-h pre and 24-h post HA. RESULTS: Mean heart rate (HR) (85±4 vs. 68±5 bpm, p≤0.001), sweat rate (0.4±0.2 vs. 0.0±0.0Lh-1, p≤0.001), and thermal sensation (6±0 vs. 5±1, p=0.050) were higher during the sauna compared to temperate exposure. Resting rectal temperature (Tre) (-0.28±0.16°C), peak Tre (-0.42±0.22°C), resting HR (-10±4 bpm), peak HR (-12±7 bpm), Tre at sweating onset (-0.29±0.17°C) (p≤0.001), thermal sensation (-0.5±0.5; p=0.002), and perceived exertion (-3±2; p≤0.001) reduced during the RHTT, following HAsauna; but not HAtemp. Plasma volume expansion was greater following HAsauna (HAsauna, 9±7%; HAtemp, 1±5%; p=0.013). Sweat rate (p≤0.001) increased and sweat NaCl (p=0.006) reduced during the RHTT following HAsauna and HAtemp. CONCLUSIONS: This novel strategy initiated HA with an attenuation of thermoregulatory, cardiovascular, and perceptual strain in females due to a measurably greater strain in the sauna compared to temperate exposure when adopted prior to STHA.