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Background:Based on the idea that therapeutic approach for oral dryness in patients with Sjögren’s syndrome (SS) should be driven by salivary glandular function, rather than the patient’s subjective feelings, the EULAR recommendations for the management of Sjögren’s syndrome with topical and systemic therapies recommend that salivary glandular function be evaluated by measuring whole salivary flows before starting therapeutic interventions and that different therapeutic approaches be provided depending on the measured salivary flow rates. Although the recommendations do not indicate a preferred therapeutic approach for SS patients with unstimulated whole salivary flows (UWSF) ≥0.1 mL/min, in clinical practice, SS patients with preserved salivary flow rates often complain of oral dryness.Objectives:To evaluate the oral health-related quality of life (OHRQoL) in SS patients with UWSF ≥0.1 ml/min.Methods:Forty-five SS patients (35 with primary SS; 43 women and 2 men; mean age, 62.4 years; mean disease duration, 6.6 years) and 23 non-SS individuals (control; 18 women and 5 men; mean age, 56.1 years) participated in this study. All SS patients met the 1999 revised Japanese Ministry of Health criteria for diagnosis of SS. Individuals with factors that can affect saliva secretion, intraoral lesion formation, or OHRQoL were excluded. The UWSF of SS patients were measured by the spitting method (mL/15 min). OHRQoL was quantitatively assessed using the Japanese version of the short-form Oral Health Impact Profile (OHIP-14; maximum possible score, 56 points), a self-administered questionnaire, at an average of 7.2 months after the UWSF measurement in SS patients and as needed in non-SS individuals. Since the assessment of dryness symptoms by ESSPRI includes more than just oral dryness, it was not used for the OHRQoL assessment in this study.Results:In SS patients, the mean UWSF was 1.1 mL/15 min; 34 (75.6%) had a UWSF <0.1 mL/min, and 11 (24.4%) had ≥0.1 mL/min. Their mean OHIP-14 score was 15.9. There was no significant difference in the percentage of patients who perceived oral dryness between the UWSF <0.1 ml/min and ≥0.1 ml/min groups (97.1% vs 81.8%, p=0.143). The OHIP-14 score also did not differ significantly between the two groups (16.6 vs 13.6, p=0.227). The OHIP-14 score of even the UWSF ≥0.1 mL/min group was significantly higher than that of the non-SS group (13.6 vs. 7.1, p=0.029). Among the OHIP-14 questions, the UWSF ≥0.1 mL/min group scored significantly higher than the non-SS group for “self-conscious,” “diet unsatisfactory,” “difficult to relax,” and “felt life less satisfying.” In addition, the UWSF ≥0.1 mL/min group tended to score higher for “trouble pronouncing words,” “uncomfortable to eat foods,” “been embarrassed,” “irritable with other people,” and “unable to function.”Conclusion:This study revealed that SS patients – even with UWSF ≥0.1 mL/min – had lower OHRQoL. Because of the wide normal range of salivary flow rates and high interindividual variability, it is considered difficult to determine whether an individual’s salivary flow rate is abnormal. Signs of oral dryness are said to appear when the salivary flow rate decreases by 40–50%. Therefore, it is more important whether there is a change in salivary flow rate over time than whether an individual has a high or low salivary flow rate. Even if the salivary flow rate is preserved in a single measurement, the possibility of having oral dryness due to a decrease in the salivary flow rate from the normal value for that patient should be considered.REFERENCES:[1] Ramos-Casals M, et al. Ann Rheum Dis 2020;79:3-18.Acknowledgements:NIL.Disclosure of Interests:Naoto Azuma: None declared, Maki Iwatani: None declared, Yuichi Yokoyama: None declared, Naoaki Hashimoto: None declared, Masao Tamura: None declared, Teppei Hashimoto: None declared, Mai Morimoto: None declared, Aki Nishioka: None declared, Masayasu Kitano: None declared, Shinichiro Tsunoda: None declared, Hajime Sano: None declared, Kiyoshi Matsui KM has received scholarship grant from Chugai Pharmaceutical Co., Ltd. and Asahi Kasei Pharma Corporation.

Background: Coded phase inversion harmonic ultrasonography, a newly available sonographic technique, enables visualisation of slow flow in minute vessels in a real time fashion with the use of a sonographic contrast agent containing monosaccharide. Our purpose was to employ this novel technique to observe microvessels in pancreatic tumours. Subjects and methods: Sixty five patients with suspicious pancreatic tumours received contrast enhanced coded phase inversion harmonic ultrasonography, contrast enhanced computed tomography, and endosonography. Final diagnoses based on histological findings were pancreatic ductal carcinomas in 49 patients, inflammatory pseudotumours with chronic pancreatitis in seven, and endocrine tumours in nine. For contrast enhanced coded harmonic ultrasonography, Levovist, a contrast agent, was injected intravenously as a bolus. When the first microbubble signal appeared in the pancreas, images of the ideal scanning plane were displayed in a real time continuous fashion (vessel images). Subsequently, interval delay scanning (perfusion images) was taken to demonstrate parenchymal flow. Tumour vascularity was evaluated by using the two types of imaging. Sensitivities for depicting pancreatic tumours were compared between three examinations. Results: Contrast enhanced ultrasonography demonstrated tumour vessels in 67% of pancreatic ductal carcinomas, although most were relatively hypovascular compared with the surrounding pancreatic tissue. The vascular patterns of tumours obtained by contrast enhanced ultrasonography were closely correlated with those obtained by contrast enhanced computed tomography. Values for sensitivity in depicting pancreatic tumours of 2 cm or less in size were 68% for contrast enhanced computed tomography, 95% for endosonography, and 95% for contrast enhanced ultrasonography. Conclusion: Contrast enhanced coded phase inversion harmonic ultrasonography successfully visualised fine vessels in pancreatic tumours and may play a pivotal role in the depiction and differential diagnosis of pancreatic tumours.

Optimization of preoperative nutritional status has been recommended and associated with improved outcomes for other oncologic procedures, but has not been studied in patients undergoing pelvic exenteration. A retrospective chart review of 199 patients was conducted. Overall survival (OS) was calculated using the Kaplan-Meier method and multivariate analysis was performed with Cox proportional hazards. 199 patients underwent PE with 61 (31%), 78 (40%) and 58 (29%) patients having colorectal, gynecologic and urologic histological diagnoses, respectively. Median OS following PE was 25 months. Preoperative serum albumin <3.5 g/dL was associated with worsened OS (HR 1.661; 95% CI 1.052–2.624) as well as increased incidence of any postoperative complication (85.9% vs 72.3%, p = 0.034), but was not associated with 90-day mortality (11.3% vs 7.9%, p = 0.457). Poor preoperative nutritional status is associated with increased complications and decreased OS. Surgeons should maximize preoperative nutritional status to improve perioperative outcomes and long-term survival. •Poor nutritional status was associated with worsened long-term survival.•Poor nutritional status is associated with increased incidence of complications.•Preoperative albumin level was not associated with 90-day mortality.•The risk of readmissions and reoperation was not increased with low albumin level. Pelvic exenteration is a radical procedure involving en bloc removal of the pelvic organs. Poor preoperative nutritional status is associated with increased complications and decreased overall survival. Nutritional optimization could improve outcomes for patients.

We attempted to develop practical methods for coral reef rehabilitation, by means of the production of juveniles obtained from sexual reproduction, for a remote island where recruitment is limited. Adult corals (broodstocks) ofAcropora tenuiswere transported 1100 km from Okinotorishima, Japan’s southernmost island in the Pacific, to a hatchery in Okinawa and maintained in land tanks. Eggs were obtained from captive spawning and the resulting larvae and juvenile corals were cultured under laboratory conditions. The present methodology enabled high survivorship and led to the successful mass production of coral juveniles. A total of 564 substrates with ~63 000 juvenile corals at the age of 10 mo were transported to the native reef. They were then transplanted in 3 experimental treatments, in order to evaluate effectiveness of protection by cages and/or hiding the juveniles under other substrates. Additionally, the effects of orientation on coral growth were tested by attaching the juveniles face down. The cages effectively protected the corals from predation and nibbling by fishes. The unshaded, upward facing corals in the cages steadily increased their coverage nearly 4-fold in ~2 yr.

Background: We aimed to compare the efficacy and safety of irinotecan/S-1 (IRIS) therapy with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer. Methods: Patients were treated with oral S-1 (80–120 mg for 14 days every 4 weeks) plus intravenous irinotecan (100 mg m −2 on days 1 and 15 every 4 weeks; IRIS group) or oral S-1 group (80–120 mg daily for 28 days every 6 weeks). The primary endpoint was progression-free survival (PFS). Results: Of 137 patients enrolled, 127 were eligible for efficacy. The median PFS in the IRIS group and S-1 monotherapy group were 3.5 and 1.9 months, respectively (hazard ratio (HR)=0.77; 95% confidence interval (CI), 0.53–1.11; P =0.18), while the median overall survival (OS) were 6.8 and 5.8 months, respectively (HR=0.75; 95% CI, 0.51–1.09; P =0.13). Response rate was significantly higher in the IRIS group than in the S-1 monotherapy group (18.3% vs 6.0%, P =0.03). Grade 3 or higher neutropenia and anorexia occurred more frequently in the IRIS group. Conclusions: There was a trend for better PFS and OS in the IRIS group that could be a treatment arm in the clinical trials for gemcitabine-refractory pancreatic cancer.

BackgroundWe have reported that the submandibular gland ultrasonography (SGUS) is a useful noninvasive and inexpensive procedure for the evaluation of the structural changes of salivary gland (SG) in Sjögren’s syndrome (SS), International Symposium on SS 2002 , EULAR 2009 , EULAR 2012 . EULAR 2015 However, our previously study demonstrated that although SGUS findings were useful for the diagnosis of SS with low salivary flow they were not for early-stage SS with normal salivary flow. EULAR 2016 Recently, ultrasound elastography has been reported to be a new tool to evaluate tissue stiffness and diagnose tumour.ObjectivesThe aim of this study was to examine the usefulness of SGUS using US staging and PD grading score in combination with shear wave elastography (SWE) in patients with SS.MethodsFifty-eight patients who fulfilled the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for SS were studied. SS patients were divided into three groups according to salivary flow using gum test (VL/SS:<5 mL/10 min. (n=21), L/SS: 5–10 mL/10 min. (n=27) and N/SS: ≧10 mL/10 min. (n=10)). All patients were examined SGUS by a single investigator who was blinded to device (TUS-A300; Canon Medical Systems, Tokyo, Japan) with a linear transducer (7.5–10MHz). The examination consisted of conventional B-mode US (US staging score), pulsed wave Doppler US (PD grading score) and SWE with quantitative assessment. US staging scores were assessed by glandular size, inhomogeneity and contrast of diagastric muscle (stage 0 to 3). PD grading scores were graded by pulsed wave pattern in pulsed wave Doppler US at the internal SG facial arteries (grade 0 to 2). With the region-of-interest (ROI) placed over the stiffest areas of the lesion on SWE, the quantitative mean of the elasticity values were measured by shear wave velocity (Vs: m/s) and elasticity (E: kPa) for each lesion.ResultsThe US staging scores of SS patients were 0.0% in stage 0; 17.2% in stage 1; 8.6% in stage 2; 74.1% in stage 3. The PD grading scores of SS patients were 20.7% in grade 0, 17.2% in grade 1, 62.1% in grade 2. The US staging and grading scores were significantly lower in N/SS patients (1.40±0.70, 0.10±0.32) than in L/SS (2.74±0.66, p<0.001, 1.59±0.69, p<0.001) and in VL/SS (2.91±0.30, p<0.001, 1.81±0.40, p<0.001) patients. The elasticity value measure by Vs and E were significantly higher in N/SS patients than in VL/SS patients (Vs: 1.90 vs 1.56 m/s, p<0.05, E: 11.2 vs 7.57 kPa, p<0.05). The Vs and E were significantly decreased as US staging score (stage 1 vs 3: 1.91 vs 1.62 m/s, p<0.05, 11.3 vs 8.21 kPa, p<0.05) and PD grading score (grade 0 vs 2: 1.90 vs 1.61 m/s, p<0.05, 11.1 vs 8.13 kPa, p<0.05) increased.ConclusionsThe present study demonstrated that the tissue elasticity was increased due to inflammation and high viscosity in the SG at the early stage, but was decreased due to structural changes in the SG at the advanced stage of the disease. The SWE may be a useful tool for elucidation of early stage pathological changes of the SG when salivary gland functions are not impaired in SS.Disclosure of InterestNone declared

BackgroundThe selective Janus kinase (JAK) inhibitor tofacitinib has demonstrated excellent efficacy for rheumatoid arthritis (RA). These results suggest the possibility that tofacitinib improves osteoclastic bone destruction of RA. However, the detailed mechanism of tofacitinib for osteoclastogenesis in RA is pooly understood. In this study, we investigated the effect of tofacitinib on serum biomarkers related to osteoclast regulation such as soluble receptor activator of NF-kappa B ligand (sRANKL) and osteoprotegerin (OPG) in patients with RA.ObjectivesTo clarify the effect of tofacitinib on osteoclast regulator in RA.MethodsFourteen patients with active RA who inadequate response to disease-modifying antirheumatic drugs (DMARDs) (mean age: 54.6 years, mean disease duration: 4.1 years, mean simplified disease activity index: 26.9, ACPA positive: 86%, oral steroid use: 29%, mean oral steroid dose: 10mg/day, MTX use: 93%, mean MTX dose:10.9mg/week, biologic DMARDs naïve: 57%) were started on treatment with tofacitinib 5mg twice daily (BID). Disease activity was assessed using the 28-joint count disease activity score-C-reactive protein sedimentation rate (DAS28-CRP) and simplified disease activity index (SDAI). Next, circulating levels of sRANKL and OPG were examined by enzyme-linked immunosorbent assay (ELISA) (sRANKL: human RANKL ELISA kit, Biomedica, OPG: human osteoprotegerin ELISA kit, Biomedica respectively) at the baseline, week 2, 4 and 12.ResultsAfter treatment of tofacitinib, SDAI score among all fourteen patients decreased significantly from 26.9±12.4 (mean±SD) at the baseline to 14.7±9.9 at week 4 (p<0.0001), to 8.3±6.1 at week 12 (p<0.0001). Baseline levels of sRANKL were significantly correlated with the levels of CRP (Spearman r2=0.488, P=0.0054). Average of sRANKL levels decreased immediately from 0.15±0.11 pmol/L at the baseline to 0.09±0.05 pmol/L at week 2 (p=0.0097), to 0.11±0.10 pmol/L at week 4 (p=0.0311), to 0.08±0.05 pmol/L at week 12 (p=0.0014). On the other hand, statistically significant changes in OPG levels were not observed during 12 weeks. Consequently, average of sRANKL/OPG ratio decreased significantly from 4.81±4.82 at the baseline to 2.62±1.84 at week 2 (p=0.0186), to 3.11±2.81 at week 4 (p=0.0191), to 2.11±1.72 at week 12 (p=0.0052). Interestingly, decreasing effects of sRANKL levels or sRANKL/OPG ratio were greater in patient with high sRANKL level at the baseline.ConclusionsHere, we show for the first time that tofacitinib has improved inflammatory bone destruction immediately through the regulation of sRANKL levels and sRANKL/OPG balance in RA. This mechanism might be a control of RANKL induction via JAK pathway inhibition in activated CD4+ T cells and synovial fibroblastsDisclosure of InterestNone declared

BackgroundSSc is a refractory of connective tissue disease that causes fibrosis of the skin and various organs. 2013 ACR/EULAR classification criteria of SSc can diagnose early phase of skin involvement. Thus we considered that YKL-40 is known to be involved in inflammation, tissue fibrosis and remodeling, is an useful marker for evaluating early diagnosis and complications in SSc. YKL-40 is expressed in the synovial membrane and cartilage fibroblast cells in Rheumatoid Arthritis. However the relationship between SSc and YKL-40 is unclear.ObjectivesTo clarify YKL-40 is useful marker in early diagnosis in the presence or absence of complications in Japanese SSc patients.MethodsStudy I: We measured serum level of YKL-40 by ELISA (Quantikine ELISA (R&D systems) ®) in 16 healthy controls and 26 SSc patients without complications: such as asthma, infection, diabetes, malignant disease, interstitial pneumonia (IP), pulmonary arterial hypertention (PAH), arthritis and other collagen disease. These complications may be increased YKL-40 levels. Study II: We measured serum level of YKL-40 by ELISA in 76 SSc patients: 42 patients without IP or PAH,17 patients with IP, 4 patients with PAH, 13 patients with IP and PAH. We were attention to IP and PAH complications as a factor involved in the prognosis in SSc.ResultsStudy I: Serum YKL-40 levels were significant higher in SSc patients without complications than in healthy controls (77.3±15.8 vs 35.0±4.5ng/ml, P=0.01). On the other hand, there is no difference of YKL-40 levels due to gender, disease duration and disease type of SSc. Study II: Serum YKL-40 levels were significantly higher in SSc patients with IP and PAH than in SSc patients without IP and PAH (66.5±15.3 vs 193.4±45.3 ng/ml, P=0.01). Serum YKL-40 levels in SSc patients with IP was 92.9±28.5 ng/ml, and with PAH was 157.5±60.2 ng/ml.ConclusionsWe could show increase in serum YKL-40 levels with SSc excluding complications in Japan. In contrast, Montagna reported that serum YKL-40 levels in 40 SSc patients was median 75.5ng/ml (24.2–584) including the organ complications such as heart, lung, kidney, arthritis and high CRP cases (median 0.4mg/dl, 0.3–7.5). The Complications and other factors may be influent to level of serum YKL-40. And, Nordenbaek reported SSc patients with elevated serum YKL-40 had shorter survival than patients with normal serum YKL-40 and died more often due to extensive interstisial or vascular fibrosing processes. However, there is no report on YKL-40 in SSc patients with PAH. We thought that the measure of serum YKL-40 levels in SSc patients with organ complications such as IP and/or PAH is very useful marker. We showed that YKL-40 levels are useful marker in early diagnosis of SSc with or without complications.ReferencesCross-sectional evaluation of YKL-40 serum concentrations in patients with systemic sclerosis. Relationship with clinical and serological aspects of disease. La Montagna G, D'Angelo S, Valentini G. J Rheumatol. 2003 Oct;30(10):2147–51.High serum levels of YKL-40 in patients with systemic sclerosis are associated with pulmonary involvement. Nordenbaek C, Johansen JS, Halberg P, Wiik A, Garbarsch C, Ullman S, Price PA, Jacobsen S. Scand J Rheumatol. 2005 Jul-Aug;34(4):293–7.Disclosure of InterestNone declared

BackgroundMac-2 binding protein is a cell-adhesive glycoprotein of the extracellular matrix secreted as a ligand of galectin-3 (Mac-2). Recently, a Wisteria floribunda agglutinin positive-M2BP (M2BP) assay developed using a lectin-antibody sandwich immunoassay has shown promise as a new fibrotic marker in liver fibrosis and interstitial lung disease (ILD) to detect unique fibrosis-related glycoalteration. Systemic sclerosis (SSc) is an intractable connective tissue disease that causes skin and organ fibrosis. Progressive fibrosis is now recognised to be one of the major causes of morbidity and mortality in SSc.ObjectivesThe aim of this study is to evaluate the utility of serum M2BP levels in patients with SSc.MethodsWe retrospectively measured serum M2BP levels in 76 patients with SSc and 16 healthy controls (HC). We excluded patients of viral hepatitis and cirrhosis. Serum levels of M2BP were measured using HISCL® M2BP glycosylation isomer Assay Kit. IHC was performed on 5 samples of normal skin, 7 stored samples of SSc skin and 2 samples of SSc-ILD lung tissue. We examined the relationship between serum M2BP levels and clinical parameters in patients with SSc.ResultsThe mean age was 62.7 years in SSc patients and 54.6 years in HC. There were 57 limited cutaneous SSc patients and 19 diffuse cutaneous SSc patients. The mean duration of SSc patients was 9.8 years. Serum M2BP levels were significantly higher in patients with SSc than in HC (0.853±0.701 cutoff index [COI], 0.325±0.111 COI, respectively; p<0.00001). Receiver operating characteristic (ROC) curve analysis indicated that serum M2BP correctly differentiated between SSc patients and HC with a sensitivity of 81.6% and specificity of 87.5%. In patients with SSc, a significant correlation was not found between serum M2BP levels and age, sex, mRSS, ILD, pulmonary artery hypertension (PAH), SSc-types, dermatoscopy findings. In multivariant analysis, disease duration was a only independent factor for higher serum M2BP levels more than 0.64 COI, serum M2BP median (odds ratio 0.935, 95% CI 0.878–0.996, p=0.0385). We detected the protein level of M2BP in SSc patient`s fibroblast of skin and SSc Patient`s proliferating type II alveolar cells adjacent to fibrotic lesions of lung tissue.ConclusionsIn this study, for the first we demonstrated that M2BP is expressed in skin and lung tissue in SSc patients in IHC and more over the serum M2BP level tends to be higher in patients with short disease duration. It is reveal that M2BP play an important role of fibrosis in early stage of SSc. The serum level of M2BP may be a novel biomarker of SSc.Disclosure of InterestNone declared

The preparation of mesoporous silica coated rf-sputterd apatite / titanium substrate and protein adsorptive property is reported. Hydroxyapatite coated titanium implant has been used, and the adsorption of proteins onto implant is very important for bond formation between bone and implant. Mesoporous silica (MPS) materials have been extensively studied as carriers of bio-molecules due to their potential practical applications in medical materials. Pore diameters of 1.5 – 30 nm of the periodic mesoporous materials are close to the diameters of target molecules and high adsorbed amount of proteins onto MPS has been reported, and also enclosure of the protein in a well-defined space may help to prevent denaturation. Previously, we reported the MPS coating on the porous hydroxyapatite (HAp) ceramics obtained by dip-coating method, and by the vapor phase synthesis. Protein adsorption on the porous HAp with the MPS coatings was evaluated using UV-VIS spectrometry, and the quantity of adsorbed amount of protein was remarkably improved. In this study, the HAp deposition on Ti substrate (HAp/Ti) was carried out by rf magnetron sputtering and hydrothermal treatment, and MPS coating on HAp/Ti using LB deposition apparatus to improve the protein adsorptive property of HAp/Ti. The quantity of adsorbed protein onto the HAp /Ti was around 12 times high, and that onto the MPS/HAp/Ti was 18 times high compared to that on Ti substrate.