Granulomatous Nodules Research Articles

Iatrogenic allogenesis and autoimmune diseases

Introduction. Iatrogenic allogenesis is currently a public health problem due to the constant increase in cases, especially in underdeveloped countries. Objective. To characterize patients diagnosed with iatrogenic allogenesis. Methods. An observational, descriptive, cross-sectional study was conducted in 23 patients with a confirmed diagnosis of iatrogenic allogenesis. Adverse reactions, the appearance of autoimmune diseases, and their association with the type of substance injected were described. Results. Women aged 30-39 years, single, and with non-university education predominated. 48% of patients received the infiltration by stylists in beauty salons. The most common infiltration area was the face, and 39% of patients did not know the substance that was injected. Granulomatous reactions, generalized pain, and nodule formation predominated, associated with all the molding agents used and with injections in the face. Contour changes and asymmetry were associated with the use of silicones and biopolymers and were more common with injections in the face and buttocks. 47.8% of patients were diagnosed with autoimmune diseases, with vasculitis and systemic lupus erythematosus being the most common. 63.6% of those diagnosed with autoimmune diseases were infiltrated with substances of unknown type. Conclusions. Granulomatous reactions, generalized pain, and nodule formation predominated, along with the diagnosis of vasculitis and systemic lupus erythematosus; these were more frequently associated with the injection of substances of unknown origin and composition

Not all granulomatous lymph nodes are of tuberculosis-a clinical challenge from diagnosis to treatment

Not all granulomatous lymph nodes are of tuberculosis-a clinical challenge from diagnosis to treatment

Differentiation of granulomatous nodules with lobulation and spiculation signs from solid lung adenocarcinomas using a CT deep learning model

BackgroundThe diagnosis of solitary pulmonary nodules has always been a difficult and important point in clinical research, especially granulomatous nodules (GNs) with lobulation and spiculation signs, which are easily misdiagnosed as malignant tumors. Therefore, in this study, we utilised a CT deep learning (DL) model to distinguish GNs with lobulation and spiculation signs from solid lung adenocarcinomas (LADCs), to improve the diagnostic accuracy of preoperative diagnosis.Methods420 patients with pathologically confirmed GNs and LADCs from three medical institutions were retrospectively enrolled. The regions of interest in non-enhanced CT (NECT) and venous contrast-enhanced CT (VECT) were identified and labeled, and self-supervised labels were constructed. Cases from institution 1 were randomly divided into a training set (TS) and an internal validation set (IVS), and cases from institutions 2 and 3 were treated as an external validation set (EVS). Training and validation were performed using self-supervised transfer learning, and the results were compared with the radiologists’ diagnoses.ResultsThe DL model achieved good performance in distinguishing GNs and LADCs, with area under curve (AUC) values of 0.917, 0.876, and 0.896 in the IVS and 0.889, 0.879, and 0.881 in the EVS for NECT, VECT, and non-enhanced with venous contrast-enhanced CT (NEVECT) images, respectively. The AUCs of radiologists 1, 2, 3, and 4 were, respectively, 0.739, 0.783, 0.883, and 0.901 in the (IVS) and 0.760, 0.760, 0.841, and 0.844 in the EVS.ConclusionsA CT DL model showed great value for preoperative differentiation of GNs with lobulation and spiculation signs from solid LADCs, and its predictive performance was higher than that of radiologists.

Single Cell Analysis of Peripheral TB-Associated Granulomatous Lymphadenitis.

We successfully employed a single cell RNA sequencing (scRNA-seq) approach to describe the cells and the communication networks characterizing granulomatous lymph nodes of TB patients. When mapping cells from individual patient samples, clustered based on their transcriptome similarities, we uniformly identify several cell types that known to characterize human and non-human primate granulomas. Whether high or low Mtb burden, we find the T cell cluster to be one of the most abundant. Many cells expressing T cell markers are clearly quantifiable within this CD3 expressing cluster. Other cell clusters that are uniformly detected, but that vary dramatically in abundance amongst the individual patient samples, are the B cell, plasma cell and macrophage/dendrocyte and NK cell clusters. When we combine all our scRNA-seq data from our current 23 patients (in order to add power to cell cluster identification in patient samples with fewer cells), we distinguish T, macrophage, dendrocyte and plasma cell subclusters, each with distinct signaling activities. The sizes of these subclusters also varies dramatically amongst the individual patients. In comparing FNA composition we noted trends in which T cell populations and macrophage/dendrocyte populations were negatively correlated with NK cell populations. In addition, we also discovered that the scRNA-seq pipeline, designed for quantification of human cell mRNA, also detects Mtb RNA transcripts and associates them with their host cell's transcriptome, thus identifying individual infected cells. We hypothesize that the number of detected bacterial transcript reads provides a measure of Mtb burden, as does the number of Mtb-infected cells. The number of infected cells also varies dramatically in abundance amongst the patient samples. CellChat analysis identified predominating signaling pathways amongst the cells comprising the various granulomas, including many interactions between stromal or endothelial cells and the other component cells, such as Collagen, FN1 and Laminin,. In addition, other more selective communications pathways, including MIF, MHC-1, MHC-2, APP, CD 22, CD45, and others, are identified as originating or being received by individual immune cell components.

Thoracale adenopathieën en neutropenie: een onverwachte diagnose

Thoracic lymphadenopathies and neutropenia: an unexpected diagnosis A 68-year-old patient, known with rheumatoid arthritis (RA) and treated with TNF-alpha antagonists, presents with a persistent cough with coloured sputum. Further examination reveals neutropenia and thoracic adenopathies. Histopathologic examination shows non-necrotizing granulomas in the thoracic lymph nodes and bone marrow. After infectious and malignant evaluation, the diagnoses of sarcoidosis and sarcoidosis-like granulomatosis by TNF-alpha antagonists are made. The clinic, imaging, laboratory findings and histopathology do not allow the doctors to distinguish between the 2 diagnoses. Several arguments point in the direction of sarcoidosis-like granulomatosis due to TNF-alpha antagonists. First, there is a temporal relationship between the initiation of the antagonists and the finding of granulomas. Additionally, the association of RA and sarcoidosis is extremely rare. Sarcoidosis-like granulomatosis due to TNF-alpha antagonists may be considered as a form of drug-induced sarcoidosis.

Increasing the scan-efficiency of pulmonary imaging at 0.55 T using iterative concomitant field and motion-corrected reconstruction.

To develop an iterative concomitant field and motion corrected (iCoMoCo) reconstruction for isotropic high-resolution UTE pulmonary imaging at 0.55 T. A free-breathing golden-angle stack-of-spirals UTE sequence was used to acquire data for 8 min with prototype and commercial 0.55 T MRI scanners. The data was binned into 12 respiratory phases based on superior-inferior navigator readouts. The previously published iterative motion corrected (iMoCo) reconstruction was extended to include concomitant field correction directly in the cost function. The reconstruction was implemented within the Gadgetron framework for inline reconstruction. Data were retrospectively reconstructed to simulate scan times of 2, 4, 6, and 8 min. Image quality was assessed using apparent SNR and image sharpness. The technique was evaluated in healthy volunteers and patients with known lung pathology including coronavirus disease 2019 infection, chronic granulomatous disease, lymphangioleiomyomatosis, and lung nodules. The technique provided diagnostic-quality images, and image quality was maintained with a slight loss in SNR for simulated scan times down to 4 min. Parenchymal apparent SNR was 4.33 ± 0.57, 5.96 ± 0.65, 7.36 ± 0.64, and 7.87 ± 0.65 using iCoMoCo with scan times of 2, 4, 6, and 8 min, respectively. Image sharpness at the diaphragm was comparable between iCoMoCo and reference images. Concomitant field corrections visibly improved the sharpness of anatomical structures away from the isocenter. Inline image reconstruction and artifact correction were achieved in <5 min. The proposed iCoMoCo pulmonary imaging technique can generate diagnostic quality images with 1.75 mm isotropic resolution in less than 5 min using a 6-min acquisition, on a 0.55 T scanner.

Macrophage polarization in lymph node granulomas from cattle and pigs naturally infected with Mycobacterium tuberculosis complex.

Tuberculosis in animals is caused by members of the Mycobacterium tuberculosis complex (MTC), with the tuberculous granuloma being the main characteristic lesion. The macrophage is the main cell type involved in the development of the granuloma and presents a wide plasticity ranging from polarization to classically activated or pro-inflammatory macrophages (M1) or to alternatively activated or anti-inflammatory macrophages (M2). Thus, this study aimed to analyze macrophage polarization in granulomas from cattle and pig lymph nodes naturally infected with MTC. Tuberculous granulomas were microscopically categorized into four stages and a panel of myeloid cells (CD172a/calprotectin), M1 macrophage polarization (iNOS/CD68/CD107a), and M2 macrophage polarization (Arg1/CD163) markers were analyzed by immunohistochemistry. CD172a and calprotectin followed the same kinetics, having greater expression in late-stage granulomas in pigs. iNOS and CD68 had higher expression in cattle compared with pigs, and the expression was higher in early-stage granulomas. CD107a immunolabeling was only observed in porcine granulomas, with a higher expression in stage I granulomas. Arg1+ cells were significantly higher in pigs than in cattle, particularly in late-stage granulomas. Quantitative analysis of CD163+ cells showed similar kinetics in both species with a consistent frequency of immunolabeled cells throughout the different stages of the granuloma. Our results indicate that M1 macrophage polarization prevails in cattle during early-stage granulomas (stages I and II), whereas M2 phenotype is observed in later stages. Contrary, and mainly due to the expression of Arg1, M2 macrophage polarization is predominant in pigs in all granuloma stages.

Activity of biogenic silver nanoparticles in planktonic and biofilm-associated Corynebacterium pseudotuberculosis.

Corynebacterium pseudotuberculosis is a gram-positive bacterium and is the etiologic agent of caseous lymphadenitis (CL) in small ruminants. This disease is characterized by the development of encapsulated granulomas in visceral and superficial lymph nodes, and its clinical treatment is refractory to antibiotic therapy. An important virulence factor of the Corynebacterium genus is the ability to produce biofilm; however, little is known about the characteristics of the biofilm produced by C. pseudotuberculosis and its resistance to antimicrobials. Silver nanoparticles (AgNPs) are considered as promising antimicrobial agents, and are known to have several advantages, such as a broad-spectrum activity, low resistance induction potential, and antibiofilm activity. Therefore, we evaluate herein the activity of AgNPs in C. pseudotuberculosis, through the determination of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), antibiofilm activity, and visualization of AgNP-treated and AgNP-untreated biofilm through scanning electron microscopy. The AgNPs were able to completely inhibit bacterial growth and inactivate C. pseudotuberculosis at concentrations ranging from 0.08 to 0.312 mg/mL. The AgNPs reduced the formation of biofilm in reference strains and clinical isolates of C. pseudotuberculosis, with interference values greater than 80% at a concentration of 4 mg/mL, controlling the change between the planktonic and biofilm-associated forms, and preventing fixation and colonization. Scanning electron microscopy images showed a significant disruptive activity of AgNP on the consolidated biofilms. The results of this study demonstrate the potential of AgNPs as an effective therapeutic agent against CL.

Histopathological Review of Granuloma in Diagnosis of Tuberculosis Lymphadenitis (TBL)

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis and is the second leading cause of death from an infectious disease. Indonesia has the highest TB cases in West Java, East Java, and Central Java. Tuberculosis lymphadenitis (TBL) represents about 30–40% of cases of extrapulmonary tuberculosis. The study aimed to study the clinical and histopathological characteristics of TBL patients. The research design in this study used an exploratory, descriptive method. Data was taken from Al Islam Hospital Bandung as medical records from January 2019 to December 2020. The result showed that TBL primarily affects patients aged 6–11 years (28%), male gender (57%), patients not working (25%), and those residing in the East Bandung area (34%). Histopathological appearance showed granulomas of caseous necrosis, epithelioid cells, and Langhan's cells, indicated by types 1, 2, and 3. The most common type was type 1 (47%), which was more widely distributed in the right neck (46%) with size 1–3 cm. In conclusion, the frequency of TBL is higher in boys aged 6–11 years, residents of the East Bandung area, and patients who did not work. Well-formed granuloma of enlarged lymph nodes in the right neck with size 1–3 cm is most commonly found in TBL.

Immune strategies of silver pomfret (Pampus argenteus) infected with Nocardia seriolae at different infection stages

Nocardia seriolae, a widespread opportunistic pathogen, has the ability to infect various economically farmed fishes, leading to prolonged disease courses and high mortality rates. In our current study, we focused on the silver pomfret (Pampus argenteus) and examined the liver, spleen, and kidney tissues at three specific N. seriolae infection phases: control (0 day), L group (infection for 5 days), and H group (infection for 15 days). Utilizing HE staining, we observed typical granulomatous nodules displaying stratified concentric layers, including caseous necrotic cells, epithelioid cells and multinucleated giant cells, fibroblasts and fibrocyte envelopes. The TUNEL assay revealed a significant presence of apoptotic cells concentrated within the renal nodules. Following the infection, there was a noticeable increase in AKP, ACP, and LZM levels in all tissues, while LPS exhibited a consistent decline. Through combined analysis of WGCNA and KEGG pathways derived from the tissue transcriptome, we identified several highly enriched pathways, such as the PI3K-Akt signaling pathway and p53 signaling pathway, in all three tissues. Key DEGs from these pathways underwent further investigation through RT-qPCR. In comparison to the control group, the L group exhibited up-regulation of genes associated with biosynthesis catabolism, whereas genes related to immune response, apoptosis, and ion transport displayed down-regulation. Interestingly, the H group showcased a stark reversal of this trend. To validate these DEGs expressions in vitro, we established a Pampus argenteus spleen cell line (PaS). By evaluating the invasion metrics of NS into PaS, we determined an optimal invasion threshold of 105 CFU/ml. The TUNEL assay demonstrated a notable presence of apoptotic signals in the 5 h and 7 h treatment groups. JC-1 assays indicated a gradual decline in membrane potential starting from the 3-h mark. As the duration of treatment increased, RT-qPCR and IHC findings highlighted an initial up-regulation followed by a subsequent down-regulation of genes associated with biosynthesis catabolism. In contrast, genes related to innate immunity displayed up-regulation, whereas genes related to adaptive immunity and ion transport exhibited an initial surge followed by a gradual decrease. Additionally, genes inhibiting apoptosis showed down-regulation. In conclusion, these findings provide valuable insights into the apoptosis mediated by N. seriolae in piscine hosts. These effects are potentially attributed to the increased expression of ion transport-related genes. Moreover, our study sheds light on the intricate molecular mechanisms underlying piscine immunological responses throughout the entire infection timeline, offering promising opportunities for disease control.

OA19 A complex case of bilateral pneumothoraces due to probable certolizumab driven rheumatoid lung nodules

OA19 A complex case of bilateral pneumothoraces due to probable certolizumab driven rheumatoid lung nodules

Needle-based confocal laser endomicroscopy for real-time granuloma detection.

Needle-based confocal laser endomicroscopy (nCLE) allows real-time microscopic imaging at the needle tip. nCLE malignancy criteria are used for tool-in-lesion confirmation during bronchoscopic lung nodule analysis. However, to date, nCLE criteria for granulomas are lacking. The aim was to identify and validate nCLE granuloma criteria and assess if blinded raters can distinguish malignant from granulomatous nCLE videos. In patients with suspected sarcoidosis, nCLE-imaging of mediastinal lymph nodes was performed during endoscopic ultrasound procedures, followed by needle aspiration. nCLE granuloma criteria were identified by comparison with pathology and final diagnoses. Additionally, nCLE-videos of granulomatous lung nodules part of prospective trials and clinical care were compared to the proposed nCLE granuloma criteria. Blinded raters validated nCLE videos of sarcoid and reactive mediastinal lymph nodes and malignant and granulomatous lung nodules twice. Granuloma criteria were identified (brighter-toned, homogeneous and well-demarcated lesions) based on nCLE-imaging in 14 sarcoidosis patients. Raters evaluated 26 nCLE-videos obtained in lymph nodes (n = 15 sarcoidosis; n = 11 reactive and total of 260 ratings). Granuloma criteria were recognized with 88% accuracy. The inter-observer (κ = 0.63, 95% CI 0.54-0.72) and intra-observer reliability (κ = 0.70 ± 0.06) were substantial. Based on 12 nCLE-videos obtained in lung nodules (n = 4 granulomas, n = 6 malignancy, n = 2 malignancy + granulomas and total of 120 ratings) granuloma and malignancy criteria were recognized with 92% and 75% accuracy. nCLE imaging facilitates real-time granuloma visualization. Blinded raters accurately and consistently recognized granulomas on nCLE-imaging and distinguished nCLE granuloma criteria from malignancy. Our data show the potential of nCLE as a real-time bronchoscopic guidance tool for lung nodule analysis.

Pathogenicity and detection method based on interferon release assay of Mycobacteria marinum isolated from sturgeon

Mycobacterium marinum is an opportunistic pathogen and can infect marine and freshwater fish. In this study, an acid-fast bacillus strain was isolated from the moribund Acipenser sinensis and identified as M. marinum via specific plate culture and phylogenetic analysis of 16S rRNA. M. marinum exhibited pathogenicity in Chinese sturgeon and hybrid sturgeon (A. schrenckii ♀ × A. baerii ♂). The histopathology results showed that granulomatous nodules were observed in the liver, spleen and kidney of the Chinese sturgeon after M. marinum infection. Nuclear necrosis and large production of hemosiderin appeared in the liver. The medullary structure of the spleen was disordered. The glomerulus was deformed and disintegrated, and the glomerular lumen was dilated in the kidney. The expressions of IFN-e1, IFN-γ, TNFα1, TNFα2, IL-1β, and IL-6 of Chinese sturgeon were significantly upregulated by M. marinum in vivo and in vitro. The whole blood ELISA detection method was constructed by IFN-γ polyclonal antibody. The infection of M. marinum in hybrid sturgeon could be judged by detecting the concentration of IFN-γ in plasma. In summary, M. marinum has a strong pathogenicity to sturgeon and could induce the immune response of the host. The sturgeon IFN-γ-ELISA detection method was expected to become a tool for diagnosing M. marinum infection in sturgeon. This study could provide the scientific basis for effectively controlling and reducing the pathogenic M. marinum disease of sturgeon in aquaculture.

CLSSL-ResNet: Predicting malignancy of solitary pulmonary nodules from CT images by chimeric label with self-supervised learning.

Pulmonary granulomatous nodules (GN) with spiculation or lobulation have a similar morphological appearance to solid lung adenocarcinoma (SADC) under computed tomography (CT). However, these two kinds of solid pulmonary nodules (SPN) have different malignancies and are sometimes misdiagnosed. This study aims to predict malignancies of SPNs by a deep learning model automatically. A chimeric label with self-supervised learning (CLSSL) is proposed to pre-train a ResNet-based network (CLSSL-ResNet) for distinguishing isolated atypical GN from SADC in CT images. The malignancy, rotation, and morphology labels are integrated into a chimeric label and utilized to pre-train a ResNet50. The pre-trained ResNet50 are then transferred and fine-tuned to predict the malignancy of SPN. Two image datasets of 428 subjects (Dataset1, 307; Dataset2, 121) from different hospitals are collected. Dataset1 is divided into training, validation, and test data by a ratio of 7:1:2 to develop the model. Dataset2 is utilized as an external validation dataset. CLSSL-ResNet achieves an area under the ROC curve (AUC) of 0.944 and an accuracy (ACC) of 91.3%, which was much higher than that of the consensus of two experienced chest radiologists (77.3%). CLSSL-ResNet also outperforms other self-supervised learning models and many counterparts of other backbone networks. In Dataset2, AUC and ACC of CLSSL-ResNet are 0.923 and 89.3%, respectively. Additionally, the ablation experiment result indicates higher efficiency of the chimeric label. CLSSL with morphology labels can increase the ability of feature representation by deep networks. As a non-invasive method, CLSSL-ResNet can distinguish GN from SADC via CT images and may support clinical diagnoses after further validation.

Peritoneal tuberculosis with a frozen abdomen in an adolescent female: A case report

Background: Peritoneal tuberculosis is a rare form of extrapulmonary tuberculosis, which can result from the reactivation of latent foci in the peritoneal cavity. &#x0D; Case presentation: A 19-year-old female presented to the gynecological oncology clinic with a two-month history of generalized abdominal pain and progressive abdominal distention. An abdominopelvic computed tomography scan revealed a cystic right adnexal lesion with massive simple ascites. A frozen abdomen was noted during exploratory laparotomy. Histological examination of the peritoneal biopsy reported granulomatous nodules with numerous epithelioid histiocytes. Postoperatively, she was managed with rifampicin, isoniazid, pyrazinamide, ethambutol, and pyridoxine for six months and recovered fully. &#x0D; Conclusion: Peritoneal tuberculosis may mimic ovarian and peritoneal malignancies. A high suspicion index of peritoneal tuberculosis should be entertained in patients presenting with nonspecific symptoms of ovarian or peritoneal cancers.

Molecular Mechanism in the Development of Pulmonary Fibrosis in Patients with Sarcoidosis.

Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of granulomas in various organs, especially lung and mediastinal hilar lymph nodes. The clinical course and manifestations are unpredictable: spontaneous remission can occur in approximately two thirds of patients; up to 20% of patients have chronic course of the lung disease (called advanced pulmonary sarcoidosis, APS) resulting in progressive loss of lung function, sometimes life-threatening that can lead to respiratory failure and death. The immunopathology mechanism leading from granuloma formation to the fibrosis in APS still remains elusive. Recent studies have provided new insights into the genetic factors and immune components involved in the clinical manifestation of the disease. In this review we aim to summarize the clinical-prognostic characteristics and molecular pathways which are believed to be associated with the development of APS.

Imbalance of Lymphocyte Subsets and CD45RA-Expressing Cells in Intrathoracic Lymph Nodes, Alveolar Compartment and Bloodstream of Pulmonary Sarcoidosis Patients.

Sarcoidosis is a systemic granulomatous disease mainly affecting the lungs and hilomediastinal lymph nodes. It is characterized by non-caseating epithelioid cell granulomas in lymph nodes and lungs. Our study aimed to evaluate and compare T, B and NK cell subsets in the alveolar compartment, lymph nodes and the bloodstream simultaneously in the same patients to elucidate the immune responses associated with the development and progression of sarcoidosis. A secondary aim was to evaluate the distribution of CD45RA-expressing cells in the different anatomical compartments. Patients suspected to have sarcoidosis and who underwent bronchoscopy with bronchoalveolar lavage (BAL), lung-draining lymph node (LLN) biopsy by EBUS-TBNA and peripheral blood (PB) sampling were included in the study. They were monitored at the Regional Referral Centre of Siena University Hospital and the Respiratory Diseases Unit of Perugia Hospital. Multicolour flow cytometry analysis through FASCLyric was performed to assess T, B and NK cell subsets. Thirty-two patients (median age (IQR) 57 (52-58) years) were consecutively and prospectively enrolled. Machine learning analysis created a model which selected CD56dim16bright, CD8, Tfc, Th17, Th12, Tfh17, Tfh2, TcemRA, ThemRA, T naïve, Tc naïve, Breg, CD1d+CD5+, Th-reg, Tfh, Th1 and CD4 cells with an accuracy of 0.9500 (kappa 0.8750). Comparative analysis found 18 cell populations that differed significantly between the three anatomical compartments. The bloodstream was enriched in ThemRA (p = 0.0416), Tfh2 (p = 0.0189), Tfh17 (p = 0.0257), Th2 (p = 0.0212), Th17 (p = 0.0177), Th-naïve (p = 0.0368), CD56dimCD16bright (p < 0.0001), CD8 (p = 0.0319), TcemRA (p < 0.0001) and Tfc cells (p = 0.0004) compared with the alveolar compartment, while Th-reg were lower in PB than BAL (p = 0.0329). The alveolar compartment was enriched in Breg (p = 0.0249) and CD1d+CD5+ (p = 0.0013) with respect to LLN samples and PB. Conversely, Tfh (p = 0.0470), Th1 (p = 0.0322), CD4 (p = 0.0486) and Tc-naïve (p = 0.0009) were more abundant in LLN than in BAL and PB. It has been speculated that changes in the relative contents of PB cells could be related to changes in production and to the selective redistribution of PB cells to granulomatous foci. This study further supports the fact that sarcoidosis is multisystemic in nature. However, the low level of immune cells in peripheral blood of patients with sarcoidosis is concerning. A re-expression of CD45RA on CD4+ and CD8+ cells could result in a reduction in peripheral immune activity. Thus, changes in the spectrum of the bloodstream may reflect both pathogenic and compensatory processes.

Macrophages and neutrophils in lymph node granulomas from Mycobacterium tuberculosis-infected macaques have immunoregulatory phenotypes

Abstract Tuberculosis (TB) is caused by infection with the Mycobacterium tuberculosis (Mtb). Lung granulomas are the defining pathologic feature of TB but Mtb can infect other organs, including lymph nodes, and causes granulomas to form in these sites. Lymph node granulomas have received less attention than lung granulomas but granulomas in these organs are sites of bacterial persistence and have implications for TB progression. Macrophage subsets and neutrophils in lymph node granulomas have not been extensively studied but the biology of these cells may yield clues that underlie the pathobiology of lymph node infection. Our objective was to describe expression of functional markers and cytokine expression by macrophage subsets and neutrophils in lymph node granulomas and to compare these myeloid cells in lymph node and lung granulomas. We used thoracic lymph node and lung granulomas from cynomolgus macaques, a nonhuman primate that experiences human-like TB pathology and course of disease, to do this work. We found that lymph node epithelioid macrophages were distinct from lymph node dendritic cells but resembled epithelioid macrophages in lung granulomas suggesting these cells share a common progenitor or exposure to common stimuli leads to a phenotypic convergence in different tissues. Macrophages expressed pro- and anti-inflammatory cytokines including type 1 interferon, a cytokine family associated with exacerbated TB. Neutrophils were present in low numbers in non-granulomatous lymph node regions but were selectively recruited to granulomas. Our data suggest that macrophages and neutrophils in lymph node granulomas have immunoregulatory properties that may contribute to local and systemic outcomes in Mtb infection. This work is supported by NIH grants R21 AI167710, R01AI164970, and the Wellcome Trust DELTA tissue program.

A study on the differential of solid lung adenocarcinoma and tuberculous granuloma nodules in CT images by Radiomics machine learning

To study the classification efficiency of using texture feature machine learning method in distinguishing solid lung adenocarcinoma (SADC) and tuberculous granulomatous nodules (TGN) that appear as solid nodules (SN) in non-enhanced CT images. 200 patients with SADC and TGN who underwent thoracic non-enhanced CT examination from January 2012 to October 2019 were included in the study, 490 texture eigenvalues of 6 categories were extracted from the lesions in the non-enhanced CT images of these patients for machine learning, the classification prediction model is established by using relatively the best classifier selected according to the fitting degree of learning curve in the process of machine learning, and the effectiveness of the model was tested and verified. The logistic regression model of clinical data (including demographic data and CT parameters and CT signs of solitary nodules) was used for comparison. The prediction model of clinical data was established by logistic regression, and the classifier was established by machine learning of radiologic texture features. The area under the curve was 0.82 and 0.65 for the prediction model based on clinical CT and only CT parameters and CT signs, and 0.870 based on Radiomics characteristics. The machine learning prediction model developed by us can improve the differentiation efficiency of SADC and TGN with SN, and provide appropriate support for treatment decisions.

Correlations Between Inflammatory Cell Infiltration and Relative Density and the Boundary Manifestation of Pulmonary Non-Neoplastic Ground Glass Nodules.

To investigate the influence factors for the various boundary manifestations of pulmonary non-neoplastic ground glass nodules (GGNs) on computed tomography (CT). From January 2015 to March 2022, a total of 280 patients with 318 non-neoplastic GGNs were enrolled. The correlations between degree of inflammatory cell infiltration and relative density (ΔCT) and the boundary manifestations of lesions were evaluated, respectively. Nongranulomatous nodules (283, 89.0%) with fibrous tissue proliferation and/or inflammatory cells as the predominant pathological findings were the most common non-neoplastic GGNs, followed by granulomatous nodules (28, 8.8%). Among nongranulomatous GGNs, cases with more and less/no inflammatory cells were 15 (10.9%) and 122 (89.1%) in 137 well-defined ones with smooth margin, 16 (24.6%) and 49 (75.4%) in 65 well-defined ones with coarse margin, 43 (91.5%) and 4 (8.5%) in 47 ill-defined ones with higher ΔCT (>151HU), and 4 (11.8%) and 30 (88.2%) in 34 ill-defined ones with lower ΔCT (< 151HU). The proportion of cases with more inflammatory cells in well-defined nodules was similar to that in ill-defined ones with lower ΔCT (P = 0.587) but significantly lower than that in ill-defined ones with higher ΔCT (P < 0.001). Among the granulomatous nodules, ill-defined cases with higher ΔCT (16, 57.1%) were the most common, and they (7/8, 87.5%) frequently had changes during short-term follow-up. Nongranulomatous nodules are the most common non-neoplastic GGNs, their diverse boundary manifestations closely correlate with degree of inflammatory cell infiltration and density difference.