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Blood Sep 2022Primary mediastinal large B-cell lymphoma (PMBCL) is a separate entity in the World Health Organization's classification, based on clinicopathologic features and a...
Primary mediastinal large B-cell lymphoma (PMBCL) is a separate entity in the World Health Organization's classification, based on clinicopathologic features and a distinct molecular signature that overlaps with nodular sclerosis classic Hodgkin lymphoma (cHL). Molecular classifiers can distinguish PMBCL from diffuse large B-cell lymphoma (DLBCL) using ribonucleic acid derived from paraffin-embedded tissue and are integral to future studies. However, given that ∼5% of DLBCL can have a molecular PMBCL phenotype in the absence of mediastinal involvement, clinical information remains critical for diagnosis. Studies during the past 10 to 20 years have elucidated the biologic hallmarks of PMBCL that are reminiscent of cHL, including the importance of the JAK-STAT and NF-κB signaling pathways, as well as an immune evasion phenotype through multiple converging genetic aberrations. The outcome of PMBCL has improved in the modern rituximab era; however, whether there is a single standard treatment for all patients and when to integrate radiotherapy remains controversial. Regardless of the frontline therapy, refractory disease can occur in up to 10% of patients and correlates with poor outcome. With emerging data supporting the high efficacy of PD1 inhibitors in PMBCL, studies are underway that integrate them into the up-front setting.
Topics: Hodgkin Disease; Humans; Lymphoma, Large B-Cell, Diffuse; Mediastinal Neoplasms; Mediastinum; Rituximab
PubMed: 34496020
DOI: 10.1182/blood.2020008376 -
Gut Microbes 2023With increasing knowledge about the gut - bone axis, more studies for treatments based on the regulation of postmenopausal osteoporosis by gut microbes are being...
BACKGROUND
With increasing knowledge about the gut - bone axis, more studies for treatments based on the regulation of postmenopausal osteoporosis by gut microbes are being conducted. Based on our previous work, this study was conducted to further investigate the therapeutic effects of GG (LGG) on ovariectomized (OVX) model rats and the immunological and microecological mechanisms involved.
RESULTS
We found a protective effect of LGG treatment in OVX rats through changes in bone microarchitecture, bone biomechanics, and CTX-I, PINP, Ca, and RANKL expression levels. LGG was more advantageous in promoting osteogenesis, which may be responsible for the alleviation of osteoporosis. Th17 cells were imbalanced with Treg cells in mediastinal lymph nodes and bone marrow, with RORγt and FOXP3 expression following a similar trend. TNF-α and IL-17 expression in colon and bone marrow increased, while TGF-β and IL-10 expression decreased; however, LGG treatment modulated these changes and improved the Th17/Treg balance significantly. Regarding the intestinal barrier, we found that LGG treatment ameliorated estrogen deficiency-induced inflammation and mucosal damage and increased the expression of GLP-2 R and tight junction proteins. Importantly, 16S rRNA sequencing showed a significant increase in the Firmicutes/Bacteroidetes ratio during estrogen deficiency. Dominant intestinal flora showed significant differences in composition; LGG treatment regulated the various genera that were imbalanced in OVX, along with modifying those that did not change significantly in other groups with respect to the intestinal barrier, inflammation development, and bile acid metabolism.
CONCLUSIONS
Overall, LGG ameliorated estrogen deficiency-induced osteoporosis by regulating the gut microbiome and intestinal barrier and stimulating Th17/Treg balance in gut and bone.
Topics: Rats; Animals; Gastrointestinal Microbiome; Lacticaseibacillus rhamnosus; T-Lymphocytes, Regulatory; Th17 Cells; RNA, Ribosomal, 16S; Osteoporosis; Estrogens; Inflammation; Probiotics
PubMed: 36941563
DOI: 10.1080/19490976.2023.2190304 -
Immunity Feb 2023Local environmental factors influence CD8 T cell priming in lymph nodes (LNs). Here, we sought to understand how factors unique to the tumor-draining mediastinal LN...
Local environmental factors influence CD8 T cell priming in lymph nodes (LNs). Here, we sought to understand how factors unique to the tumor-draining mediastinal LN (mLN) impact CD8 T cell responses toward lung cancer. Type 1 conventional dendritic cells (DC1s) showed a mLN-specific failure to induce robust cytotoxic T cells responses. Using regulatory T (Treg) cell depletion strategies, we found that Treg cells suppressed DC1s in a spatially coordinated manner within tissue-specific microniches within the mLN. Treg cell suppression required MHC II-dependent contact between DC1s and Treg cells. Elevated levels of IFN-γ drove differentiation Treg cells into Th1-like effector Treg cells in the mLN. In patients with cancer, Treg cell Th1 polarization, but not CD8/Treg cell ratios, correlated with poor responses to checkpoint blockade immunotherapy. Thus, IFN-γ in the mLN skews Treg cells to be Th1-like effector Treg cells, driving their close interaction with DC1s and subsequent suppression of cytotoxic T cell responses.
Topics: Humans; CD8-Positive T-Lymphocytes; Interferon-gamma; Lung Neoplasms; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Regulatory
PubMed: 36736322
DOI: 10.1016/j.immuni.2023.01.010 -
Immunity Oct 2023Lung-resident memory B cells (lung-BRMs) differentiate into plasma cells after reinfection, providing enhanced pulmonary protection. Here, we investigated the...
Lung-resident memory B cells (lung-BRMs) differentiate into plasma cells after reinfection, providing enhanced pulmonary protection. Here, we investigated the determinants of lung-BRM differentiation upon influenza infection. Kinetic analyses revealed that influenza nucleoprotein (NP)-specific BRMs preferentially differentiated early after infection and required T follicular helper (Tfh) cell help. BRM differentiation temporally coincided with transient interferon (IFN)-γ production by Tfh cells. Depletion of IFN-γ in Tfh cells prevented lung-BRM differentiation and impaired protection against heterosubtypic infection. IFN-γ was required for expression of the transcription factor T-bet by germinal center (GC) B cells, which promoted differentiation of a CXCR3 GC B cell subset that were precursors of lung-BRMs and CXCR3 memory B cells in the mediastinal lymph node. Absence of IFN-γ signaling or T-bet in GC B cells prevented CXCR3 pre-memory precursor development and hampered CXCR3 memory B cell differentiation and subsequent lung-BRM responses. Thus, Tfh-cell-derived IFN-γ is critical for lung-BRM development and pulmonary immunity, with implications for vaccination strategies targeting BRMs.
Topics: Humans; T-Lymphocytes, Helper-Inducer; Interferon-gamma; Memory B Cells; T Follicular Helper Cells; Influenza, Human; Germinal Center; Cell Differentiation; Receptors, CXCR3
PubMed: 37699392
DOI: 10.1016/j.immuni.2023.08.015 -
Zhongguo Dang Dai Er Ke Za Zhi =... Jul 2019Patients with pertussis can have a variety of complications, including pneumonia and subconjunctival hemorrhage. Severe complications, such as pulmonary hypertension and... (Review)
Review
Patients with pertussis can have a variety of complications, including pneumonia and subconjunctival hemorrhage. Severe complications, such as pulmonary hypertension and encephalopathy, can be life-threatening. Younger children with pertussis may lack the characteristic clinical manifestations of pertussis, and therefore, a deeper understanding of the complications of pertussis may help to improve the diagnosis, treatment, and prognosis of pertussis. However, there is still no standard for the diagnosis and treatment of pertussis complications, and there are great differences in diagnostic name, basis, and data used in different reports. This article reviews the complications of pertussis which have been reported so far, such as pulmonary complications (pneumonia, pulmonary hypertension, pneumothorax, and mediastinal or subcutaneous emphysema), fractures, hernias, circulatory system complications, nervous system complications (convulsion, encephalopathy, hemorrhage, and hematoma), urinary system complications, and secondary infections, so as to provide a reference for the clinical diagnosis and treatment of pertussis complications, scientific research on pertussis complications, and the promotion of standardized diagnosis and treatment of pertussis complications.
Topics: Brain Diseases; Humans; Pneumonia; Prognosis; Seizures; Whooping Cough
PubMed: 31315774
DOI: 10.7499/j.issn.1008-8830.2019.07.018 -
Turk Gogus Kalp Damar Cerrahisi Dergisi Jan 2024Mediastinal tumors are the most common thoracic tumor in the pediatric population. They include a spectrum of tumors, and most are malignant. These lesions can be... (Review)
Review
Mediastinal tumors are the most common thoracic tumor in the pediatric population. They include a spectrum of tumors, and most are malignant. These lesions can be anatomically and radiologically classified by means of compartments; anterior, middle, and posterior. Symptoms, signs, localization of the tumor, age of the child, and tumor markers are key points of diagnosis. Surgical approaches are typically needed for diagnosis, but sometimes tru-cut needle biopsies may be sufficient. Mediastinoscopy, mediastinotomy, and video-assisted thoracoscopic surgery may be used in the diagnostic workup of mediastinal tumors in children as they are used in adults. Frequently, diagnosis and treatment are both established by means of surgery. Surgery remains the mainstay of treatment of most benign and malignant nonlymphoid tumors. Combined modality of treatment incorporating chemotherapy and radiotherapy is often required in malignant tumors and is associated with high survival rates in these patients.
PubMed: 38584788
DOI: 10.5606/tgkdc.dergisi.2024.25799 -
Pediatric Radiology May 2023Autosomal dominant mutations in the coatomer-associated protein alpha (COPA) gene cause an immune dysregulation disorder associated with pulmonary hemorrhage, lymphoid...
BACKGROUND
Autosomal dominant mutations in the coatomer-associated protein alpha (COPA) gene cause an immune dysregulation disorder associated with pulmonary hemorrhage, lymphoid hyperplasia, arthritis, and glomerulonephritis.
OBJECTIVE
To describe the thoracic, musculoskeletal, and renal imaging findings of COPA syndrome with a focus on the evolution of the pulmonary findings.
MATERIALS AND METHODS
With approval of the Institutional Review Board, consensus retrospective review of findings on chest radiography and computed tomography (CT), musculoskeletal radiography and magnetic resonance imaging (MRI), and renal ultrasound (US) was performed for pediatric COPA syndrome patients. COPA syndrome patients < 18 years of age presenting between 1992 and 2019 were identified from an institutional rheumatology registry.
RESULTS
Twelve pediatric COPA syndrome patients (mean age of 6.5 years at first imaging exam; 6 females) were identified. Imaging exams available for review included 45 chest CT exams on 12 patients, 37 musculoskeletal exams on 4 patients, and 10 renal US exams on 5 patients. All 12 had abnormal chest CT exams, with findings including ground-glass opacities (12/12), cysts (8/12), septal thickening (9/12), nodules (8/12), fibrosis (7/12), crazy-paving (2/12), consolidation (1/12), hilar/mediastinal lymphadenopathy (11/12), and chest wall deformity (5/12). Nine had at least one follow-up chest CT, which showed improvement in nodules (7/9), ground-glass opacities (4/9), and lymphadenopathy (9/9), but worsening of septal thickening (3/9), cyst formation (3/9), and fibrosis (3/9). Four had musculoskeletal imaging revealing synovitis (2/4), bone erosions (1/4), tenosynovitis (1/4), enthesitis (1/4), and subcutaneous nodules (1/4). Five had at least one renal US, revealing renal size abnormalities (4/5) and cortical hyperechogenicity (3/5).
CONCLUSION
The most prevalent imaging finding of COPA syndrome is diffuse lung disease related to early childhood-onset recurrent pulmonary hemorrhage and lymphoid hyperplasia that may progress to pulmonary fibrosis. Other imaging findings manifesting later in childhood or adolescence relate to arthritis and glomerulonephritis.
Topics: Child; Female; Humans; Arthritis; Coatomer Protein; Fibrosis; Glomerulonephritis; Hemorrhage; Hyperplasia; Kidney Diseases; Lung; Lung Diseases; Lymphadenopathy; Retrospective Studies; Syndrome; Male
PubMed: 36746811
DOI: 10.1007/s00247-023-05600-1 -
Japanese Journal of Clinical Oncology May 2021Previous reports on transarterial treatment for lung cancer were reviewed. The bronchial arterial infusion therapy has a long history since 1964. Better local control... (Review)
Review
Previous reports on transarterial treatment for lung cancer were reviewed. The bronchial arterial infusion therapy has a long history since 1964. Better local control with less doses of anti-neoplastic agents was warranted by trying transarterial administration to lung and mediastinal tumors. It is reported that both primary and metastatic tumors are fed by bronchial or other systemic arteries. The bronchial arterial embolization for hemoptysis has been introduced for clinical practice since 1973. Hemoptysis by not only benign but also malignant diseases has been well controlled by embolization. In recent decades, the technical elements for transarterial treatments have markedly improved. They make it possible to carry out precise procedures of selective catheter insertion to the tumor relating arteries. Current concepts of transarterial treatment, technical aspects and treatment outcomes are summarized. Tentative result from chemo-embolization for advanced lung cancer using recent catheter techniques was also described. It provides favorable local control and survival merits. It is considered that a population of lung cancer patients can benefit from transarterial management using small doses of anti-neoplastic agents, with less complications and less medical costs.
Topics: Bronchial Arteries; Catheterization, Peripheral; Disease Progression; Embolization, Therapeutic; Hemoptysis; Humans; Lung; Lung Neoplasms; Treatment Outcome
PubMed: 33855367
DOI: 10.1093/jjco/hyab050