Search

Mycoplasma arthritis that caused by Mycoplasma bovis exhibit severe lameness. This disease is difficult to cure with antibiotics, but the detailed pathological mechanisms have not been fully clarified. In this study, we examined the effects of intra-articular inoculation with M. bovis on immunological responses in calf joints. We inoculated three calves each with M. bovis or phosphate buffer saline (control) into the right stifle joint and dissected them at 15 days postinoculation. Mycoplasma bovis-inoculated calves exhibited swelling of the stifle joint, increases in synovial fluid, fibrin deposition, and cartilage thinning. Intracellular M. bovis was detected in synovial tissues analyzed by immunohistochemistry and transmission electron microscopy. Messenger RNA expressions of interleukin (IL)-1β, IL-6, IL-8, IL-12p40, and IL-17A in synovial fluid cells and synovial tissues from M. bovis-inoculated calves were significantly higher than those from control calves. Protein levels of these cytokines in synovial fluid from M. bovis-inoculated calves were markedly higher than those from control calves. Our study clarified that inoculation with M. bovis into the stifle joint induced the production of inflammatory cytokines by synovial fluid cells and synovial tissues, causing a severe inflammatory response in joints. Additionally, M. bovis could invade cells in synovial tissues, which may have aided it in evading antibiotics and host immune surveillance.

Mycoplasma bovis(M. bovis) is a significant worldwide pathogen of cattle. Neutrophils have an important role in the innate immune response during infection withM. bovis. However, even though neutrophils accumulate inM. bovisinfection, the interaction ofM. bovisand neutrophils has not been fully elucidated. We attempted to elucidate the innate immune response of neutrophils stimulated withM. bovisand evaluate the transcriptome and functional analysis of bovine neutrophils stimulated withM. bovis. Proinflammatory cytokines, such as inducible nitric oxide (iNOS), which was the most increased gene in transcriptome analysis, were increased in quantitative polymerase chain reaction analysis of bovine neutrophils stimulated with live or heat-killedM. bovis. Nitric oxide and intracellular reactive oxygen species production of neutrophils stimulated withM. boviswas significantly increased. Neutrophils stimulated withM. bovisshowed an increased ratio of nonapoptotic cell death compared to unstimulated controls. We demonstrated that neutrophil extracellular traps (NETs) formation was not recognized in neutrophils stimulated with liveM. bovis. However, heat-killedM. bovisinduced NETs formation. We also showed the interaction withM. bovisand bovine neutrophils regarding proinflammatory cytokine gene expression and functional expression related to NETs formation. Live and killedM. bovisinduced innate immune responses in neutrophils and had the potential to induce NETs formation, but liveM. bovisescaped NETs.

Polyvinyl alcohol (PVA) composite materials made by mixing graphene and carbon nanotubes (CNTs) without chemically bonding them resulted in severe coagulation and deteriorated rigidity and ductility. We succeeded in improving the rigidity and ductility by proposing a G-CNT/PVA material fabricated by combining graphene and CNTs bonded through amide functionality. The proposed G-CNT/PVA has strength, rigidity, and ductility values of 24.0 MPa, 0.99 GPa, and 148.0%, respectively, at a nanocarbon content of 10 wt%. The electric resistance of the proposed G-CNT/PVA composite could be increased drastically by chemical bonding, while the nanocarbon (graphene, CNT) PVA composite materials, which had conventionally been conductive, now had sheet resistances of 87.02–0.300 kΩ/□. The G-CNT/PVA composite was found to have similar strength, rigidity, and ductility to conventional nanocarbon materials, whilst dramatically increasing resistivity; thereby, the G-CNT/PVA can be a suitable candidate for insulators of stretchable devices and conductive nanocarbon materials.

Previous works have demonstrated considerable variability in hospital cleanliness in Japan, suggesting that contamination is driven by factors that are currently poorly controlled. We undertook 16S rRNA sequence analysis to study population structures of hospital environmental microbiomes to see which factor(s) impacted contamination. One hundred forty-four samples were collected from surfaces of three hospitals with distinct sizes (“A”: >500 beds, “B”: 100–500 beds, “C”

Central nervous system (CNS) involvement is a serious complication in patients with diffuse large B-cell lymphoma (DLBCL) and evaluating CNS risk is an important issue. Using the standard international prognostic index (IPI) and CNS-IPI, a recently proposed model including IPI risk factors and adrenal/kidney involvement, we assessed CNS risk in 1220 untreated DLBCL patients who received R-CHOP without prophylaxis. According to the standard IPI, the cumulative incidences of CNS involvement at 2 years were 1.3, 4.6, 8.8, and 12.7% in the low-, low-intermediate-, high-intermediate-, and high-risk groups, respectively (p .001). This result is comparable with that of the CNS-IPI. Patients with breast involvement tended to have lower risk according to the standard IPI but showed frequent CNS involvement, similar to patients with testis involvement. The standard IPI is also a useful predictor of CNS involvement. Patients with breast/testis involvement would be candidates for prophylaxis regardless of the standard IPI risk.

Mycoplasma bovis is a pathogenic bacterium in bovines that causes huge global economic losses. Numerous factors play important roles in M. bovis pathogenesis; however, the host immune response involved in M. bovis infection has not been fully elucidated. We aimed to determine the characteristics of the host immune response to Mycoplasma infection. We evaluated the responsiveness of bovine peripheral blood mononuclear cells (PBMCs) stimulated with M. bovis via microarray analysis. The transcriptional abundance of innate immune-related genes IL-36A, IL-27, IFN-γ, and IL-17 in PBMCs increased after M. bovis exposure. Upon M. bovis infection, there was increased expression of the lymphocyte activated genes basic leucine zipper transcription factor (BATF) and signaling lymphocytic activation molecule family members 1 and 7 (SLAMF 1 and SLAMF 7) in PBMCs compared with that in unstimulated cells. The study revealed that the transcriptional abundance of innate immunity genes in PBMCs increased during M. bovis infection. This induced the activation of PBMCs, giving rise to an immune response, which is followed by the development of the inflammatory response. The results from this study could be used as the basis for the development of novel vaccine candidates against M. bovis.

Almost all re-entry capsules such as HAYABUSA re-entry capsule are dynamically unstable in transonic region. We researched dynamic stability characteristics of Mars entry capsule (70 deg sphere-cone capsule model) at low speed. In order to avoid significant sting interference, the tests were conducted using magnetic suspension balance system (MSBS). Angle of attack and Reynolds number effects on drag coefficients were measured. Dynamic stability derivatives were measured by forced oscillation method. Drag coefficients were barely affected by Reynolds number and angle of attack. The dynamic stability derivatives of Mars entry capsule were small negative value. These results showed that Mars entry capsule was slightly dynamically unstable., 形態: 図版あり, Physical characteristics: Original contains illustrations, 資料番号: DS1640260001

Mycoplasma bovis causes chronic arthritis in calves, presenting as osteolysis in affected joints. Matrix metalloproteinase-3 (MMP-3), an enzyme involved in cartilage degradation, is produced by synovial cells. Production of this proteinase is regulated by interleukin (IL)-1β, which is produced by mononuclear cells. Both factors are known to play important roles in osteolysis in human autoimmune and bacterial arthritis. However, the pathophysiology of Mycoplasma arthritis (MA) has not been elucidated. In this study, we evaluated the levels of MMP-3 and IL-1β in synovial fluid (SF) from MA calves and examined the effect of IL-1β on MMP-3 expression in bovine synovial cells in vitro. Levels of MMP-3 and IL-1β in SF from MA calves were significantly higher than those of clinically healthy calves. Mycoplasma bovis induced significant increases in the expression of IL-1β mRNA and protein in mononuclear cells, compared with cells not exposed to M. bovis. Interestingly, the supernatant of mononuclear cells stimulated with M. bovis contained high levels of IL-1β, which induced higher expression of MMP-3 mRNA and protein in synovial cells than direct stimulation by M. bovis. Recombinant bovine IL-1β also induced increased MMP-3 mRNA and protein expression in synovial cells. Our results indicate that M. bovis induces IL-1β expression by bovine mononuclear cells, and this cytokine then promotes MMP-3 production by synovial cells. These findings suggest that MMP-3 and IL-1β are key factors in the development of osteolysis in MA calves.

Mycoplasma bovis is a destructive pathogen that causes large economic losses in rearing cattle for beef and dairy worldwide. M. bovis causes suppression of and evades the host immune response; however, the mechanisms of host immune function involved in M. bovis mastitis have not been elucidated. The purpose of this study was to elucidate the characteristics of the bovine immune response to mycoplasmal mastitis. We evaluated the responsiveness of the bovine mammary gland following infusion of M. bovis. Somatic cell counts and bacterial counts in milk from the infected quarter were increased. However, the proliferation of peripheral blood mononuclear cells (blood MNCs) and mononuclear cells isolated from M. bovis-stimulated mammary lymph nodes (lymph node MNCs) did not differ from that in the unstimulated cells. Transcriptome analysis revealed that the mRNA levels of innate immune system-related genes in blood MNCs, complement factor D (CFD), ficolin 1 (FCN1), and tumor necrosis factor superfamily member 13 (TNFSF13) decreased following intramammary infusion of M. bovis. The mRNA levels of immune exhaustion-related genes, programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), lymphocyte activation gene 3 (LAG3), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) of milk mononuclear cells (milk MNCs) in the infected quarter were increased compared with those before infusion. Increase in immune exhaustion-related gene expression and decrease in innate immune response-related genes of MNCs in quarters from cows were newly characterized by M. bovis-induced mastitis. These results suggested that M. bovis-induced mastitis affected the immune function of bovine MNCs, which is associated with prolonged duration of infection with M. bovis.

We retrospectively analyzed the prognosis of patients with diffuse large B cell lymphoma (DLBCL) and a bulky mass at diagnosis. We retrospectively analyzed clinical data for 29 consecutive DLBCL patients with an initial bulky mass receiving R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy from 2004 to 2011. Bulky disease was defined as a measurable tumor mass >10 cm in diameter or a mediastinal mass >1/3 of the chest diameter. Patients with primary mediastinal large B-cell lymphoma were excluded. The median age was 65 years (20–78 years) and the maximum tumor diameter was 11.5 cm (10.0–17.0 cm). Complete response and partial response were achieved in 14 patients each, while 1 patient had progressive disease. The 3-year overall survival (OS) rate and progression-free survival (PFS) rate were 66 and 56 %, respectively. Findings on post-treatment positron emission tomography-computed tomography (PET–CT) were significantly associated with OS (34 % for patients with abnormal uptake vs. 75 % for those without, P = 0.014), and were also associated with PFS (36 vs. 83 %, respectively, P

This study evaluated the efficacy of central nervous system (CNS) prophylaxis using intrathecal methotrexate (IT-MTX) in patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively studied 322 patients who achieved first complete remission (CR) after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. The CNS prophylaxis consisted of four doses of IT-MTX (15 mg) with hydrocortisone (25 mg) administered after CR was achieved. Forty patients (12%) received CNS prophylaxis (group A) and 282 patients (88%) did not (group B). Three patients in group A (8%) and eight in group B (3%) experienced isolated CNS relapse during the first CR, although this difference was not statistically significant (p = 0.14). Ten of 11 CNS relapses occurred in the brain parenchyma with (n = 3) or without (n = 7) leptomeningeal involvement, and the remaining patient had exclusive leptomeningeal involvement. In patients with DLBCL attaining CR after R-CHOP, IT-MTX administration was insufficient to prevent CNS relapse.

Objectives The tumor microenvironment, including tumor-infiltrating lymphocytes and myeloid-derived cells, is an important factor in the pathogenesis and clinical behavior of malignant lymphoma. However, the prognostic significance of peripheral lymphocytes and monocytes in lymphoma remains unclear. Methods We evaluated the prognostic impact of the absolute lymphocyte count (ALC), absolute monocyte count (AMC), and lymphocyte/monocyte ratio (LMR) in 359 diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Results The median follow-up time of the surviving patients was 58 months. Low ALC and an elevated AMC were both associated with poor survival rates. Receiver operating characteristic curve analysis showed that LMR was the best predictor of survival, with 4.0 as the cutoff point. Patients with LMR ≤4.0 were more likely to have an aggressive tumor, and this was associated with poor treatment responses. Patients with LMR ≤4.0 at diagnosis had significantly poorer overall survival (OS) and progression-free survival (PFS) than those with LMR >4.0. Multivariate analysis, which included prognostic factors of the International Prognostic Index, showed LMR ≤4.0 to be an independent predictor for the OS (hazard ratio [HR], 2.507; 95% confidence interval [CI], 1.255–5.007; P = 0.009) and PFS (HR, 2.063; 95% CI, 1.249–3.408; P = 0.005). Conclusions The LMR at diagnosis, as a simple index which reflects host systemic immunity, predicts clinical outcomes in DLBCL patients treated with R-CHOP.

The 3q27 and 18q21 chromosomal translocations are major hallmarks in B-cell lymphoma. We aimed to determine the frequencies of these translocations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) and to evaluate their prognostic impact in the rituximab era. This study included 98 FL and 93 DLBCL patients whose abnormal karyotypes had been detected using G-banding. Patients uniformly underwent R-CHOP therapy : doxorubicin, cyclophosphamide, vincristine, prednisolone, and rituximab ; survivors were followed up for 29 months (median). The 3q27 and 18q21 translocations were detected in 14 and 77 FL patients and 14 and 22 DLBCL patients, respectively. Overall survival (OS) and progression-free survival (PFS) did not differ significantly between the groups with 3q27, 18q21, concurrent 3q27 and 18q21 translocations, and other chromosomal abnormalities for FL and DLBCL. There were no significant differences in OS and PFS between patients with 3q27 translocation-positive FL and those with 3q27 translocation-positive DLBCL or between the patients with 18q21 translocation-positive FL and those with 18q21 translocation-positive DLBCL. The presence of 3q27 and 18q21 translocations did not correlate with the clinical outcomes of FL or DLBCL patients following R-CHOP treatment. 〔J Clin Exp Hematop 53(2) : 107-114, 2013〕

The study aims to clarify the temporal changes in nursing care needs before and after surgery in acute care wards in hospitals. Surveys were carried out on nursing care needs of inpatients in a surgery ward of one hospital and also in two wards of another hospital. The results obtained from surveys are as follows,1) In surgery wards, Days 0 and 1 postsurgery were determined to be the period when the severity level of surgical patients is highest based on nursing care needs. The requirement of medical assistance practice with a level A of nursing care continues to be high for a few days after this initial care period, whereas that for day-to-day supportive practice with a level B of nursing care needs is largely reduced after that initial period. 2) The number of beds located close to the nursing base can be calculated as follows. Necessary beds for the patient with intensive nursing care located close to the nursing base is [number of operations ×3.29] beds when examining it from temporal changes in nursing care needs A, and [number of operations ×2.17] beds when examining it from temporal changes in nursing care needs B. 3) It was a difficult situation to be used for only perioperative patient in the bedroom which was close to the nursing base.

The maximum standard uptake value (SUVmax) of the whole body on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) reflects the tumor aggressiveness in non-Hodgkin lymphoma (NHL). To clarify the correlation between SUVmax at the biopsy site and the proliferation potential of tumor cells, we studied 36 patients with untreated NHL and five with untreated Hodgkin lymphoma (HL) by measuring the Ki-67 proliferation index (MIB-1 labeling index) in biopsy specimens. The measured MIB-1 labeling index was categorized into seven levels: nearly 0%, 5-20%, 21-40%, 41-60%, 61-80%, 81-95%, and nearly 100%. Twenty-four lymph nodes (LNs) and 17 extranodal (EN) sites were biopsied. The reviewed diagnosis was eight indolent lymphomas, two mantle-cell lymphomas, 26 aggressive lymphomas, and five HLs. A positive correlation was observed between the SUVmax at the biopsy site and the MIB-1 labeling index in the 36 patients with NHL (r = 0.69, p < 0.001). The correlations were also observed in LN group (r = 0.60, p = 0.006) and EN group (r = 0.87, p < 0.001), respectively. In the five patients with HL, the MIB-1 labeling index was uniformly categorized in nearly 100%. The SUVmax correlates with the proliferation potential in the case of NHL.

Starting a full-scale operation of computerized information system on medical treatment and patient care, it is possible to exchange information anywhere in wards through computer terminals. It is therefore that the location and the number of nursing bases are regarded as with small limitation to distribute near to patients' beds. Personal Nursing Base (PNB) is defined as a nursing base closely located to patients' beds either in the form of fixed setting or on wheels. The paper aims at clarifying the efficiency of PNB concept compared with ordinary nursing bases in terms of shortening walking distances of nursing staff.The followings are the results of the surveys carried out in four hospital wards;1) In three wards of the wards surveyed, PNB has been introduced. Moreover, the team nursing has been introduced in all wards, and each team is composed of one leader nurse and some member nurses.2) Member nurses often taking records and references at PNBs located in ward passages.3) In patients' rooms, activities of records and references are not frequently happened in the case of wards introducing computerized information system.4) Member nurses tried to communicate with a team leader or matron.5) Confirmation and discussion among nursing staff are not carried out by the mobile phones but by direct conversation.6) Computer simulation shows that one PNB in each working area is effective for shortening the walking distance of nurses while more numbers of PNB have no effect.

We retrospectively analyzed, and herein discuss, the outcomes of and prognostic factors for 35 untreated multiple myeloma patients less than 65 years of age who received induction therapies with bortezomib (Bor) and dexamethasone (BD) for the purpose of up-front autologous peripheral blood stem cell transplantation (SCT). The overall response rate was 77% (27 cases, including 4 [11%] complete response and 13 [37%] very good partial response cases). The rate of SCT accomplishment was 51% (18 cases). The 3 year-progression free survival (PFS) rate for the SCT group was significantly higher than that of the non-SCT group (41% vs 0%, P=0.0037). This result reflects the significantly more severe adverse effects of induction therapy for the non-SCT than the SCT group. Among reasons for SCT drop-out, 29% of cases suffered severe peripheral neuropathy with features such as irreversible numbness and pain. The analysis of PFS revealed a cytogenetic factor, favorable chromosomal type at diagnosis, to predict a better outcome (P values on univariate and multivariate analyses were 0.0004 and 0.0405, respectively). Our observations suggest establishment of induction therapy, aimed at reducing adverse effects and overcoming unfavorable cytogenetic abnormalities, to be necessary for improving the outcomes of patients with multiple myeloma.

The prognostic implications of infra-diaphragmatic (InD) versus supra-diaphragmatic (SpD) primary lesions in limited-stage diffuse large B-cell lymphoma (DLBCL) remains unknown. This retrospective study aimed to assess the prognostic impact of spD and InD lesions as well as presence of gastrointestinal (GI) involvements in adults with limited-stage DLBCL. We analyzed data from 178 patients with limited-stage DLBCL who were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy at 7 institutions of the Yokohama City University Hematology Group between 2003 and 2009. The median age was 63 years (range, 18-80 years). The primary sites were SpD in 109 patients, and InD in 69. No statistical differences in progression-free survival (PFS) or overall survival (OS) were observed between patients with SpD lesions and those with InD lesions. However, when patients with SpD lesions, InD lesions with (n=35), and without (n=34) GI involvement were compared, the presence of GI lesions was associated with favorable PFS. The multivariate analysis revealed that SpD or InD localization had no independent effect on PFS or OS, whereas the presence of GI lesions was correlated with favorable PFS (P=0.024, HR 0.09).

The levels of serum beta-2 microglobulin (β2MG) are determined mainly from lymphoid tissue. To examine its prognostic value in Hodgkin lymphoma (HL), we conducted a retrospective analysis. We analyzed 67 patients with HL diagnosed and treated at seven institutes of the Yokohama City University Hematology Group between 1998 and 2011. The patients included 40 males and 27 females with a median age of 41 years (range 16–81 years). The HL subtypes were nodular sclerosis classical HL in 37 patients, mixed cellular classical HL in 23, lymphocyte-rich classical HL in 6, and nodular lymphocyte-predominant HL in 1. The 4-year overall survival (OS) rate of all 67 patients was 89 %. Patients with β2MG levels ≥2.5 mg/L (n = 18) showed inferior progression-free survival (PFS; 4-year PFS rate, 42 %) and inferior OS (4-year OS rate, 60 %) compared to patients who had β2MG levels

Loss of human leukocyte antigen (HLA)-DR expression may be related to a poor prognosis of diffuse large B-cell lymphoma (DLBCL), and tumor-associated macrophages (TAMs) may influence tumor progression. We retrospectively reviewed 36 patients with newly diagnosed DLBCL who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy at Kanagawa Cancer Center in Japan from 2004 to 2010. HLA-DR expression by lymphoma cells was evaluated using flow cytometry, and TAMs in lymphoma tissue were detected by immunohistochemistry for CD68 as a marker of macrophages and CD163 as a marker of M2 TAMs. Three-year overall survival was, respectively, 100% versus 69.6% in the HLA-DR "bright" and "not bright" groups (p = 0.012). Patients from the HLA-DR "not bright" group with strong CD163 expression had a much worse prognosis than other patients. The HLA-DR status shown by flow cytometry can be used to predict the prognosis of patients with DLBCL receiving R-CHOP therapy and prognostic accuracy can be increased by also assessing TAMs.

A 43-year-old male with a history of autosomal dominant polycystic kidney disease (ADPKD) was admitted to our center with severe abdominal pain and was diagnosed with acute pancreatitis. CT showed multiple cysts in the liver and both kidneys along with ADPKD and a cystic mass, 4 cm in diameter, in the pancreatic head. The main pancreatic duct was dilated to 1 cm in diameter. The patient was diagnosed with acute pancreatitis due to intraductal papillary mucinous tumor (IPMT), and pancreatoduodenectomy was performed. Histologic examination revealed a multiloculated cystic tumor filled with mucin in the head of the pancreas. Microscopically, the tumor was diagnosed as adenocarcinoma and was found to have invaded the main pancreatic duct. Although, in addition to our case, only seven cases with association between ADPKD and malignant neoplasms have been reported, five of these cases had neoplasms arising from the pancreas. Therefore, we suggest that some genetic interactions may exist between ADPKD and pancreatic carcinogenesis.

The prognostic significance of extranodal metastasis (ENM) in colorectal cancer (CRC) is disregarded by the TNM classification system. The influence of ENM on survival among locally advanced CRC patients was examined.We reviewed retrospectively the clinical course of 263 patients who underwent surgical resection of locally advanced CRC at our Department between 2005 and 2009. We analyzed the prognostic factors with special reference to the clinicopathological factors of primary tumors.Thirty-eight cases of ENM were detected among patients with CRC. Compared with ENM negative cancers, ENM-positive cancers were associated with poorer tumor differentiation grade (p=0.026) and higher prevalence of TNM-stage (p0.0001), T-status (p=0.024), N-status (p0.0001) and postoperative recurrence (p0.0001). In univariate analysis, TNM-stage (p0.0035), T-status (p=0.002), N-status (p0.0024) and positive ENM (p0.0001) were significant predictors of poor survival. Multivariate analyses showed a positive ENM to be a highly significant independent predictor of mortality (HR=1.98, 95% CI=1.23- 3.23, p=0.0053). Survival analyses using Kaplan-Meier curves demonstrated that patients with ENM-positive cancers had significantly poorer survival than patients with ENM-negative cancers. Patients with ENM-negative cancers did not show significantly different survival from patients with node-negative cancers (p=0.272, data not shown).ENM appears to be a strong independent negative prognostic factor of poor survival in locally advanced CRC.

To demonstrate the feasibility of solo laparoscopic colorectal resection (SLCR) is performed by the laparoscopist only. This study is an evaluation of the feasibility of SLCR for patients with colorectal cancer.Fifty-one consecutive patients received SLCR from 2008 to 2009. The procedure was performed with four trocars and one laparoscopist. The short-term outcomes and complications were investigated retrospectively.The median age of the patients was 67 years (range 42-81). The median operating time for SLCR was 168 minutes (range 90-268). For one patient (1.96%) conversion to open surgery was required. Anastomotic leakage developed in 1 (1.96%) patient and ileus developed in 2 (3.9%). The median postoperative hospital stay was 8 (range 6-60) days without in-hospital deaths.In our experience, SLCR for patients with colorectal cancer is feasible and compares favorably with the standard technique. The diminished need for human operative assistance provides significant economic and organizational benefits.

Oxaliplatin, which is effective for colorectal cancer (CRC) in combination with 5-fluorouracil (5-FU) and leucovorin (LV), is widely used for metastatic CRC. With the increasing use of oxaliplatin, however, serious adverse events have been experienced, including hematologic and neurologic toxicities. The aim of this study was to evaluate whether tri-weekly modified FOLFOX6 (mFOLFOX6) maintenance chemotherapy is associated with a low incidence of severe hematologic and neurologic toxicities in the treatment of patients with metastatic CRC.We developed a new treatment regimen with mFOLFOX6 biweekly for 8-10 consecutive cycles (induction phase) followed by a 3-week rest period, after which treatment was resumed with cycles of tri-weekly mFOLFOX6 at standard doses (maintenance phase). Validity and complications were investigated retrospectively.Twenty-nine patients were enrolled in this study. The median progression-free survival (PFS) and overall survival (OS) times were 9.4 months and 23 months, respectively. All patients had peripheral neuropathy during treatment, but grade 3 neurotoxicity was observed in only 2 patients (6.9%).mFOLFOX6 maintenance chemotherapy was associated with a very low incidence of grade 3 hematologic and neurologic toxicities. The toxicities associated with PFS and OS were comparable to those reported in the treatment of patients with metastatic CRC. A tri-weekly mFOLFOX maintenance strategy of alternative treatment with a less-toxic regimen may reduce toxicity and maintain efficacy.

Central nervous system (CNS) events, including CNS relapse and progression to CNS, are known to be serious complications in the clinical course of patients with lymphoma. This study aimed to evaluate the risk of CNS events in patients with diffuse large B-cell lymphoma in the rituximab era. We performed a retrospective survey of Japanese patients diagnosed with diffuse large B-cell lymphoma who underwent primary therapy with R-CHOP chemoimmunotherapy between September 2003 and December 2006. Patients who had received any prophylactic CNS treatment were excluded. Clinical data from 1221 patients were collected from 47 institutions. The median age of patients was 64 years (range, 15-91 years). We noted 82 CNS events (6.7%) and the cumulative 5-year probability of CNS events was 8.4%. Patients with a CNS event demonstrated significantly worse overall survival (P < 0.001). The 2-year overall survival rate after a CNS event was 27.1%. In a multivariate analysis, involvement of breast (relative risk [RR] 10.5), adrenal gland (RR 4.6) and bone (RR 2.0) were identified as independent risk factors for CNS events. We conclude that patients with these risk factors, in addition to patients with testicular involvement in whom CNS prophylaxis has been already justified, are at high risk for CNS events in the rituximab era. The efficacy and manner of CNS prophylaxis in patients for each involvement site should be evaluated further.

Background: Malignant lymphoma with central nervous system (CNS) involvement has an extremely poor prognosis. We retrospectively studied the risk factors for CNS involvement in patients with diffuse large B-cell lymphoma (DLBCL) treated by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab (R) -CHOP chemotherapy. Patients and methods: We studied 375 consecutive patients who were newly diagnosed with DLBCL between 1996 and 2006. Patients with primary CNS involvement and patients who received CNS prophylaxis were excluded. All the patients received CHOP (n = 172) or R-CHOP (n = 203) chemotherapy. The following variables were assessed for their potential to predict CNS involvement: gender, age, serum lactate dehydrogenase (LDH) level, performance status, clinical stage, number of extranodal involvements, International Prognostic Index (IPI), bone marrow involvement, presence of a bulky mass, presence of B symptom, and treatment. Results: CNS involvement was observed in 13 cases (3.5%). In univariate analysis, LDH more than normal range, LDH more than twice as normal range, high IPI, bone marrow involvement, and systemic relapse were the predictors for CNS involvement. In multivariate analysis, no risk factors were detected for CNS involvement. The use of rituximab did not have an impact on CNS involvement. Conclusions: The incidence of CNS involvement dose not decrease in rituximab-era.

Heme oxygenase (HO)-1, a heme-degrading enzyme inducible by various stimuli, plays a key role in the regulation of inflammatory response in monocytes/macrophages. The serum HO-1 level is remarkably increased in patients with secondary hemophagocytic syndrome (HPS) or adult-onset Still’s disease. We measured serum HO-1 levels in patients with a variety of hematological diseases, including secondary HPS, by means of ELISA. Serum HO-1 levels were significantly higher in 22 patients with HPS (134.7 ± 116.2 ng/mL, P < 0.0001) at diagnosis than in 80 patients with other hematological diseases. The most effective cutoff point between HPS and other conditions was 14.5 ng/mL, with 100.0% sensitivity and 96.3% specificity. In HPS patients, the serum HO-1 levels showed the highest correlation with serum ferritin (r = 0.682, P = 0.0005), which reflects the disease activity of HPS. Moreover, both HO-1 and ferritin levels were reduced in parallel after successful treatment in patients with HPS, irrespective of underlying diseases. However, HO-1 levels were not elevated in patients with other causes of hyperferritinemia. These data demonstrate that serum HO-1 can distinguish secondary HPS from other hematological diseases, including those associated with hyperferritinemia.

A 14-year-old girl was referred for a large tumor of the left kidney, with intraspinal and vertebral metastases. Left nephrectomy and intraspinal tumor resection were performed. The histology of both tumors was nephroblastoma with no anaplasia and favorable histology, and they were diagnosed as stage IV. The tumor bed and vertebras were irradiated. We started chemotherapy according to the DD-4A regimen of Japanese Wilms' Tumor Study Group. The vertebral metastasis was additionally irradiated. The patient has remained in disease-free remission for 45 months after the surgical resection. Intensive multimodality therapy including DD-4A regimen of National Wilms' Tumor Study can result in long-term disease-free remission.

International audience; OBJECTIVES: Platelet activation, which may lead to thrombus formation, is poorly understood after valve surgery when analysed by flow cytometry. It is still unclear whether platelet activation is due to the implanted prosthesis itself or to its aortic or mitral position. The present prospective study was aimed at assessing platelet P-selectin expression, platelet-leukocyte conjugate formation and platelet microparticles and comparing biological, bileaflet and tilting disc valvular prostheses in aortic position. METHODS: Thirty-three patients were included (15 bioprostheses, 11 bileaflet and 7 tilting disc mechanical valves). Blood samples were analyzed by flow cytometry immediately before surgery, on postoperative day 8 (D8) and 2 months after surgery (M2). RESULTS: At D8, patients with bileaflet valves demonstrated a significant increase in platelet-leukocyte conjugates and in platelet microparticles whereas only platelet-monocyte conjugates were significantly increased in patients with bioprostheses. At M2, platelet activation had returned to the basic level observed prior to surgery in the bileaflet valve group whereas, it was still increased in the bioprosthesis group. Neither at D8 nor at M2 did patients with tilting disc mechanical valves demonstrate any platelet activation. CONCLUSIONS: Platelet activation after aortic valve replacement was observed with the use of bioprostheses and bileaflet mechanical valves, but not with tilting disc mechanical valves.

Background: Some studies evaluating differences in clinical features and outcome between supra-diaphragmatic (SpD) and infra-diaphragmatic (InD) primary lesions in Hodgkin lymphoma (HL) have been reported (Cancer 1991;68:1476-1481: Haematologica 2006;91:32-39). In regard to non-Hodgkin's lymphoma, there exist some previous studies that report on outcomes of patients with gastrointestinal (GI) involvement (J Clin Oncol 2005;23:2797-2804; Cancer 2003;97:2462-73). However, no studies comparing outcome between SpD and InD primary lesions have been conducted for patients with diffuse large B cell lymphoma (DLBCL). Thus, we retrospectively evaluated outcome differences between SpD and InD lesions, and the prognostic impact of GI involvement in limited-stage DLBCL. Patients and Methods: We analyzed data from 178 patients with limited-stage DLBCL who were treated with rituximab plus cyclophosphamide (CPA), doxorubicin (DXR), vincristine (VCR), and prednisone (PSL; R-CHOP) therapy at 7 institutions of the Yokohama City University Hematology Group between 2003 and 2009. Patients who needed a dose reduction of more than 20% per cycle of R-CHOP therapy were excluded from the study. We classified the patients into SpD lesions group or InD lesions group according to the location of lesions. The patients in the InD lesions group were subsequently classified into InD with GI involvement group or InD without GI involvement group according to the presence of GI lesions. The impact of primary site location on patient outcome was evaluated using univariate and multivariate analyses. Results: The study cohort included 104 men and 74 women with a median age of 63 years (range, 18-80 years). All patients were categorized as Ann Arbor stage I (n = 66) or II (n = 112). The primary sites were SpD in 109 patients and InD in 69 patients. There were no significant differences in distribution between the SpD lesions group and the InD lesions group with respect to age, sex, Ann Arbor stage, the IPI score, ECOG performance status, and the presence of a bulky mass. Significantly more patients in the InD group presented with B symptoms (P = 0.003). Comparing patients in the InD lesions group presenting with (n = 35) or without (n = 34) GI involvement, resulted in similar findings with respect to clinical characteristics. The group with GI involvement consisted of 20 patients with stomach lesions (57%), 7 with small intestine lesions (20%), 7 with colon lesions (20%), and 1 with both colon and rectum lesions (3%). The median observation period for all surviving patients was 52 months (range, 3 – 94 months). The 4-year progression-free survival (PFS) and overall survival (OS) rates of all 178 patients were 84% and 91%, respectively. Twenty-six patients presented with disease progression after R-CHOP therapy. In total, 16 patients died: 14 of recurrent lymphoma, 1 of secondary malignancy (acute lymphoblastic leukemia), and 1 as a result of an accident. No statistical differences in PFS or OS were observed between patients with SpD lesions and those with InD lesions (4-year PFS rate: 87% and 81%, respectively; P = 0.31; Fig 1; 4-year OS rates: 92% and 86%, respectively; P = 0.31). When patients were classified and assessed according to primary site location, and their GI involvement status, which were SpD group, InD with GI involvement group, or InD without GI involvement group, the PFS rate was higher in SpD group (4-year PFS rates 86%), and InD with GI involvement group (4-year PFS rates 97%) than InD without GI involvement group (4-year PFS rates 67%; P = 0.036, and P = 0.003, respectively; Fig 2). However, no significant differences in regard to OS were observed among 3 groups (4-year OS rates: 93%, 97%, and 78%, respectively; P = 0.09). The multivariate analysis revealed that SpD or InD localization had no independent effect on PFS or OS. In addition, primary sites according to the presence of GI lesions were incorporated into the multivariate analysis, whereas SpD, and InD were excluded as overlapping variable. The multivariate analysis revealed that the presence of GI involvement in patients with InD lesions was an independent prognostic factor in predicting favorable PFS (P = 0.024, HR 0.09). Conclusion: No outcome differences were observed between SpD and InD lesions in limited-stage DLBCL. However, the presence of GI lesions was associated with a favorable prognosis. Disclosures No relevant conflicts of interest to declare.

Background: Tumor lysis syndrome (TLS) is a severe complication associated with anticancer chemotherapy and may become fatal. Serum uric acid (sUA) is known to play an important role in the pathology of TLS. Rasburicase, which catalyzes the oxidation of sUA to its soluble metabolite, has often been used for the prophylaxis and management of TLS. However, the optimal dose has not yet been established. Methods: We retrospectively collected data on 23 patients with non-Hodgkin lymphoma who received rasburicase at single institution between May 2012 and December 2013 for the prophylaxis of TLS before first-line chemotherapy, and we assessed clinical background, response to the drug, and occurrence of TLS. Results: The median age of the patients was 59 years (range, 28–85 years), and 14 patients were male. With regard to patients' TLS disease risk, 2 cases were designated as low risk, 6 were designated as intermediate risk, and 6 were designated as high risk. All patients had elevated serum lactate dehydrogenase levels with a high tumor burden and/or aggressive disease. The median level of sUA was 7.8 mg/dL (range, 1.3–16.4 mg/dL) and was considered elevated in 12 patients. The mean total dose of rasburicase per body weight was 0.24 mg/kg (range, 0.10–0.66 mg/kg). Patients with low or intermediate risk disease were all well managed with only 1 day of drug administration. Among the high-risk disease patients, 6 required longer duration of administration, up to 3 days, but none of the patients developed clinical TLS. Conclusions: A reduced dose of rasburicase may be effective for prophylactic TLS treatment in Japanese lymphoma patients.

Background Peripheral T-cell lymphoma (PTCL) is known to have an aggressive clinical course and be associated with poor survival. The International Prognostic Index (IPI) score and the Prognostic Index for T-cell lymphoma (PIT) have been suggested as methods to predict the prognosis of PTCL. Ferritin, the iron storage protein, is associated with chronic inflammation. Although higher levels of serum ferritin are detected in many cancer patients, the significance of elevated serum ferritin as a prognostic factor for lymphoma has yet to be established. Thus, our retrospective study aimed to examine the prognostic value of serum ferritin levels in PTCL. Patients and Methods Serum ferritin levels were evaluated in 78 patients with PTCL, who were treated with anthracycline-containing regimens in 8 institutions affiliated to the Yokohama City University Hematology Group between 1998 and 2011. Fourteen patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP); 44 receivedpirarubicin, cyclophosphamide, vincristine, and prednisone (THP-COP); 3 received THP-COP followed by radiotherapy; 3 received up-front autologous peripheral blood stem cell transplantation; and 14 received THP-COP at 2-week intervals in a clinical trial. Results The study population comprised 50 male and 28 female patients with a median age of 64 years at the time of diagnosis (range, 16–83 years). With regard to the PTCL subtype, 39 patients had PTCL, not otherwise specified, and 39 had angioimmunoblastic T-cell lymphoma. Twelve patients had localized disease and 66 patients had advanced Ann Arbor stage lymphoma. Twenty-three patients had a poor Eastern Cooperative Oncology Group performance status (PS) of 2–4. B symptoms were present in 34 patients. Risk stratification according to the IPI was as follows: low risk, 9 patients; low–intermediate risk, 20 patients; high–intermediate (HI) risk, 30 patients; and high (H) risk, 19 patients. According to the PIT, 4 patients were categorized into group 1, 25 into, group 2 , 28 into, group 3, 21 into, as group 4. The median observation period for the surviving patients was 50 months. The median serum ferritin level was 183 ng/ml (range, 5–14,622 ng/ml). Factors associated with a poor overall survival (OS) in univariate analysis were HI and H risk status with regard to IPI (P = 0.024), assignment to group 3 or 4 with regard to PIT (P = 0.017), poor performance status (P< 0.001), and ferritin levels ≥ 300 ng/ml (P< 0.001). The 4-year OS rate of all 78 patients was 54%. The 4-year OS rate was poorer in patients with serum ferritin levels ≥300 ng/ml (n = 21) than in those with serum ferritin levels< 300ng/ml (n = 57; 22% vs. 65%; P< 0.001) (Figure). Multivariate analysis including each factor comprising the IPI (age, lactate dehydrogenase level, PS, Ann Arbor stage, and number of extranodal lesions), gender, bone marrow involvement, and serum ferritin level showed that poor PS (P = 0.002, relative risk [RR] 3.6) and a serum ferritin level ≥300 ng/ml (P = 0.014, RR 2.7) were independent risk factors for poor OS. Conclusion The serum ferritin level is a useful prognostic marker for PTCL. Disclosures: No relevant conflicts of interest to declare.

Background The prognosis of diffuse large B-cell lymphoma (DLBCL) has considerably improved during the last decade, mainly due to the addition of rituximab to chemotherapy. However, a significant proportion of patients still experience relapses after achieving first complete remission (CR), leading to poor survival. Although a specific predictor of relapse of non-Hodgkin’s lymphoma has not been identified thus far, recently, the peripheral blood lymphocyte/monocyte ratio (LMR) at diagnosis, which reflects the host’s immune status, was reported to predict clinical outcomes in DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, the significance of LMR as a predictor of relapse in DLBCL patients in remission is not clear. The aim of this study was to assess whether LMR at 6 months after remission is a predictor of relapse after R-CHOP therapy in DLBCL patients. Methods From 2003 to 2009, 357 consecutive DLBCL patients were diagnosed, treated with R-CHOP, and followed up at 1 of the 7 participating hospitals in Japan. Of these, 315 DLBCL patients achieved CR after 6–8 cycles of R-CHOP therapy. Among the 315, those who were in remission for more than 6 months (n = 280) were enrolled in this study. The cumulative incidence of relapse was calculated from 6 months after CR to the first subsequent relapse or last follow-up. The effects of risk factors of relapse were assessed in univariate and multivariate Cox regression analyses. In multivariate analysis, risk factors tested at the time of diagnosis, confirmed remission and 6 months after remission included gender, International Prognostic Index at diagnosis (age > 60 years, elevated lactate dehydrogenase level, poor Eastern Cooperative Oncology Group performance status [ECOG PS], the presence of 2 or more extranodal involvement sites, and advanced clinical stage), and LMR ≤ 3.3. Results The study included 161 men and 119 women, with a median age of 64 years at diagnosis (range, 18–80 years). The median LMR at 6 months after remission was 3.7 (range, 0.5–18.0). The median observation period for surviving patients was 63 months. In all, 35 (12.5%) patients had confirmed relapse after achieving first CR, with a median time to relapse of 23 months (range, 6–61 months). The estimated 5-year cumulative incidence rate of relapse for the entire cohort was 14.7%. According to the LMR at 6 months after remission, the 5-year cumulative incidence rate for LMR ≤ 3.3 was 17.0% compared to 12.7% for LMR > 3.3 (P = 0.188). In the univariate analysis, advanced clinical stage at diagnosis (hazard ratio [HR] = 2.61, 95% confidence interval [CI], 1.33–5.13, P = 0.005) and poor ECOG PS at diagnosis (HR = 2.62, 95% CI, 1.19–5.77, P = 0.017) were associated with the occurrence of relapse. Multivariate analysis identified advanced clinical stage at diagnosis (HR = 2.42, 95% CI, 1.11–5.27, P = 0.026) and LMR ≤ 3.3 at 6 months after remission (HR = 2.10, 95% CI, 1.01–4.35, P = 0.047) as the risk factors for relapse. Conclusions The LMR at 6 months after remission is an independent predictor of relapse in first CR in DLBCL patients treated with R-CHOP. Disclosures: No relevant conflicts of interest to declare.

Background Serum beta-2 microglobulin (β2MG) is an HLA class I protein. Its concentration is determined mainly from lymphoid tissue. Previous reports demonstrated that serum β2MG levels tend to increase with the stage of Hodgkin lymphoma (HL; Eur. J. Cancer. 1979; 15: 791-796: Cancer. 1980; 45: 318-326). Thus, this retrospective study aimed to examine the prognostic value of serum β2MG levels in HL. Patients and Methods We analyzed the data of 67 patients with previously untreated HL whose serum β2MG levels had been evaluated at diagnosis and who were treated at 7 institutions of the Yokohama City University Hematology Group between 1998 and 2011. We assessed the associations between survival and serum β2MG levels, all factors comprising the international prognostic index (sex, age, Ann Arbor stage, albumin levels, hemoglobin levels, white blood cell counts and lymphocyte counts at diagnosis), performance status, lactate dehydrogenase levels, and number of extra-nodular lesions, using univariate and multivariate analyses. Results The patients included 40 men and 27 women with a median age of 41 years (range, 16- 81 years). The HL subtype was nodular sclerosis classical HL in 37 patients, mixed cellular classical HL in 23 patients, lymphocyte-rich classical HL in 6 patients, and nodular lymphocyte-predominant HL in 1 patient. The Ann Arbor stage of HL was stage I in 9 patients, stage II in 30 patients, stage III in 19 patients, and stage IV in 9 patients. All the patients were treated with doxorubicin, bleomycin, vinbrastine, and dacarbazine (ABVD) therapy alone (n = 37) or ABVD therapy plus involved-field radiation therapy (IFRT; n = 30). The clinical stage of HL in the patients treated with ABVD therapy alone was stage II in 11 patients, stage III in 17, and stage IV in 9. The clinical stage of HL in the patients who received ABVD plus IFRT was stage I in 9 patients, stage II in 19, and stage III in 2. The median observation period in the surviving patients was 53 months (range, 5- 123 months). The 4-year progression-free survival (PFS) and overall survival (OS) rates of all 67 patients were 76% and 89%, respectively. Thirteen patients had disease progression after treatment of HL. In total, 9 patients died: 3 of recurrent lymphoma, 2 of infection, 1 of acute circulatory failure during chemotherapy for HL, 1 of secondary malignancy, 1 of brain hemorrhage, and 1 of pulmonary chronic graft versus host disease. The patients with serum β2MG levels ³2.5 µg/mL showed inferior PFS (n = 18; 4-year PFS rate, 42%) compared to those with serum β2MG levels below Conclusion Therefore serum β2MG level at diagnosis is a useful prognostic marker for patients with HL. Disclosures: No relevant conflicts of interest to declare.

Background Vascular lesion is one of most critical manifestations in patients with Behcet’s disease (BD), whereas there are some regional differences in the clinical features. Objectives This study characterizes clinical features and therapeutic approaches in Japanese vasculo-BD patients. Methods We retrospectively analyzed clinical data of 105 BD patients (male 71, female 34) with vascular lesions from 6 institutes which belong to Behcet’s Disease Research Committee, Ministry of health, labor, and Welfare, Japan. All patients met the Japan Diagnostic Criteria (2003), and presented with more than one vascular lesions in arteries and veins, but superficial thrombophlebitis was not included as vascular involvement. Results The diagnosis of BD in the enrolled patients was made at 35.5 years old, while the initial vascular event appeared at 42.7 years old. Frequency of HLA-B51 positive was lower in vasculo-BD patients (41%) than the others (51%). Eye involvement and epididymitis were less frequent in vasculo-BD patients, whereas intestinal lesions were more commonly found. The vascular lesions were distributed in the venous system (71%), the arterial system (31%) and the pulmonary vessels (25%), all of which were determined by imaging modalities including contrast CT, angiography, ultrasonography, pulmonary perfusion scan, MRI, and PET. As treatment, corticosteroids and immunosuppressants such as MTX, cyclosporine, and azathioprine were used in 73% and 35%, respectively, whereas 18 patients (17%) had surgical operation. Of 5 patients treated with Infliximab, 2 patients received endovascular or surgical intervention for the vascular lesions, resulting in improvement. Any anticoagulant and/or anti-platelet agents were used in 82.9 % of patients, including warfarin in 58.1% and aspirin 49.5%. These agents-related bleeding events were found 9 times in 8 patients, all of them were minor and recovered after discontinuation of the agents. Eight patients have died, and 4 of them were associated with vascular involvement including hemoptysis in 2 patients who did not receive anticoagulant and anti-platelet agents. Conclusions The present study shows that the distribution of vascular lesions and therapeutic approaches in Japanese BD patients were similar with those from other countries according to previous reports. However, our data suggest that fatal pulmonary bleeding caused by anticoagulant and anti-platelet agents is rare in Japanese BD patients, though these agents are commonly used in Japan. Disclosure of Interest None Declared

Background Though musculoskeletal ultrasonography (MSUS) is largely recognized as a useful imaging modality to enhance disease assessment and management in patients with rheumatoid arthritis (RA), it remains a challenge that MSUS are poor objectivity and reliability in evaluating RA lesions. Objectives To improve objectivity of MSUS, we developed the two programs; automatic acquisition of the most appropriate Power Doppler (PD) gain (Quick Scan) and automatic extraction of appropriate image. In this study we assessed the efficacy and validity of these programs. Methods Joints of RA patients were evaluated with Aplio XG possessing the two new programs by 2 experts in MSUS blindly each other. First, to assess validity of Quick Scan, the variation in PD gain values obtained by using Quick Scan between two examiners was compared to those obtained manually. Next, one examiner conventionally adjusted PD gain and captured appropriate still images which showed maximum PD signals indicating synovitis, whereas the other examined the same joints by using Quick Scan and storing movies of a whole extent of the joints. According to an algorithm that chooses the image of maximum PD pixel ratio after excluding occasions of increased PD signals by moving noise or normal blood flow, several images were automatically extracted from movies. PD scores of still and moving images as well as those of the automatically-extracted images were evaluated later by another expert. PD signals were graded from 0 to 3 with semi-quantitative method in each joint. Results Seventeen cases, 62 joints, and 117 lesions were assessed. After pushing key of Quick Scan, PD gain was adjusted automatically within a second. The evaluation of PD gain adjustment was done in 30 joints and the gain values obtained by Quick Scan tended to be more similar between the examiners (Δ1.33±0.92) than those adjusted manually (Δ2.60±4.47) (p=0.067). PD scores evaluated from moving images and those of the automatically-extracted images from the movies were well matched (κ coefficient 0.85) and 75% of the automatically-extracted images coincided with the sites of movies which the expert chose for evaluating PD score. Concordant rate between PD scores of conventionally-captured images and those of the automatically-extracted images was also good (κ coefficient 0.74). These results showed that the image-extracted algorithm as well as usage of two programs to evaluate synovitis was considered reasonable and proper. Moreover, the scores of automatically-extracted images were higher than those of still images in 17 joints, which suggested that the appropriate PD gain obtained by Quick Scan and automatic extraction program without subjective eyes may contribute to prevent the examiners from missing PD signals. Conclusions These new programs enable MSUS operators to evaluate arthritis objectively, efficiently, and accurately. Disclosure of Interest None Declared

Background Although “clinical remission” has been a realistic goal of treatment in rheumatoid arthritis (RA), its definition is still controversial. In fact, progressive joint destruction is often observed even during persistent DAS28-based remission, 12 suggesting that the criteria are not satisfactory for target of treatment. There is accumulating evidence that ultrasonography (US) is helpful for judgment of the disease remission. Objectives Here we investigated whether US can predict Boolean remission in RA patients who had been satisfied with DAS28-based remission criteria. Methods Twenty-seven RA patients who had been in DAS28-based clinical remission (DAS28-ESR Results Five patients dropped out of the study due to clinical flare-up, while DAS28 remission had been maintained for 2 years in 22 patients, including 16 patients (73%) who met Boolean remission criteria at the end of study. Both total GS score and total PD score at baseline were significantly lower in Boolean remission group than non-remission group (7.75 ± 6.02 vs 16.0 ± 11.3, p = 0.012, and 1.06 ± 1.14 vs 6.33 ± 6.99, p = 0.020, respectively). There was no significant difference in other baseline parameters, including duration of disease, duration of remission, mTSS, and disease activity composite parameters between the two groups. The cut-off values for total GS and PD scores calculated from the ROC curves were total GS scores > 7 and total PD scores > 2. The area under the ROC curves for total GS and PD scores were 0.82 (95% CI = 0.60 to 0.95, p = 0.0004) and 0.82 (95% CI = 0.60 to 0.95, p = 0.013). Among the factors for Boolean remission criteria at 2 years, high patient global assessment score was associated with high total GS score at the entry, while high swollen joint count was related to high total PD score. On the other hand, progression of mTSS was associated with high total PD score, but not with total GS score, at the entry. Conclusions This study shows that none or low grade of GS and PD findings in US are associated with the achievement of Boolean remission in near future. Thus, US is essential for assessment and prediction of “deeper remission” of RA. References Mulherin D, Fitzgerald O, Bresnihan B. Clinical improvement and radiological deterioration in rheumatoid arthritis: evidence that the pathogenesis of synovial inflammation and articular erosion may differ. Br J Rheumatol 1996; 35 :1263-8. Molenaar ET, Voskuyl AE, Dinant HJ, et al. Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission. Arthritis Rheum 2004; 50 :36-42. Disclosure of Interest None Declared

Background “Clinical remission” has been a realistic goal of treatment in rheumatoid arthritis (RA). However, there is evidence that subclinical synovitis is associated with progression of structural damage even after achieving clinical remission, 12 which could reflect the inadequate sensitivity of the conventional clinical approaches to detect synovitis. Objectives Here we prospectively assessed RA patients in clinical remission to clarify whether ultrasonography (US) can predict long-term radiographic progression during persistent clinical remission. Methods Twenty-seven RA patients in clinical remission (DAS28-ESR Results Twenty-two patients maintained clinical remission during the 2-year follow-up, while 5 had clinical flare-up. The persistent remission group was further divided into 7 progressing cases (32%) and 15 non-progressing cases (68%) based on X-ray findings. There was no significant difference in age (51.4±7.74 vs 59.2±12.1 years, p =0.15) and disease duration (7.3±3.9 vs 6.7±3.7 years, p =0.74) at entry between the two groups. Progressive radiographic destruction was strongly associated with total PD score at entry, but not with total GS score. Progressive radiographic destruction in any joints was found in 7 of 11 patients (64%) having more than 2 of total PD score at entry, but none of the other 11 having PD score 0 or 1. There was no significant association of therapeutic agents with radiographic progressing. When the persistent clinical remission group was further divided into 12 TNF inhibitor (TNFi)-free and 10 TNFi-treated cases, total PD score was significantly higher in patients with radiographic progression than in those without progression in both the TNFi-free (2.75±0.83 vs 0.63±0.86, p =0.0039) and TNFi-treated groups (10.3±7.93 vs 1.14±1.36, p =0.029). However, no significant difference was found in radiographic progression between the TNFi-free and TNFi-treated groups when these are compared in the same total PD score categories. Conclusions PDUS detects latent synovitis causing joint destruction even in the clinical remission of RA patients, irrespective of TNFi therapy. Thus, US is a potent tool for prediction of joint prognosis during clinical remission of RA. References Mulherin D, Fitzgerald O, Bresnihan B. Clinical improvement and radiological deterioration in rheumatoid arthritis: evidence that the pathogenesis of synovial inflammation and articular erosion may differ. Br J Rheumatol 1996;35:1263-8. Molenaar ET, Voskuyl AE, Dinant HJ, et al. Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission. Arthritis Rheum 2004;50:36-42. Disclosure of Interest None Declared