Post-interventional infectious complications in percutaneous transabdominal lymphatic interventions: an observational study.

The purpose of this retrospective study was to evaluate the occurrence of infectious complications and inflammatory reactions after transabdominal lymphatic-interventions. 63 lymphatic-interventions were performed in 60 patients (male/female: 35/25; mean age 56 [9-85] years) [chylothorax n = 48, chylous ascites n = 7, combined chylothorax/chylous ascites n = 5]. Post-interventional clinical course and laboratory findings were analyzed in the whole cohort as well as subgroups without (group A; n = 35) and with peri-interventional antibiotics (group B; n = 25) (pneumonia n = 16, drainage-catheter inflammation n = 5, colitis n = 1, cystitis n = 1, transcolonic-access n = 2). No septic complications associated with the intervention occurred. Leucocytes increased significantly, peaking on post-interventional day-1 (8.6 ± 3.9 × 106 cells/mL vs. 9.8 ± 4.7 × 106 cells/mL; p = 0.009) and decreased thereafter (day-10: 7.3 ± 2.7 × 106 cells/mL, p = 0.005). CRP-values were pathological in 89.5% of patients already at baseline (40.1 ± 63.9 mg/L) and increased significant on day-3 (77.0 ± 78.8 mg/L, p < 0.001). Values decreased thereafter (day-15: 25.3 ± 34.4 mg/L, p = 0.04). In subgroup B, 13/25 patients had febrile episodes post-interventionally (pneumonia n = 11, cystitis n = 1, drainage-catheter inflammation n = 1). One patient developed biliary peritonitis despite continued antibiotics and underwent cholecystectomy. Baseline leucocytes and CRP-levels were higher in group B than A, but with comparable post-interventional profiles. Clinically relevant infectious complications associated with transabdominal lymphatic-interventions are rare irrespective of peri-interventional antibiotic use. Post-interventional elevation of leucocytes and CRP are observed with normalization over 10-15 days.

Deep learning for standardized, MRI-based quantification of subcutaneous and subfascial tissue volume for patients with lipedema and lymphedema.

OBJECTIVES: To contribute to a more in-depth assessment of shape, volume, and asymmetry of the lower extremities in patients with lipedema or lymphedema utilizing volume information from MR imaging. METHODS: A deep learning (DL) pipeline was developed including (i) localization of anatomical landmarks (femoral heads, symphysis, knees, ankles) and (ii) quality-assured tissue segmentation to enable standardized quantification of subcutaneous (SCT) and subfascial tissue (SFT) volumes. The retrospectively derived dataset for method development consisted of 45 patients (42 female, 44.2 ± 14.8 years) who underwent clinical 3D DIXON MR-lymphangiography examinations of the lower extremities. Five-fold cross-validated training was performed on 16,573 axial slices from 40 patients and testing on 2187 axial slices from 5 patients. For landmark detection, two EfficientNet-B1 convolutional neural networks (CNNs) were applied in an ensemble. One determines the relative foot-head position of each axial slice with respect to the landmarks by regression, the other identifies all landmarks in coronal reconstructed slices using keypoint detection. After landmark detection, segmentation of SCT and SFT was performed on axial slices employing a U-Net architecture with EfficientNet-B1 as encoder. Finally, the determined landmarks were used for standardized analysis and visualization of tissue volume, distribution, and symmetry, independent of leg length, slice thickness, and patient position. RESULTS: Excellent test results were observed for landmark detection (z-deviation = 4.5 ± 3.1 mm) and segmentation (Dice score: SCT = 0.989 ± 0.004, SFT = 0.994 ± 0.002). CONCLUSIONS: The proposed DL pipeline allows for standardized analysis of tissue volume and distribution and may assist in diagnosis of lipedema and lymphedema or monitoring of conservative and surgical treatments. KEY POINTS: • Efficient use of volume information that MRI inherently provides can be extracted automatically by deep learning and enables in-depth assessment of tissue volumes in lipedema and lymphedema. • The deep learning pipeline consisting of body part regression, keypoint detection, and quality-assured tissue segmentation provides detailed information about the volume, distribution, and asymmetry of lower extremity tissues, independent of leg length, slice thickness, and patient position.

From research to clinical practice: a European neuroradiological survey on quantitative advanced MRI implementation.

OBJECTIVE: Quantitative MRI (qMRI) methods provide versatile neuroradiological applications and are a hot topic in research. The degree of their clinical implementation is however barely known. This survey was created to illuminate which and how qMRI techniques are currently applied across Europe. METHODS: In total, 4753 neuroradiologists from 27 countries received an online questionnaire. Demographic and professional data, experience with qMRI techniques in the brain and head and neck, usage, reasons for/against application, and knowledge of the QIBA and EIBALL initiatives were assessed. RESULTS: Two hundred seventy-two responders in 23 countries used the following techniques clinically (mean values in %): DWI (82.0%, n = 223), DSC (67.3%, n = 183), MRS (64.3%, n = 175), DCE (43.4%, n = 118), BOLD-fMRI (42.6%, n = 116), ASL (37.5%, n = 102), fat quantification (25.0%, n = 68), T2 mapping (16.9%, n = 46), T1 mapping (15.1%, n = 41), PET-MRI (11.8%, n = 32), IVIM (5.5%, n = 15), APT-CEST (4.8%, n = 13), and DKI (3.3%, n = 9). The most frequent usage indications for any qMRI technique were tissue differentiation (82.4%, n = 224) and oncological monitoring (72.8%, n = 198). Usage differed between countries, e.g. ASL: Germany (n = 13/63; 20.6%) vs. France (n = 31/40; 77.5%). Neuroradiologists endorsed the use of qMRI because of an improved diagnostic accuracy (89.3%, n = 243), but 50.0% (n = 136) are in need of better technology, 34.9% (n = 95) wish for more communication, and 31.3% need help with result interpretation/generation (n = 85). QIBA and EIBALL were not well known (12.5%, n = 34, and 11.0%, n = 30). CONCLUSIONS: The clinical implementation of qMRI methods is highly variable. Beyond the aspect of readiness for clinical use, better availability of support and a wider dissemination of guidelines could catalyse a broader implementation. KEY POINTS: • Neuroradiologists endorse the use of qMRI techniques as they subjectively improve diagnostic accuracy. • Clinical implementation is highly variable between countries, techniques, and indications. • The use of advanced imaging could be promoted through an increase in technical support and training of both doctors and technicians.

Transfer of MHC-class-I molecules among liver sinusoidal cells facilitates hepatic immune surveillance.

BACKGROUND & AIMS: In the liver, antigen-presenting cell populations such as Kupffer cells, liver dendritic cells, and liver sinusoidal endothelial cells (LSECs) participate through cross-presentation to CD8 T cells (CTLs) in hepatic immune-regulation and immune-surveillance. The participation of hepatic stellate cells (HSCs) in immune regulation is controversial. Here we studied HSC's contribution to antiviral CTL immunity. METHODS: Flow cytometric analysis of MHC-I molecules at the cell surface of liver cells from mice with cell-type restricted MHC-I expression. Mice with HSC-restricted MHC-I expression were infected with a hepatotropic virus and analyzed for development of viral hepatitis after CTL transfer. RESULTS: HSCs transferred MHC-I molecules to LSECs and these molecules were employed for LSEC cross-presentation to CTLs. Such transfer of MHC-I molecules was sufficient to support in vivo LSEC cross-presentation of soluble antigens to CTLs. Importantly, this transfer of MHC-I molecules contributed to anti-viral CTL immunity leading to development of immune-mediated hepatitis. CONCLUSIONS: Our findings demonstrate transfer of MHC-I molecules among sinusoidal liver cell populations as a potent mechanism to increase anti-viral CTL effector function. The transfer of MHC-I molecules from HSCs supplies LSECs with additional MHC-I molecules for their own cell-intrinsic cross-presentation. Such cross-allocation of MHC-I molecules in liver cell populations is distinct from cross-dressing that occurs among immune cell populations in lymphoid tissues where peptide-loaded MHC-I molecules are transferred. Our findings thus reveal a novel mechanism that increases local cross-presentation and CTL effector function in the liver, which may be instrumental for immune-surveillance during viral infection of antigen-presenting liver cells.

RIG-I detects infection with live Listeria by sensing secreted bacterial nucleic acids.

Immunity against infection with Listeria monocytogenes is not achieved from innate immune stimulation by contact with killed but requires viable Listeria gaining access to the cytosol of infected cells. It has remained ill-defined how such immune sensing of live Listeria occurs. Here, we report that efficient cytosolic immune sensing requires access of nucleic acids derived from live Listeria to the cytoplasm of infected cells. We found that Listeria released nucleic acids and that such secreted bacterial RNA/DNA was recognized by the cytosolic sensors RIG-I, MDA5 and STING thereby triggering interferon ß production. Secreted Listeria nucleic acids also caused RIG-I-dependent IL-1ß-production and inflammasome activation. The signalling molecule CARD9 contributed to IL-1ß production in response to secreted nucleic acids. In conclusion, cytosolic recognition of secreted bacterial nucleic acids by RIG-I provides a mechanistic explanation for efficient induction of immunity by live bacteria.

Lack of PPARγ in myeloid cells confers resistance to Listeria monocytogenes infection.

The peroxisomal proliferator-activated receptor γ (PPARγ) is a nuclear receptor that controls inflammation and immunity. Innate immune defense against bacterial infection appears to be compromised by PPARγ. The relevance of PPARγ in myeloid cells, that organize anti-bacterial immunity, for the outcome of immune responses against intracellular bacteria such as Listeria monocytogenes in vivo is unknown. We found that Listeria monocytogenes infection of macrophages rapidly led to increased expression of PPARγ. This prompted us to investigate whether PPARγ in myeloid cells influences innate immunity against Listeria monocytogenes infection by using transgenic mice with myeloid-cell specific ablation of PPARγ (LysMCre×PPARγ(flox/flox)). Loss of PPARγ in myeloid cells results in enhanced innate immune defense against Listeria monocytogenes infection both, in vitro and in vivo. This increased resistance against infection was characterized by augmented levels of bactericidal factors and inflammatory cytokines: ROS, NO, IFNγ TNF IL-6 and IL-12. Moreover, myeloid cell-specific loss of PPARγ enhanced chemokine and adhesion molecule expression leading to improved recruitment of inflammatory Ly6C(hi) monocytes to sites of infection. Importantly, increased resistance against Listeria infection in the absence of PPARγ was not accompanied by enhanced immunopathology. Our results elucidate a yet unknown regulatory network in myeloid cells that is governed by PPARγ and restrains both listeriocidal activity and recruitment of inflammatory monocytes during Listeria infection, which may contribute to bacterial immune escape. Pharmacological interference with PPARγ activity in myeloid cells might represent a novel strategy to overcome intracellular bacterial infection.