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Only a limited group of patients with non-small-cell lung cancer (NSCLC) is eligible for treatment with a curative intent. Adrenalectomy for a solitary adrenal metastasis of NSCLC may be curative when combined with resection of the primary tumor. It is unclear whether resection of an isolated adrenal metastasis is justified in patients with a second metastasis. We report a case of successful adrenalectomy with adjuvant chemotherapy in a patient who was previously treated with a right lower lobe resection and subsequent Gamma Knife treatment of an intracranial metastasis. At 20-month follow-up, patient was in a good clinical condition without signs of recurrent disease. In selected cases, adrenalectomy with adjuvant chemotherapy for an adrenal metastasis of NSCLC may be performed successfully, with good short-term results, even after earlier treatment of a cerebral metastasis. [ABSTRACT FROM AUTHOR]

Background: Individual risk prediction of 5-year locoregional recurrence (LRR) and contralateral breast cancer (CBC) supports decisions regarding personalised surveillance. The previously developed INFLUENCE tool was rebuild, including a recent population and patients who received neoadjuvant systemic therapy (NST)., Methods: Women, surgically treated for nonmetastatic breast cancer, diagnosed between 2012 and 2016, were selected from the Netherlands Cancer Registry. Cox regression with restricted cubic splines was compared to Random Survival Forest (RSF) to predict five-year LRR and CBC risks. Separate models were developed for NST patients. Discrimination and calibration were assessed by 100x bootstrap resampling., Results: In the non-NST and NST group, 49,631 and 10,154 patients were included, respectively. Age, mode of detection, histology, sublocalisation, grade, pT, pN, hormonal receptor status ± endocrine treatment, HER2 status ± targeted treatment, surgery ± immediate reconstruction ± radiation therapy, and chemotherapy were significant predictors for LRR and/or CBC in non-NST patients. For NST patients this was similar, but excluding (y)pT and (y)pN status, and including presence of ductal carcinoma in situ, axillary lymph node dissection and pathologic complete response. For non-NST patients, the Cox and RSF models were integrated in the online tool with 5-year AUCs of 0.77 (95%CI:0.77-0.77) and 0.68 (95%CI:0.67-0.68)] for LRR and CBC prediction, respectively. For NST patients, the RSF model performed best (AUCs 0.77 (95%CI:0.76-0.78) and 0.73 (95%CI:0.69-0.76) for LRR and CBC, respectively). Regarding calibration, observed-predicted differences were all <1 %., Conclusion: This INFLUENCE 3.0 models showed moderate performance in LRR and CBC prediction. The models have been made available as online tool to enable clinical decision support regarding personalised follow-up., Competing Interests: Declaration of coompeting interest Tom A. Hueting declares employment at Evidencio. The other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

For deep partial-thickness burns no consensus on the optimal treatment has been reached due to conflicting study outcomes with low quality evidence. Treatment options in high- and middle-income countries include conservative treatment with delayed excision and grafting if needed; and early excision and grafting. The majority of timing of surgery studies focus on survival rather than on quality of life. This study protocol describes a study that aims to compare long-term scar quality, clinical outcomes, and patient-reported outcomes between the treatment options. A multicentre prospective study will be conducted in the three Dutch burn centres (Rotterdam, Beverwijk, and Groningen). All adult patients with acute deep-partial thickness burns, based on healing potential with Laser Doppler Imaging, are eligible for inclusion. During a nine-month baseline period, standard practice will be monitored. This includes conservative treatment with dressings and topical agents, and excision and grafting of residual defects if needed 14-21 days post-burn. The subsequent nine months, early surgery is advocated, involving excision and grafting in the first week to ten days post-burn. The primary outcome compared between the two groups is long-term scar quality assessed by the Patient and Observer Scar Assessment Scale 3.0 twelve months after discharge. Secondary outcomes include clinical outcomes and patient-reported outcomes like quality of life and return to work. The aim of the study is to assess long-term scar quality in deep partial-thickness burns after conservative treatment with delayed excision and grafting if needed, compared to early excision and grafting. Adding to the ongoing debate on the optimal treatment of these burns. The broad range of studied outcomes will be used for the development of a decision aid for deep partial-thickness burns, to fully inform patients at the point of consent to surgery and support optimal person-centred care., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Salemans et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Distinguishing asthma and COPD can pose challenges in clinical practice. Increased group 1 innate lymphoid cells (ILC1s) have been found in the lungs and peripheral blood of COPD patients, while asthma is associated with elevated levels of ILC2s. However, it is unclear whether the inflammatory characteristics of ILC1s and ILC2s differ between COPD and asthma. This study aims to compare peripheral blood ILC subsets and their expression of inflammatory markers in COPD patients, asthma patients and controls., Methods: The study utilised multi-colour flow cytometry to analyse peripheral blood ILC populations in clinically stable COPD patients (n=38), asthma patients (n=37), and smoking (n=19) and non-smoking (n=16) controls., Results: Proportions of peripheral blood inflammatory CD4 + ILC1s were significantly higher in COPD patients than in asthma. Proportions of CD4 - ILC1s were increased in COPD patients compared to asthma patients and smoking controls. Frequencies of CD117 - ILC2s were significantly reduced in COPD patients compared with asthma patients. In contrast, the fraction of inflammatory CD45RO + cells within the CD117 - ILC2 population was significantly increased. Principal component analyses showed that combined features of the circulating ILC compartment separated COPD patients from asthma patients and both control groups., Conclusion: Our in-depth characterisation of ILC1 and ILC2 populations in peripheral blood revealed significant differences in their phenotypes between COPD and asthma patients and smoking or non-smoking controls. These findings suggest a role for both ILC subsets in COPD disease pathology, independent of smoking history, and may have implications for patient stratification and therapy development., Competing Interests: Conflict of interest: All authors declare that they have no conflicts of interest related to the topic., (Copyright ©The authors 2024.)

Rationale: Disease course in sarcoidosis is highly variable. Bronchoalveolar lavage fluid and mediastinal lymph nodes show accumulation of activated T cells with a T-helper (Th)17.1 signature, which correlates with non-resolving sarcoidosis. We hypothesize that the peripheral blood (PB) T cell phenotype may correlate with outcome., Objectives: To compare frequencies, phenotypes and function of circulating T cell populations in sarcoidosis patients with healthy controls (HCs) and correlate these parameters with outcome., Methods: We used multi-color flow cytometry to quantify activation marker expression on PB T cell subsets in treatment-naïve patients and HCs. The disease course was determined after 2-year follow-up. Cytokine production was measured after T cell stimulation in vitro., Measurements and Main Results: We observed significant differences between patients and HCs in several T cell populations, including CD8 + and CD4 + T cells, Th1/Th17 subsets, CD4 + T memory stem cells, regulatory T cells (Tregs) and γδ T cells. Decreased frequencies of CD4 + T cells and increased frequencies of Tregs and CD8 + γδ T cells correlated with worse outcome. Naïve CD4 + T cells displayed an activated phenotype with increased CD25 expression in patients with active chronic disease at 2-year follow-up. A distinctive Treg phenotype with increased expression of CD25, CTLA4, CD69, PD-1 and CD95 correlated with chronic sarcoidosis. Upon stimulation, both naïve and memory T cells displayed a different cytokine profile in sarcoidosis compared to HCs., Conclusions: Circulating T cell subpopulations of sarcoidosis patients display phenotypic abnormalities that correlate with disease outcome, supporting a critical role of aberrant T cell activation in sarcoidosis pathogenesis., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Current cultural competence training needs were assessed as baseline measurement in Dutch physician assistant (PA) students and PA alumni that were not specifically trained in cultural competence. In particular, differences in cultural competency between PA students and PA alumni were assessed., Methods: In this cross-sectional, observational cohort study knowledge, attitude, and skills and self-perceived overall cultural competence were assessed in Dutch PA students and alumni. Demographics, education and learning needs were collected. Total cultural competence domain scores as well as percentage of maximum scores were calculated., Results: A total of 40 PA students and 96 alumni (female:75%; Dutch origin:97%) consented to participate. Cultural competence behavior was moderate in both groups. In contrast, general knowledge and exploration of patients' social context were insufficient, i.e., 53% and 34%, respectively. Self-perceived cultural competence was significantly higher in PA alumni (6.5 ± 1.3, mean ± SD) than in students (6.0 ± 1.3; P < 0.05). Low heterogeneity among PA students and educator exists. Seventy percent of the respondents considers cultural competence important and the majority expressed a need for cultural competence training., Conclusions: Dutch PA students and alumni have moderate overall cultural competence, but insufficient knowledge and exploring social context. Based on these outcomes the curriculum of the master of science program for physician assistant will be adapted.Emphasis should be made to increase the diversity of PA students to stimulate cross-cultural learning and developing a diverse PA workforce., (© 2023. The Author(s).)

Mechanical forces are translated into biochemical stimuli by mechanotransduction channels, such as the mechanically activated cation channel Piezo2. Lung Piezo2 expression has recently been shown to be restricted to endothelial cells. Hence, we aimed to investigate the role of Piezo2 in regulation of pulmonary vascular function and structure, as well as its contribution to development of pulmonary arterial hypertension (PAH). The expression of Piezo2 was significantly reduced in pulmonary microvascular endothelial cells (MVECs) from patients with PAH, in lung tissue from mice with a Bmpr2 +/R899X knock-in mutation commonly found in patients with pulmonary hypertension, and in lung tissue of monocrotaline (MCT) and sugen-hypoxia-induced PH (SuHx) PAH rat models, as well as from a swine model with pulmonary vein banding. In MVECs, Piezo2 expression was reduced in response to abnormal shear stress, hypoxia, and TGFβ stimulation. Functional studies in MVECs exposed to shear stress illustrated that siRNA-mediated Piezo2 knockdown impaired endothelial alignment, calcium influx, phosphorylation of AKT, and nitric oxide production. In addition, siPiezo2 reduced the expression of the endothelial marker PECAM-1 and increased the expression of vascular smooth muscle markers ACTA2, SM22a, and calponin. Thus, Piezo2 acts as a mechanotransduction channel in pulmonary MVECs, stimulating shear-induced production of nitric oxide and is essentially involved in preventing endothelial to mesenchymal transition. Its blunted expression in pulmonary hypertension could impair the vasodilator capacity and stimulate vascular remodeling, indicating that Piezo2 might be an interesting therapeutic target to attenuate progression of the disease. NEW & NOTEWORTHY The mechanosensory ion channel Piezo2 is exclusively expressed in lung microvascular endothelial cells (MVECs). Patient MVECs as well as animal models of pulmonary (arterial) hypertension showed lower expression of Piezo2 in the lung. Mechanistically, Piezo2 is required for calcium influx and NO production in response to shear stress, whereas stimuli known to induce endothelial to mesenchymal transition (EndMT) reduce Piezo2 expression in MVECs, and Piezo2 knockdown induces a gene and protein expression pattern consistent with EndMT.

Pulmonary arterial hypertension (PAH) is rare disease that is categorized as idiopathic (IPAH) when no underlying cause can be identified. Lungs of most patients with IPAH contain increased numbers of T cells and dendritic cells (DCs), suggesting involvement of the immune system in its pathophysiology. However, our knowledge on circulating immune cells in IPAH is rather limited. We used flow cytometry to characterize peripheral blood DCs and T cells in treatment-naive IPAH patients, compared with connective-tissue disease-PAH (CTD-PAH) patients and healthy controls (HCs). At diagnosis, T-helper (Th) cells of IPAH patients were less capable of producing TNFα, IFNγ, IL-4 and IL-17 compared to HCs. IPAH patients showed a decreased frequency of Th2 cells and significantly enhanced expression of the CTLA4 checkpoint molecule in naive CD4 + T cells and both naive and memory CD8 + T cells. Frequencies and surface marker expression of circulating DCs and monocytes were essentially comparable between IPAH patients and HCs. Principal component analysis (PCA) separated IPAH patients-but not CTD-PAH patients-from HCs, based on T-cell cytokine profiles. At 1-year follow-up, the frequencies of IL-17 + production by memory CD4 + T cells were increased in IPAH patients and accompanied by increased proportions of Th17 and Tc17 cells, as well as decreased CTLA4 expression. Treatment-naive IPAH patients displayed a unique T-cell phenotype that was different from CTD-PAH patients and was characterized by reduced cytokine-producing capacity. These findings point to involvement of adaptive immune responses in IPAH, which may have an implication for the development of therapeutic interventions.

Introduction: Previous studies have shown an increase of T cells and chemokines in vascular lesions of patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, detailed characterization of these T cells is still lacking, nor have treatment effects been evaluated., Methods: We included 41 treatment-naive CTEPH patients at diagnosis, 22 patients at 1-year follow-up, and 17 healthy controls (HCs). Peripheral blood T cells were characterized by flow cytometry for subset distribution, cytokine expression and activation marker profile. We used multiplex immunofluorescence to identify CCR6 + T cells in endarterectomy tissue from 25 patients., Results: At diagnosis, proportions of CCR6 + CD4 + T cells were increased in CTEPH patients compared with HCs. Patients displayed a significantly reduced production capacity of several cytokines including TNFα, IFNγ, GM-CSF and IL-4 in CD4 + T cells, and TNFα and IFNγ in CD8 + T cells. CD4 + and CD8 + T cells showed increased expression of the immune checkpoint protein CTLA4. Multivariate analysis separated CTEPH patients from HCs, based on CCR6 and CTLA4 expression. At 1-year follow-up, proportions of CCR6 + CD4 + T cells were further increased, IFNγ and IL-17 production capacity of CD4 + T cells was restored. In nearly all vascular lesions we found substantial numbers of CCR6 + T cells., Conclusion: The observed increase of CCR6 + T cells and modulation of the IFNγ and IL-17 production capacity of circulating CD4 + T cells at diagnosis and 1-year follow-up - together with the presence of CCR6 + T cells in vascular lesions - support the involvement of the Th17-associated CCR6 + T cell subset in CTEPH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 van Uden, Koudstaal, van Hulst, van den Bosch, Vink, Bergen, Lila, van den Bosch, Bresser, Kool, von der Thüsen, Hendriks and Boomars.)

Introduction: Autoreactivity against pulmonary vascular structures is thought to be involved in idiopathic pulmonary arterial hypertension (IPAH), but the underlying mechanisms remain poorly understood. We hypothesised that aberrant B-cell activation contributes to IPAH aetiology., Methods: Mice with enhanced B-cell activation due to B-cell-specific overexpression of the B-cell receptor (BCR) signalling molecule Bruton's tyrosine kinase (BTK) were subjected to lung injury and examined for several pulmonary hypertension (PH) indices. Peripheral blood lymphocytes from patients with IPAH (n=13), connective tissue disease-associated PAH (CTD-PAH, n=9), congenital heart disease PAH (n=7), interstitial lung disease associated PH (n=17) and healthy controls (n=19) were characterised by 14-colour flow cytometry., Results: Following pulmonary injury, BTK-overexpressing mice showed prolonged activation of B cells and CXCR5 + follicular T-helper (Tfh) cells, as well as features of PH development. Patients with CTD-PAH and CHD-PAH displayed reduced proportions of circulating non-switched-memory B cells (p=0.03, p=0.02, respectively). Interestingly, we observed increased BTK protein expression in naive (p=0.007) and memory B-cell subsets of patients with IPAH and CTD-PAH. BTK was particularly high in patients with IPAH with circulating autoantibodies (p=0.045). IPAH patients had low frequencies of circulating CXCR5 + Tfh cells (p=0.005). Hereby, the increased BTK protein expression in B cells was associated with high proportions of Tfh17 (p=0.018) and Tfh17.1 (p=0.007) cells within the circulating Tfh population., Conclusions: Our study shows that pulmonary injury in combination with enhanced B-cell activation is sufficient to induce PH symptoms in mice. In parallel, immune homeostasis in patients with IPAH is compromised, as evidenced by increased BCR signalling and cTfh17 polarisation, indicating that adaptive immune activation contributes to IPAH disease induction or progression., Competing Interests: Competing interests: MSW reports research grants from Boehringer Ingelheim, Hoffmann-La Roche, Galapagos, Respivant outside the submitted work (all paid to her institution)., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Competing Interests: The authors declare no conflict of interest.

The pathogenesis of idiopathic pulmonary arterial hypertension (IPAH) is not fully understood, but evidence is accumulating that immune dysfunction plays a significant role. We previously reported that 31-week-old Tnfaip3 DNGR1-KO mice develop pulmonary hypertension (PH) symptoms. These mice harbor a targeted deletion of the TNFα-induced protein-3 ( Tnfaip3 ) gene, encoding the NF-κB regulatory protein A20, specifically in type I conventional dendritic cells (cDC1s). Here, we studied the involvement of dendritic cells (DCs) in PH in more detail. We found various immune cells, including DCs, in the hearts of Tnfaip3 DNGR1-KO mice, particularly in the right ventricle (RV). Secondly, in young Tnfaip3 DNGR1-KO mice, innate immune activation through airway exposure to toll-like receptor ligands essentially did not result in elevated RV pressures, although we did observe significant RV hypertrophy. Thirdly, PH symptoms in Tnfaip3 DNGR1-KO mice were not enhanced by concomitant mutation of bone morphogenetic protein receptor type 2 ( Bmpr2 ), which is the most affected gene in PAH patients. Finally, in human IPAH lung tissue we found co-localization of DCs and CD8+ T cells, representing the main cell type activated by cDC1s. Taken together, these findings support a unique role of cDC1s in PAH pathogenesis, independent of general immune activation or a mutation in the Bmpr2 gene.

Background: Conventional type 1 dendritic cells (cDC1s) control anti-viral and anti-tumor immunity by inducing antigen-specific cytotoxic CD8 + T-cell responses. Controversy exists whether cDC1s also control CD4 + T helper 2 (Th2) cell responses, since suppressive and activating roles have been reported. DC activation status, controlled by the transcription factor NF-κB, might determine the precise outcome of Th-cell differentiation upon encounter with cDC1s. To investigate the role of activated cDC1s in Th2-driven immune responses, pulmonary cDC1s were activated by targeted deletion of A20/Tnfaip3, a negative regulator of NF-κB signaling., Methods: To target pulmonary cDC1s, Cd207 (Langerin)-mediated excision of A20/Tnfaip3 was used, generating Tnfaip3 fl/fl xCd207 +/cre (Tnfaip3 Lg-KO ) mice. Mice were exposed to house dust mite (HDM) to provoke Th2-mediated immune responses., Results: Mice harboring Tnfaip3-deficient cDC1s did not develop Th2-driven eosinophilic airway inflammation upon HDM exposure, but rather showed elevated numbers of IFNγ-expressing CD8 + T cells. In addition, Tnfaip3 Lg-KO mice harbored increased numbers of IL-12-expressing cDC1s and elevated PD-L1 expression in all pulmonary DC subsets. Blocking either IL-12 or IFNγ in Tnfaip3 Lg-KO mice restored Th2 responses, whereas administration of recombinant IFNγ during HDM sensitization in C57Bl/6 mice blocked Th2 development., Conclusions: These findings indicate that the activation status of cDC1s, shown by their specific expression of co-inhibitory molecules and cytokines, critically contributes to the development of Th2 cell-mediated disorders, most likely by influencing IFNγ production in CD8 + T cells., (© 2020 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Up to 78 % of patients with inflammatory breast cancer (IBC) present with axillary lymph node involvement and up to 40 % with distant metastases. Previous studies indicate that 2-deoxy-2-( 18 F)fluoro-d-glucose ([ 18 F]FDG) positron emission tomography/computed tomography (PET/CT) might be used for initial staging in patients with inflammatory breast cancer (IBC). In other cancer types, [ 18 F]FDG PET/CT has been demonstrated to be a sensitive technique, providing complementary information on locoregional and distant disease to conventional imaging modalities. This systematic review showed that 18 F]FDG PET/CT detects additional locoregional lymph node metastases and distant metastases in 10.3 % of patients, that were not detected with standard staging imaging. Compared with conventional imaging procedures, [ 18 F]FDG PET/CT had better diagnostic performance for detection of locoregional and distant metastases and should standardly be used in the diagnostic work-up of IBC patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: Information regarding the effects of resection of the primary tumor in stage IV inflammatory breast cancer (IBC) is scarce. We analyzed the impact of resection of the primary tumor on overall survival (OS) in a large stage IV IBC population., Materials and Methods: Patients diagnosed with stage IV IBC between 2005 and 2016 were selected from the Netherlands Cancer Registry, excluding patients without any treatment. To correct for immortal time bias, we performed a landmark analysis including patients alive at least six months after diagnosis. With propensity score matching, patients undergoing surgery of the primary tumor were matched to patients not receiving surgery. Multivariable Cox proportional hazard analyses were performed to determine the association between treatment strategy and OS in the non-matched and matched cohort., Results: Of the 580 included patients after landmark analysis, 441 patients (76%) received only non-surgical treatments and 139 (24%) underwent surgery (96% mastectomy). Median follow-up was 28.8 and 20.0 months in the surgery and no surgery group, respectively. Surgery in the non-matched cohort was independently associated with better survival (HR0.56[95%CI:0.42-0.75]). In the matched cohort (n = 202), surgically treated patients had improved survival over nonsurgically treated patients (p < 0.005). Multivariable analysis of the matched cohort revealed that surgery was still associated with better survival (HR0.62[95%CI:0.44-0.87])., Conclusion: Although residual confounding and confounding by severity cannot be ruled out, this study suggests that surgery of the primary tumor is associated with improved OS and should be considered as part of the treatment strategy in stage IV IBC., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Pulmonary arterial hypertension (PAH) is a cardiopulmonary disease characterized by an incurable condition of the pulmonary vasculature, leading to increased pulmonary vascular resistance, elevated pulmonary arterial pressure resulting in progressive right ventricular failure and ultimately death. PAH has different underlying causes. In approximately 30-40% of the patients no underlying risk factor or cause can be found, so-called idiopathic PAH (IPAH). Patients with an autoimmune connective tissue disease (CTD) can develop PAH [CTD-associated PAH (CTD-PAH)], suggesting a prominent role of immune cell activation in PAH pathophysiology. This is further supported by the presence of tertiary lymphoid organs (TLOs) near pulmonary blood vessels in IPAH and CTD-PAH. TLOs consist of myeloid cells, like monocytes and dendritic cells (DCs), T-cells, and B-cells. Next to their T-cell activating function, DCs are crucial for the preservation of TLOs. Multiple DC subsets can be found in steady state, such as conventional DCs (cDCs), including type 1 cDCs (cDC1s), and type 2 cDCs (cDC2s), AXL + Siglec6 + DCs (AS-DCs), and plasmacytoid DCs (pDCs). Under inflammatory conditions monocytes can differentiate into monocyte-derived-DCs (mo-DCs). DC subset distribution and activation status play an important role in the pathobiology of autoimmune diseases and most likely in the development of IPAH and CTD-PAH. DCs can contribute to pathology by activating T-cells (production of pro-inflammatory cytokines) and B-cells (pathogenic antibody secretion). In this review we therefore describe the latest knowledge about DC subset distribution, activation status, and effector functions, and polymorphisms involved in DC function in IPAH and CTD-PAH to gain a better understanding of PAH pathology.

Background: It is currently unknown why allergen exposure or environmental triggers in patients with mild-to-moderate asthma result in T H 2-mediated eosinophilic inflammation, whereas patients with severe asthma often present with T H 17-mediated neutrophilic inflammation. The activation state of dendritic cells (DCs) is crucial for both T H 2 and T H 17 cell differentiation and is mediated through nuclear factor κB activation. Ablation of TNF-α-induced protein 3 (TNFAIP3), one of the crucial negative regulators of nuclear factor κB activation in myeloid cells and DCs, was shown to control DC activation., Objective: In this study we investigated the precise role of TNFAIP3 in myeloid cells for the development of T H 2- and T H 17-cell mediated asthma., Methods: We exposed mice with conditional deletion of the Tnfaip3 gene in either myeloid cells (by using the lysozyme M [LysM] promotor) or specifically in DCs (by using the Cd11c promotor) to acute and chronic house dust mite (HDM)-driven asthma models., Results: We demonstrated that reduced Tnfaip3 gene expression in DCs in either Tnfaip3 CD11c or Tnfaip3 LysM mice dose-dependently controlled development of T H 17-mediated neutrophilic severe asthma in both acute and chronic HDM-driven models, whereas wild-type mice had a purely T H 2-mediated eosinophilic inflammation. TNFAIP3-deficient DCs induced HDM-specific T H 17 cell differentiation through increased expression of the T H 17-instructing cytokines IL-1β, IL-6, and IL-23, whereas HDM-specific T H 2 cell differentiation was hampered by increased IL-12 and IL-6 production., Conclusions: These data show that the extent of TNFAIP3 expression in DCs controls T H 2/T H 17 cell differentiation. This implies that reducing DC activation could be a new pharmacologic intervention to treat patients with severe asthma who present with T H 17-mediated neutrophilic inflammation., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Chronic exposure to environmental triggers, such as house dust mite (HDM), drives T helper 2 (Th2) cell-mediated asthma. Recent evidence has shown that B-T cell interaction, and in particular germinal centre reactions and follicular T helper (Tfh) cells are required for the development of eosinophilic airway inflammation in HDM-driven models containing a sensitization and challenge phase. Whether B-T cell interactions are essential for pulmonary eosinophilic inflammation following chronic allergen provocation remains unknown., Aims: In this study, we investigated the importance of B-T cell interaction in the development of eosinophilic airway inflammation and pulmonary remodelling in a chronic HDM-driven asthma model., Methods: We exposed C57BL/6, Cd40l -/- , and Mb1 -/- mice to HDM three times a week for five consecutive weeks., Results: Chronic HDM exposure induced a pronounced eosinophilic allergic airway inflammation in broncho-alveolar lavage fluid (BALf) and lung tissue, associated with the formation of immunologically active inducible bronchus-associated lymphoid tissue (iBALT) in the lungs. The absence of B cells or lack of CD40L signalling did not hamper eosinophilic inflammation in the airways, although the number of Tfh and Th2 cells was substantially reduced in the lungs. Importantly, type 2 innate lymphoid cell (ILC2) numbers in BALf and lung were not affected by the absence of B cells or B-T cell interaction. Furthermore, eosinophilic airway inflammation is not sufficient to induce pulmonary remodelling and airway hyperresponsiveness., Conclusion and Clinical Relevance: From these findings, we conclude that B-T cell interaction is required for robust Tfh and Th2 cell induction, but not essential for eosinophilic airway inflammation during a chronic HDM-driven asthma model., (© 2016 John Wiley & Sons Ltd.)

Inflammatory breast cancer (IBC) is the most aggressive entity of breast cancer. Management involves coordination of multidisciplinary management and usually includes neoadjuvant chemotherapy, ablative surgery if a tumor-free resection margin is expected and locoregional radiotherapy. This multimodal therapeutic approach has significantly improved patient survival. However, the median overall survival among women with IBC is still poor. By elucidating the biologic characteristics of IBC, new treatment options may become available. We performed a comprehensive review of the English-language literature on IBC through computerized literature searches. The objective of the current review is to present an overview of the literature related to the biology, imaging and multidisciplinary treatment of inflammatory breast cancer., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)