Driving chronicity in rheumatoid arthritis: perpetuating role of myeloid cells

Acute inflammation is a complex and tightly regulated homeostatic process that includes leukocyte migration from the vasculature into tissues to eliminate the pathogen/injury, followed by a pro-resolving response promoting tissue repair. However, if inflammation is uncontrolled as in chronic diseases such as Rheumatoid Arthritis (RA) it leads to tissue damage and disability. Synovial tissue inflammation in RA patients is maintained by sustained activation of multiple inflammatory positive-feedback regulatory pathways in a variety of cells including myeloid cells. In this review, we will highlight recent evidence uncovering biological mechanisms contributing to the aberrant activation of myeloid cells that contributes to perpetuation of inflammation in RA, and discuss emerging data on anti-inflammatory mediators contributing to sustained remission that may inform a novel category of therapeutic targets

Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a global health problem, and current therapy for COPD is poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. Imbalance of oxidant/antioxidant balance caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g. NF-κB), autophagy and unfolded protein response leading to chronic lung inflammatory response. Cigarette smoke also activates canonical/alternative NF-κB pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervening COPD

CIRSE Standards of Practice on Thermal Ablation of Bone Tumours.

Percutaneous thermal ablation is an effective, minimally invasive means of treating a variety of focal benign and malignant osseous lesions. To determine the role of ablation in individual cases, multidisciplinary team (MDT) discussion is required to assess the suitability and feasibility of a thermal ablative approach, to select the most appropriate technique and to set the goals of treatment i.e. curative or palliative. This document will presume the indication for treatment is clear and approved by the MDT and will define the standards required for the performance of each modality. CIRSE Standards of Practice documents are not intended to impose a standard of clinical patient care, but recommend a reasonable approach to, and best practices for, the performance of thermal ablation of bone tumours. The writing group was established by the CIRSE Standards of Practice Committee and consisted of five clinicians with internationally recognised expertise in thermal ablation of bone tumours. The writing group reviewed the existing literature on thermal ablation of bone tumours, performing a pragmatic evidence search using PubMed to search for publications in English and relating to human subjects from 2009 to 2019. Selected studies published in 2020 and 2021 during the course of writing these standards were subsequently included. The final recommendations were formulated through consensus. Recommendations were produced for the performance of thermal ablation of bone tumours taking into account the biologic behaviour of the tumour and the therapeutic intent of the procedure. Recommendations are provided based on lesion characteristics and thermal modality, for the use of tissue monitoring and protection, and for the appropriately timed application of adjunctive procedures such as osseus consolidation and transarterial embolisation. Percutaneous thermal ablation has an established role in the successful management of bone lesions, with both curative and palliative intent. This Standards of Practice document provides up-to-date recommendations for the safe performance of thermal ablation of bone tumours

Shunt dysfunction patterns after transjugular intrahepatic portosystemic shunt creation using a combination of a generic stent-graft and bare-stents.

Even though transjugular intrahepatic portosystemic shunt (TIPS) using Fluency Stent-grafts provides good shunt patency rates, shunt dysfunction is a great concern after TIPS creation, occurring in up to 20% of cases within one year. The objective of this study was to describe shunt dysfunction patterns after TIPS creation using a combination of generic stent-grafts/bare-stents. Single-center retrospective study of all TIPS revisions between January 2005 and December 2020. TIPS revision angiograms were analyzed for stents' positions, stenoses' diameters, and stenoses' locations. Out of 99 TIPS, a total of 33 TIPS revisions were included. The median time to TIPS revision was 10.4 months. Angiograms showed four patterns of TIPS dysfunction-associated features (DAF), defined as follows: Type 1 was defined as stenosis located after the stent end in the hepatic vein (HV), type 2 as intra-stent stenosis located in the hepatic vein, type 3 as intra-stent stenosis or a kink in the parenchymal tract or the portal vein end of the TIPS, and type 4 as a complete TIPS occlusion. Types 1, 2, 3, and 4 were seen in 23 (69.7%), 5 (15.2%), 2 (6.1%), and 3 (9.1%) TIPS respectively. TIPS revision was successful in 30 (90.1%) patients with median pre- and post-TIPS revision PSG of 18.5 mmHg and 8 mmHg respectively (p < .001). Our results illustrate the four angiographic patterns of TIPS DAF after TIPS creation using a combination of generic stent-grafts/bare-stents and emphasize the need for appropriate stent length extending to the HV/inferior vena cava junction

Abscopal effect induced by cryoablation in a 55-year-old patient with metastatic dedifferentiated liposarcoma: a case report.

Metastatic dedifferentiated liposarcoma (DDLPS) is primarily managed with chemotherapy, yet with poor response rate. Locoregional therapies, such as radiotherapy and percutaneous cryoablation, can provide palliation for inoperable metastatic sarcomas. In rare instances, those ablative therapies can elicit an immune-mediated regression of untreated metastases in a process named the abscopal effect. With the growing use of immunotherapy, reports on the abscopal effect have become more frequent during the last decade. A 55-year-old patient with no prior medical history was diagnosed with a stage IV DDLPS. The patient was first treated with induction chemotherapy followed by en bloc resection and adjuvant radiotherapy. After two local relapses treated with chemotherapy, the patient developed a systemic disease progression. While progressing on immunochemotherapy, the patient underwent palliative percutaneous cryoablation. Three months after the procedure, the <sup>18</sup> fluorodeoxyglucose positron emission tomography/computed tomography ( <sup>18</sup> FDG PET/CT) showed regression of the distant metastasis alongside the regression of the cryoablated tumor, suggesting an abscopal effect. The occurrence of the abscopal effect after progressive disease suggests that cryoablation triggered a systemic immune response, highlighting the potential of this treatment combination. However, it remains a rare phenomenon, and further research and clinical trials are required to determine optimal treatment sequencing

Preclinical evaluation of the atraumatic nature of a spring loaded blunt tip coaxial needle in a swine model

International audiencePurpose: To test in vivo in an animal model the inherent atraumatic characteristics of the spring loaded blunt tip of a coaxial needle (Gangi-SoftGuard®, Apriomed, Sweden) against a conventional sharp stylet coaxial needle.Material and Methods: The study was conducted on a 40 kg male swine that was its own control for a vascular trauma model. The procedure consisted of voluntary attempts to transfix and traverse the artery/aorta under continuous real-time angiogram. Test and control needles were positioned in the region of the intercostal, superior mesenteric and femoral/deep femoral arteries, and in the aorta. Computed tomography (CT) angiogram was performed post trauma to check for bleeding in the form of extravasation of contrast material. One attempt was performed per site and needle, except for the intercostal artery where a second attempt was done with the test needle, resulting in a total of 4 and 5 tests for the control and test needles, respectively.Results: With the spring loaded blunt tip, no vascular trauma or bleeding was noted in the intercostal, superior mesenteric and femoral arteries, nor in the aorta. Vascular spasm that recovered with time was noted during the second attempt to transfix the same intercostal artery. There were consistent vascular traumas and bleedings with the control needle in all three tested arteries and the aorta, confirmed on angiogram as well as CT angiogram.Conclusion: The atraumatic feature offered by the spring loaded blunt tip prevented vascular trauma during the 5 attempts made to transfix the artery/aorta in a swin

Maintained Smoking Cessation for 6 Months Equilibrates the Percentage of Sputum CD8+ Lymphocyte Cells with That of Nonsmokers

Little is known about the longitudinal effects of smoking cessation on sputum inflammatory cells. We aimed to investigate the changes in sputum inflammatory cells and T-lymphocyte subpopulations after 6 and 12 months smoking cessation. Induced sputum was obtained from 68 healthy smokers before and after 6 months (n = 21) and 1 year (n = 14) smoking cessation and from ten healthy never-smokers. Inflammatory cells were identified by morphology and T-lymphocyte subpopulations by flow cytometry. Sputum macrophages were decreased after 12 months of smoking cessation in comparison to baseline, while neutrophils increased. Moreover, CD8+ T-cells were decreased in smokers before smoking cessation compared to never-smokers and increased in smokers after 6 months of smoking cessation in comparison to baseline; result that was maintained after 1 year of smoking cessation. These novel findings indicate that smoking cessation can equilibrate certain inflammatory cells of smokers with those of nonsmokers, within 6 months of smoking cessation

Prognostic value of CT-based skeletal muscle and adipose tissue mass and quality parameters in patients with liver metastases and intrahepatic cholangiocarcinoma undergoing Yttrium-90 radioembolization.

To investigate baseline patient characteristics associated with the risk of computed tomography (CT)-based sarcopenia and assess whether sarcopenia and other morphometric parameters influence survival outcomes in patients with liver metastases and cholangiocarcinoma after Yttrium-90 radioembolization. We retrospectively analyzed 120 cancer patients (mean age, 62 ± 13.3 years, 61 men) who underwent preprocedural CT. Skeletal muscle index (SMI) was measured at the L3 vertebral level to identify sarcopenia. The Cox proportional hazard model was performed to assess the prognostic value of the variables, and Kaplan-Meier analysis with log-rank text was used for overall survival (OS) assessment. Sarcopenia was diagnosed in 70 patients (58.3%). The multivariate regression analysis demonstrated that male sex, body mass index (BMI), visceral fat radiation attenuation (VFRA), skeletal muscle radiation attenuation (SMRA), and subcutaneous fat radiation attenuation (SFRA) were associated with the incidence of sarcopenia with the odds ratio of 8.81 (95% CI, 2.09-37.1, p = 0.003), 0.64 (95% CI, 0.48-0.85, p = 0.002), 1.23 (95% CI, 1.06-1.42, p = 0.006), 0.79 (95% CI, 0.69-0.91, p = 0.001) and 0.84 (95% CI, 0.76-0.93, p = 0.001), respectively. Age, skeletal muscle index, and tumor subtypes were independent prognostic factors for OS with the hazard ratio of 1.03 (95% CI, 1.01-1.05, p = 0.01), 0.92 (95% CI, 0.86-0.99, p = 0.021) and 2.09 (95% CI, 1.31-3.33 p = 0.002), respectively. In patients with intrahepatic cholangiocarcinoma, median OS was significantly longer in the non-sarcopenic group than in the sarcopenic patient (25.9 versus 6.5 months, p = 0.029). Male sex, BMI, VFRA, SMRA, and SFRA were associated with the incidence of sarcopenia. SMI value could be used as a biomarker for OS in patients treated with Yttrium-90 radioembolization. Question The prognostic significance of CT-based sarcopenia and other morphometric parameters in patients with liver metastases and cholangiocarcinoma undergoing Yttrium-90 radioembolization remains unclear. Findings A high skeletal muscle index has been identified as an independent protective factor for overall survival in cancer patients treated with Yttrium-90 radioembolization. Clinical relevance The negative impact of CT-based sarcopenia has been confirmed in the context of Yttrium-90 radioembolization. Clinicians should strive to prevent the progression of sarcopenia or maintain skeletal muscle index in perioperative management

Selective accumulation of langerhans-type dendritic cells in small airways of patients with COPD

<p>Abstract</p> <p>Background</p> <p>Dendritic cells (DC) linking innate and adaptive immune responses are present in human lungs, but the characterization of different subsets and their role in COPD pathogenesis remain to be elucidated. The aim of this study is to characterize and quantify pulmonary myeloid DC subsets in small airways of current and ex-smokers with or without COPD.</p> <p>Methods</p> <p>Myeloid DC were characterized using flowcytometry on single cell suspensions of digested human lung tissue. Immunohistochemical staining for langerin, BDCA-1, CD1a and DC-SIGN was performed on surgical resection specimens from 85 patients. Expression of factors inducing Langerhans-type DC (LDC) differentiation was evaluated by RT-PCR on total lung RNA.</p> <p>Results</p> <p>Two segregated subsets of tissue resident pulmonary myeloid DC were identified in single cell suspensions by flowcytometry: the langerin+ LDC and the DC-SIGN+ interstitial-type DC (intDC). LDC partially expressed the markers CD1a and BDCA-1, which are also present on their known blood precursors. In contrast, intDC did not express langerin, CD1a or BDCA-1, but were more closely related to monocytes.</p> <p>Quantification of DC in the small airways by immunohistochemistry revealed a higher number of LDC in current smokers without COPD and in COPD patients compared to never smokers and ex-smokers without COPD. Importantly, there was no difference in the number of LDC between current and ex-smoking COPD patients.</p> <p>In contrast, the number of intDC did not differ between study groups. Interestingly, the number of BDCA-1+ DC was significantly lower in COPD patients compared to never smokers and further decreased with the severity of the disease. In addition, the accumulation of LDC in the small airways significantly correlated with the expression of the LDC inducing differentiation factor activin-A.</p> <p>Conclusions</p> <p>Myeloid DC differentiation is altered in small airways of current smokers and COPD patients resulting in a selective accumulation of the LDC subset which correlates with the pulmonary expression of the LDC-inducing differentiation factor activin-A. This study identified the LDC subset as an interesting focus for future research in COPD pathogenesis.</p

Anatomical Quantitative Volumetric Evaluation of Liver Segments in Hepatocellular Carcinoma Patients Treated with Selective Internal Radiation Therapy: Key Parameters Influencing Untreated Liver Hypertrophy.

Background: Factors affecting morphological changes in the liver following selective internal radiation therapy (SIRT) are unclear, and the available literature focuses on non-anatomical volumetric assessment techniques in a lobar treatment setting. This study aimed to investigate quantitative changes in the liver post-SIRT using an anatomical volumetric approach in hepatocellular carcinoma (HCC) patients with different levels of treatment selectivity and evaluate the parameters affecting those changes. This retrospective, single-institution, IRB-approved study included 88 HCC patients. Whole liver, liver segments, tumor burden, and spleen volumes were quantified on MRI at baseline and 3/6/12 months post-SIRT using a segmentation-based 3D software relying on liver vascular anatomy. Treatment characteristics, longitudinal clinical/laboratory, and imaging data were analyzed. The Student's t-test and Wilcoxon test evaluated volumetric parameters evolution. Spearman correlation was used to assess the association between variables. Uni/multivariate analyses investigated factors influencing untreated liver volume (uLV) increase. Results: Most patients were cirrhotic (92%) men (86%) with Child-Pugh A (84%). Absolute and relative uLV kept increasing at 3/6/12 months post-SIRT vs. baseline (all, p ≤ 0.005) and was maximal during the first 6 months. Absolute uLV increase was greater in Child-Pugh A5/A6 vs. ≥B7 at 3 months (A5, p = 0.004; A6, p = 0.007) and 6 months (A5, p = 0.072; A6, p = 0.031) vs. baseline. When the Child-Pugh class worsened at 3 or 6 months post-SIRT, uLV did not change significantly, whereas it increased at 3/6/12 months vs. baseline (all p ≤ 0.015) when liver function remained stable. The Child-Pugh score was inversely correlated with absolute and relative uLV increase at 3 months (rho = -0.21, p = 0.047; rho = -0.229, p = 0.048). In multivariate analysis, uLV increase was influenced at 3 months by younger age (p = 0.013), administered &lt;sup&gt;90&lt;/sup&gt; Y activity (p = 0.003), and baseline spleen volume (p = 0.023). At 6 months, uLV increase was impacted by younger age (p = 0.006), whereas treatment with glass microspheres (vs. resin) demonstrated a clear trend towards better hypertrophy (f = 3.833, p = 0.058). The amount (percentage) of treated liver strongly impacted the relative uLV increase at 3/6/12 months (all f ≥ 8.407, p ≤ 0.01). Conclusion: Liver function (preserved baseline and stable post-SIRT) favored uLV hypertrophy. Younger patients, smaller baseline spleen volume, higher administered &lt;sup&gt;90&lt;/sup&gt; Y activity, and a larger amount of treated liver were associated with a higher degree of untreated liver hypertrophy. These factors should be considered in surgical candidates undergoing neoadjuvant SIRT