Tuberculous Granuloma Research Articles

Tuberculous Granuloma of Thyroid Gland Mimicking Metastatic Thyroid Carcinoma: A Case Report and Review of Literature

Tuberculosis is a problem to public health, especially in developing countries. However, involvement of the thyroid gland is rare. Herein, a 53-yearold woman with complaint of painless swelling on the right side of her neck is presented. Nodular goiter was detected in addition to multiple lymphadenopathies on the right cervical region. Tuberculosis was diagnosed based on histological findings in both the thyroid gland and cervical lymph nodes contrary to our expectation which was thyroid carcinoma.

Histology and Immunohistochemistry Localization of ESAT6 Expression on Caseous and Non-caseous Granuloma of Extrapulmonary Tuberculosis

Background: TB diagnosis by histopathological examination is based on the presence of epithelioid granuloma with caseous necrosis. The absence of caseous necrosis will make it difficult to distinguish between TB and non-TB granulomas. The use of ESAT-6 as a confirmative examination of TB immunohistochemically has not been fully used nor are there sufficient data showing the features of ESAT-6 immunolocalization in a granuloma. The purpose of the study was to identify differences in ESAT-6 expression in caseous and noncaseous EPTB granulomas.Methods: A cross sectional study using 66 samples of formalin fixed paraffin embedded tissues from several anatomical lesions.The samples previously diagnosed as tuberculous granuloma were evaluated histologically and immunohistochemically. Mann Whitney tests were used for statistical analysis. Result: There were no significant differences in histological findings and immunohistochemical staining of ESAT-6 on macrophages of caseous and non-caseous granuloma of EPTB. ESAT-6 protein was expressed on cytoplasm of epithelioid macrophages, foamy macrophages, Langhans type giant cells and some necrosis areas in the granulomas.Conclusions: This study showed that macrophages of caseous and non-caseous granuloma of EPTB expressed ESAT-6 protein in the same way. This finding supports the use of the anti ESAT-6 antibody as a complementary diagnostic test in diagnosing granuloma of EPTB.

Cutaneous tuberculosis in children from the northeastern region of Morocco

IntroductionIn Morocco, tuberculosis is an endemic disease. The aim of this study was to trace the epidemiological, paraclinical, therapeutic, and progressive characteristics of cutaneous tuberculosis (CT) in children. Materials and method: This multicenter retrospective and prospective study concerned all pediatric patients followed for CT in our region. The diagnosis was based on comparing clinical, immunological, bacteriological, and histological data. ResultsWe found 147 cases of CT, of which 16 cases (10%) were children. The average age was 10.5 years, with extremes ranging from 15 months to 16 years. The sex ratio was 0.75. Deterioration in general condition and weight loss were noted in three cases, and none of the patients was immunocompromised. The clinical forms were essentially scrofuloderma tuberculosis in nine cases (57%), gummas in five cases (35%), a single case each of verrucous tuberculosis and lupus vulgaris. The histological study of the lesions confirmed the diagnosis for all cases by showing a tuberculous granuloma. Multifocal forms were found in one case. Antibacillary treatment was recommended for 6 months in all patients except in the child with a multifocal form whose treatment was prolonged to 9 months. The progression was favorable with total healing in all cases except in a single case that retained sequelae such as bone deformities and scars in most cases. DiscussionCutaneous tuberculosis in children is dominated by scrofuloderma and gummy lesions in our region. Despite deterioration in the general condition and weight loss in three cases, none of these children was immunocompromised. Therapeutic management was then carried out based on several clinical and paraclinical arguments and the histological study. Even if the compulsory BCG vaccine in Morocco prevents serious forms, early diagnosis remains the only way to reduce the risk of complications. ConclusionCutaneous tuberculosis concerns our pediatric population, multibacillary forms of cutaneous localization is the most frequent one, although the BCG vaccine in Morocco is compulsory.

Micro-Computed Tomography Analysis of the Human Tuberculous Lung Reveals Remarkable Heterogeneity in Three-dimensional Granuloma Morphology.

Rationale: Our current understanding of tuberculosis (TB) pathophysiology is limited by a reliance on animal models, the paucity of human TB lung tissue, and traditional histopathological analysis, a destructive two-dimensional approach that provides limited spatial insight. Determining the three-dimensional (3D) structure of the necrotic granuloma, a characteristic feature of TB, will more accurately inform preventive TB strategies.Objectives: To ascertain the 3D shape of the human tuberculous granuloma and its spatial relationship with airways and vasculature within large lung tissues.Methods: We characterized the 3D microanatomical environment of human tuberculous lungs by using micro computed tomography, histopathology, and immunohistochemistry. By using 3D segmentation software, we accurately reconstructed TB granulomas, vasculature, and airways in three dimensions and confirmed our findings by using histopathology and immunohistochemistry.Measurements and Main Results: We observed marked heterogeneity in the morphology, volume, and number of TB granulomas in human lung sections. Unlike depictions of granulomas as simple spherical structures, human necrotic granulomas exhibit complex, cylindrical, branched morphologies that are connected to the airways and shaped by the bronchi. The use of 3D imaging of human TB lung sections provides unanticipated insight into the spatial organization of TB granulomas in relation to the airways and vasculature.Conclusions: Our findings highlight the likelihood that a single, structurally complex lesion could be mistakenly viewed as multiple independent lesions when evaluated in two dimensions. In addition, the lack of vascularization within obstructed bronchi establishes a paradigm for antimycobacterial drug tolerance. Lastly, our results suggest that bronchogenic spread of Mycobacterium tuberculosis reseeds the lung.

The T-lymphocytes of peripheral blood reflect the phase of activity tuberculous granuloma

Abstract Forms are tubercular inflammation expose them to many. Assessment tuberculous granuloma activity carried out on the basis of pathological examination of the data in the postoperative period. However, the study of immunological parameters may open the way to a minimally invasive method for evaluating the activity on the basis of immunological data. The purpose of this study was the comparative evaluation of quantitative and functional state of T-lymphocytes in different phases tuberculous granuloma activity. The study involved 56 people: 31 - tuberculous granuloma, 25 were healthy volunteers. Patients with tuberculous granuloma were differentiated into two cohorts: active tuberculous granuloma, tuberculous granuloma in the phase of moderate activity subsides. The studies to identify subpopulations of T-lymphocytes and the establishment of functional activity of the cells. The statistical unit included the use of Statistica for Windows v.6.1. It has been established that the T-cell component of the immune system in patients with active tuberculous granuloma characterized by increasing expression of CD25+ and HLA-DR on T-lymphocytes, CD95+ markers on T-helper, reduction of γδ-T-cells as well as increasing the number T-NK-lymphocytes and T-reg-cells. Tuberculous granuloma in the phase of moderate and subside activity accompanied by increased CD25+ and CD95+ expression on T-lymphocytes and T-helpers, as well as a decrease in HLA-DR expression on T-lymphocytes. Notes the intention expressed by the reduction in the number of NK-cells and increase γδ-T-cells associated with increases in the number of T-reg. These data allow the use of laboratory immunological parameters for indirect estimation tuberculous granuloma activity.

Transformation of the T-lymphocyte profile in peripheral blood upon resection of tuberculous lung granuloma

It is known that subpopulations of peripheral blood T-lymphocytes in patients with tuberculous lung granuloma may be used for determining patient's condition and monitoring pathological process. The aim of this study was to monitor the number and functional state of peripheral blood T-lymphocytes upon resection of tuberculous granuloma of the lungs. Twenty-two patients with tuberculous lung granuloma were examined, including 12 men (54.5%) and 10 women (45.5%). The patients with immune-dependent diseases and HIV were not eligible for the study. All these patients underwent resection of the granuloma by minimally invasive method. The blood samples were examined twice: before and 5-7 days after surgery, i.e., total T-cell numbers, (CD45+CD3+), their subpopulations were also determined (CD3+CD4+, CD3+CD8+, CD3+CD4-CD8-, CD3+CD4+CD8+, CD3brightCD4-, CD3+CD16+CD56+, CD3+HLA-DR+, CD3+CD25+, CD3+CD25+HLA-DR+), as well as CD3+CD25+/CD3+HLA-DR+ ratio, performed by means of Coulter Epicx XL instrument (Beckman Coulter, USA). In addition, the changes in B- and NK-cell numbers were studied. Due to small size of the groups, distribution was considered abnormal, and the Wilcoxon Matched-Pair Test was used. The differences were considered significant at pw 0.05. The statistical programs Statistica v. 12.5.192.7 (StatSoft, USA) and GraphPad Prism v. 8.0.2 (GraphPad Software, USA) were used in the work. Resection of tuberculous granuloma of the lungs was followed by redistribution of T-, B-, and NK-cell numbers, as compared with preoperative level. The B-cell population increased by 35.8%, whereas the number of NK-cells decreased by 18.9% (pw 0.05). Despite such significant changes in two other populations, total number of T-lymphocytes decreased only slightly: the changes ranged within 3.2% for absolute counts, and 3.8% (pw 0.05) for relative values. The changes of T-cell subpopulation profile were different. During the postsurgical period, a 4.8% decrease in the CD3+CD4+-cell number was observed, whereas reduction in CD3+CD8+ subpopulation was more significant, and amounted to 26.2% (pw 0.05). The number of doublepositive cells increased by 13.6% (pw 0.05); γσT-cell counts decreased by 20.8% (pw 0.05), and absolute number of TNK-cells increased by 32.4%. A decreased number of γσT-cells in early postoperative period could be considered a favorable criterion for assessing the patient's condition, since some previous studies provide information about increased number of these cells in patients with tuberculous granuloma. Increased HLA-DR expression on T-lymphocytes may be another favorable factor, since the patients with tuberculous granuloma are known to have lesser amounts of such cells in peripheral blood than healthy persons. In general, a search for expression of activation molecules showed that there is a decrease of T-cells expressing CD25+, and an increased number of CD3+HLA-DR+-cells. The T-lymphocyte population co-expressing both CD25+ and HLA-DR+ shifts to the normal ranges after the surgery. The obtained data are supposed for monitoring results of treatment in the patients.

A non-canonical type 2 immune response coordinates tuberculous granuloma formation and epithelialization

The central pathogen-immune interface in tuberculosis is the granuloma, a complex host immune structure that dictates infection trajectory and physiology. Granuloma macrophages undergo a dramatic transition in which entire epithelial modules are induced and define granuloma architecture. In tuberculosis, relatively little is known about the host signals that trigger this transition. Using the zebrafish-Mycobacterium marinum model, we identify the basis of granuloma macrophage transformation. Single-cell RNA-sequencing analysis of zebrafish granulomas and analysis of Mycobacterium tuberculosis-infected macaques reveal that, even in the presence of robust type 1 immune responses, countervailing type 2 signals associate with macrophage epithelialization. We find that type 2 immune signaling, mediated via stat6, is absolutely required for epithelialization and granuloma formation. In mixed chimeras, stat6 acts cell autonomously within macrophages, where it is required for epithelioid transformation and incorporation into necrotic granulomas. These findings establish the signaling pathway that produces the hallmark structure of mycobacterial infection.

Macrophage-specific responses to human- and animal-adaptedtubercle bacilli reveal pathogen and host factors drivingmultinucleated cell formation.

The Mycobacterium tuberculosis complex (MTBC) is a group of related pathogens that cause tuberculosis (TB) in mammals. MTBC species are distinguished by their ability to sustain in distinct host populations. While Mycobacterium bovis (Mbv) sustains transmission cycles in cattle and wild animals and causes zoonotic TB, M. tuberculosis (Mtb) affects human populations and seldom causes disease in cattle. The host and pathogen determinants underlying host tropism between MTBC species are still unknown. Macrophages are the main host cell that encounters mycobacteria upon initial infection, and we hypothesised that early interactions between the macrophage and mycobacteria influence species-specific disease outcome. To identify factors that contribute to host tropism, we analysed blood-derived primary human and bovine macrophages (hMϕ or bMϕ, respectively) infected with Mbv and Mtb. We show that Mbv and Mtb reside in different cellular compartments and differentially replicate in hMϕ whereas both Mbv and Mtb efficiently replicate in bMϕ. Specifically, we show that out of the four infection combinations, only the infection of bMϕ with Mbv promoted the formation of multinucleated giant cells (MNGCs), a hallmark of tuberculous granulomas. Mechanistically, we demonstrate that both MPB70 from Mbv and extracellular vesicles released by Mbv-infected bMϕ promote macrophage multinucleation. Importantly, we extended our in vitro studies to show that granulomas from Mbv-infected but not Mtb-infected cattle contained higher numbers of MNGCs. Our findings implicate MNGC formation in the contrasting pathology between Mtb and Mbv for the bovine host and identify MPB70 from Mbv and extracellular vesicles from bMϕ as mediators of this process.

TGFβ restricts expansion, survival, and function of T cells within the tuberculous granuloma

CD4 Tcell effector function is required for optimal containment of Mycobacterium tuberculosis (Mtb) infection. IFNɣ produced by CD4 Tcells is a key cytokine that contributes to protection. However, lung-infiltrating CD4 Tcells have a limited ability to produce IFNɣ, and IFNɣ plays a lesser protective role within the lung than at sites of Mtb dissemination. In a murine infection model, we observed that IFNɣ production by Mtb-specific CD4 Tcells is rapidly extinguished within the granuloma but not within unaffected lung regions, suggesting localized immunosuppression. We identified a signature of TGFβ signaling within granuloma-infiltrating Tcells in both mice and rhesus macaques. Selective blockade of TGFβ signaling in Tcells resulted in an accumulation of terminally differentiated effector CD4 Tcells, improved IFNɣ production within granulomas, and reduced bacterial burdens. These findings uncover a spatially localized immunosuppressive mechanism associated with Mtb infection and provide potential targets for host-directed therapy.

Retroperitoneoscopic nephrectomy versus open surgery for non-tuberculous pyonephrotic nonfunctioning kidney: a single-center experience.

BackgroundPatients with obstructive pyonephrotic nonfunctioning kidney (OPNK) often require simple nephrectomy for long-term severe clinical symptoms. We aimed to analyze the outcomes of retroperitoneal laparoscopy versus open surgery for OPNK.MethodsThe study included clinical data of 69 patients with non-tuberculous OPNK from January 2015 to June 2019 in a single center. The patients were divided into laparoscopic group (LS, N=33) and open surgery group (OS, N=36). Those whose pathological findings were xanthogranulomatous inflammation or tuberculous granuloma were excluded. Statistical analysis compared the two groups in terms of basic demographic characteristics, preoperative laboratory examination results, and intraoperative and postoperative observation indicators.ResultsThe results showed that non-tuberculous OPNK were more common in women (female/male =4:1). Compared with the LS group, patients in the OS group had higher white blood cells (WBC; P=0.010) and neutrophils (P=0.005) counts before surgery. The main clinical symptoms were low back pain, pyuria, and fever; among them, low back pain combined with pyuria was in the majority. More intraoperative hypotension events were observed in the OS group (P=0.007). Notably, subgroup analysis showed larger stone size happened in the OS group (OR 3.538, 95% CI, 1.337, 9.208). No statistical difference was found in the duration of surgery between the two groups while the length of postoperative hospitalization and retroperitoneal drainage, and postoperative blood transfusion rate increased significantly in the OS group. Postoperative use of non-steroidal anti-inflammatory drugs was more common in the LS group, while opioid analgesics were in the OS group (P=0.0006). There was no statistical difference in other complications.ConclusionsIn conclusion, considering the advantages of LS in terms of postoperative blood transfusion, surgical drainage and length of hospital stay, we recommend it for non-tubercular OPNK when the stone load of pyonephrosis side was less than 280 mm2 and the preoperative WBC and neutrophil count were within the normal range.

How I treat immune thrombocytopenia – a global view

How I treat immune thrombocytopenia – a global view

Radiation semiotics of tuberculous lesions of the hip joint

SummarySpecific tuberculous lesion of the hip joint is the second most common lesion among all forms of osteoarticular tuberculosis. Diagnosis of this lesion causes significant difficulties both in the presence and absence of the pul-monary process. This is due to the non-specificity of clini-cal and anamnestic signs, which leads to the erroneous diagnosis, viz. degenerative joint damage (coxarthrosis), and prolonged unjustified monitoring and treatment of such patients. Over the past 10 years, the widespread in-troduction of modern high-tech methods of radiation ex-amination (such as computer tomography and magnetic resonance imaging) into clinical practice allows for more detailed imaging of specific and non-specific changes in the hip joint, in contrast to radiography. The article presents the long-term experience of the Saint-Peters-burg State Research Institute of Phthisiopulmonology, Ministry of Healthcare, Russian Federation, modern diag-nostics of tuberculosis lesions of the hip joint, describes the features of the pathomorphology of the joint lesion (including in children of different age groups) which is the basis for radiation imaging of pathology. In adults, the primary localization of tuberculous granuloma is in the bones forming the acetabulum, where the red bone marrow is preserved, while in children, TB granuloma is formed in any of the bones forming the hip joint. The pos-sibilities of modern radiological methods of visualization of this pathology are described for their correct selection by the treating physicians in case of suspected hip tuber-culous lesion. Differential diagnostic signs of the most common hip diseases are presented: non-specific coxitis, aseptic necrosis of the femoral head, coxarthrosis, which will allow treating physicians and radiologists to correctly interpret the changes detected by radiation imaging methods when assessing changes in the hip joint.

Systems biology predicts that fibrosis in tuberculous granulomas may arise through macrophage-to-myofibroblast transformation.

Mycobacterium tuberculosis (Mtb) infection causes tuberculosis (TB), a disease characterized by development of granulomas. Granulomas consist of activated immune cells that cluster together to limit bacterial growth and restrict dissemination. Control of the TB epidemic has been limited by lengthy drug regimens, antibiotic resistance, and lack of a robustly efficacious vaccine. Fibrosis commonly occurs during treatment and is associated with both positive and negative disease outcomes in TB but little is known about the processes that initiate fibrosis in granulomas. Human and nonhuman primate granulomas undergoing fibrosis can have spindle-shaped macrophages with fibroblast-like morphologies suggesting a relationship between macrophages, fibroblasts, and granuloma fibrosis. This relationship has been difficult to investigate because of the limited availability of human pathology samples, the time scale involved in human TB, and overlap between fibroblast and myeloid cell markers in tissues. To better understand the origins of fibrosis in TB, we used a computational model of TB granuloma biology to identify factors that drive fibrosis over the course of local disease progression. We validated the model with granulomas from nonhuman primates to delineate myeloid cells and lung-resident fibroblasts. Our results suggest that peripheral granuloma fibrosis, which is commonly observed, can arise through macrophage-to-myofibroblast transformation (MMT). Further, we hypothesize that MMT is induced in M1 macrophages through a sequential combination of inflammatory and anti-inflammatory signaling in granuloma macrophages. We predict that MMT may be a mechanism underlying granuloma-associated fibrosis and warrants further investigation into myeloid cells as drivers of fibrotic disease.

Painful ophthalmoplegia - a hospital based prospective observational study from south Kerala

Introduction and Objectives: Painful ophthalmoplegia is a clinical syndrome due to various underlying causes. The objective of the study is to determine the underlying pathological entities responsible for this potentially fatal condition. Various primary headache syndromes, facial pain syndromes and post traumatic and postsurgical pain syndromes were ruled out clinically. Materials and Methods: 107 patients satisfying our research definition of painful opthalmoplegia were enrolled in this study. The data was collected and analyzed systematically. Results and Interpretation: The common etiological causes for painful ophthalmoplegia are idiopathic inflammation of orbit (22 patients /20.5%), Tolosa hunt syndrome (13 patients /11.21%) followed by orbital cellulitis (11 patients /10.28%) fungal granuloma and mononeuritis multiplex (10 patients each /9.34%) granulomatosis with polyangiitis and tuberculous granuloma (5patients each/4.67%). Conclusions: most cases of painful opthalmoplegia are amenable to medical management provided an early and prompt diagnosis is made using appropriate diagnostic tools. Keywords: Opthalmoplegia, Periorbital pain, Tolosa hunt syndrome, Superior orbital fissure, Cavernous sinus, Orbital apex, Fungal granuloma, Tuberculous granuloma.

An immunomodulatory role for the Mycobacterium tuberculosis Acr protein in the formation of the tuberculous granuloma.

The tuberculous granuloma is a compact aggregate of dormant bacteria encapsulated by host macrophages. It is commonly regarded as a product of the host defense designed to isolate infectious mycobacteria. This work demonstrates that exposure of macrophages to the Mtb heat-shock protein Acr leads to overproduction of the chemokine CXCL16, allowing the mycobacterium to exploit the innate immune response. This induction of chemokine expression is hypothesized to occur through activation of ADAM proteases, providing an immunomodulatory role for Mtb Acr in the formation of the granuloma.

Diagnostic value of CXCR3 and its ligands in spinal tuberculosis.

The present study aimed to investigate whether C-X-C motif chemokine receptor 3 (CXCR3) and its ligands may aid in diagnosing spinal tuberculosis (ST). A total of 36 patients with ST and 20 healthy controls were enrolled in the present study. The morphology of tuberculous granuloma in spinal tissue was observed by hematoxylin and eosin staining. The presence and distribution of acid-fast bacilli (AFB) were observed by Ziehl-Neelsen (ZN) staining. The protein expression of Ag85B, IFN-γ, and CXCR3 and its ligands (CXCL9 and CXCL10) were detected by immunohistochemistry. The levels of IFN-γ, CXCR3, CXCL9 and CXCL10 in peripheral blood of patients with ST and healthy controls were detected by reverse transcription-quantitative polymerase chain reaction and ELISA. Typical tuberculous granuloma was observed in the ST close tissue. AFB was observed by ZN staining. Positive expression of Ag85B was found in the surrounding caseous necrotic tissue of the tuberculous granuloma. IFN-γ, CXCR3, CXCL9 and CXCL10 were expressed in the tissue surrounding the tuberculous granuloma and their expression levels were markedly higher than those in the distant tissues. The levels of IFN-γ, CXCR3, CXCL9 and CXCL10 in peripheral blood of patients with ST were significantly higher than those in the healthy controls. Receiver operating characteristic curve analysis demonstrated that IFN-γ, CXCR3 and CXCL10 were more reliable diagnostic markers in terms of sensitivity and specificity. IFN-γ, CXCR3, CXCL9 and CXCL10 were highly expressed in the lesion tissue and peripheral blood samples of patients with ST, and IFN-γ, CXCR3 and its ligands aided in diagnosing ST.

Elevation in the counts of IL-35-producing B cells infiltrating into lung tissue in mycobacterial infection is associated with the downregulation of Th1/Th17 and upregulation of Foxp3+Treg

IL-35 is an anti-inflammatory cytokine and is thought to be produced by regulatory T (Treg) cells. A previous study found that IL-35 was upregulated in the serum of patients with active tuberculosis (ATB), and IL-35-producing B cells infiltrated to tuberculous granuloma of patients with ATB. Purified B cells from such patients generated more IL-35 after stimulation by antigens of Mycobacterium tuberculosis and secreted more IL-10. However, the function and the underlying mechanisms of IL-35-producing B cells in TB progression have not been investigated. The present study found that the expression of mRNA of IL-35 subsets Ebi3 and p35 was elevated in mononuclear cells from peripheral blood, spleen, bone marrow, and lung tissue in a mouse model infected with Mycobacterium bovis BCG, as tested by real-time polymerase chain reaction. Accordingly, the flow cytometry analysis showed that the counts of a subset of IL-35+ B cells were elevated in the circulating blood and in the spleen, bone marrow, and lung tissue in BCG-infected mice, whereas anti-TB therapy reduced IL-35-producing B cells. Interestingly, BCG infection could drive the infiltration of IL-35-producing B cells into the lung tissue, and the elevated counts of IL-35-producing B cells positively correlated with the bacterial load in the lungs. Importantly, the injection of exogenous IL-35 stimulated the elevation in the counts of IL-35-producing B cells and was associated with the downregulation of Th1/Th17 and upregulation of Foxp3+Treg.The study showed that a subset of IL-35-producing B cells might take part in the downregulation of immune response in mycobacterial infection.

Identification and Treatment of Tuberculosis in Pediatric Recipients of Allogeneic Hematopoietic Stem Cell Transplantation: Case Series and Review of the Literature.

BackgroundTuberculosis is a rare but life-threatening complication in patients who received hematopoietic stem cell transplantation. Early identification and intervention are essential to prevent severe complications.Case PresentationWe report two pediatric patients who developed tuberculosis after receiving hematopoietic stem cell transplantation for thalassemia major among 330 recipients between January 2012 and August 2019. Patient A presented with pulmonary tuberculosis and patient B presented with lymph node tuberculosis mimicking post-transplantation lymphoproliferative disorder associated with Epstein–Barr virus reactivation. Patient B’s condition was deteriorated, and shortly after the initiation of anti-tuberculosis therapy, the patient was found to have disseminated pulmonary tuberculosis. Patient B was also found to have tuberculous granulomas, an uncommon manifestation of tuberculosis causing severe airway obstruction. Both patients developed critical respiratory failure and required mechanical ventilation; however, they recovered with almost full resolution of pulmonary lesions after multiple treatment adjustments.ConclusionTuberculosis must be carefully evaluated in all pediatric patients that receive hematopoietic stem cell transplantation, regardless of the identification of other pathogens. Prophylactic tuberculosis therapy should be considered for high-risk pediatric hematopoietic stem cell transplantation recipients from tuberculosis-endemic regions.

Bactericidal Activity of Liposomal Form of Lytic Mycobacteriophage D29 in Cell Models of Tuberculosis Infection In Vitro.

The use of lytic mycobacteriophages to treat tuberculosis under conditions of acquired resistance to anti-tuberculosis drugs is one of the most practical ways to improve the effectiveness of therapy and reduce the spread of this disease. We studied the efficacy of antimycobacterial action of mycobacteriophage D29 encapsulated into 400-nm liposomes in cell models of tuberculosis infection in vitro. The antimycobacterial action of lytic mycobacteriophage D29 used in free or liposome-encapsulated forms was demonstrated on cell models of intracellularly infected RAW264.7 macrophages and tuberculous granuloma formed by human blood mononuclear cells. The experiments demonstrated pronounced advantage of liposomal form of mycobacteriophage according to the criteria of their penetration into macrophages and lysis of Mycobacterium tuberculosis in culture.

Solitary solid pulmonary nodules: a CT-based deep learning nomogram helps differentiate tuberculosis granulomas from lung adenocarcinomas.

To evaluate the differential diagnostic performance of a computed tomography (CT)-based deep learning nomogram (DLN) in identifying tuberculous granuloma (TBG) and lung adenocarcinoma (LAC) presenting as solitary solid pulmonary nodules (SSPNs). Routine CT images of 550 patients with SSPNs were retrospectively obtained from two centers. A convolutional neural network was used to extract deep learning features from all lesions. The training set consisted of data for 218 patients. The least absolute shrinkage and selection operator logistic regression was used to create a deep learning signature (DLS). Clinical factors and CT-based subjective findings were combined in a clinical model. An individualized DLN incorporating DLS, clinical factors, and CT-based subjective findings was constructed to validate the diagnostic ability. The performance of the DLN was assessed by discrimination and calibration using internal (n = 140) and external validation cohorts (n = 192). DLS, gender, age, and lobulated shape were found to be independent predictors and were used to build the DLN. The combination showed better diagnostic accuracy than any single model evaluated using the net reclassification improvement method (p < 0.05). The areas under the curve in the training, internal validation, and external validation cohorts were 0.889 (95% confidence interval [CI], 0.839-0.927), 0.879 (95% CI, 0.813-0.928), and 0.809 (95% CI, 0.746-0.862), respectively. Decision curve analysis and stratification analysis showed that the DLN has potential generalization ability. The CT-based DLN can preoperatively distinguish between LAC and TBG in patients presenting with SSPNs. • The deep learning nomogram was developed to preoperatively differentiate TBG from LAC in patients with SSPNs. • The performance of the deep learning feature was superior to that of the radiomics feature. • The deep learning nomogram achieved superior performance compared to the deep learning signature, the radiomics signature, or the clinical model alone.