Tissue In Close Proximity Research Articles

Periarterial or perivenous invasion is an independent indicator of lymph node metastasis in invasive breast carcinoma of no special type

Pathological diagnosis of breast cancer often includes cases of lymph node metastases without lymphatic or lymphovascular invasion by the primary tumor. In this study, to resolve this discrepancy, we designed a sensitive method to detect lymphatic invasion and correlate it with lymph node metastasis. Elastica van Gieson (EVG) staining and D2–40 immunohistochemistry revealed the abundant distribution of lymphatic vessels around blood vessels in the mammary tissue in close proximity to the elastic fibers around the arteries and veins. Based on the histological location of the blood and lymphatic vessels, we hypothesized that, in breast cancer, perivascular invasion is similar to lymphatic invasion and correlates with the presence of lymph node metastasis. Using EVG staining, perivascular invasion was histologically classified into periarterial invasion (periA), perivenous invasion (periV), and periarterial or perivenous invasion (periA/V). We tested our method and compared it to other methods commonly used for identifying lymphatic invasion in 105 patients with invasive breast carcinoma of no special type (IBC-NST) who received minimal preoperative therapy. The correlation between perivascular invasion and lymph node metastasis in these patients was statistically analyzed, including findings related to lymphatic invasion, such as retractile artifacts and perineural invasion. PeriA, periV, and periA/V showed significant correlations with lymph node metastasis. PeriA/V had high sensitivity and negative predictive value. The odds ratio (OR) for periV was significantly high in the univariate analysis, while the ORs for periA/V, retraction artifacts, and perineural invasion were significantly high in both the univariate and multivariate analyses. In particular, periA/V revealed a strong correlation with lymph node metastasis (OR: 61.8). These findings indicate that the IBC-NST periA/V ratio is a sensitive pointer of lymphatic invasion and could be an independent and reliable indicator of lymph node metastasis.

CD4+ T Cell Effector Status Is Dependent on Aryl Hydrocarbon Receptor Activation during High Salt Diet

Recent studies suggest that patients with hypertension and individuals that consume a HSD are depleted of numerous tryptophan-derived indoles and other AHR-binding metabolites that are key in intestinal CD4+ T cell homeostasis. Thus, the inappropriate immunologic response by CD4+ T cells, and their role in hypertension, may be due in part to loss of AHR activation. Therefore, we hypothesized that AHR activation contributes to maintaining effector T cell status in salt-sensitive mice. To examine the influence of a representative homeostatic or proinflammatory environment and the subsequent response to salt, we cultured naïve CD4+ T cells under homeostatic cytokine or pathogenic cytokine conditions and exposed the cultures to increased NaCl conditions with or without the AHR-activating metabolite, FICZ (6-Formylindolo(3,2-b)-carbazole). TH17 cells cultured under homeostatic high salt conditions were depressed with a concomitant increase in response to FICZ. In contrast, TH17 cells cultured under pathogenic high salt conditions had augmented IL-17A-expressing cells without a response to AHR activation. These data suggest that excess salt is disrupting the ability to induce IL-17A and increasing AHR activity overcomes this disruption to promote IL-17A, without expansion of the pathogenic TH17 pool, and this observation was specific to non-pathogenic microenvironments (homeostatic TH17: media: 11±0.6%, +NaCl: 4.9±0.3%*, +NaCl/FICZ: 9.9±0.8%, of CD4; pathogenic TH17: media: 1.0±0.2%, +NaCl: 2.2±0.2%*, +NaCl/FICZ: 2.2±0.2%*, *vs respective media, n=8/group). Given these data, we then fed salt-sensitive mice (nitric oxide synthase inhibition) a HSD or a HSD supplemented with the AHR agonist indole-3-carbinol (I3C) and examined Peyer’s patches, a lymphoid tissue in close proximity to intestinal lumen contents enriched with salt and the I3C-metabolites and noted expansion of non-pathogenic TH17 cells. In conclusion, increasing AHR ligand availability through supplementing I3C may provide a gut-centric experimental approach in targeting experimental salt-sensitivity as it relates to immunologic disturbances. F31HL151264. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

New insights into the functional morphology of calceoli in Amphipoda (Crustacea)

Calceoli are putative sensory organs which are known in limnic, marine, and subterranean amphipods for almost 200 years. Despite an otherwise comprehensive understanding of the sensory organs of crustaceans, we still have not unambiguously understood their function. Since calceoli are mainly found on the antennae of male animals, previous studies suggested a chemosensory function mainly related to reproduction. Here, we use a combination of light and electron microscopic techniques to examine the calceoli of Gammarus locusta (Linnaeus 1758) and Oediceroides calmani (Walker 1906), to provide an overview over these structures, and in addition reveal nervous tissue in close proximity to the calceoli. The calceoli of both species are cuticular structures and consist of proximal and distal elements, a stalk and a receptacle that connects both regions. The two studied calceoli differ in the structure of their proximal and distal element, as well as in their receptacle. This study provides new insight into the functional morphology of the antenna and calceolus. Histological sections through the antennae and the calceoli indicate that the calceoli might possess a mechanosensory function.

Endovascular transmural access to carotid artery perivascular tissues: safety assessment of a novel technique

BackgroundRecent advances in endovascular devices have allowed access and targeting of perivascular tissues of the peripheral circulation. The perivascular tissues of the cervical and cranial circulations have many important structures...

Biomechanical Assessment of Macro-Calcification in Human Carotid Atherosclerosis and Its Impact on Smooth Muscle Cell Phenotype.

Intimal calcification and vascular stiffening are predominant features of end-stage atherosclerosis. However, their role in atherosclerotic plaque instability and how the extent and spatial distribution of calcification influence plaque biology remain unclear. We recently showed that extensive macro calcification can be a stabilizing feature of late-stage human lesions, associated with a reacquisition of more differentiated properties of plaque smooth muscle cells (SMCs) and extracellular matrix (ECM) remodeling. Here, we hypothesized that biomechanical forces related to macro-calcification within plaques influence SMC phenotype and contribute to plaque stabilization. We generated a finite element modeling (FEM) pipeline to assess plaque tissue stretch based on image analysis of preoperative computed tomography angiography (CTA) of carotid atherosclerotic plaques to visualize calcification and soft tissues (lipids and extracellular matrix) within the lesions. Biomechanical stretch was significantly reduced in tissues in close proximity to macro calcification, while increased levels were observed within distant soft tissues. Applying this data to an in vitro stretch model on primary vascular SMCs revealed upregulation of typical markers for differentiated SMCs and contractility under low stretch conditions but also impeded SMC alignment. In contrast, high stretch conditions in combination with calcifying conditions induced SMC apoptosis. Our findings suggest that the load bearing capacities of macro calcifications influence SMC differentiation and survival and contribute to atherosclerotic plaque stabilization.

Design of a Split Ring Resonator Integrated with On‐Chip Terahertz Waveguides for Colon Cancer Detection

AbstractFinite element method (FEM) simulations (employing ANSYS High Frequency Structure Simulator, HFSS) are used to investigate the response of terahertz (THz) frequency range split‐ring resonators (SRRs) integrated with on‐chip THz waveguides to cancerous tissues. Two‐port S‐parameter simulations are performed to obtain the transmission spectra (S21) of a planar Goubau line (PGL) integrated with an SRR. Permittivity and loss tangent of the colonic tissues are both taken into account in the numerical simulation. The transmission spectra of the SRR integrated PGL are obtained for cancerous and healthy tissues in close proximity to the SRR, and it is found that they can be distinguished by the resonant frequency shift of the SRR induced by dielectric loading. The electric field distribution and magnitude near the SRR for various capacitive gap widths of SRR are investigated to understand how the gap width affects the maximum electric field magnitude and the vertical extent of the electric field in the gap area. The simulated imaging of colonic tissue consisting of healthy and cancerous tissues using the SRR integrated PGL device with a protective layer on it is performed, showing how the technique could in principle be used to distinguish tumor margins with realistic THz dielectric parameters.

A Feasibility Study of Deep Learning-Based Auto-Segmentation Directly Used in VMAT Planning Design and Optimization for Cervical Cancer.

PurposeTo investigate the dosimetric impact on target volumes and organs at risk (OARs) when unmodified auto-segmented OAR contours are directly used in the design of treatment plans. Materials and MethodsA total of 127 patients with cervical cancer were collected for retrospective analysis, including 105 patients in the training set and 22 patients in the testing set. The 3D U-net architecture was used for model training and auto-segmentation of nine types of organs at risk. The auto-segmented and manually segmented organ contours were used for treatment plan optimization to obtain the AS-VMAT (automatic segmentations VMAT) plan and the MS-VMAT (manual segmentations VMAT) plan, respectively. Geometric accuracy between the manual and predicted contours were evaluated using the Dice similarity coefficient (DSC), mean distance-to-agreement (MDA), and Hausdorff distance (HD). The dose volume histogram (DVH) and the gamma passing rate were used to identify the dose differences between the AS-VMAT plan and the MS-VMAT plan.Results Average DSC, MDA and HD95 across all OARs were 0.82–0.96, 0.45–3.21 mm, and 2.30–17.31 mm on the testing set, respectively. The D99% in the rectum and the Dmean in the spinal cord were 6.04 Gy (P = 0.037) and 0.54 Gy (P = 0.026) higher, respectively, in the AS-VMAT plans than in the MS-VMAT plans. The V20, V30, and V40 in the rectum increased by 1.35% (P = 0.027), 1.73% (P = 0.021), and 1.96% (P = 0.008), respectively, whereas the V10 in the spinal cord increased by 1.93% (P = 0.011). The differences in other dosimetry parameters were not statistically significant. The gamma passing rates in the clinical target volume (CTV) were 92.72% and 98.77%, respectively, using the 2%/2 mm and 3%/3 mm criteria, which satisfied the clinical requirements.ConclusionsThe dose distributions of target volumes were unaffected when auto-segmented organ contours were used in the design of treatment plans, whereas the impact of automated segmentation on the doses to OARs was complicated. We suggest that the auto-segmented contours of tissues in close proximity to the target volume need to be carefully checked and corrected when necessary.

Intracellular Amplifiers of Reactive Oxygen Species Affecting Mitochondria as Radiosensitizers.

Simple SummaryProdrugs that increase the level of reactive oxygen species (ROS) specifically in cancer cells while not affecting normal cells can potentially act as radiosensitizers for side effect free radiotherapy (RT). However, previously known ROS-amplifying prodrugs were found to not beuseful for this purpose. Since functional mitochondria are necessary for RT-resistance, we assumed that the problem could be solved by using dual prodrugs as radiosensitizers, both targeting mitochondria and simultaneously inducing ROS. In this paper, we explored this possibility. In particular, we developed an N-alkylaminoferrocene-based prodrug (2c) effective at low μMolar concentrations. Upon conversion to its active form 2c_BA in aqueous solution, it is efficiently taken up by cancer cells. This leads to the decrease of their mitochondrial membrane potential and the amplification of both, intracellular mitochondrial and total ROS generation. We found that 2c_BA acts as an efficient radiosensitizer in human head and neck squamous carcinoma cells in vitro.Radiotherapy (RT) efficacy can be improved by using radiosensitizers, i.e., drugs enhancing the effect of ionizing radiation (IR). One of the side effects of RT includes damage of normal tissue in close proximity to the treated tumor. This problem can be solved by applying cancer specific radiosensitizers. N-Alkylaminoferrocene-based (NAAF) prodrugs produce reactive oxygen species (ROS) in cancer cells, but not in normal cells. Therefore, they can potentially act as cancer specific radiosensitizers. However, early NAAF prodrugs did not exhibit this property. Since functional mitochondria are important for RT resistance, we assumed that NAAF prodrugs affecting mitochondria in parallel with increasing intracellular ROS can potentially exhibit synergy with RT. We applied sequential Cu+-catalyzed alkyne-azide cycloadditions (CuAAC) to obtain a series of NAAF derivatives with the goal of improving anticancer efficacies over already existing compounds. One of the obtained prodrugs (2c) exhibited high anticancer activity with IC50 values in the range of 5–7.1 µM in human ovarian carcinoma, Burkitt’s lymphoma, pancreatic carcinoma and T-cell leukemia cells retained moderate water solubility and showed cancer specificity. 2c strongly affects mitochondria of cancer cells, leading to the amplification of mitochondrial and total ROS production and thus causing cell death via necrosis and apoptosis. We observed that 2c acts as a radiosensitizer in human head and neck squamous carcinoma cells. This is the first demonstration of a synergy between the radiotherapy and NAAF-based ROS amplifiers.

Co-emergence of cardiac and gut tissues promotes cardiomyocyte maturation within human iPSC-derived organoids.

During embryogenesis, paracrine signaling between tissues in close proximity contributes to the determination of their respective cell fate(s) and development into functional organs. Organoids are invitro models that mimic organ formation and cellular heterogeneity, but lack the paracrine input of surrounding tissues. Here, we describe a human multilineage iPSC-derived organoid that recapitulates cooperative cardiac and gut development and maturation, with extensive cellular and structural complexity in both tissues. We demonstrate that the presence of endoderm tissue (gut/intestine) in the organoids contributed to the development of cardiac tissue features characteristic of stages after heart tube formation, including cardiomyocyte expansion, compartmentalization, enrichment of atrial/nodal cells, myocardial compaction, and fetal-like functional maturation. Overall, this study demonstrates the ability to generate and mature cooperative tissues originating from different germ lineages within a single organoid model, an advance that will further the examination of multi-tissue interactions during development, physiological maturation, and disease.

Clinical Feasibility of Multi-Acquisition Variable-Resonance Image Combination-Based T2 Mapping near Hip Arthroplasty.

Background: Hip arthroplasty is increasingly prevalent, and early detection of complications can improve outcomes. Quantitative magnetic resonance imaging (qMRI) methods using multi-acquisition variable-resonance image combination (MAVRIC) may allow for the assessment of soft tissues in close proximity to hip arthroplasty devices. Question/Purposes: We sought to determine the clinical feasibility of MAVRIC-based T2 mapping as a qMRI approach for assessing synovial reactions in patients with a hip arthroplasty device. We hypothesized that there would be differences in T2 metrics by synovial type, clinical impression, and clinical findings related to synovitis. Methods: We conducted a cross-sectional study of 141 subjects with 171 hip arthroplasties with greater than 1 year post-implantation. We enrolled subjects who had had a primary total hip arthroplasty or hip resurfacing arthroplasty between May 2019 and March 2020, excluding those with a revision hip arthroplasty and those with standard safety contraindications for receiving an MRI. Institutional standard 2D fast spin echo (FSE), short-tau inversion recovery (STIR), and susceptibility-reduced MAVRIC morphological MR images were acquired for each hip and followed by a dual-echo acquisition MAVRIC T2 mapping sequence. Results: While 131 subjects (81%) were classified as having a "normal" synovial reaction, significantly longer T2 values were found for fluid synovial reactions compared with mixed reactions. In addition, subjects with synovial dehiscence and decompression present had T2 prolongation. Larger synovial volumes were found in subjects with low-signal intensity deposits. Conclusions: MAVRIC-based T2 mapping is clinically feasible and there are significant quantitative differences based on type of synovial reaction. Patients undergoing hip arthroscopy revision surgery will warrant comparison of T2 values with direct histologic assessment of a tissue sample obtained intraoperatively. The approach used in this study may be used for a quantitative evaluation and monitoring of soft tissues around metal implants.

Exploring Metabolic Adaptations to the Acidic Microenvironment of Osteosarcoma Cells Unveils Sphingosine 1-Phosphate as a Valuable Therapeutic Target.

Simple SummaryBy studying the role of tumor acidosis in osteosarcoma, we have identified a novel lipid signaling pathway that is selectively activated in acid-induced highly metastatic cell subpopulation. Furthermore, when combined to low-serine/glycine diet, the targeting of this acid-induced lipid pathway by the FDA-approved drug FTY720 significantly impaired tumor growth. This new knowledge will provide a giant leap in the understanding of the molecular mechanisms responsible for sarcoma relapses and metastasis. Finally, we paved the way to the recognition of a novel biomarker, as our data provided evidence of significantly high circulating levels in the serum of osteosarcoma patients of S1P, a lipid member of the identified acid-driven metabolic pathway.Acidity is a key player in cancer progression, modelling a microenvironment that prevents immune surveillance and enhances invasiveness, survival, and drug resistance. Here, we demonstrated in spheroids from osteosarcoma cell lines that the exposure to acidosis remarkably caused intracellular lipid droplets accumulation. Lipid accumulation was also detected in sarcoma tissues in close proximity to tumor area that express the acid-related biomarker LAMP2. Acid-induced lipid droplets-accumulation was not functional to a higher energetic request, but rather to cell survival. As a mechanism, we found increased levels of sphingomyelin and secretion of the sphingosine 1-phosphate, and the activation of the associated sphingolipid pathway and the non-canonical NF-ĸB pathway, respectively. Moreover, decreasing sphingosine 1-phosphate levels (S1P) by FTY720 (Fingolimod) impaired acid-induced tumor survival and migration. As a confirmation of the role of S1P in osteosarcoma, we found S1P high circulating levels (30.8 ± 2.5 nmol/mL, n = 17) in the serum of patients. Finally, when we treated osteosarcoma xenografts with FTY720 combined with low-serine/glycine diet, both lipid accumulation (as measured by magnetic resonance imaging) and tumor growth were greatly inhibited. For the first time, this study profiles the lipidomic rearrangement of sarcomas under acidic conditions, suggesting the use of anti-S1P strategies in combination with standard chemotherapy.

Cardiac Adipose Tissue Contributes to Cardiac Repair: a Review

Cardiac adipose tissue is a metabolically active adipose tissue in close proximity to heart. Recent studies emphasized the benefits of cardiac adipose tissue in heart remodeling, such as reducing infarction size, enhancing neovascularization and regulating immune response, through a series of cellular mechanisms. In the present manuscript, we provide a comprehensive review regarding the role of cardiac adipose tissue in cardiac repair. We focus on different cardiac adipose tissues according to their distinguished anatomical structures. This review summarizes the latest evidence on the relationship between cardiac adipose tissue and cardiac repair. Cardiac adipose tissues (CAT) were systematically reviewed in the current manuscript which focused on the components of CAT, debates about cardiac adipose stem cells and their effect on heart.

Assessing the Intrinsic Radiation Efficiency of Tissue-Implanted UHF Antennas

Dielectric loss occurring in tissues in close proximity to UHF-implanted antennas is an important factor in the performance of medical implant communication systems. Common practice in numerical analysis and testing is to utilize radiation efficiency (RE) measures external to the tissue phantom employed. This approach means that RE is also dependent on the phantom used and antenna positioning, making it difficult to understand antenna performance and minimize near-field tissue losses. Therefore, an alternative methodology for determining the intrinsic radiation performance of implanted antennas that focuses on assessing structural and near-field tissue losses is presented. The new method is independent of the tissue phantom employed and can be used for quantitative comparison of designs across different studies. The intrinsic RE of an implant antenna is determined by assessing the power flow within the tissue phantom at a distance of at least $\lambda _{g}/2$ from the radiating structure. The simulated results are presented for canonical antennas at 403 and 2400 MHz in homogeneous muscle and fat phantoms. These illustrate the dominance of propagating path losses in high-water content tissues such as muscle, whereas near-field dielectric losses may be more important in low-water tissues such as fat due to the extended reactive near-field.

Study of the Dosing Tissue Distraction Clinical Efficacy in the Soft Tissue Defects Treatment of Various Etiologies in the Lower Extremities

Justification The most methods of extensive skin and soft tissue defects are aimed at accelerating wound healing and preventing infectious complications. To improve the effectiveness of such defects treatment, a method of dosed tissue distraction (MDTD) is used, consisting in the application of a continuously acting load to the area of healthy soft tissue in close proximity to the wound defect. Purpose It performed the evaluation of the medico-social effectiveness of the introduction into clinical practice of developed methods and devices for implementing MDTD in the treatment of skin and soft tissue defects of the extremities. Methods 407 patients were treated with wound defects of the extremities, which were divided into two groups: the main group – 198 patients in whose treatment MDTD was applied using original methods and devices; comparison group – 209 patients, in whose treatment standard treatment methods were applied. Comparison of the long-term results of treatment according to the frequency of repeated operations, complications, indicators of quality of life, frequency of disability. Results The use of MDTD is characterized by better performance compared with the use of standard approaches. There is a decrease in the frequency of performing reconstructive plastic surgery after inpatient treatment (9-10 times), remote complications by 2.6 times, a reduced value of the Vancouver scale (by 28.8%), quality of life indicators higher levels. The use of the proposed approach is characterized by a shorter duration of treatment (by 26.0%), duration of disability (1.4 times), cases of disability (2.2 times). Conclusion The use of MDTD is characterized by high medical and social efficiency, allows to reduce the cost of treating extensive skin and soft tissue defects by reducing the length of hospitalization, the frequency of repeated rehabilitation and reconstructive operations, accelerated recovery of patients, improving the quality of life and reducing the incidence of disability

Imaging of Atrioventricular Nodal Conduction Tissue in Porcine Hearts Using Optical Coherence Tomography.

Optical coherence tomography (OCT) employs near-infrared light to image the microstructure of different tissues. Clinically, it has been used to image the walls of coronary arteries. In research settings, one of the applications for OCT is visualizing endocardial and subendocardial structures. The present experiment sought to determine whether OCT can identify native conduction tissues in adult porcine hearts. During the study, the right atrial endocardial surfaces of excised adult porcine hearts were exposed. The triangle of Koch was imaged with the OCT system and the conduction tissue was identified. The area was then prepared for histologic examination with Masson’s trichrome stain. The results of histologic preparations and OCT images were then compared. Ultimately, nine porcine hearts were examined using this methodology. OCT imaging successfully identified subendocardial structures presumed to be the compact atrioventricular node. Histologic images of the preparations delineated the different tissue types and conduction tissue was easily identified. The location of distinctive hyporeflective areas in the OCT images correlated with the location of conduction tissue in the histology images. In light of the findings of this study, it is suggested that atrioventricular nodal tissue can be identified by OCT in freshly dissected unfixed porcine hearts. OCT images distinguished the differentiated conduction tissue in close proximity with the endocardium, myofibers, and fibrous tissue, and the success of this was verified with histology. This technology may be useful for the direct visualization of the native conduction system during procedures in the operating room and electrophysiology laboratory. Further studies with perfused tissue samples and live animal experiments are needed to better assess the efficacy of this novel application.

Diffuse Large B-Cell Lymphoma Remodels the Fibroblastic Reticular Network That Acquires Aberrant Immunosuppressive Capabilities; Implications for the Regulation of Anti-Tumor Immunity in the Immuno-Oncology Era

Immunotherapy has demonstrated potential to reactivate or transfer T cell immunity and regress tumors, offering hope to relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, many DLBCL patients do not experience therapeutic benefit, likely owing to a lack of pre-existing anti-tumor immunity and/or poorly understood immunosuppressive mechanisms in the tumor microenvironment (TME). Understanding the different obstacles that cytotoxic T cells face in the DLBCL TME will help the development of novel therapeutic approaches to overcome them and optimize immunotherapy. Stroma-associated gene signatures reflecting fibroblast and immune cell activity as well as angiogenesis have been associated with outcome in DLBCL but the biology underlying these signatures has been understudied. Here we have examined beyond tumor ‘effacement’ and hypothesized that, rather than being sparse bystanders, lymph node stromal cells may be important players in driving immune suppression in lymphoma.Multiplex immunofluorescence (IF) confocal microscopy analysis of the major stromal cell subsets revealed a marked expansion and remodeling of podoplanin, PDPN+ fibroblastic reticular cells (FRCs) in DLBCL lymph node tissue TME biopsies across GCB and ABC subtypes (n=40) compared to reactive control tissues (n=10). FRC myofibroblasts were similarly remodeled in tumors from the transgenic mouse model of DLBCL (Iμ-HABCL6, n=10) compared to wild type littermates (n=5). These altered PDPNhigh, αSMAhigh FRC networks were interspersed within effaced lymph node tissues in close proximity to DLBCL tumor cells.To model the interactions between tumor cells and FRCs, we established 2D and 3D co-culture platforms that combined DLBCL cells (or non-malignant control B-cells) and PDPN+ FRCs derived from human or murine lymph node tissues. These quantitative assays have shown that tumor cells activate FRCs promoting their proliferation, increased expression of PDPN, marked elongation/stretching and subsequent reduced ability to contract 3D collagen matrix (non-contractile) (P<.01). Exposure to tumor cells caused uncoupling of PDPN from RHOA signaling and redistribution of PDPN into lipid rafts, permitting FRC stretching. FRCs purified from both human and murine tumor lymph nodes showed the same activated morphology and phenotype, demonstrating that our co-culture systems recapitulate in vivo findings. Screening experiments have shown that lymphoma-expressed membrane and soluble lymphotoxins (LTα1β2, LTα3) as well as TNFα significantly contribute to the remodeling of FRCs (P<.01). Co-culture assays have revealed evidence for mutualistic interaction as FRCs, that express BAFF, promote the survival of DLBCL cells in 3D matrix gels (P<.01). Expanded lymphoma PDPNhigh FRCs in situ co-expressed BAFF compared to a more restricted expression profile (marginal zone FRCs) in reactive lymph node tissues. Flow cytometry revealed that lymphoma FRCs exhibit a cancer-associated fibroblast (CAF)-like immunophenotype including upregulation of fibroblast activation protein (FAP) and αSMA, as well as immunomodulatory MHC class I, PD-L1 and PD-L2 molecules compared to control FRCs (P<.01).An important function of FRCs in regulating immunity is attracting and maintaining T cells by secreting chemokines and promoting their migration along the network. Functional assays revealed that T cells show significantly reduced chemotaxis as well motility (quantitative time-lapse movies) across 2D and 3D lymphoma FRC networks compared to control FRCs (P<.01). Multiplex IF analysis revealed reduced CCL19 and CCL21-expressing FRCs in DLBCL compared to the reactive control FRC network as well as low numbers of tumor-infiltrated CD8+ T cells, which localized closely with remodeled FRCs. We next determined whether lymphoma FRCs (CAFs) could negatively regulate T cell function. Triple culture autologous assays (murine and human) have shown that prior exposure of tumor-infiltrated CD8+ T cells to FRCs significantly decreased their cytolytic killing activity against tumor cells (P<.01).In conclusion our data indicate that DLBCL tumor cells convert FRCs into immunosuppressive CAFs, which exhibit altered immumomodulatory activities at different levels that we believe has important implications for the regulation of anti-tumor immunity as well as response to immunotherapy. DisclosuresVardi:Gilead: Research Funding; Janssen: Honoraria. Ramsay:Roche Glycart AG: Research Funding; MedImmune: Research Funding; Celgene Corporation: Research Funding.

Percutaneous Electrochemical Debridement of the Plantaris Tendon.

Plantaris tendon disorders are a well-known source of midportion Achilles tendinopathy. Plantaris tendon thickening and fibrous tissue formation between the tendons are the histologic abnormalities that are typically observed. Surgical approaches (scraping of the Achilles medial and ventral paratendinous tissues and excision of the plantaris tendon) have already shown good clinical outcomes; despite this, the cost-benefit ratio of these interventions may be unfavorable, and their accessibility is limited. Percutaneous needle electrolysis is a minimally invasive ablative technique increasingly being considered for the treatment of tendinopathies and associated conditions. Herein we introduce a novel procedure to treat plantaris tendon-related midportion Achilles tendinopathy. The procedure starts with the ultrasound-guided insertion of an uncoated needle (diameter, 0.30-0.40 mm; length, 30 mm) between the plantaris and Achilles tendons. Subsequently, galvanic current (intensity, 2 mA) is locally transferred, which induces instant nonthermal electrochemical ablation of the intertendinous tissues in close proximity to the needle, finally debriding the plantaris tendon. To further promote its release, the second part of the procedure involves partial tenotomy of the lateral peripheral aspects of the plantaris tendon. Usually, the session does not exceed 30 min. Percutaneous needle electrolysis may be considered as a valid alternative to surgery. The outpatient procedure presented herein is, in fact, safe and quick to perform. In addition, long suspension of working or sporting activities after treatment is not required. Future investigations are needed to ascertain the short- and long-term therapeutic outcomes of plantaris tendon-related midportion Achilles tendinopathy treatment, in particular by comparing them with those obtained with other mini-invasive interventions.

RF Energy Absorption by Biological Tissues in Close Proximity to Millimeter-Wave 5G Wireless Equipment

In this paper, mechanisms of RF energy absorption by body tissue in close proximity to wireless equipment, are studied using numerical simulations at frequencies above 24 GHz. It is shown that at millimeter-wave (mmW) frequencies, of relevance for 5G mobile communications, and for realistic source to body separation distances, the contribution from the reactive near-field to the energy deposition in the tissue is small. Furthermore, the interaction between the source and the exposed body is modest. The results suggest that the effects of the near-field body interactions are small when evaluating electromagnetic field compliance at mmW frequencies.

Cytokeratin 19 expression in early oral squamous cell carcinoma and their metastasis: Inadequate biomarker for one-step nucleic acid amplification implementation in sentinel lymph node biopsy procedure.

Intraoperative analysis of lymph nodes during a sentinel lymph node biopsy (SLNB) procedure could result in one-step surgery for early oral squamous cell carcinoma (OSCC) with an occult nodal metastasis. One-step nucleic acid amplification rapidly detects cytokeratin 19 (CK19) RNA with high accuracy. Sensitivity and specificity of CK19 expression in OSCC was evaluated. Immunohistochemical CK19 expression was done in 207 patients with OSCC with 65 cases of paired nodal metastases. CK19 was expressed in 65% of all OSCC and even less in early OSCC (56%), with poor correlation between primary tumor and (occult) nodal metastasis. Furthermore, ectopic glandular tissue in close proximity of lymph nodes showed strong CK19 expression. CK19 lacks both sensitivity and specificity as a biomarker for nodal metastasis in OSCC, which questions the suitability for CK19-based one-step nucleic acid amplification in SLNB procedures. Therefore, future studies should focus on other biomarkers, because the concept of fast intraoperative diagnostics during SLNB remains attractive.

Osteoarthritis: Inflammation and fibrosis in adipose tissue of osteoarthritic joints.

The infrapatellar fat pad and other adipose tissues in close proximity to the joint have been linked with osteoarthritis (OA), but the nature of this relationship is unclear. Two new studies elucidate the features of intra-articular adipose tissues in OA and raise important questions for future investigations.