Robot-assisted thoracic surgery versus video-assisted thoracic surgery for mediastinal lesions.

Background: Robot-assisted thoracic surgery (RATS) has become widely used for mediastinal procedures since 2018 when it was included in insurance coverage in Japan. Few studies have compared the surgical outcomes of RATS with the more established video-assisted thoracic surgery (VATS) approach to mediastinal surgery. We aimed to compare the perioperative outcomes of VATS and RATS to examine the advantages of the RATS approach in a single institutional cohort. Methods: A total of 144 patients who underwent VATS and 46 who underwent RATS mediastinal surgery between 2014 and 2022 were enrolled. We compared clinicopathological features such as age, sex, smoking history, respiratory function, surgical field, laterality, surgical procedure, board certification of the surgeon, and histology between the two groups. Perioperative outcomes including operation time, volume of blood lost, number of conversion cases to open surgery, duration of chest drainage, postoperative hospital stay, and postoperative complications were also reviewed. Results: The comparison of patient characteristics between the groups showed significant differences in median age (VATS, 52.5 years; RATS, 67.0 years; P=0.001), combined resection of surrounding tissues of the tumor (VATS, 2.1%; RATS, 10.9%; P=0.02), board certification of the surgeon (VATS, 53.5%; RATS, 100.0%; P<0.001), and histology (RATS group had a higher percentage of thymic epithelial tumors, P=0.01). Regarding perioperative outcomes, the median operation time was 120 min in the VATS group and 88 min in the RATS group, showing a significant difference (P=0.03). There were no significant differences in the volume of blood lost, incidence of conversion to open chest surgery, duration of chest drainage, postoperative length of stay in hospital, and incidence of perioperative complications. In the perioperative outcomes of cases operated on by board-certified surgeons, the median operation time (VATS, 117 min; RATS, 88 min; P=0.02) and median postoperative length of stay in hospital (VATS, 7 days; RATS, 6 days; P=0.001) showed significant differences, while other postoperative outcomes were not significantly different. Conclusions: RATS for mediastinal surgery is as safe as the VATS approach and may result in a shorter operative time and postoperative hospital stay. Further analysis of RATS for mediastinal surgery in a larger cohort is warranted.

Diagnosis and management of intercostal intramuscular hemangioma: an updated review.

BACKGROUND: Intramuscular hemangioma (IMH) is an uncommon type of hemangioma, and primary IMH of the intercostal muscle is even rarer. Only a few reports describe IMH of the intercostal muscle, and there are no review articles on this topic. We report our experience with a younger female patient, who underwent video-assisted thoracic surgery with tumor resection and review the previous literatures of intercostal IMH. CASE PRESENTATION: An asymptomatic 17-year-old woman showed a 29-mm, homogeneous, intrathoracic nodule in the left chest wall, attached to the second and third ribs on computed tomography. We performed exploratory thoracoscopic surgery and the tumor was excised without surrounding rib resection. Histopathologic examination of the surgical specimen revealed proliferation of small blood vessels within the surrounding striated muscle, leading to the diagnosis of intercostal IMH. The surgical margin was negative. The patient's postoperative course was uneventful, and there has been no evidence of recurrence for more than 18 months after surgery. CONCLUSIONS: We describe a case of intercostal IMH, who received tumor resection with clear excision margin without surrounding rib resection. Preoperative diagnosis is challenging due to its rarity, but intercostal IMH should be recalled as a differential diagnosis of chest wall tumor. Tumor excision without surrounding rib resection is acceptable for intercostal IMH, when there is a good possibility of achieving negative surgical margin.

[Robot-assisted Thoracic Surgery for Mediastinal Tumor].

In Japan, robot-assisted thoracic surgery (RATS) was introduced in thoracic surgery in 2001, but it did not become widespread. However, surgery for mediastinal tumors and lobectomy for lung cancer with RATS were covered by insurance in 2018 and are currently becoming popular as a general practice, following video-assisted thoracic surgery(VATS). Forty-six patients with mediastinal tumors were treated by RATS from February 2014 to November 2022 in our institution. Theoretically, the RATS approach is performed from one side in a semi-supine position under CO2 insufflation as with the VATS approach of our institution. In the case of extended thymectomy, a bilateral approach is performed by changing the patient's position. The median surgery time was 88 min, and the median surgery time in unilateral and bilateral approaches were 79 and 208 min, respectively. Blood loss during surgery was quite minimum, and no patients required conversion to VATS or thoracotomy. Regarding adverse events, postoperative bleeding was observed in one patient (2.2%). RATS has been successfully introduced and expanded safely for mediastinal tumors. Considering further expansion of RATS indications while conducting verification by comparison with VATS in the future is necessary.

Dynamics of thoracic endometriosis in the pleural cavity.

BACKGROUND: Thoracic endometriosis-related pneumothorax is a secondary spontaneous pneumothorax caused by thoracic endometriosis. Diaphragmatic endometriosis is well-studied, but visceral and/or parietal pleural lesions are not. Although surgery is an effective treatment, postoperative recurrence rates are unsatisfactory probably due to inadequate understanding of underlying pathophysiology. We aimed to clarify the clinicopathological features of thoracic endometriosis. METHODS: In total, 160 patients who underwent thoracoscopic surgery from a single institution with histopathologically proven thoracic endometriosis from January 2015 to December 2019 were included. Clinicopathological characteristics and surgical outcomes were assessed retrospectively. RESULTS: The cohort median age was 41 (range 22-53) years. Pneumothorax was right-sided in 159 (99.4%) and left-sided in only 1 (0.6%) case. Visceral and parietal pleural lesions were diagnosed in 79 (49.4%) and 71 (44.4%) patients, respectively. In total, 104 visceral pleural lesions and 101 parietal pleural lesions were detected. The S4 region and the dorsal 6th intercostal space contained the largest number of visceral pleural (66 lesions) and parietal pleural lesions (25 lesions), respectively. Histopathological evaluation revealed endometriotic tissues, existing in the outer external elastic layer in all lesions, were localized or invaded deeply. The median follow-up period was 370 (range, 6-1824) days. The Kaplan-Meier method revealed that the 1- and 2-year postoperative recurrence rates were 13.8% and 19.3%, respectively. CONCLUSIONS: Visceral pleural endometriotic lesions may be disseminated from the visceral pleural surface and infiltrate into the pleura. Intraoperatively, careful observation of the specific sites, such as the visceral pleura of S4 and the parietal pleura of 6th intercostal space, is important to reduce postoperative recurrence.

A successful trimodality therapy for difficult-to-diagnose primary mediastinal dedifferentiated liposarcoma, which originated from the perihilar fat and invaded the right lungs.

A 40-year-old man with high fever, hemoptysis, and fatigue showed a 10-cm mass in the middle and lower lobes of the right lung on computed tomography. Histological examination of transbronchial biopsy specimens showed sheets of small round tumor cells and mild staining for CD99. Primary Ewing sarcoma was suspected, and a trimodality therapy consisting of chemotherapy, intensity-modulated radiation therapy, and right pneumonectomy with surrounding tissue resection was performed. In surgical specimens, negative outcome of NKX2.2 in immunostaining and EWSR1 rearrangement in fluorescence in situ hybridization did not support the diagnosis of Ewing sarcoma. Positive immunostaining for MDM2 and CDK4 led to a diagnosis of dedifferentiated liposarcoma, which probably originated from an adipose tissue of the right perihilar mediastinum, and then invaded the lungs. The postoperative course was uneventful, without recurrence for more than 16 months.

Successful treatment of bilateral multiple pulmonary arteriovenous malformations in a patient with brain abscess and severe hypoxemia using a combination of transcatheter embolotherapy and surgical resection: a case report.

BACKGROUND: A pulmonary arteriovenous malformation is an abnormal dilated blood vessel that makes direct communication between a pulmonary artery and pulmonary vein and can be associated with hypoxemia or neurological complications, including brain abscess and cerebral infarction. Treatment of pulmonary arteriovenous malformation includes surgical resection and transcatheter embolotherapy, however the adaptation of therapies should be considered when a patient is in bad condition. CASE PRESENTATION: A 51-year-old man was admitted after developing fever, consciousness disorder, and hypoxemia. Magnetic resonance imaging of the brain showed a brain abscess. Bilateral pulmonary arteriovenous malformations were found by contrast computed tomography. Because of a family history of pulmonary arteriovenous malformation, a history of epistaxis, and the existence of oral mucosa telangiectasia, he was diagnosed with hereditary hemorrhagic telangiectasia and brain abscess caused by intrapulmonary right-to-left shunt. The brain abscess improved with antibiotic treatment; however, the administration of oxygen did not ameliorate his hypoxemia. His hypoxemia was exacerbated by positive pressure ventilation. Considering his systemic and respiratory condition, we considered surgery to involve a high degree of risk. After controlling his brain abscess and pneumonia, transcatheter embolotherapy was performed. This improved his systemic condition, enabling surgical treatment. CONCLUSIONS: This middle-aged patient suffering from brain abscess and severe hypoxemia with multiple pulmonary arteriovenous malformations was successfully treated by a combination of transcatheter embolotherapy and surgery. The adaptation and combination of therapies, as well as the sequence of treatments, should be considered depending on the patient status and lesions.

Surgical outcomes of pulmonary metastasectomy for head and neck cancer in the current era of advances in chemotherapy and immunotherapy.

OBJECTIVE: The innovation of novel systemic chemo/immunotherapy for metastatic head and neck cancer might contribute to prognostic improvement. We aimed to clarify the recent characteristics and outcomes of pulmonary metastasectomy for head and neck cancer. METHODS: Twenty-five patients who underwent pulmonary metastasectomy from January 2011 to December 2016 were included. The clinicopathological factors and survival were assessed by retrospective chart reviews. RESULTS: The median follow-up period was 39 months (range, 7-94 months). The median age was 66 years (range, 20-89 years), and 23 males were included. The primary tumor locations were as follows: pharynx (n = 12), nasal/paranasal cavity (n = 5), larynx (n = 4), and others (n = 4). The 5-year overall survival rate was 49%. In the univariate analysis, a history of local recurrence before pulmonary metastasis was an independent predictor of a poor prognosis. In 90% of patients with recurrence after pulmonary metastasectomy, the site of recurrence was the lung. Eight patients achieved long-term survival without any evidence of recurrence (median: 45 months). Molecular targeting chemotherapy and immune-checkpoint inhibitors were used in five patients with systemic recurrence after pulmonary metastasectomy, leading to preferable survival. CONCLUSIONS: In the current era of advances in systemic chemotherapy and immunotherapy, surgical indication has not changed for resectable pulmonary metastases and selected patients can still benefit from pulmonary metastasectomy. Further investigation is needed to clarify the significance of systemic therapy in patients with pulmonary metastasis of head and neck cancer.

Systematic method for a deep learning-based prediction model for gamma evaluation in patient-specific quality assurance of volumetric modulated arc therapy.

PURPOSE: This study aimed to develop and evaluate a novel strategy for establishing a deep learning-based gamma passing rate (GPR) prediction model for volumetric modulated arc therapy (VMAT) using dummy target plan data, one measurement process, and a multicriteria prediction method. METHODS: A total of 147 VMAT plans were used for the training set (two sets of 48 dummy target plans) and test set (51 clinical target plans). The dummy plans were measured using a diode array detector. We developed an original convolutional neural network that accepts coronal and sagittal dose distributions to predict the GPRs of 36 pairs of gamma criteria from 0.5%/0.5 mm to 3%/3 mm. Sixfold cross-validation and model averaging were performed, and the mean training result and mean test result were derived from six trained models that were produced during cross-validation. RESULTS: Strong or moderate correlations were observed between the measured and predicted GPRs in all criteria. The mean absolute errors and root mean squared errors of the test set (clinical target plan) were 0.63 and 1.11 in 3%/3 mm, 1.16 and 1.73 in 3%/2 mm, 1.96 and 2.66 in 2%/2 mm, 5.00 and 6.35 in 1%/1 mm, and 5.42 and 6.78 in 0.5%/1 mm, respectively. The Pearson correlation coefficients were 0.80 in the training set and 0.68 in the test set at the 0.5%/1 mm criterion. CONCLUSION: Our results suggest that the training of the deep learning-based quality assurance model can be performed using a dummy target plan.

Is conventional management of primary spontaneous pneumothorax appropriate?

OBJECTIVE: This study aimed to evaluate the recurrence rate after primary and secondary conservative treatments and to clarify the validity of current primary spontaneous pneumothorax management by comparing secondary conservative treatment and surgical outcomes. METHODS: Data from 166 patients with primary spontaneous pneumothorax treated at a single site between September 2015 and March 2019 were retrospectively evaluated. Patient characteristics of those who received primary conservative therapy (n = 166) and secondary conservative therapy (n = 28) were summarized. The outcomes from patients who experienced recurrence (n = 64) were compared based on those who underwent surgery (n = 24) and those who underwent secondary conservative therapy (n = 28). RESULTS: The post-treatment day 60 recurrence rate was 27.1 and 49.5% cases in the primary and secondary treatment groups, respectively, which was significantly higher after secondary treatment than after primary treatment with conservative therapy (p = 0.032). The post-treatment one-year recurrence rate was 13.5 and 57.9% in patients who underwent surgery and secondary conservative treatment, respectively; secondary conservative treatment resulted in a significantly higher recurrence rate than surgery (p < 0.001). CONCLUSIONS: There is evidence for guidelines that recommend surgery for recurrent primary spontaneous pneumothorax after primary conservative therapy based on its lower and more delayed post-treatment recurrence rate than secondary treatment with conservative therapy.

Establishment of anti-C1q monoclonal antibodies to measure serum C1q levels discriminating disease severity subsets of rheumatoid arthritis within 5 years of onset.

Objectives: To establish anti-C1q monoclonal antibodies which can measure serum C1q levels discriminating disease severity subsets of rheumatoid arthritis (RA) within 5 years of onset.Methods: In this multi-centre, longitudinal, observational study, 122 RA patients [102 females, baseline age 58.5 years, rheumatoid factor (RF) positivity 78.7%, serum C-reactive protein (CRP) 1.2 mg/dl, and concomitant methotrexate (MTX) 4.9 mg/week (29.5%)] within 5 years of onset (disease duration 21.0 months) were enrolled from 1985 to 2000. Patients were not treated by more than 8 mg/week of MTX or biologics which may strongly affect the course of joint destruction. Disease severity at 10-15 years of onset was classified according to the number of destructed joints of overall 68 joints on plain radiographs (36 patients were mild RA group involving only peripheral joints and 86 were severe RA group involving large axial joints). Baseline serum C1q levels were evaluated by ELISA with newly developed 4 monoclonal anti-C1q antibodies, and compared between two groups as well as conventional RA disease activity markers.Results: There were no significant differences between two groups in baseline conventional RA disease activity markers such as RF, erythrocyte sedimentation rate, CRP, and matrix metalloproteinase-3. However, compared to mild RA group, severe RA group showed higher baseline serum C1q levels (µg/ml) evaluated by anti-C1q monoclonal antibodies of no.33 (104.8 ± 22.3 vs. 118.3 ± 19.3; p = .0024), no. 40 (102.6 ± 21.9 vs 121.2 ± 22.3; p = .000069), no. 54 (102.1 ± 22.5 vs. 119.3 ± 26.9; p = .00052), and no. 76 (105.6 ± 21.8 vs. 122.6 ± 26.4; p = .00043). Receiver operating characteristic curve analysis revealed that in patients with serum C1q levels of ≥110.5 µg/ml (measured by antibody no. 40), 78.9% (75/95) belonged to severe RA group.Conclusion: Measuring serum C1q levels of RA within 5 years of onset by newly developed anti-C1q antibodies may be useful in predicting the prognosis of disease severity evaluated by the extent of joint destruction.

Shoulder and elbow evaluation of pitchers in National High School Baseball Invitational Tournaments and National High School Baseball Championships from 1993 to 2016 in Japan.

BACKGROUND: Shoulder and elbow examinations for pitchers have been performed in Japan's National High School Baseball Invitational Tournaments (NHSBITs) and National High School Baseball Championships (NHSBCs) since 1993. However, for years the results have not been analyzed. The purpose of this study was to evaluate changes in the condition of shoulders and/or elbows of pitchers from 1993 to 2016. MATERIALS AND METHODS: Pitchers in NHSBITs and NHSBCs, 1994-2016, were examined together with those who received a trial examination (Trial) in the NHSBC 1993. Shoulder and elbow symptoms were comprehensively graded into five categories; none, mild, moderate, severe and dysfunction. Standard plain radiographs of the shoulder and elbow were obtained. Average Annual Percent Changes (AAPCs) in the percentages of pitchers with symptoms and positive radiographic findings were analyzed. RESULTS: The percentages of pitchers with moderate or worse symptoms in the shoulder or elbow were 14.6% and 13.8%, respectively, in the Trial, 1.1% and 1.1% in NHSBITs and 1.3% and 2.0% in NHSBCs. The AAPC of pitchers with a symptomatic shoulder in NHSBITs was reduced over the study period, at -3.36% (P < 0.05), but that in NHSBCs was unchanged at -1.01%. The AAPCs of pitchers with a symptomatic elbow in NHSBITs and in NHSBCs decreased, at -3.13% and -3.33%, respectively (P < 0.05), while that of pitchers with residual apophyseal fragmentation at the ulnar collateral ligament insertion increased at +2.79% (P < 0.05). The decreased percentages of symptomatic pitchers suggest that joint condition is well controlled in high school days; however, the increased frequency of radiographic findings suggests the necessity of protection against overuse in younger players. CONCLUSIONS: The percentages of pitchers with symptomatic shoulders and elbows in NHSBITs and those with symptomatic elbows in NHSBCs have decreased over the 23 years. However, the increased frequency of residual medial humeral epicondyle apophyseopathy should be noted.

Nurse-like cells in rheumatoid arthritis: Formation of survival niches cooperating between the cell types.

Nurse-like cells (NLCs) established from bone marrow and synovial tissue of rheumatoid arthritis (RA) patients were found to promote maturation and differentiation of B lineage cells as well as T cells. In co-culture of RA-NLCs and B cells, tight physical interactions (pseudoemperipolesis) developed, which resulted in activation of both cell types. RA-NLCs also supported myeloid cell maturation, promoting their differentiation into tartrate-resistant acid phosphatase-positive mononuclear cells, which are precursor cells of osteoclasts. In RA synovial tissue, the characteristic dendritic-shaped cells (the DCs) were electron microscopically found to form direct physical interactions with adjacent plasma cells (PCs) suspecting to be pseudoemperipolesis. The numbers of PCs accumulating in various areas tended to correlate with the numbers of the DCs, which appeared to have RA-NLC functions forming survival niches for PCs. Immunohistochemical staining analysis indicated that CD14+ cells including the DCs formed survival niches for CD138+ PCs by RA-NLC functions. Quantitative dual immunofluorescence staining studies of these areas indicated that the majority of CD14+ cells were of myeloid lineage. These survival niches promoted by RA-NLCs appear to play important roles in supporting immunological functions in RA bone marrow and synovial tissues.

Serial block-face scanning electron microscopy combined with double-axis electron beam tomography provides new insight into cellular relationships.

To evaluate the advantages of combination of two advanced electron microscopic technologies such as serial block-face scanning electron microscopy and double-axis electron beam tomography, we analyzed the three-dimensional morphology of cellular relationships between dendritic and plasma cells in the synovial membrane from patients with rheumatoid arthritis, using the combined approach.

Abnormal networks of immune response-related molecules in bone marrow cells from patients with rheumatoid arthritis as revealed by DNA microarray analysis.

INTRODUCTION: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis that progresses to destruction of cartilage and bone. Bone marrow (BM) cells have been shown to contribute to this pathogenesis. In this study, we compared differentially expressed molecules in BM cells from RA and osteoarthritis (OA) patients and analyzed abnormal regulatory networks to identify the role of BM cells in RA. METHODS: Gene expression profiles (GEPs) in BM-derived mononuclear cells from 9 RA and 10 OA patients were obtained by DNA microarray. Up- and down-regulated genes were identified by comparing the GEPs from the two patient groups. Bioinformatics was performed by Expression Analysis Systemic Explorer (EASE) 2.0 based on gene ontology, followed by network pathway analysis with Ingenuity Pathways Analysis (IPA) 7.5. RESULTS: The BM mononuclear cells showed 764 up-regulated and 1,910 down-regulated genes in RA patients relative to the OA group. EASE revealed that the gene category response to external stimulus, which included the gene category immune response, was overrepresented by the up-regulated genes. So too were the gene categories signal transduction and phosphate metabolism. Down-regulated genes were dominantly classified in three gene categories: cell proliferation, which included mitotic cell cycle, DNA replication and chromosome cycle, and DNA metabolism. Most genes in these categories overlapped with each other. IPA analysis showed that the up-regulated genes in immune response were highly relevant to the antigen presentation pathway and to interferon signaling. The major histocompatibility complex (MHC) class I molecules, human leukocyte antigen (HLA)-E, HLA-F, and HLA-G, tapasin (TAP) and TAP binding protein, both of which are involved in peptide antigen binding and presentation via MHC class I molecules, are depicted in the immune response molecule networks. Interferon gamma and interleukin 8 were overexpressed and found to play central roles in these networks. CONCLUSIONS: Abnormal regulatory networks in the immune response and cell cycle categories were identified in BM mononuclear cells from RA patients, indicating that the BM is pathologically involved in RA.

Opinions of Japanese rheumatology physicians regarding clinical practice guidelines.

OBJECTIVE: To examine the views of rheumatology physicians concerning clinical practice guidelines in Japan, and changes to them following the dissemination of new guidelines for rheumatoid arthritis (RA) in 2004. DESIGN: Two cross-sectional questionnaire surveys, the first conducted before publication of new evidence-based RA clinical practice guidelines and the second conducted after implementation. SETTING: Rheumatology-focused practices in Japan. PARTICIPANTS: A random sample of physicians registered with the Japan Rheumatism Foundation who satisfied the registration criteria with regard to experience with RA care. RESULTS: The percentage of guideline users increased from 48 to 60% following publication of the new RA guidelines in 2004 (P < 0.01). The majority agreed that clinical practice guidelines support decision-making in practice, although the proportion of supportive responses decreased slightly in the second survey, from 83 to 77% (P < 0.01) for decision-making, while concern about restricting physician autonomy increased from 18 to 22% (P = 0.01). While only 39% of physicians felt that clinical practice guidelines would contribute to malpractice litigation, the proportion of physicians who were concerned that clinical practice guidelines would be used to bring legal action against providers was larger than that who expected they would defend providers (58 vs 30%, P < 0.001). CONCLUSIONS: Clinical practice guidelines are well accepted among Japanese rheumatology physicians, albeit that the proportion decreased slightly after the introduction of new guidelines. One reason for this may be concern about the use of the guidelines in malpractice litigation. To facilitate implementation, trends in physician support for the guidelines should be closely monitored.

Specifically modified osteopontin in rheumatoid arthritis fibroblast-like synoviocytes supports interaction with B cells and enhances production of interleukin-6.

OBJECTIVE: Osteopontin (OPN) is expressed by fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA), but its pathologic role is still obscure. The present study was undertaken to analyze the role of OPN in RA by focusing on its effects on cell-cell interactions between FLS and B lymphocytes. METHODS: FLS obtained from 10 patients with RA and 10 non-RA subjects and a B lymphocyte cell line were studied. The characteristics of OPN expression by FLS were analyzed by Western blotting, immunoprecipitation, and immunofluorescence studies. In cocultures of FLS and B lymphocytes, the effects of OPN on adhesion of B lymphocytes to FLS and the consequent production of interleukin-6 (IL-6) were analyzed in experiments involving overexpression and knockdown of OPN and inhibitory studies with an OPN-blocking antibody. In vivo, the expression of OPN in RA synovium was examined by immunohistochemistry. RESULTS: A specifically modified 75-kd form of OPN was predominantly expressed in RA FLS, and this was associated with expression of >200-kd thrombin-cleaved OPN that was crosslinked with fibronectin and localized on the surface of the FLS. In FLS-B lymphocyte cocultures, 75-kd OPN-positive FLS produced a significantly higher amount of IL-6 than did 75-kd OPN-negative FLS. When the FLS were separated from B lymphocytes or cultured alone, the production of IL-6 was low and was not significantly different between these 2 culture conditions. Moreover, OPN overexpression enhanced production of IL-6 in 75-kd OPN-positive FLS-B lymphocyte cocultures. Addition of the OPN-blocking antibody inhibited the adhesion of B lymphocytes to FLS. Immunohistochemical analyses revealed that localization of IL-6-positive cells coincided with the sites at which OPN and B lymphocytes were colocalized. CONCLUSION: Specifically modified 75-kd OPN was expressed by RA FLS. This form of OPN affected FLS-B lymphocyte interactions by supporting the adhesion of B lymphocytes to FLS and enhancing the production of IL-6.

Adenovirus-mediated gene transfer of adiponectin reduces the severity of collagen-induced arthritis in mice.

Adiponectin (APN) is a hormone released by adipose tissue with anti-inflammatory properties. The purpose of this study was to examine the therapeutic effects of systemic delivery of APN in murine arthritis model. Collagen-induced arthritis (CIA) was induced in male DBA1/J mice, and adenoviral vectors encoding human APN (Ad-APN) or beta-galactosidase (Ad-beta-gal) as control were injected either before or during arthritis progression. Systemic APN delivery at both time points significantly decreased clinical disease activity scores of CIA. In addition, APN treatment before arthritis progression significantly decreased histological scores of inflammation and cartilage damage, bone erosion, and mRNA levels of pro-inflammatory cytokines in the joints, without altering serum anti-collagen antibodies levels. Immunohistochemical staining showed significant inhibition of complement C1q and C3 deposition in the joints of Ad-APN infected CIA mice. These results provide novel evidence that systemic APN delivery prevents inflammation and joint destruction in murine arthritis model.

The interaction of monocytes with rheumatoid synovial cells is a key step in LIGHT-mediated inflammatory bone destruction.

Formation of osteoclasts and consequent joint destruction are hallmarks of rheumatoid arthritis (RA). Here we show that LIGHT, a member of the tumour necrosis factor (TNF) superfamily, induced the differentiation into tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) of CD14(+) monocytes cocultured with nurse-like cells isolated from RA synovium, but not of freshly isolated CD14(+) monocytes. Receptor activator of nuclear factor-kappaB ligand (RANKL) enhanced this LIGHT-induced generation of TRAP-positive MNCs. The MNCs showed the phenotypical and functional characteristics of osteoclasts; they showed the expression of osteoclast markers such as cathepsin K, actin-ring formation, and the ability to resorb bone. Moreover, the MNCs expressed both matrix metalloproteinase 9 (MMP-9) and MMP-12, but the latter was not expressed in osteoclasts induced from CD14(+) monocytes by RANKL. Immunohistochemical analysis showed that the MMP-12-producing MNCs were present in the erosive areas of joints in RA, but not in the affected joints of osteoarthritic patients. These findings suggested that LIGHT might be involved in the progression of inflammatory bone destruction in RA, and that osteoclast progenitors might become competent for LIGHT-mediated osteoclastogenesis via interactions with synoviocyte-like nurse-like cells.

Serum adiponectin concentrations correlate with severity of rheumatoid arthritis evaluated by extent of joint destruction.

Adiponectin is a hormone released by adipose tissue with antidiabetic, antiatherogenic, and anti-inflammatory properties. The present observational study focused on the relation between serum adiponectin level and the disease severity of established rheumatoid arthritis (RA). Ninety patients with more than 5-year diagnosis of RA and 42 age- and BMI-matched control were enrolled. The severity of RA was evaluated according to the number of destructed joints of overall 68 joints on plain radiographs (37 patients had mild RA and 53 had severe RA). Serum adiponectin level was significantly higher in the severe RA group (17.7+/-6.7 microg/ml) than in the control (9.1+/-3.8 microg/ml) and mild RA groups (13.9+/-6.5 microg/ml) (control vs. mild RA group, P<0.001; mild RA vs. severe RA group, P<0.01). These results suggest that increased number of joint destruction is associated with hyperadiponectinemia in established RA patients.