Mediastinal Nodes Research Articles

Inhibition of B cell activation by Ibrutinib improves cardiac function in experimental myocardial infarction in mice

Abstract Background Bruton's tyrosine kinase (BTK) is a key downstream mediator of B cell receptor (BCR) signaling. Upon BCR cross-linking, phosphorylated BTK modulates B cell activation, proliferation, and differentiation. Ibrutinib, which is clinically used in B-cell malignancies, irreversibly binds to the BTK kinase domain and blunts downstream BTK signaling. Purpose Here, we aimed to monitor B cell dynamics and activation in experimental myocardial infarction (MI) in mice, and evaluate the effect of B cell inhibition by Ibrutinib in cardiac function. Methods MI was induced in male 10-week-old C57BL/6 mice by permanent LAD ligation and Ibrutinib (25 mg/kg/day) was given in the drinking water. After 3, 7, 14, and 28 days, single cell suspensions were prepared for flow cytometry from peripheral blood, spleen, mediastinal lymph nodes (MLNs), and the bone marrow, as well as from the remote and infarcted myocardium. Total B cells and B cell subsets were quantified in the different locations by flow cytometry and B cell activation was monitored by BTK551 phosphorylation. After 28 days, cardiac function was evaluated by echocardiography. Results We found that total B cell numbers decrease in blood and spleen, and increase in MLNs, while plasma cells and plasmablasts increased in the infarcted heart on day 7 and 14 after MI. In the bone marrow, hematopoietic stem cells (HSC) increase after MI, while common lymphoid progenitors (CLP) and early-stage B cell progenitors (pre-pro and pro B cells) peak at day 7 after MI. The later-stage B cell progenitors (pre and immature B cells) showed a biphasic response, with an early decrease after 7 days and a later increase on day 14. Compared to the control group (vehicle), Ibrutinib treatment decreased B cell numbers in MLN and spleen by 27% and 14%, respectively, as well as decreased mature B cells by 28% in the bone marrow on day 28 after MI. Both BTK expression and phosphorylation in pro-B cells were inhibited by Ibrutinib by 8% and 15%, respectively. The inhibition of BTK phosphorylation was also evident in MLNs and spleen. Notably, Ibrutinib-treated mice showed an improved cardiac function on day 28 after MI, with stroke volume (SV) elevated by 41%, left ventricular ejection fraction (LVEF) elevated from 20% to 36% (p < 0.05), and fractional shortening (FS) elevated from 8.8% to 17.59% (p < 0.05). Conclusion Experimental MI leads to B cell lymphopoiesis in the bone marrow, mobilization into the infarcted myocardium, and activation in peripheral lymphoid organs. Ibrutinib treatment inhibits B cell development in the bone marrow, as well as B cell activation in peripheral lymphoid organs, and improves cardiac function post MI. Our data provides a meaningful insight for targeting B cells for the clinical treatment of patients with MI.Figure

Lymphatic-macrophage crosstalk during neonatal mouse heart regeneration and transition to fibrotic repair

Abstract Background In adult mice, myocardial infarction (MI) activates the cardiac lymphatics, which undergo sprouting angiogenesis (lymphangiogenesis) and function to drain interstitial fluid and traffic macrophages to mediastinal lymph nodes (MLNs). This prevents oedema and reduces inflammatory immune cell content to improve cardiac function. Purpose Given the importance of the adult cardiac lymphatics in macrophage clearance after injury, we investigated their role across the neonatal "regenerative window". At post-natal day 1 (P1) neonatal mice fully regenerate their heart following MI, in a macrophage-dependent manner, whereas equivalent injury at day 7 (P7) leads to scarring driven by pro-fibrotic macrophages. We hypothesised that lymphatics respond and function differently during this "window," to clear macrophage-specific subtypes depending upon their requirement for regeneration versus fibrotic repair. Methods & Results Extensive lymphatic growth and sprouting was evident in intact neonatal hearts until P16, with strain-dependent developmental differences. The response to injury revealed limited lymphangiogenesis and minimal clearance of macrophages from P1 compared to P7 infarcted hearts, as determined by adoptive transfer experiments and monitoring of cleared macrophages to MLNs. This is coincident with maturation of lymphatic endothelial cell junctions across the neonatal period via transition from "zipper" (impermeable) to "button" (permeable) -type junctions. To gain molecular insight into the mechanisms underpinning lymphatic endothelium macrophage interactions at P1 versus P7, we generated unbiased single cell RNA sequencing datasets from neonatal heart samples after MI and observed altered signalling between lymphatic endothelial cells and macrophages across the neonatal period, including altered expression of the lymphangiocrine factor Reelin (RELN). Finally, in mice lacking the lymphatic endothelial receptor-1 (LYVE1), that exhibit impaired transmigration of interstitial macrophages to lymphatic vessels, magnetic resonance imaging (MRI) revealed a surprising impaired functional outcome in P1 mice 28 days post-MI. Given our observations that pro-regenerative macrophages at P1 are not trafficked, this suggested a distinct role for LYVE1 in tissue-resident (TR) macrophages, consistent with its expression in developing and post-natal hearts. Macrophage-specific deletion of Lyve1 during neonatal heart injury revealed impaired heart regeneration, characterised by reduced neovascular response and function, suggesting a hitherto unappreciated role for LYVE1 in regulating the pro-regenerative function of TR macrophages. Conclusions Collectively, we reveal that cardiac lymphatics are developmentally compromised for immune cell clearance in early neonates, which enables retention of pro-regenerative TR macrophages, and that LYVE1 plays an essential role in TR macrophages enabling heart regeneration via the induction of coronary angiogenesis.

Sarcoidosis of mediastinal and abdominal (visceral) lymph nodes, lungs, liver, goldbladder, spleen, complicated by phlegmonous cholecystitis

The article contains a description of generalized sarcoidosis diagnosed morphologically after cholecystectomy for phlegmonous cholecystitis.

Differences of in vitro immune responses between patent and pre-patent Litomosoides sigmodontis-infected mice are independent of the filarial antigenic stimulus used.

Lymphatic filariasis and onchocerciasis are neglected tropical diseases and cause significant public health problems in endemic countries, especially in sub-Saharan Africa. Since the human parasites are not viable in immune-competent mice, animal models have been developed, among them Litomosoides sigmodontis which permits a complete life cycle in BALB/c mice, including the development of patent infections with circulating microfilariae (Mf, the worm's offspring). To investigate the immunomodulatory properties of helminths in vitro, antigenic extracts can be prepared from different life cycle stages of the L. sigmodontis model, including adult worms, but the methods to prepare these antigens differ between research groups. This study analyzed whether different centrifugation methods during the preparation of an antigenic extract, the gender of used worms, or the different fractions (soluble or pellet) altered filarial-specific CD4+ Tcell responses. These cells were isolated from pre-patent or patent/chronic infected mice, hence those without and those with Mf, respectively. Ex vivo immune responses were compared at these two different time points of the infection as well as the parasitic parameters. Worm burden and cell infiltration were elevated in the thoracic cavity (TC) and draining mediastinal lymph nodes at the pre-patent stage. Within the TC, eosinophils were significantly up-regulated at the earlier time point of infection which was further reflected by the eosinophil-related eotaxin-1 levels. Regarding the production of cytokines by re-stimulated CD4+ T cells in the presence of different antigen preparations, cytokine levels were comparable for all used extracts. Our data show that immune responses differ between pre-patent and patent filarial infection, but not in response to the different antigenic extracts themselves.

Cryoprobe biopsy versus mechanical biopsies in pulmonary diagnostics.

Biopsy tools have been essential in improving the diagnostic accuracy of bronchoscopic procedures. Of these tools, cryobiopsy has emerged as a promising technique for diagnosing thoracic diseases. This review summarizes the existing data comparing cryobiopsies to other mechanical biopsy methods for sampling endobronchial, parenchymal, and mediastinal targets. Initially adopted for managing airway stenoses, the use of cryoprobes has expanded to diagnosing endobronchial lesions, parenchymal opacities, and mediastinal lymph node pathologies. Studies have demonstrated that cryobiopsy offers a higher diagnostic yield than forceps biopsy alone. By leveraging the Joule-Thomson effect to freeze and collect larger tissue samples compared to traditional methods, cryobiopsy improves diagnostic accuracy and helps in better characterizing the nature of the lesions. While the risk of complications, such as pneumothorax and hemorrhage are comparable to, or higher than traditional biopsy methods, cryobiopsy's enhanced diagnostic capabilities make it a valuable tool in the assessment of pulmonary disease. Compared with other mechanical biopsy techniques, cryoprobe biopsies significantly enhance the diagnostic yield for endobronchial lesions, interstitial lung disease, pulmonary nodules, and mediastinal lymph nodes.

Neurosarcoidosis Masquerading as Spinal Stenosis.

A 65-year-old woman was admitted to the neurology department with a suspected demyelinating disease due to complaints of progressive pain and weakness in both upper and lower limbs, as well as urinary incontinence. MRI of the spine revealed complex disc osteophyte with compression of the spinal cord in the cervical and lumbar spine at several vertebral levels, and localized enhancement in the cervical spine at the site of maximal spinal canal stenosis. During her hospitalization, the patient underwent extensive evaluation to rule out any systematic inflammatory diseases, infections, and malignancy. Chest CT revealed bilateral mediastinal lymphadenopathy. Transbronchial mediastinal lymph node biopsy showed numerous non-necrotizing granulomas without evidence of malignancy. After a thorough and careful exclusion of a demyelinating, infectious, and paraneoplastic myelopathies, and based on clinical, radiographic, and pathological findings, the patient was diagnosed with both neurosarcoidosis and spondylotic myelopathy. She was then treated for neurosarcoidosis, including glucocorticosteroids, azathioprine, and a biosimilar of the anti-TNF alpha agent infliximab, resulting in both clinical and radiographic improvement. Intramedullary spinal neurosarcoidosis is very rare and may present with clinical features of spondylotic myelopathy, with typical imaging findings occurring only in areas of spinal canal stenosis.

ALK-positive Anaplastic Large Cell Lymphoma Involving the Spinal Cord

Abstract Introduction/Objective ALK-positive anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for approximately 3% of non-Hodgkin lymphoma cases in the adult population. Lymph node involvement is most commonly seen, followed by extra-nodal involvement of the skin, soft tissue, and bone. Central nervous system involvement is rare at the time of diagnosis. This case study features a patient with systemic ALK-positive ALCL involving multiple nodal and extra-nodal sites, most notably the spinal cord. Methods/Case Report A 22-year-old female presented to the hospital with worsening back pain accompanied by neurological symptoms. MRI scans of her spine revealed extensive patchy abnormal marrow signal with enhancement of the thoracolumbar vertebrae (T1-L2) and adjacent extension into the spinal canal (T3-T7, T10-L1, L3-S1) and paraspinal soft tissues. A laminectomy of the T5-T7 and T11-T12 levels was performed for surgical decompression, and epidural and paraspinal resection specimens were submitted. These specimens, along with an excisional axillary lymph node biopsy, demonstrated ALK-positive ALCL after comprehensive immunohistochemical studies. In-situ hybridization for EBV was negative. CHOP therapy was initiated, but treatment was complicated by Candidemia and disseminated intravascular coagulation. The patient rapidly declined and passed away less than a month after hospital admission. At autopsy, enlargement of lymph nodes, the left ovary (17.8 g), and spleen (383.6 g) were noted on gross examination. A solid, white-tan lesion (2.1 x 0.9 x 0.8 cm) was found in the left ovary. Necrosis and infiltrates of large, pleomorphic lymphoid cells with irregular nuclear contours and prominent nucleoli were seen on microscopic examination of the spinal cord and leptomeninges, vertebral bone marrow, mediastinal lymph nodes, spleen, and left ovary. Consistent with previously submitted surgical specimens, the viable neoplastic cells stained strongly positive for ALK-1, CD4, and CD30. Results (if a Case Study enter NA) NA Conclusion This case study highlights an atypical presentation of ALCL with a fatal outcome. Given the availability of effective treatment options, prompt diagnosis is crucial to improving survival outcomes. Additional research is necessary to elucidate the clinical and pathological features of ALCL. The differential for back pain is broad, but including this entity for patients with similarly insidious clinical presentations can prevent a delay in diagnosis that allows for rapid progression of disease.

Synchronous endometrial and minor salivary gland carcinomas – role of molecular diagnostics amid lack of clinical suspicion

Abstract Introduction/Objective Synchronous malignancies account for 3-5% of all tumor diagnoses but can be challenging to detect if one or both tumors are rare histologic subtypes and clinical suspicion is lacking. Molecular diagnostics are critical for accurate diagnosis in these difficult cases to guide appropriate patient care. Methods/Case Report We report the case of a 49-year-old female who was diagnosed with a high-grade, mixed- histology endometrial adenocarcinoma a few years back. She was found to have hilar and mediastinal nodal carcinoma of uncertain differentiation a couple of months after her initial diagnosis, clinically labelled as metastatic endometrial carcinoma. Following neoadjuvant chemotherapy, her hysterectomy showed complete pathologic response, and was found to be POLE ultramutated on NGS. Follow-up PET scan in 2023 showed progression of hilar/endobronchial thickening, as well as interval increase in size of mediastinal nodes, again presumed to be endometrial metastases, despite the POLE mutant status. Repeat sampling was performed from both the sites, along with comprehensive molecular profiling. Cytology from the nodes and surgical pathology from the endobronchial lesion showed similar morphology consisting of hyperchromatic basaloid cells in cribriform arrangement with tubular structures containing myxoid stromal material, negative for PAX-8, ER, p40, and TTF1 immunostains, inconsistent with endometrial metastasis. Molecular studies including FISH and NGS showed MYB1::NFIB fusion characteristic of adenoid cystic carcinoma and absence of POLE mutation, definitively refuting the clinically suspected progression of endometrial metastasis. Molecular testing confirmed that the endobronchial tumor and mediastinal nodal involvement were caused by a second primary, distinct from her POLE-ultramutated endometrial carcinoma which disappeared with chemotherapy. Her extended molecular workup also revealed a pathogenic mutation in BRIP1, suggesting a genetic cancer predisposition syndrome requiring referral for genetic counseling. Results (if a Case Study enter NA) NA Conclusion Molecular pathology is an invaluable tool for unravelling diagnostic complexity. Pathologists must integrate cytomorphology, molecular genetics and knowledge of cancer biology to steer the clinical teams towards the best patient care.

Regularity and correlation analysis of regional lymph node metastasis in nonoperative patients with non-small cell lung cancer based on positron emission tomography/computed tomography images

BackgroundDefinitive concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced, inoperable non-small cell lung cancer (NSCLC). Previous studies have mainly focused on examining local failure and recurrence patterns after surgery and the principles of lymph node metastasis (LNM) in surgical candidates with NSCLC. However, these studies were just only able to guide postoperative radiotherapy (PORT) and the patterns of LNM in patients with resected NSCLC was inadequate to represent that in locally advanced inoperable NSCLC patients for guiding target volume delineation of CCRT. In this study, we aimed to analyze the metastasis regularities and establish the correlations between different lymph node levels in NSCLC patients without any intervention using positron emission tomography/computed tomography (PET/CT) images.MethodsOverall, 358 patients with N1–N3 NSCLC admitted in our hospital between 2018 and 2022 were retrospectively analyzed. The diagnosis of metastatic lymph nodes was reviewed and determined using the European Organization for Research and Treatment of Cancer standard and the standardized value of the PET/CT examination. Univariate and multivariate analysis were performed to investigate the correlations between the different levels were evaluated by using of the chi-square test and logistic regression model.ResultsThe lymph nodes with the highest metastasis rates in patients with left lung cancer were in order as follows: 10L, 4L, 5, 4R, and 7; while in those with right lung cancer they were 10R, 4R, 7, 2R, and 1R. Notably, we found left lung patients were more likely to have contralateral hilar, mediastinal and supraclavicular lymph nodes involved, and the right lung group exhibited a higher propensity for ipsilateral mediastinum and supraclavicular lymph node invasion. Furthermore, correlation analysis revealed there were significant correlative patterns in the LNM across different levels.ConclusionsThis study elucidated the patterns of primary LNM in patients with NSCLC who had not undergone surgery (without any treatment interventions) and the correlations between lymph node levels. These findings were expected to provide useful reference for target volume delineation in definitive concurrent chemoradiotherapy in locally advanced NSCLC patients.

7200 A Unique Case Of Hypercalcemia From Primary Hyperparathyroidism With Thymoma And Concurrent Pulmonary Tuberculosis

Abstract Disclosure: S. Jing Hang Randy: None. L. Huiling: None. Background: Several case reports have reported the rare association of thymoma with primary hyperparathyroidism. We describe a unique case of hypercalcemia with such association but was also found to have concurrent pulmonary tuberculosis. Clinical Case: A 50-year-old Indian female with a significant history of anterior mediastinal mass underwent median sternotomy with mass resection and was found to have peri-operative hypercalcemia. Her only complaint was chronic cough. Initial investigations showed high adjusted calcium 2.78 mmol/L (2.15– 2.50 mmol/L), normal phosphate 1.1 mmol/L (0.8– 1.4 mmol/L) and high PTH 24.7 pmol/L (1.6– 6.9 pmol/L). Apart from the mediastinal mass, a whole-body CT scan showed multiple prominent mediastinal lymph nodes with non-specific subcentimetre lung nodules. The post-operative finding was a Type AB thymoma with necrotizing granulomatous inflammation in adjacent station I lymph node. Differentials for patient’s hypercalcemia included primary hyperparathyroidism, malignancies such as lymphomas and infectious causes in particular tuberculosis. Her 25-OH Vitamin D was low at 9 ug/L (30 - 100 ug/L), 1,25-dihydroxyvitamin D was elevated at 205 pg/mL (18-64 pg/mL) while creatinine, ALP, serum ACE and PTHrP were unremarkable. She was subsequently admitted for worsening hypercalcemia, fever and left pleural effusion with generalized lymphadenopathy where she underwent an Endobronchial Ultrasound-guided Transbronchial Needle Aspirate of station IV lymph nodes before being started on tuberculosis treatment. The AFB culture showed Mycobacterium Tuberculosis Complex thereafter. Parathyroid sonography revealed a 2.2cm x 0.9cm x 0.8cm lobulated hypoechoic lesion posterior to the inferior pole of left thyroid lobe. However, a confirmatory sestamibi scan could only be done 6 weeks post-thymectomy given the raw surgical bed, with a possibility of false-negative result for cervical parathyroid adenoma given a recent thymectomy. It subsequently showed a hyperfunctioning left inferior parathyroid nodule with no other suspicious focal uptake in the neck or mediastinum. Patient underwent a focused left parathyroidectomy. Histology showed features consistent with parathyroid adenoma. A stepwise trajectory of her calcium normalization was observed with hydration, intravenous zoledronic acid for her osteoporosis, tuberculosis treatment, adjuvant radiation therapy for her thymoma with margins involvement, and parathyroidectomy. Conclusion: This case illustrates the challenges faced while considering localizing scans for primary hyperparathyroidism with recent thymectomy given the common embryological origin of inferior parathyroid and thymus. It also demonstrates the possible co-existence of separate pathologies in hypercalcemia and the need to exercise prudent clinical judgement to further evaluate for these various etiologies. Presentation: 6/2/2024

Low false-positive lymph nodes for 18F-fibroblast activation protein inhibitors PET/computed tomography in preoperative staging of patients with nonsmall cell lung cancer.

This study aimed to evaluate the diagnostic accuracy of 18F-fibroblast activation protein inhibitor (FAPI) PET/computed tomography (CT) in identifying primary tumors and mediastinal lymph node metastases in nonsmall cell lung cancer (NSCLC), with histopathological findings serving as the reference standard. Nineteen patients underwent preoperative 18F-FAPI PET/CT and subsequent surgery; of these, 13 also underwent 18F-fluorodeoxyglucose (FDG) PET/CT within 1 week. The diagnostic accuracy of primary tumors and lymph node metastases was evaluated for both modalities. Semiquantitative parameters, including maximum standardized uptake values (SUVmax) and target-to-background ratios (TBRs), for both primary tumors and lymph node metastases were assessed for both modalities. For primary tumors, 18 of 19 (94.7%) showed positive results on 18F-FAPI PET/CT scans. In 13 patients who also underwent 18F-FDG PET/CT, 18F-FAPI PET/CT demonstrated a higher detection rate compared with 18F-FDG PET/CT (100% vs. 69.1%). The overall accuracy of lymph node assessment with 18F-FAPI PET/CT (95.9-97.1%) was significantly higher compared to 18F-FDG PET/CT (51.0%). Malignant lymph nodes exhibited significantly higher SUVmax and TBR on 18F-FAPI scans (SUVmax: 7.0 vs. 0.9, P < 0.001; TBRmuscle: 5.0 vs. 0.8, P < 0.001) than on 18F-FDG scans (SUVmax: 3.9 vs. 1.8, P = 0.01), except for the liver TBR on 18F-FDG scans (TBRliver: 1.8 vs. 1.0, P = 0.055). 18F-FAPI could be utilized in the preoperative staging of NSCLC to mitigate the incidence of false positives associated with 18F-FDG, due to its higher accuracy in identifying mediastinal lymph node metastasis.

Cadmium-induced lung injury disrupts immune cell homeostasis in the secondary lymphoid organs in mice

Cadmium is a well-known toxic heavy metal that poses significant health risks, particularly through inhalation, smoking, and the consumption of contaminated food. Exposure to cadmium is linked to the development and exacerbation of chronic lung diseases such as pulmonary fibrosis and chronic obstructive pulmonary disease (COPD). This study investigated the systemic effects of intratracheal cadmium chloride (0.5mg/kg) instillation in C57BL/6 mice. All parameters, including inflammation assessment, lung function evaluation (using Flexi-vent), and immunophenotyping of T-cells in secondary lymphoid organs (spleen and mediastinal lymph nodes), were analyzed 14 days after Cd exposure. The results demonstrated that cadmium exposure led to significant immune cell infiltration in bronchoalveolar lavage (BAL) fluid, altered pro-inflammatory cytokine levels, and was associated with impaired lung function, characterized by increased lung resistance and Newtonian resistance. Analysis of T-cell populations revealed no significant changes in total T-cells in mediastinal lymph nodes and spleen, but a decrease in CD4+ T-cells and an increase in CD8+ T-cells were observed. These findings suggest that cadmium disrupts T-cell homeostasis in secondary lymphoid organs. Further research is crucial to elucidate the mechanisms underlying cadmium-induced lung injury and immune dysregulation, essential for developing effective therapeutic interventions against chronic lung diseases caused by cadmium exposure.

A case of neoadjuvant targeted therapy with pralsetinib for locally advanced lung adenocarcinoma with RET fusion mutation

This case report details the successful treatment of a 68-year-old male patient with locally advanced RET-rearranged lung adenocarcinoma using neoadjuvant pralsetinib. The patient initially presented with a suspicious right upper lobe nodule, which was later diagnosed as lung adenocarcinoma following genetic testing that revealed a RET exon 12 fusion. After 2 months of neoadjuvant treatment with pralsetinib, a significant radiological response was observed, with a reduction in tumor size and metabolic activity. Subsequently, the patient underwent video-assisted thoracoscopic right upper lobectomy and mediastinal lymph node dissection. Postoperative pathological analysis revealed a major pathological response, with only 5% residual tumor cells in the primary lesion and no viable tumor cells in the lymph nodes. Postoperative pathological staging of TNM was ypT1aN0M0, stage IA1(AJCC, 8th edition). The patient recovered well after surgery, demonstrating the potential efficacy of neoadjuvant pralsetinib in locally advanced RET-rearranged lung adenocarcinoma. However, further clinical validation is required to establish the role of neoadjuvant targeted therapy and postoperative adjuvant therapy in this patient population.

Mediastinal lymph node metastases from prostate cancer: Enhanced diagnostic accuracy of PET/CT with 18F-DCFPyL versus 18F-choline

Mediastinal lymph node metastases from prostate cancer: Enhanced diagnostic accuracy of PET/CT with 18F-DCFPyL versus 18F-choline

A case report on incidentally detected pulmonary sclerosing pneumocytoma: a diagnostic challenge

Introduction and importance: Pulmonary sclerosing pneumocytoma (PSP) is a rare non-cancerous lung tumor that is usually asymptomatic, but may cause respiratory distress if it becomes large. PSPs are often detected incidentally because of their slow growth, lack of symptoms, characteristic radiographic features, and increased use of imaging studies. Although it is not a malignant tumor, it can mimic malignancy on imaging and histology, leading to misdiagnosis and unnecessary surgery. Case presentation: A 23-year-old asymptomatic female was incidentally diagnosed with PSP during evaluation for a breast fibroadenoma. A chest CT revealed a 3 cm lobulated mass in the left upper lobe. Cytology showed malignant cells with necrotic debris. Immunohistochemistry was positive for TTF-1 and EMA, negative for p63 and AE1/AE3. Histopathology confirmed a well-circumscribed benign neoplasm, consistent with pulmonary sclerosing pneumocytoma. There was no mediastinal lymph node invasion, and the post-surgery prognosis was good. Clinical discussion: PSP is a slow-growing tumor that is often asymptomatic until it reaches a significant size. Owing to their well-circumscribed margins and the presence of calcifications, they are often detected incidentally during imaging studies, such as routine chest radiography or CT scans for unrelated conditions. Although these tumors are often incidental, it is important to diagnose and treat them appropriately to prevent potential complications and malignant transformation. Conclusion: The findings of this study contribute to the existing literature, increase awareness of this rare tumor, and provide insights into its diagnosis, treatment, and follow-up.

Remifentanil Target-controlled Infusion Versus Standard of Care for Conscious Sedation During Ultrasound-guided Transbronchial Needle Aspiration and Biopsy: A Randomized, Prospective, Control Study.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure that has become an important tool in the diagnosis and staging of mediastinal lymph node lesions in lung cancer. Adequate sedation is an important part of the procedure as it provides patient comfort and potentially increases diagnostic yield. The sedation modality varies among centers and includes moderate sedation/conscious sedation, deep sedation, and general anesthesia. The object of this study will be the evaluation of patient's comfort and level of satisfaction with the involved health care providers (bronchoscopist and anesthesiologist) of remifentanil administration in target-controlled infusion (TCI) for conscious sedation in patients undergoing EBUS‑TBNA, with a prospective randomized study design versus the of standard sedation protocol with midazolam and/or fentanest and/or propofol. This study was carried out at the "Campus Biomedico di Roma" University Hospital between September 2021 and November 2021, with a total number of 30 patients enrolled who met the eligibility criteria, randomly divided into 2 groups: group 1 "REMIFENTANIL TCI" (experimental group) where the patients performed the EBUS-TBNA procedure under conscious sedation with infusion of remifentanil TCI with a target between 3 ng/mL and 6ng/mL and group 2 "STANDARD" (control group) with patients undergoing conscious sedation with the association of midazolam and/or fentanest and/or propofol in refracted boluses based on clinical needs. Complications, safety, and level of satisfaction of the operator, the anesthesiologist, and the patient were evaluated. The results show that sedation with remifentanil in TCI can improve the comfort level of patients, reducing the risks associated with the procedure (lower frequency of oversedations and hypotension), allowing for greater intraprocedural safety. Furthermore, the level of satisfaction of the anesthesiologist and that of the operator appears to be significantly higher in the Remifentanil group. The execution of a mild to moderate sedation with Remifentanil in TCI in patients undergoing EBUS is safe, tolerated, and allows to obtain greater intraprocedural comfort. Further studies and larger and more representative samples are obviously needed to confirm and strengthen the validity of a remifentanil TCI-based sedation in endoscopic diagnostics.

Interleukin 9 mediates T follicular helper cell activation to promote antibody responses.

Antigen-specific humoral responses are orchestrated through complex interactions among immune cells in lymphoid tissues, including the collaboration between B cells and T follicular helper (Tfh) cells. Accumulating evidence indicates a crucial role for interleukin-9 (IL-9) in the formation of germinal centers (GCs), enhancing the generation of class-switched high-affinity antibodies. However, the exact function of IL-9 in Tfh cell regulation remains unclear. In this study, we examined the humoral immune responses of CD4Cre/+Il9rafl/fl mice, which lack an IL-9-specific receptor in Tfh cells. Upon intraperitoneal immunization with sheep red blood cells (SRBCs), CD4Cre/+Il9rafl/fl mice displayed diminished levels of SRBC-specific IgG antibodies in their sera, along with reduced levels of GC B cells and plasma cells. Notably, Il9ra-deficient Tfh cells in the spleen exhibited decreased expression of their signature molecules such as B-cell lymphoma 6, C-X-C chemokine receptor 5, IL-4, and IL-21 compared to control mice. In models of allergic asthma induced by house dust mite (HDM) inhalation, CD4Cre/+Il9rafl/fl mice failed to elevate serum levels of HDM-specific IgE and IgG. This was accompanied by reductions in Tfh cells, GC B cells, and plasma cells in mediastinal lymph nodes. Furthermore, group 2 innate lymphoid cells (ILC2s) were identified as producers of IL-9 under immunizing conditions, possibly induced by leukotrienes released by activated IgD+ B cells around the T-B border. These observations may indicate the critical role of IL-9 receptor signaling in the activation of Tfh cells, with ILC2s potentially capable of supplying IL-9 in organized lymphoid tissues.

Use of Endobronchial Ultrasound Guided Mediastinal Cryobiopsy in Addition to Endobronchial Ultrasound Guided Transbronchial Needle Aspiration and Rapid on Site Evaluation for Evaluation of Enlarged Mediastinal Nodes ( Case series )

Use of Endobronchial Ultrasound Guided Mediastinal Cryobiopsy in Addition to Endobronchial Ultrasound Guided Transbronchial Needle Aspiration and Rapid on Site Evaluation for Evaluation of Enlarged Mediastinal Nodes ( Case series )

The stage-by-stage treatment of critical aortic stenosis and progressive atherosclerosis of the coronary arteries that occurred three decades after radiation therapy for Hodgkin’s lymphoma. Clinical case

Modern treatment programs for Hodgkin’s lymphoma include both drug antitumor therapy and radiation exposure. When conducting remote radiation therapy on the mediastinal lymph nodes, damage to the heart, thoracic aorta and lungs is possible. Such late cardiovascular complications as damage to the valvular apparatus and progressive atherosclerosis of the coronary arteries, leading to obstruction with the subsequent development of coronary heart disease, more often occurred after the use of extended radiation fields and high total focal doses. The article presents a clinical case of a 64-year-old patient with Hodgkin’s lymphoma, who successfully underwent staged cardiac surgery for severe aortic stenosis and progressive atherosclerosis with calcification of the coronary arteries due to radiation exposure.

Transesophageal endoscopic ultrasound-guided aspiration of mediastinal lymph node. Clinical case

In oncologic practice, metastatic lesions in the mediastinal lymph nodes are primarily associated with lung cancer because of its high morbidity. However, lesions in mediastinal lymph nodes are quite common in the context of various other benign and malignant processes. Therefore, due to the anatomy of this zone, difficulties of visualization of specific lymph node groups, complicated differential diagnosis of benign and malignant processes, the problem of sampling biological materials from the affected area remains important and unsolved. Transesophageal endoscopic ultrasound-guided aspiration is a highly effective and safe method of diagnosis and staging of oncologic diseases associated with metastatic lesions in the mediastinal lymph nodes.