Inflammatory Nodes Research Articles

Tularemia: A rare cause of pediatric lymph nodes adenitis

Adenopathy in pediatrics can have many different causes: infectious, tumoral, and inflammatory. We report the case of an 8-year-old patient with a febrile popliteal ulceration associated with an inflammatory satellite inguinal lymph node adenitis. Serological tests and polymerase chain reaction analyses confirmed the diagnosis of ulceroglandular tularemia. An appropriate antimicrobial therapy led to a full recovery. This case reminds us to consider tularemia as a potential emergent disease in children presenting with subacute to chronic lymphadenopathy and thereby to choose the correct diagnostic tool and appropriate antimicrobial therapy.

Establishment of Ectopic Xenografts Derived from Human Glioblastoma in Immunocompetent Mouse Model Treated with Pesticide

Background: In this study, we suggested an experimental procedure demonstrating the im-pact of pesticide on the development of ectopic xenografts of human glioblastomas in im-muno-competent Balb/c mice. Method: In this in-vivo study, the mice were treated with or without a mixture of pesticide (Glyphosate and Chlorpyrifos), using a concentration corresponding to 1/8 of LD50 of each pesticide. The pesticides were injected intraperitoneally every 72 hours. The human glioblastoma cell suspension was cultured with tumor cerebrospinal fluid CSF and then injected subcutaneously into the treated and not treated mice with a mixture of pesticide (Glyphosate and Chlorpyrifos) following 18 days after the beginning of the experi-ment. Results: The body mass index of the male and female mice treated with pesticide was statis-tically (P = 0.0048) higher than those not treated with pesticides. 66.6% of the mice treated with pesticides and xenografts of glioblastoma developed masses at the injection site. The histological analysis revealed that 41.66% of the masses were astrocytic tumors. The other found masses corresponded to inflammatory lymph nodes and fibroblastic tissue formations. Conclusion: The treatment of mice with pesticide mixture was found to allow the develop-ment of glioblastoma xenografts in immunocompetent mice.

A multi-approach and multi-scale platform to model CD4+ T cells responding to infections.

Immune responses rely on a complex adaptive system in which the body and infections interact at multiple scales and in different compartments. We developed a modular model of CD4+ T cells, which uses four modeling approaches to integrate processes at three spatial scales in different tissues. In each cell, signal transduction and gene regulation are described by a logical model, metabolism by constraint-based models. Cell population dynamics are described by an agent-based model and systemic cytokine concentrations by ordinary differential equations. A Monte Carlo simulation algorithm allows information to flow efficiently between the four modules by separating the time scales. Such modularity improves computational performance and versatility and facilitates data integration. We validated our technology by reproducing known experimental results, including differentiation patterns of CD4+ T cells triggered by different combinations of cytokines, metabolic regulation by IL2 in these cells, and their response to influenza infection. In doing so, we added multi-scale insights to single-scale studies and demonstrated its predictive power by discovering switch-like and oscillatory behaviors of CD4+ T cells that arise from nonlinear dynamics interwoven across three scales. We identified the inflamed lymph node’s ability to retain naive CD4+ T cells as a key mechanism in generating these emergent behaviors. We envision our model and the generic framework encompassing it to serve as a tool for understanding cellular and molecular immunological problems through the lens of systems immunology.

Lymph-Derived Neutrophils Primarily Locate to the Subcapsular and Medullary Sinuses in Resting and Inflamed Lymph Nodes.

Neutrophils are the first immune cells to be recruited from the blood to the tissue site of an infection or inflammation. It has been suggested that neutrophils are capable of migrating from the infected tissue via lymphatic vessels to the draining lymph nodes. However, it remains elusive as to which areas within the lymph nodes can be reached by such reversely migrating cells. To address this question, we applied a model for adoptive neutrophil transfer into the afferent lymphatic vessel that drains towards the popliteal lymph node in mice. We showed that resting and in vitro-activated neutrophils did not enter the lymph node parenchyma but localized primarily in the subcapsular and medullary sinuses. Within the medulla, neutrophils show random migration and are able to sense laser-induced sterile tissue injury by massively swarming to the damaged tissue site. Co-injected dendritic cells supported the entry of resting neutrophils into the lymph node parenchyma via the subcapsular sinus. In contrast, in vivo-activated adoptively transferred neutrophils were capable of migrating into the interfollicular areas of the lymph node. Collectively, the data presented here give further insights into the functional behavior of neutrophils within the lymph nodes.

Assessing tumor metabolic heterogeneity of non-small cell lung cancer with total body PET-CT imaging on the uExplorer: Analysis of dynamic changes of 18F-FDG uptake.

e20549 Background: Total body positron emission tomography (PET) of uExplorer enables imaging of highly quantitative parameters beyond the standardized uptake value (SUV). The aim of this prospective study is to assess the dynamic changes of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake in characterizing tumor heterogeneity of non-small cell lung cancer (NSCLC). Methods: Sixteen NSCLC patients were prospectively enrolled in a prospective study (NCT04654234, GASTO-1067) between September 2020 and December 2020. All patients underwent a dynamic total-body 18F-FDG PET/CT scan before any treatment. The primary lung tumor, metastatic regional lymph node and inflammatory lymph node were manually delineated by a nuclear medicine physician and a radiation oncologist. Total Body PET was acquired between 0 – 60 mins after the injection of FDG from the subject’s feet. We compared lesion heterogeneity and different image-derived PET metrics including the SUV-mean, Patlak-derived influx rate constant (Ki) and distribution volume (DV). Results: The SUV-mean and Ki-mean of primary lung tumor and metastatic lymph node were significantly higher than inflammatory lymph node (p < 0.001), while there was no significantly different of DV(p > 0.05). By the scatter plot of SUV-mean and Ki-mean of primary lung tumor, 9 patients had been separated into high dynamic FDG metabolic (H-DFM) group and 7 in low DFM(L-DFM) group. The SUV-mean(p = 0.0002) and Ki-mean(p = 0.0002) of primary lung tumor were significantly higher in H-DFM group, whereas there is no difference in metastatic lymph node of both group. Interestingly, the SUV-mean and Ki-mean of primary lung tumor were higher than that of metastatic lymph node(p = 0.0002) in H-DFM group. On the contrast, the SUV-mean and Ki-mean of primary lung tumor were lower than that of metastatic lymph node(p = 0.05) in L-DFM group. There is no significant difference of DV-mean among primary lung tumor, metastatic lymph node and inflammatory lymph node in both arms. Conclusions: The results demonstrated that dynamic parameters from total body PET scan has the potential of providing complementary information of tumor heterogeneity in NSCLC than conventional static SUV imaging. The characteristics of H-DFM and L-DFM group could be taken into account for evaluation of further treatment response.

Dynamic 18F-FDG Total body PET Imaging as a predictive marker of induction chemo-immunotherapy response in locally advanced non-small cell lung cancer.

e20551 Background: The purpose of this study was to evaluate the efficacy of dynamic 18F-FDG total body PET imaging as a predictive maker of induction chemo-immunotherapy response in locally advanced non-small cell lung cancer(NSCLC) by a prospective study. Methods: Stage IIIA-IIIC NSCLC patients were prospectively enrolled in a prospective total body PETCT study ( NCT04654234, GASTO-1067) and a randomized phase II clinical trial ( NCT04085250) between September 2020 and December 2020. All patients underwent a dynamic total-body 18F-FDG PET/CT scan before any treatment and after 2 cycles of induction chemo-immunotherapy (docetaxel+cisplatin+nivolumab). The primary lung tumor, metastatic regional lymph node and inflammatory lymph node before and after treatment were manually delineated by a nuclear medicine physician and a radiation oncologist. Total Body PET was acquired between 0 – 60 mins after the injection of FDG from the subject’s feet. Patients was separated into high dynamic FDG metabolic (H-DFM) group and low DFM(L-DFM) group by the scatter plot of SUV-mean and Ki-mean of primary lung tumor. We compared lesion heterogeneity and different image-derived PET metrics including the metabolic tumor volume(MTV), SUV total lesion glycolysis(SUV-TLG), Patlak-derived influx rate constant (Ki) TLG (Ki-TLG). Results: Fifteen patients were analyzed, 8 patients was in H-DFM group and 7 in L-DFM group. Patients in H-DFM group had significant decreased levels of MTV(p < 0.001), SUV-TLG(p < 0.001) and Ki-TLG(p < 0.001) both in primary lung tumor and metastatic lymph node by the induction chemo-immuotherapy. However, patients in L-DFM group only had a significant reduction of MTV in primary lung tumor(p < 0.05). There was no significant difference in the MTV of metastatic lymph node(p > 0.5), the SUV-TLG(p > 0.5) and Ki-TLG(p > 0.5) of primary lung tumor and metastatic lymph node, before and after induction chemo-radiotherapy. Conclusions: Patients in H-DFM group had the better treatment response of induction chemo-immunotherapy with significant decreased levels of MTV, SUV-TLG and Ki-TLG. Dynamic 18F-FDG Total body PET Imaging could be regard as a potential predictive marker of induction chemo-immunotherapy response in the setting of LA-NSCLC.

Granulomatous inflammation in lymph nodes draining cancer: significant association or just coincidence- Diagnostic dilemma

Causes of granulomatous inflammation are broadly divided into infective and non infective. Infective causes Includes myocbacterial, fungal or parasitic origin. Non infective includes: Foreign body granuloma, sarcoidosis, crohn’s disease. Granuloma formation seen in cancer patients may be due to previous chemotherapy or radiation therapy. However in many cases mechanism in granuloma formation and its therapeutic outcome in cancer patients remains unknown. Careful scrutiny in all cases is required where coexisting malignancy was suspected along with granuloma formation in lymph nodes draining cancers. Exact cause of granuloma formation in lymph nodes draining cancer remains unknown however immunological reaction to tumour antigens is proposed theory .These granuloma may represent impending metastasis or already existing metastasis in patients who received neoadjuvant chemoradiation. Keywords: Granuloma, Lymph nodes, Metastasis, Chemoradiation.

Diagnosis of cervico facial lymphadenopathy by color doppler ultrasound

Aim: The aim of the research is to establish diagnosis of diseases in cervico facial lymphadenopathy by colour Doppler ultrasound. The purpose of the present study is to study the clinical aspects of lymph node and the changes in node in colour doppler ultrasonography. Materials and Methods: Patients were clinically examined by bimanual palpation for cervico facial lymphadenopathy and their colour doppler ultrasound findings were recorded. Biopsy was done to confirm ultrasound findings. Results: The internal architecture of the node, the pattern of colour doppler flow, vascular resistance were assessed in various inflammatory and malignant lymph nodes. Conclusion: The utility of colour doppler ultrasound is really beneficial in establishing the regional lymph node enlargement as inflammatory and metastatic node. Keywords: Lymphnode, Colour doppler, Ultrasound, Reactive nodes, Necrosis, Blood flow.

Transverse colon invasion from intrahepatic cholangiocarcinoma with lymph node metastasis in the regional mesocolon: a case report

BackgroundIntrahepatic cholangiocarcinoma (ICC) is an aggressive cancer with high frequency of extrahepatic metastasis at diagnosis. However, there have been very few reports of direct invasion to transverse mesocolon with lymph node metastasis in the regional mesocolon.Case presentationA 71-year-old man presented to our hospital with anorexia and weight loss. Abdominal computed tomography (CT) revealed enlarged gallbladder wall with intrahepatic tumor extended from the gallbladder. The transverse colon was located adjacent to the gallbladder and its wall was thickened, indicating tumor invasion. Some enlarged lymph nodes were observed in the transverse mesocolon, suggesting metastatic or inflammatory lymph node swelling. Percutaneous liver biopsy detected poorly differentiated adenocarcinoma. After confirming the absence of remote metastasis and peritoneal dissemination, surgical resection including right hepatectomy and right hemicolectomy was performed. The pathological diagnosis was adenosquamous carcinoma of the liver and lymph node metastasis in the transverse mesocolon. The surgical margins were negative and R0 resection was achieved. Although adjuvant chemotherapy was administered, follow-up CT detected multiple metastases to the lung 4 months after surgery. The patient died 12 months after the operation.ConclusionsDirect colon invasion from ICC may cause lymph node metastasis in the regional mesocolon. Careful assessment is necessary for the diagnosis of enlarged lymph nodes in ICC with direct colon invasion.

Metastatic status of sentinel lymph nodes in breast cancer determined with photoacoustic microscopy via dual-targeting nanoparticles

Detection of sentinel lymph nodes (SLNs) is critical to guide the treatment of breast cancer. However, distinguishing metastatic SLNs from normal and inflamed lymph nodes (LNs) during surgical resection remains a challenge. Here, we report a CD44 and scavenger receptor class B1 dual-targeting hyaluronic acid nanoparticle (5K-HA-HPPS) loaded with the near-infra-red fluorescent dye DiR-BOA for SLN imaging in breast cancer. The small sized (~40 nm) self-assembled 5K-HA-HPPSs accumulated rapidly in the SLNs after intradermal injection. Compared with normal popliteal LNs (N-LN), there were ~3.2-fold and ~2.4-fold increases in fluorescence intensity in tumour metastatic SLNs (T-MLN) and inflamed LNs (Inf-LN), respectively, 6 h after nanoparticle inoculation. More importantly, photoacoustic microscopy (PAM) of 5K-HA-HPPS showed a significantly distinct distribution in T-MLN compared with N-LN and Inf-LN. Signals were mainly distributed at the centre of T-MLN but at the periphery of N-LN and Inf-LN. The ratio of PA intensity (R) at the centre of the LNs compared with that at the periphery was 5.93 ± 0.75 for T-MLNs of the 5K-HA-HPPS group, which was much higher than that for the Inf-LNs (R = 0.2 ± 0.07) and N-LNs (R = 0.45 ± 0.09). These results suggest that 5K-HA-HPPS injection combined with PAM provides a powerful tool for distinguishing metastatic SLNs from pLNs and inflamed LNs, thus guiding the removal of SLNs during breast cancer surgery.

Microbiological assessment of sheep lymph nodes with lymphadenitis found during post-mortem examination of slaughtered sheep: implications for veterinary-sanitary meat control

BackgroundMicrobiological examination of lesions found in slaughtered animals during meat inspection is an important part of public health protection as such lesions may be due to zoonotic agents that can be transmitted by meat. Examination of inflamed lymph nodes also plays a particular important role, as lymphadenitis may reflect a more widespread infection. Such lesions in sheep are mainly caused by pyogenic bacteria but also mycobacteria are occasionally found. Meat inspection data from 2017 to 2018 from southern Poland, especially from the Małopolska region, indicate that purulent or caseous lymphadenitis involving the mediastinal and tracheobronchial lymph nodes (MTLNs) is a common finding. The primary aim of the current study was to determine the aetiology of these lesions. Furthermore, it was investigated how presence of lesions was correlated with age and grazing strategy of affected sheep.ResultsPost-mortem examination revealed purulent or caseous lymphadenitis in the MTLNs of 49 out of 284 animals (17.3%). Subsequent microbiological examination revealed the presence of Corynebacterium pseudotuberculosis (34.7%), Streptococcus dysgalactiae subsp. equisimilis (34.7%), Staphylococcus aureus (8.2%), Enterococcus spp. (2.0%), Trueperella pyogenes (2.0%), and β-haemolytic strains of Escherichia coli (2.0%). Mycobacterium spp. and Rhodococcus equi were not detected. In older sheep, the probability of the presence of purulent or caseous lymphadenitis was higher than in younger, and the risk was increasing by 1.5% with each month of life. Sheep grazing locally had 4.5-times greater risk of having purulent or caseous lymphadenitis than individuals summer grazing in the mountains.ConclusionThe most common aetiological agents of purulent or caseous lymphadenitis in the MTLNs of sheep in the Małopolska region were C. pseudotuberculosis and S. dysgalactiae subsp. equisimilis. Particular attention during post-mortem examination should be paid to the carcasses of older sheep and sheep grazing on permanent pastures, as they seem more prone to develop purulent or caseous lymphadenitis.

Role of Pre-operative Inflammatory Markers as Predictors of Lymph Node Positivity and Disease Recurrence in Well-Differentiated Pancreatic Neuroendocrine Tumours: Pancreas2000 Research and Educational Program (Course 9).

Pancreatic neuroendocrine tumours (PNET) is a rare disease and in the absence of metastases, surgical resection is recommended. Key factors affecting survival in PNETs are the stage and grade of the disease, but there is increasing evidence suggesting lymph node involvement is associated with shorter disease-free and overall survival. Ability to predict the likelihood of lymph node involvement at the time of diagnosis would affect surgical decision making in these patients. A systemic inflammatory index such as neutrophil to lymphocyte ratio or platelet to lymphocyte ratio has been associated with poor prognosis in several cancers.Method: This study is a retrospective multi-centre study. The data including pre-operative inflammatory markers such as haemoglobin, neutrophil, lymphocyte counts and pathological data including number of positive lymph nodes, tumour grade and size, are collected to assess the association between inflammatory index and lymph node involvement.Conclusion: This study aims to assess the value of routinely available pre-operative haematological markers in predicting lymph node involvement in non-functioning PNETs.

Granulomatous inflammation in lymph nodes of the head and neck-a retrospective analysis of causes in a population with very low incidence of tuberculosis.

The purpose of this study was to investigate the risk of the patient having: (1) TB, (2) sarcoidosis, (3) atypical mycobacteria, or (4) malignant disease, if FNAC or histology from a cervical lymph node shows granulomatous inflammation (GI). And to elucidate clinical characteristics associated with these causes of GI, patients with a pathological diagnosis of GI in head and neck lymph nodes were identified though a search of the Danish national pathology database. Charts were reviewed to identify the final clinical diagnosis and specific clinical characteristics. For the most common clinical diagnoses, association to clinical characteristics was analyzed using logistic regression (Odense University Hospital January 2006 to December 2015). We included 121 patients. Clinical diagnoses fell into the following categories: sarcoidosis (26%), tuberculosis (TB) (22%), cat scratch disease (6%), atypical mycobacteriosis (7%), malignancy (2%), and other (4%). In 33% of cases, the diagnosis was unknown. In the pediatric group, atypical mycobacteriosis was the most frequent clinical diagnosis (50%). TB and sarcoidosis were dependent variables in regression analysis. Characteristics significantly related to TB were histology showing necrotizing GI, gland localization in level 3-6, and origin other than Danish and TB being the tentative diagnosis. Characteristics significantly related to sarcoidosis were histology showing non-necrotizing GI, gland localization in level 3-6, the patient being of Danish origin, and unknown duration of symptoms. TB and sarcoidosis were the most common clinical diagnoses, and they were associated with specific clinical characteristics. In a third of cases, a specific clinical diagnosis was never given.

18F-fluorocholine PET/CT in MEN1 Patients with Primary Hyperparathyroidism.

Primary hyperparathyroidism (HPT1) is the most frequent endocrinopathy in multiple endocrine neoplasia type 1 (MEN1). Its surgical management is challenging. We aimed to describe and compare the imaging findings of parathyroid ultrasound (US), sestaMIBI scintigraphy (sestaMIBI), and 18F-fluorocholine (FCH) PET/CT in a series of MEN1 patients with HPT1. Retrospective analysis of a cohort of MEN1 patients with HPT1 assessed by parathyroid US, sestaMIBI scintigraphy and SPECT/CT, and FCH-PET/CT for potential surgery between 2015 and 2019. Twenty-two patients with a confirmed diagnosis of MEN1 who presented with HPT1 and were assessed by the 3 imaging modalities were included. After imaging workups, 11 patients were operated on for the first time, 4 underwent a redo surgery, and 7 did not undergo an operation. The overall patient-based positivity rate of imaging was 91% (20 of 22) for parathyroid US and 96% (21 of 22) for both sestaMIBI and FCH-PET/CT. The 3 imaging modalities demonstrated negative findings in 1/22 patient who did not undergo surgery. Overall, 3 pathologic glands were not detected by any imaging technique. SestaMIBI and FCH-PET/CT both resulted in the same 3 false-positive results in ectopic areas with a significant uptake on two thymic carcinoid tumors and one inflammatory lymph node. FCH-PET/CT provided more surgically relevant data than sestaMIBI in 4/11 patients with initial surgery and in 1/4 patient who underwent redo surgery. Compared to sestaMIBI scintigraphy, FCH-PET/CT provides additional information regarding the number of pathologic parathyroid glands and their localization in MEN1 patients with HPT1.

IDO, TDO, and AHR overexpression is associated with poor outcome in diffuse large B-cell lymphoma patients in the rituximab era.

Although Indoleamine 2,3-dioxygenase (IDO), tryptophan-2,3-dioxygenase (TDO), and aryl hydrocarbon receptor (AHR) are involved in cancer immune escape, their prognostic impact on diffuse large B-cell lymphoma (DLBCL) is unknown.To examine the prognostic impact of IDO, TDO, and AHR on patients with DLBCL.This was a retrospective study on treatment-naïve patients with newly diagnosed DLBCL at the Henan Province People's Hospital between 01/2012 and 06/2015. Patients with inflammatory reactive lymph nodes were included as controls. All cases were reviewed by 2 pathologists. IDO, TDO, and AHR positivity was determined through immunochemistry. Survival was examined using the Kaplan-Meier method and multivariable Cox analyses.The positive expression of TDO (50.0% vs 16.7%, P = .005) and AHR (60.0% vs 8.3%, P < .001) were higher in DLBCL than in inflammatory control. The overall survival of IDO, TDO, and AHR positive expression in DLBCL patients was 34.6, 26.7, and 32.2 months, respectively, which is significantly shorter than that of the corresponding negative patients (49.0 months, P = .04; 58.2 months, P < .001; 58.0 months, P < .001; respectively). The multivariable analysis showed that TDO expression and Ann-Arbor stage were independently associated with PFS (TDO: HR = 8.347, 95%CI: 2.992–23.289, P < .001; stage: HR = 2.729, 95%CI: 1.571–4.739, P < .001) and OS (TDO: HR = 9.953, 95%CI: 3.228–30.686, P < .001; stage: HR = 2.681, 95%CI: 1.524–4.719, P = .001) in DLBCL patients.Overexpression of IDO, TDO, and AHR is associated with poor survival of patients with DLBCL and could be involved in the immune escape of cancer cells. Further studies are necessary to determine whether these proteins can be targeted by treatment regimens.

Suppurative cervical lymphadenitis in adult: An analysis of predictors for surgical drainage

ObjectiveLymphadenitis can be treated successfully by empirical antibiotic therapy. However, inflamed lymph nodes can progress into an abscess with local and/or systemic reaction, which requires more complex treatment strategies. The study aim to analyze possible predictors for abscess formation within inflamed nodes that require surgical drainage. Materials and MethodsWe retrospectively enrolled 241 patients with acute or sub-acute cervical lymphadenitis. Demographic including, lymph node characteristics, management, and final diagnosis were recorded. Predictors for abscess formation within the lymph node that required surgical drainage were evaluated using univariate and multivariate analysis. Patient and lymph node characteristics that differentiated suppurative cervical lymphadenitis (SCL) from other lymphadenitis were also analyzed. ResultsThere were 41 cases of SCL, 173 cases of uncomplicated cervical lymphadenitis, and 27 cases of tuberculous cervical lymphadenitis (TBLN). Abscess was surgically drained in 39 patients, while 2 patients received a needle aspiration. In 9 patients, SCL complications included cellulitis of the neck soft tissue, supraglottic swelling, internal jugular vein thrombosis, and sepsis. Two patients were diagnosed with melioidosis and actinomycosis after drainage. Multivariate analysis showed that an immunocompromised host, male sex, and receiving prior inadequate treatment were predictors for surgical drainage. TBLN patients had similar manifestations as SCL patients. However, affected nodes in SCL patients were singular, painful, and showed fluctuation. ConclusionsFollowing SCL diagnosis, abscess drainage and appropriate antibiotic treatment should be considered. Aspiration or surgical drainage can be effective in certain patients. Pathogen isolation and tissue biopsy should be performed to ensure accurate diagnosis and antibiotic selection. In addition, TBLN and melioidosis should be considered, especially in endemic areas.

Bioinformatics analysis of whole slide images reveals significant neighborhood preferences of tumor cells in Hodgkin lymphoma.

In pathology, tissue images are evaluated using a light microscope, relying on the expertise and experience of pathologists. There is a great need for computational methods to quantify and standardize histological observations. Computational quantification methods become more and more essential to evaluate tissue images. In particular, the distribution of tumor cells and their microenvironment are of special interest. Here, we systematically investigated tumor cell properties and their spatial neighborhood relations by a new application of statistical analysis to whole slide images of Hodgkin lymphoma, a tumor arising in lymph nodes, and inflammation of lymph nodes called lymphadenitis. We considered properties of more than 400, 000 immunohistochemically stained, CD30-positive cells in 35 whole slide images of tissue sections from subtypes of the classical Hodgkin lymphoma, nodular sclerosis and mixed cellularity, as well as from lymphadenitis. We found that cells of specific morphology exhibited significantly favored and unfavored spatial neighborhood relations of cells in dependence of their morphology. This information is important to evaluate differences between Hodgkin lymph nodes infiltrated by tumor cells (Hodgkin lymphoma) and inflamed lymph nodes, concerning the neighborhood relations of cells and the sizes of cells. The quantification of neighborhood relations revealed new insights of relations of CD30-positive cells in different diagnosis cases. The approach is general and can easily be applied to whole slide image analysis of other tumor types.

P643 Development of quantitative ultrasonographic activity score in ileal Crohn’s disease

Abstract Background Intestinal ultrasound (IUS) is as an accurate bedside tool for monitoring Crohn’s disease (CD). However, there is no validated quantitative ultrasonographic score for evaluation of the activity of intestinal inflammation in CD. Such a score may facilitate the use of IUS-based monitoring in clinical practice and in clinical trials in CD. For magnetic resonance enterography (MRE), the magnetic resonance index of activity (MaRIA) is most commonly used. Thus, the aim of our study was to correlate IUS data for the terminal ileum with segmental MARIA score for the terminal ileum in order to devise a quantitative inflammatory index for IUS. Methods In this retrospective cohort study, the data of CD patients who were followed in the Gastroenterology Department at Sheba medical centre between January 2016 and December 2018 were extracted. Inclusion criteria were age &amp;gt;18 and an interval&amp;lt;3 months between MRE and IUS. MaRIA score for the terminal ileum was compared with ultrasonographic features of inflammation that included: bowel wall thickness (continuous variable), echogenicity of the bowel wall, pseudostratification of the bowel wall layers, inflammatory mesenteric fat and lymph nodes, hyperemia present on colour Doppler flow and complications (nominal variable). A linear regression model that included the significantly correlated variables was constructed. Results Forty-two patients with established Crohn’s disease were included. A stepwise multiple regression model was constructed to predict MaRIA score using US features. Two variables were found to be independently significant in the explanatory model, terminal ileum thickness (r = 0.68, p = 0.001) and US fat proliferation (r = 0.45, p = 0.019). A model was constructed as follows: MaRIA = 7 + 2.5 * TI US thickness (mm) + 7 * US fat proliferation (0 = no, 1 = yes). This model has an R2 of 0.51 for explaining the variability in the results. Conclusion Quantitative IUS measurements are significantly correlated with segmental MaRIA score in the terminal ileum; a simple computational model for prediction can be constructed; however,, the accuracy of such model to predict segmental MaRIA was moderate. Additional work to develop quantitative IUS parameters in CD is merited.

Sensing of HIV-1 by TLR8 activates human T cells and reverses latency

During HIV infection, cell-to-cell transmission results in endosomal uptake of the virus by target CD4+ T cells and potential exposure of the viral ssRNA genome to endosomal Toll-like receptors (TLRs). TLRs are instrumental in activating inflammatory responses in innate immune cells, but their function in adaptive immune cells is less well understood. Here we show that synthetic ligands of TLR8 boosted T cell receptor signaling, resulting in increased cytokine production and upregulation of surface activation markers. Adjuvant TLR8 stimulation, but not TLR7 or TLR9, further promoted T helper cell differentiation towards Th1 and Th17. In addition, we found that endosomal HIV induced cytokine secretion from CD4+ T cells in a TLR8-specific manner. TLR8 engagement also enhanced HIV-1 replication and potentiated the reversal of latency in patient-derived T cells. The adjuvant TLR8 activity in T cells can contribute to viral dissemination in the lymph node and low-grade inflammation in HIV patients. In addition, it can potentially be exploited for therapeutic targeting and vaccine development.

TNF-Induced Interstitial Lung Disease in a Murine Arthritis Model: Accumulation of Activated Monocytes, Conventional Dendritic Cells, and CD21+/CD23- B Cell Follicles Is Prevented with Anti-TNF Therapy.

Interstitial lung disease (ILD) is a well-known extra-articular manifestation of rheumatoid arthritis (RA). RA-associated ILD (RA-ILD) exists on a wide spectrum, with variable levels of inflammatory and fibrotic activity, although all subtypes are regarded as irreversible pathologic conditions. In both articular and pulmonary manifestations, TNF is a significant pathogenic factor. Whereas anti-TNF therapy alleviates joint pathologic conditions, it exacerbates fibrotic RA-ILD. The TNF-transgenic (TNF-Tg) murine model of RA develops both inflammatory arthritis and an ILD that mimics a cellular nonspecific interstitial pneumonia pattern dominated by an interstitial accumulation of inflammatory cells with minimal-to-absent fibrosis. Given the model's potential to elucidate the genesis of inflammatory RA-ILD, we aim to achieve the following: 1) characterize the cellular accumulations in TNF-Tg lungs, and 2) assess the reversibility of inflammatory ILD following anti-TNF therapy known to resolve TNF-Tg inflammatory arthritis. TNF-Tg mice with established disease were randomized to anti-TNF or placebo therapy and evaluated with imaging, histology, and flow cytometric analyses, together with wild-type controls. Flow cytometry of TNF-Tg versus wild-type lungs revealed significant increases in activated monocytes, conventional dendritic cells, and CD21+/CD23- B cells that are phenotypically distinct from the B cells in inflamed nodes, which are known to accumulate in joint-draining lymph nodes. In contrast to human RA-ILD, anti-TNF treatment significantly alleviated both joint and lung inflammation. These results identify a potential role for activated monocytes, conventional dendritic cells, and CD21+/CD23- B cells in the genesis of RA-ILD, which exist in a previously unknown, reversible, prefibrotic stage of the disease.