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This Personal Account describes the authors' foray into DNA-encoded libraries. The article addresses several key aspects of this hit generation technology, from the development of new synthetic methodology to the subsequent conception, design, and delivery of a DNA-encoded library. In particular, we have been engaged in adapting photocatalytic reactions to the idiosyncratic requirements of DNA-encoded chemistry. We have chosen one such methodology, namely a photocatalytic [2+2] cycloaddition reaction, to showcase how we employed property-based computational analyses to guide the selection and validation of building blocks for the production of a library. Ultimately, these novel bond disconnections and design principles led to the assembly of a DNA-encoded library that is composed of structurally diverse compounds within largely desirable property space and, therefore, well positioned to deliver novel chemical matter for drug discovery programs.

Objective: To assess the contribution and safety of bronchoscopic cryobiopsy vs traditional forceps biopsy used in clinical practice for diagnosing diffuse parenchymal lung disease (DPLD). Patients and Methods: We identified 271 patients who underwent bronchoscopic biopsy for DPLD at Mayo Clinic, MN (June 1, 2013, through September 30, 2017). Medical records were reviewed including prebiopsy clinical and radiographic impressions. Diagnostic yield was assessed in terms of a specific histologic pattern resulting in a diagnosis when combined with the clinical-radiologic context. Clinical utility was defined as a biopsy result deemed useful in patient management. Results: The cohort included 120 cryobiopsy and 151 forceps biopsy cases with mean age 61±14 years and 143 (53%) men. Diagnostic yield (55% vs 41%; odds ratio [OR], 1.73; 95% CI, 1.07 to 2.83; P=.026) and clinical utility (60% vs 40%; OR, 2.21; 95% CI, 1.36 to 3.63; P=.001) were higher for the cryobiopsy group, and the association remained after control for prebiopsy clinical impressions (OR, 2.21; 95% CI, 1.22 to 4.08; P=.010 and OR, 3.23; 95% CI, 1.76 to 6.10; P

Musculoskeletal involvement is one of the major causes of impairment in daily life of patients with systemic sclerosis (SSc). Several hand radiographic findings can be seen in SSc patients; however, their association with clinical features and autoantibodies remains unclear. Here, we analyzed 124 SSc patients with their hand X-rays and clinical and serological features. Abnormal findings in hand X-rays including acro-osteolysis, calcinosis, flexion contracture, erosive change, joint space narrowing, and subluxation were observed in 110 patients (68%). These X-ray findings were more prevalent in patients with longer disease duration and digital ischemic changes. The majority of erosions were typical for erosive hand osteoarthritis, which was seen in 19% of patients. Hand X-ray findings were associated with involved organs; acro-osteolysis with interstitial lung disease, calcinosis with pulmonary arterial hypertension and gastrointestinal tract involvement, and flexion contracture with gastrointestinal tract involvement. Those findings were also relevant to autoantibodies; acro-osteolysis was more common in SSc patients with anti-Scl70 antibody but less in patients with anticentromere antibody. Calcinosis was more prevalent in patient with anticentromere antibody. In our study, organ involvements and SSc-associated autoantibodies showed associations with hand radiographic abnormalities. Hand X-ray findings might reflect underlying pathogenesis and autoantibody profiles in SSc patients.Key Points• Hand X-ray abnormalities were observed in approximately two-thirds of patients with SSc.• Erosive osteoarthritis was more prevalent in SSc patients than general population.• Hand X-ray findings were associated with disease duration, organ involvements, and SSc-associated autoantibodies, reflecting underlying pathogenesis.

Smart agriculture is recommended for labor-saving, refinement and high quality production of rice cultivation with safety and security. The Terrestrial laser measurement has the advantage of acquiring 3D point cloud information with high accuracy and high density, but there is a disadvantage that it becomes difficult to measure the base of rice plant when paddy rice grew. In this study, the 3D point cloud information obtained by terrestrial laser measurement was used to three-dimensionally measure the growth state in the field corresponding to the growing period in time series. The growth characteristics of the whole field as a community were extracted as a representative value of mean growth. Then we attempted extraction of individual differences in growth and growth unevenness, as the deviation from the mean value of the field in terms of the growth characteristics of each strain focused on the individual plants. it is difficult to observe the root of the rice during the growing period, it was used for analyzing the growth quantity as the growth difference height for each growing period by obtaining the difference of the elevation value of the rice at the early stage of growth and at each stage of growing. The spatial variation in the growth quantity of the whole field area and the local area was calculated, the range of the deviation for evaluating the mean variation and the growth abnormality was examined, and the setting of the threshold for evaluating the growth normal and abnormality was examined.

To investigate the effects of continuous intervention with branched chain amino acids-enriched nutritional supplements from the acute phase to convalescent rehabilitation wards in inpatients with gait impairments. Open-label, randomized, parallel-group comparison study (UMIN Clinical Trials Registry ID: UMIN000018640). Acute care and convalescent rehabilitation wards We studied 80 patients undergoing stand/gait training. Participants in the intervention group (RJ group) received nutritional supplements (jelly foods comprising 2500 mg BCAA and 20 IU vitamin D) twice a day until hospital discharge. The primary outcome was the motor components of the Functional Independence Measure (FIM-m), and the secondary outcome was skeletal muscle mass index. Analyses were conducted on 55 patients who were able to perform stand/gait training continuously from the acute until the recovery phases. FIM-m was significantly elevated in the RJ group and the control group, but no difference was noted between the two groups. Only the RJ group showed a significant increase in skeletal muscle mass index, and the amount of variation was significantly different between the two groups (the control group decreased an average of 2.2% and the RJ group increased an average of 4.3%; P = 0.014). A significant decrease in body weight was found only in the control group (P = 0.084). Nutritional interventions using branched chain amino acids (BCAA)-enriched nutritional supplements demonstrated no significant difference in activities of daily living; however, an increase in skeletal muscle mass was noted. Skeletal muscle mass and body weight differed significantly between the two groups, and BCAA-enriched nutritional supplements intake in acute and convalescent rehabilitation wards may be effective for the prevention of malnutrition and sarcopenia.

Scimitar syndrome is a rare constellation of congenital conditions pertaining to partial anomalous pulmonary venous return. Radiographically, these anomalous pulmonary veins can resemble a scimitar, and have heterogeneous clinical presentations. We present an unusual case of scimitar syndrome with associated recurrent pneumonia. We will briefly review the literature on scimitar syndrome as well as discuss how a predisposition to recurrent pneumonia may develop in this unusual variant of a rare clinical entity.

We herein report a rare case of a 66-year-old man with refractory chylothorax. Although he had been treated with moderate doses of prednisolone (PSL) on suspicion of pleuritis with Sjogren syndrome, the pleural effusion expanded after the reduction of prednisolone. Further workup including histopathological examinations of pleura led to the diagnosis of IgG4-RD with bilateral chylothorax without any leakage from the thoracic duct. Combination therapy with high-dose PSL plus rituximab successfully decreased the pleural effusion. This is a very rare case of IgG4-related pleuritis with chylothorax and the first report of its successful treatment with rituximab.

We sought to clarify the safety and tolerability of ultrasound (US)-guided synovial needle biopsy in hand and knee joints in Japanese arthritis patients.A total of nine consecutive arthritis patients were recruited and scheduled for US-guided synovial needle biopsies. Patients completed a safety questionnaire and patient-reported outcomes (PRO) data of joint pain, stiffness, and swelling pre- and postbiopsy. We also recorded patients' characteristics and willingness to undergo a second biopsy by the same technique. All synovial needle biopsy samples were assessed with pathological and microbial examination to verify whether clinical evaluation was possible.Five and 4 patients underwent US-guided biopsy from hand and knee joints, respectively. PRO data showed no significant differences in pain, swelling, or stiffness levels before and after biopsy, with a mean 11.8 samples collected per procedure. No significant complications, including joint infection, bleeding, or vasovagal signs, were reported. Histologically adequate synovial tissue was identified in 83 (78%) samples. We were able to submit the biopsy samples to pathological and bacterial analysis to exclude septic arthritis.We demonstrated that a minimally invasive US-guided needle biopsy is a safe and well-tolerated procedure and the synovial tissue collected was of adequate quality for pathological analysis.

Background Although catheter ablation targeting ganglionated plexi (GP) playing an important role in formation of triggers and substrates of atrial fibrillation (AF) has been reported as one of the effective ablation strategies in non-paroxysmal AF (non-PAF) patients, its effectiveness varies among the study groups. More recently, ablation targeting spatiotemporal electrogram dispersion (STED) areas, assumed to contain AF drivers in forms of rotational activation is proposed. However, the optimal ablation strategy for non-PAF is still controversial since the exact mechanisms of non-PAF are not well understood. Purpose To investigate the effectiveness of GP ablation for autonomic modification and STED ablation for modulation of AF drivers. Methods Consecutive 149 non-PAF patients who underwent STED ablation in our center were enrolled. We detected STED areas within the whole left and right atrium during AF using PentaRay®, and ablated them. If AF was terminated during STED ablation, we finished the procedure without burning the remaining STED areas. If not, electrical cardioversion was applied. The outcome was compared with that in consecutive 156 non-PAF patients undergoing GP ablation previously in our center. Results (1) The clinical characteristics were comparable between two groups (see Table). (2) A Kaplan-Meier curve showed that there was no significant difference between the freedom rates from non-PAF/non-paroxysmal atrial tachycardia (non-PAT) after single procedure in STED group and GP group (Figure, left). (3) However, the freedom rates from non-PAT in STED group was significantly lower than that GP group (Figure, right). Conclusions The recurrence type of atrial arrhythmia after ablation was remarkably different between ablation of STED and GP. STED ablation might eliminate fibrillatory conduction and control AF driver in patients with non-PAF. Freedom from atrial arrhythmia Funding Acknowledgement Type of funding source: None

A fluorescence-yield wavelength-dispersive x-ray absorption spectroscopy technique in the soft x-ray region, by which the x-ray absorption spectra are recorded without scanning the monochromator, has been developed. The wavelength-dispersed soft x rays, in which the wavelength (photon energy) continuously changes as a function of the position, illuminate the sample, and the emitted fluorescence soft x rays at each position are separately focused by an imaging optics onto each position at a soft x-ray detector. Ni L-edge x-ray absorption spectra for Ni and NiO thin films taken in the wavelength-dispersive mode are shown in order to demonstrate the validity of the technique. The development of the technique paves the way for a real-time observation of time-dependent processes, such as surface chemical reactions, with much higher gas pressure compared to the electron-yield mode, as well as under magnetic and electric fields.

Objectives The regulation system for oxidative stress in systemic sclerosis (SSc) remains unclear. This study aimed to clarify the possible involvement of ataxia telangiectasia mutated (ATM), which plays a key role in DNA repair and redox balance, in the pathogenesis of SSc. Methods Thirty patients with SSc and 15 healthy controls were enrolled. Expression of ATM and phosphorylated ATM (pATM), an activated form of ATM, in phagocytes in whole blood samples was analysed by FACS. Correlations between expression levels of ATM/pATM and clinical parameters of SSc patients were statistically analysed. Peripheral monocytes were cultured with an ATM-specific inhibitor (KU55933), and reactive oxygen species production in the cells was measured. Results Expression level of pATM in peripheral monocytes and neutrophils from SSc patients was significantly lower than those in healthy controls (P = 0.04 and P Conclusion Our data revealed that decreased ATM activation in monocytes was associated with SSc-interstitial lung disease and that impaired ATM activation in monocytes may contribute to the disease process of SSc via uncontrolled reactive oxygen species production.

This case highlights the importance of recognizing any new soft tissue abnormalities in cancer patients with an indwelling pleural catheter (IPC) or who has had an IPC. This report also describes the first case of catheter tract metastasis (CTM) due to renal cell carcinoma (RCC) and the second case of CTM post‐IPC removal., The importance of recognizing new nodules or subcutaneous mass in patients who has had indwelling pleural catheter (IPC) or overlying the IPC site is highlighted. This report describes the first case of catheter tract metastasis (CTM) due to renal cell carcinoma (RCC) and the second case of CTM post‐IPC removal.

Introduction: Central airway obstruction (CAO) often requires repeated interventional procedures which offer variable efficacy, a time-limited effect, and have inherent limitations. Paclitaxel has been used to prevent restenosis in blood vessels. The literature describing the use of paclitaxel to prevent recurrent airway stenosis is limited. We sought to describe our experience using a paclitaxel-coated balloon (PCB) for CAO. Material and methods: We performed a retrospective review of all patients who underwent PCB airway dilation. We collected: basic demographics, details of the CAO, details of the bronchoscopes used, PCB size, PCB dilation pressure, duration of PCB inflation, concurrent non-PCB interventions, estimated pre- and post-PCB CAO luminal diameter, follow up bronchoscopy date and luminal diameter, and spirometry results. Results: PCB dilation was performed in 10 cases on 5 patients. Eight PCB dilations were performed for CAO related to distal airway stent stenosis. Concurrent non-PCB interventions were performed with 6 PCB dilations. Nine cases documented improvements and 1 was unchanged immediately post-PCB dilation. Median luminal diameter pre-PCB dilation was 2 mm. Immediately post-PCB dilation, the median change in luminal diameter was 2 mm. Follow up bronchoscopy information was available for 9 cases. For these 9 cases, luminal diameter was unchanged in 5 and worse in 4 when compared to immediate post-PCB dilation. Conclusion: PCB dilation in benign CAO produced a modest effect in this cohort of challenging airways. Larger prospective studies are needed to assess how a PCB would perform when compared to a non-drug coated balloon. Keywords: Paclitaxel balloon dilation, Central airway obstruction, Balloon dilation, Airway stenosis, Airway stricture

A bronchopleural fistula (BPF) is a communication between the pleural space and the bronchial tree. BPFs are challenging to diagnose and are associated with a high morbidity and mortality. Sequential balloon occlusion is commonly used for localization of a BPF. We describe our experience with 4 cases of successful localization of the BPF by instillation of methylene blue into the pleural space through a pigtail catheter, with simultaneous bronchoscopic visualization of dye in the tracheobronchial tree. Two patients were treated with endobronchial valves and 3 had a surgical thoracic muscle flap placed.

Airway complications after lung transplant occur in approximately 10–15% of the recipients and often occur at the anastomosis, largely due to ischemia. To decrease anastomotic ischemia, surgeons minimize the length of the donor bronchus. However, a shortened donor bronchus creates technical challenges if a stent is required to treat an airway complication. We present a case of a lung transplant recipient with the combination of left main stem bronchial malacia and a triad of severe strictures at the left anastomosis, entrance to the left upper lobe, and left lower lobe. After failing several attempts using other modalities, success was achieved with in situ creation of a bifurcated fully covered balloon-expandable metallic stent. We describe a novel technique of punching a side branch hole through the wall of the stent to allow a left upper lobe stent to be placed through a stent directed into the left lower lobe in a Y configuration with a good clinical outcome.

Introduction: Bronchopleural fistula (BPF) is a feared complication of pulmonary resection. Fistula plugs (FP) have been described as an adequate treatment in anorectal disease. We describe our early experience placing an FP in the treatment of BPF. Materials and methods: We retrospectively reviewed 5 patients for whom a FP was placed for BPF at our institution. Demographic data, initial perioperative information, method and technique of FP placement, and success is reported. Results: Five patients (4 male, 1 female) with a median age of 63 years (range, 57–76 years) underwent 6 FP placements for BPF. Two patients were post-pneumonectomy and 3 patients post-lobectomy. The median time to presentation following surgery was 118 days (range 22–218). Upon bronchoscopic or operative re-evaluation, 3 patients had successful cessation of their air leak at 0, 1 and 4 days. Two of three patients subsequently underwent a thoracic muscle flap placement to augment healing. One patient had a persistent air leak despite 2 separate FP placements. The air leak stopped with endobronchial valves (EBV) which were deployed proximal to the FP, 9 days after placement of the FP. Another patient had a successful muscle flap placed 80 days after FP placement. There were no complications associated with the FP. Three of five patients were deemed successfully treated with FP placement alone. Conclusion: In patients with a postoperative BPF and pleural window, placement of a FP had a modest success rate and can be considered as a treatment modality option for BPF. Keywords: Bronchopleural fistula, Fistula plug, Persistent air leak, Prolong air leak

We examined the feasibility of ultrasound diagnosis of insulin-derived localized amyloidosis (IDLA). In addition to ultrasound detectability and findings, the insulin absorption rate, insulin dosage and hemoglobin A1c (HbA1c) levels before and after shifting the insulin injection site were investigated for 22 cases of IDLA. The detectability of IDLA on ultrasound was 100%; 59.1% was palpable lumps and 40.9% was not palpable. The palpable type had lower echo intensity and were harder than the non-palpable type. Blood flow decreased in IDLA, especially in the palpable type. IDLA, especially the palpable type, had a low insulin absorption rate. HbA1c level and insulin dosage decreased after shifting the injection site. The palpable type had more insulin reduction than the non-palpable type. Characteristic ultrasound images of IDLA were acquired. As the non-palpable type could be identified by ultrasound, its diagnosis encourages changing the insulin injection site; hence, ultrasound diagnosis of IDLA can enhance insulin treatment.

Background: Artificial intelligence (AI) techniques including deep learning have been rapidly evolving and have yielded appreciable benefits in many fields in recent years. In rheumatology field, however, these techniques have not been used often. Objectives: In an early phase of development of an AI-based automatic radiographic evaluating system for bone destruction, we aimed to develop learning-based models to automatically detect hand joint region, ankylosis and subluxation in radiographic images. Methods: A total of 130 radiographic image sets of both hands were randomly obtained from rheumatoid arthritis patients who had visited our division at Keio University Hospital in 2015. Well-trained rheumatologists determined the boundaries of regions of MP and PIP/IP joints and evaluated the presence of ankylosis and subluxation of each joint in radiographs. These evaluations of hand joints were performed using our developed annotation software tool [1]. In learning phase, joint images were randomly divided into five sets for 5-fold cross validation. As deep learning models, we utilized Single Shot Multibox Detector (SSD) method [2] with ensemble learning for detecting ankylosis and subluxation of MP and PIP/IP joint regions. Results: Our model showed 100% detection rate of MP and PIP/IP joint regions. As a performance of detecting hand joint ankylosis and subluxation, our model presented precision values of 0.85 and 0.73, recall values of 0.94 and 0.79, and F-measure values of 0.90 and 0.76, respectively. Conclusion: Deep learning-based models to automatically detect hand joint region, ankylosis and subluxation in radiographic images were developed with relatively small samples, which suggests that the predictive performance may increase by collecting more training dataset. Next, we are elaborating a plan for a deep learning-based evaluating system for erosion and joint space narrowing. References [1] Izumi K, Hashimoto M, Suzuki K, Endoh T, Doi K, Iwai Y, Jinzaki M, Ko S, Takeuchi T. Detecting Hand Joint Ankylosis in Radiographic Images Using Deep Learning: A Step in Developing Automatic Radiographic Scoring System for Bone Destruction. Arthritis Rheumatol 2018;70(suppl 10). [2] Liu W, Anguelov D, Erhan D, Szegedy C, Reed S, Fu CY, Berg AC. SSD: single shot multibox detector. European Conference on Computer Vision (ECCV) 2016. Acknowledgement: Keisuke Izumi and Kanata Suzuki are contributed equally. Disclosure of Interests: Keisuke Izumi Grant/research support from: Asahi Kasei Pharma, Speakers bureau: Asahi Kasei Pharma Corp, Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co., Kanata Suzuki Employee of: Fujitsu Laboratories Ltd., Masahiro Hashimoto: None declared, Toshio Endoh Employee of: Fujitsu Laboratories Ltd., Kentaro Doi Employee of: Fujitsu Ltd., Yuki Iwai Employee of: Fujitsu Ltd., Jun Inamo: None declared, Yuichiro Ota: None declared, Nobuhiko Kajio: None declared, Jun Kikuchi: None declared, Komei Sakata: None declared, Satoshi Takanashi: None declared, Chihiro Takahashi: None declared, Hiroshi Takei: None declared, Hiroya Tamai: None declared, Kazuoto Hiramoto: None declared, Yuko Kaneko Speakers bureau: AbbVie, Eisai Pharmaceutical, Chugai Pharmaceutical Co., Ltd., Bristol Myers Squibb, Astellas Pharma Inc., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Janssen Pharmaceutical K.K., Eli Lilly Japan K.K., Santen Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co. Ltd. and UCB Japan Co. Ltd., Masahiro Jinzaki: None declared, Shigeru Ko Grant/research support from: Fujitsu Ltd., Tsutomu Takeuchi Grant/research support from: Astellas Pharma Inc, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie GK, Asahikasei Pharma Corp., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Eisai Co., Ltd., AYUMI Pharmaceutical Corporation, Nipponkayaku Co. Ltd., Novartis Pharma K.K., Grant/research support from: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Grant/research support from: Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., Celltrion Inc., Nipponkayaku Co. Ltd., and UCB Japan, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Abbivie GK, Nipponkayaku Co.Ltd, Janssen Pharmaceutical K.K., Astellas Pharma Inc., Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Taisho Toyama Pharmaceutical Co. Ltd., GlaxoSmithKline K.K., UCB Japan Co. Ltd., Consultant for: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Consultant for: Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Asahi Kasei Medical K.K., AbbVie GK, Daiichi Sankyo Co., Ltd., Bristol Myers Squibb, and Nipponkayaku Co. Ltd., Speakers bureau: Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., AbbVie GK, Asahi Kasei Pharma Corp., Taisho Toyama Pharmaceutical Co., Ltd., SymBio Pharmaceuticals Ltd., Janssen Pharmaceutical K.K., Celltrion Inc., Nipponkayaku Co. Ltd., and UCB Japan, Speakers bureau: AbbVie, Asahi Kasei, Astellas, AstraZeneca, AYUMI, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly Japan, Janssen, Mitsubishi Tanabe, Nippon Kayaku, Novartis, Pfizer Japan Inc, Taiho, Taisho Toyama, Takeda, Teijin, Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Astellas Pharma Inc, Diaichi Sankyo Co. Ltd., Eisai Co. Ltd., Sanofi K.K., Teijin Pharma Ltd., Takeda Pharmaceutical Co. Ltd., Novartis Pharma K.K.

Background Few studies have assessed associations of non-enzymatic antioxidant capacity (NEAC) in the overall diet with all-cause or specific mortality, and their results have been inconsistent. Objectives The present study investigated the association between dietary NEAC and all-cause or cause-specific mortality. Methods The study was a large-scale population-based prospective cohort study in Japan consisting of 42,520 men and 50,207 women aged 44-76 y, who had no history of cancer, stroke, ischemic heart disease, or chronic liver disease. We evaluated FFQ-based dietary NEAC with use of published databases in which the NEACs of individual foods were analyzed by ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Dietary NEAC was calculated by multiplying the estimated NEAC with the consumed amount and summing up those values for all foods, and was categorized in quartiles. We identified death and cause of death with use of residential registry and death certificates. HRs and 95% Cls for death from the second survey, which was conducted from April 1995 to December 2014 were estimated with Cox proportional hazards regression analysis. Results After 1,498,308 person-years of follow-up, 12,978 total deaths occurred. The multivariable-adjusted HRs (95% Cls) for all-cause mortality for the highest compared with the lowest quartile of FRAP and ORAC were 0.85 (0.80, 0.89) and 0.84 (0.79, 0.89), respectively. Dietary NEACs were inversely associated with mortality from cardiovascular disease (CVD), but not from cancer. The multivariable-adjusted HRs (95% Cls) for CVD for the highest compared with the lowest quartile of FRAP and ORAC were 0.83 (0.75, 0.92) and 0.79 (0.70, 0.89), respectively. Conclusions Higher dietary NEACs from FRAP and ORAC were associated with lower risk of all-cause mortality and mortality from CVD in Japanese adults.

The health care-associated pneumonia (HCAP) criteria have a limited ability to predict pneumonia caused by drug-resistant bacteria and favor the overutilization of broad-spectrum antibiotics. We aimed to derive and validate a clinical prediction score with an improved ability to predict the risk of pneumonia due to drug-resistant pathogens compared to that of HCAP criteria. A derivation cohort of 200 microbiologically confirmed pneumonia cases in 2011 and 2012 was identified retrospectively. Risk factors for pneumonia due to drug-resistant pathogens were evaluated by logistic regression, and a novel prediction score (the drug resistance in pneumonia [DRIP] score) was derived. The score was then validated in a prospective, observational cohort of 200 microbiologically confirmed cases of pneumonia at four U.S. centers in 2013 and 2014. The DRIP score (area under the receiver operator curve [AUROC], 0.88 [95% confidence interval {CI}, 0.82 to 0.93]) performed significantly better ( P = 0.02) than the HCAP criteria (AUROC, 0.72 [95% CI, 0.64 to 0.79]). At a threshold of ≥4 points, the DRIP score demonstrated a sensitivity of 0.82 (95% CI, 0.67 to 0.88), a specificity of 0.81 (95% CI, 0.73 to 0.87), a positive predictive value (PPV) of 0.68 (95% CI, 0.56 to 0.78), and a negative predictive value (NPV) of 0.90 (95% CI, 0.81 to 0.93). By comparison, the performance of HCAP criteria was less favorable: sensitivity was 0.79 (95% CI, 0.67 to 0.88), specificity was 0.65 (95% CI, 0.56 to 0.73), PPV was 0.53 (95% CI, 0.42 to 0.63), and NPV was 0.86 (95% CI, 0.77 to 0.92). The overall accuracy of the HCAP criteria was 69.5% (95% CI, 62.5 to 75.7%), whereas that of the DRIP score was 81.5% (95% CI, 74.2 to 85.6%) ( P = 0.005). Unnecessary extended-spectrum antibiotics were recommended 46% less frequently by applying the DRIP score (25/200, 12.5%) than by use of HCAP criteria (47/200, 23.5%) ( P = 0.004), without increasing the rate at which inadequate treatment recommendations were made. The DRIP score was more predictive of the risk of pneumonia due to drug-resistant pathogens than HCAP criteria and may have the potential to decrease antibiotic overutilization in patients with pneumonia. Validation in larger cohorts of patients with pneumonia due to all causes is necessary.

Pulmonary epithelioid hemangioendothelioma (PEHE) is a rare vascular tumor of endothelial origin first described in 1975 as intravascular bronchioloalveolar tumor. Since then, >100 cases have been reported, and most cases require surgical lung biopsy for diagnosis. We report the case of a 46-year-old man with a diagnosis of PEHE from endobronchial biopsies of an intraluminal nodule, a rare presentation of this disease. We summarize a review of the literature and the bronchoscopic findings of PEHE.

Background:Residual synovitis can be detected by sensitive modalities such as ultrasonography in patients with rheumatoid arthritis in clinical remission. On the other hand, a previous study has shown that ultrasound-guided treatment provides modest benefit compared to a conventional strategy aiming clinical remission in early patients. It is still unclear how discordant clinical remission is from imaging remission by ultrasonography in patients treated with biologic agentsObjectives:To clarify the discordance between clinical remission and imaging remission in patients with rheumatoid arthritis treated with biologic agents.Methods:Patients with rheumatoid arthritis who were treated with biologic agents and in clinical remission defined as disease activity score for 28 joints (DAS28)Results:A total of 41 patients were enrolled with 22 patients treated with tumor necrosis factor (TNF)-α inhibitors and 19 with interleukin (IL)-6 inhibitors. The mean age, female ratio, the mean disease duration, and the mean duration of clinical remission were 60 years old, 87%, 5.1 years and 11.5 years. The imaging remission by ultrasonography was observed only in 51.2 %. When patients were divided according to biologic agents, baseline characteristics including median age, disease duration and clinically remission duration were comparable between both groups, while the rates of seropositivity and the stage of radiological progression was higher in IL-6 group (seropositivity, p=0.04; radiological progression, p=0.02). The mean DAS28 was 1.93 in the TNFα group and 1.02 in the IL-6 group. The discordance of clinical remission and imaging remission was observed in 28.6% of the TNFα group and 71.4% of the IL-6 group (p=0.03). The residual synovitis scores of GS and PD in 44 joints were significantly lower in the TNFα than the IL-6 group (GS, 1.1±1.8 vs 4.7 ± 4.6, pConclusion:Our results showed that there was substantial discordance between clinical remission and imaging remission, especially in the patients treated with IL-6 inhibitors. In patients treated with biologic agents, clinical remission should be assessed more stringently than the usual 2.6, and ulltrasound-guided management may be useful.References:[1]Smolen JS, et al. Ann Rheum Dis 2020;0:1–15.[2]Iwamoto T, et al. Arthritis Care Res (Hoboken). 2014;66(10):1576-81[3]Tanaka Y. Ann Rheum Dis 2010;69:1286 –91[4]Kaneko Y, et al. Ann Rheum Dis 2018;77:1268–1275[5]Brown AK, et al. Arthritis Rheum 2008;58: 2958 – 67.Acknowledgments:We would like to thank Harumi Kondo for their assistance.Disclosure of Interests:Yasushi Kondo: None declared, Yuko Kaneko Speakers bureau: Dr. Kaneko reports personal fees from AbbVie, personal fees from Astellas, personal fees from Ayumi, personal fees from Bristol-Myers Squibb, personal fees from Chugai, personal fees from Eisai, personal fees from Eli Lilly, personal fees from Hisamitsu, personal fees from Jansen, personal fees from Kissei, personal fees from Pfizer, personal fees from Sanofi, personal fees from Takeda, personal fees from Tanabe-Mitsubishi, personal fees from UCB, Shuntaro Saito: None declared, Yuichiro Ohta: None declared, Komei Sakata: None declared, Yumiko Inoue: None declared, Chihiro Takahashi: None declared, Kazuoto Hiramoto: None declared, Jun Inamo: None declared, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi & Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd.

The electronic health record is a primary source of information for all professional groups participating in ICU rounds. We previously demonstrated that, individually, all professional groups involved in rounds have significant blind spots in recognition of patient safety issues in the electronic health record. However, it is unclear how team dynamics impacts identification and verbalization of viewed data. Therefore, we created an ICU rounding simulation to assess how the interprofessional team recognized and reported data and its impact on decision-making.Each member of the ICU team reviewed a simulated ICU chart in the electronic health record which contained embedded patient safety issues. The team conducted simulated rounds according to the ICU's existing rounding script and was assessed for recognition of safety issues.Academic medical center.ICU residents, nurses, and pharmacists.None.Twenty-eight teams recognized 68.6% of safety issues with only 50% teams having the primary diagnosis in their differential. Individually, interns, nurses, and pharmacists recognized 30.4%, 15.6%, and 19.6% of safety items, respectively. However, there was a negative correlation between the intern's performance and the nurse's or the pharmacist's performance within a given team. The wide variance in recognition of data resulted in wide variance in orders. Overall, there were 21.8 orders requested and 21.6 orders placed per case resulting in 3.6 order entry inconsistencies/case. Between the two cases, there were 145 distinct orders place with 43% being unique to a specific team and only 2% placed by all teams.Although significant blind spots exist in the interprofessional team's ability to recognize safety issues in the electronic health record, the inclusion of other professional groups does serve as a partial safety net to improve recognition. Electronic health record-based, ICU rounding simulations can serve as a test-bed for innovations in ICU rounding structure and data collection.

Background Many survivors of the Great East Japan Earthquake that occurred in 2011 were at risk of deteriorating health, especially elderly people living in disaster-stricken areas. The objectives of this prospective study were: a) to clarify the different lifestyle and psychosocial factors associated with frailty by sex among the non-disabled elderly survivors, and b) to describe the differences in characteristics stratified by the degree of disaster-related housing damage. Methods We followed 2261 Japanese survivors aged ≥65 years (45.3% male; mean age, 71.7 years) without disability or frailty who completed a self-administered questionnaire at baseline. All participants completed a baseline questionnaire in 2011 and at least one identical follow-up questionnaire between 2012 and 2015 regarding lifestyle (smoking status, alcohol intake, physical activity, sedentary lifestyle, and dietary intake) and psychosocial factors (self-rated health, standard of living, psychological distress, and social networks). Frailty was defined as a score of ≥5 on the Kihon Checklist, which is used by the Japanese government to certify the need for long-term care insurance. Adjusted odds ratios and 95% confidence intervals with frailty as the dichotomous dependent variable and health factors as the independent variables were calculated using a multilevel model for repeated measures by sex, followed by stratification analyses by the degree of housing damage. Results Over the 4-year study period, 510 participants (22.6%) developed frailty. In the post-disaster setting, many of the psychosocial factors remained more prevalent 4 years later among survivors with extensive housing damage. The presence of risk factors regarding the development of frailty differed by the degree of housing damage. Among men, psychological distress, in parallel with a poor social network, was related to frailty among only the participants with extensive housing damage and those living in temporary housing, whereas among women, worsening psychological distress was associated only with no damage and no displaced survivors. Among women with extensive damage and displacement, health outcomes such as overweight and diabetes and poor social networks were strongly related to frailty. Conclusions Lifestyle and psychosocial factors associated with the risk of frailty differ by sex and the degree of housing damage. Electronic supplementary material The online version of this article (10.1186/s12877-018-0828-x) contains supplementary material, which is available to authorized users.

Background Twenty eight joints that are usually evaluated for disease activity score of rheumatoid arthritis (RA) do not include ankles and metatarsophalangeal joints. Although foot synovitis of patients in remission is clinically important in that it associates to relapse and worse physical function,1 composite markers without an assessment of foot have demonstrated poor performance in detecting foot synovitis.2 Objectives The aim of this study was to investigate the frequency and impact of residual synovitis in ankles and feet in patients with RA. Methods Patients with RA who underwent both physical examination and ultrasonography (US) on 44 joints including hands, fingers, ankles, and metatarsophalangeal joints between April 2016 and January 2018 in Keio University Hospital were enrolled. We compared patients with swollen joints of feet and ankles and those without, and then analysed those who did not have swollen joints by physical examination but were detected to have synovitis by US. Results Sixty one patients were enrolled in the study. The mean age was 58.5 years old, the disease duration was 7.1 years, and 85% were female. Among them, 21 patients had joint swelling in feet and ankles and 40 patients did not by physical examination. The patients in the former group showed significantly higher disease activity (DAS28 4.0 vs 2.4, p Conclusions The residual synovitis in ankles and feet did not reflect in remission criteria by DAS28 but did by Boolean criteria. It caused a discordance in global assessments between patient and estimator. References [1] Wechalekar MD, Lester S, Hill CL, Lee A, Rischmueller M, Smith MD, Walker JG, Proudman SM. Active Foot Synovitis in Patients With Rheumatoid Arthritis: Unstable Remission Status, Radiographic Progression, and Worse Functional Outcomes in Patients With Foot Synovitis in Apparent Remission. Arthritis Care Res (Hoboken)2016;68(11):1616–1623. [2] Wechalekar MD1, Lester S, Proudman SM, Cleland LG, Whittle SL, Rischmueller M, Hill CL. Active foot synovitis in patients with rheumatoid arthritis: applying clinical criteria for disease activity and remission may result in underestimation of foot joint involvement. Arthritis Rheum2012;64(5):1316–22. Disclosure of Interest None declared

Background The 2010 rheumatoid arthritis (RA) classification criteria has been verified to classify patients early as having RA more efficiently than the 1987 criteria. However, sensitivity of this criteria decreased remarkably in patients whose rheumatoid factor (RF) and anticitrullinated antibodies (ACPA) were both negative. Modern imaging technique including ultrasound (US) and magnetic resonance imaging (MRI) are more sensitive than physical examination for detecting joint inflammation objectively, however, US may offer only slight additional value when assessing patients with positive ACPA and RF. Reliability and value of inflammatory findings detected by US and MRI in seronegative, undifferentiated arthritis (UA) patients are still unclear. Objectives To clarify benefits of US and MRI for predicting futuristic diagnosis of RA in UA patients with neither ACPA nor RF. Methods Consecutive, untreated, early arthritis patients who underwent both US and contrast enhanced MRI of 22 sites including bilateral wrists, MCP and PIP joints were enrolled. Synovitis and tenosynovitis were defined as inflammatory findings of US and MRI. Concordance between swollen joint counts (SJC) by experienced physician, inflammatory findings of US and MRI were assessed. We defined UA as non-fulfilment of the 2010 RA classification criteria and the clinical diagnosis pf RA as the initiation of disease modifying anti-rheumatic drugs. Results Seventy one patients were included in the analysis. Fifty eight (82%) were female, the median age was 63 years old, and the mean symptom duration 3 months. Forty eight (67.6%) did not fulfil the 2010 criteria being defined as UA, among which thirty six were seronegative. In all patients, the concordance of detecting inflammation was quite high between MRI and US (κ: 0.67–0.70). In 36 seronegative UA patients, SJC detected by physical examinations were fewer than US or MRI (2.2 vs 3.9, p Conclusions Our study suggested that both US and MRI inflammation findings are reliable with a good concordance and can be useful as predictor for futuristic development of RA in UA patients without ACPA and RF. References [1] Kaneko Y, et al. Rheumatology (Oxford). 2011Jul;50(7):1268–74. [2] Zufferey P, et al. Joint Bone Spine. 84(3): 299–303, 2017 [3] Kawashiri S, et al. Mod Rheumatol (2013) 23:36–43 [4] Hirata A, et al. Arthritis Care Res (Hoboken). 2017Jun;69(6):801–806. Disclosure of Interest None declared

Background Ataxia-telangiectasia mutated (ATM) is a protein kinase associated with ataxia-telangiectasia (AT), which is an autosomal recessive disorder due to defective functional activity of ATM. Telangiectasia, seen in AT, is also well known as one of the major characteristics of systemic sclerosis (SSc). ATM plays an important role not only in DNA damage repairing system, but also in the process of regulation of oxidative stress. 1 Moreover, it has been reported that oxidative stress may contribute to disease process of SSc 2 3 . Based on these background, we hypothesised that ATM may play a substantial role in the pathogenesis of SSc. However, the possible association between ATM activity and SSc development is not fully understood. Objectives To clarify the role of ATM in the pathogenesis of SSc, we demonstrated the expression and activation level of ATM in circulating immune cells and analysed the association with clinical characteristics of the patients. Methods Whole blood samples were collected from twenty-four patients with SSc and 12 healthy controls (HC). Expression levels of total ATM and active phosphorylated ATM (pATM) were examined in each immune cell subset (neutrophil, monocyte, T cell, B cell and NK cell) by mean fluorescence intensity (MFI) using flow cytometer. Each MFI level of ATM and pATM was compared between patients with SSc and HC, and was analysed the correlation with clinical characteristics of SSc patients, retrospectively collected from patients’ records. Results The expression level of pATM was significantly lower in monocytes, neutrophils, and T cells in SSc as compared with HC (1887 ±128 vs 2386±181, p=0.03; 10265±861 vs 16087±1218, p=0.0004; 1326±73 vs 1675±103, p=0.009; respectively), whereas no significant difference in total ATM level was observed in each cell subset between two groups. Notably, the expression levels of pATM in monocytes of the patients with interstitial lung disease (ILD) was lower than that of the patients without ILD (1663 ±136 vs 1999±96, p=0.05). Furthermore, there was a tendency of correlation between pATM level in monocyte and parameters of pulmonary function test, such as forced vital capacity. No significant differences and/or correlation between pATM expression level in other cell subsets and clinical parameters of the patients, such as SSc subtype, SSc-specific autoantibodies, presence of pulmonary arterial hypertension, gastrointestinal involvement, digital tip ulcer, pitting scar and modified Rodnan skin score were observed. Conclusions In SSc, phosphorylated level of ATM in monocytes, neutrophils, and T cells was significantly lower than that of HC. Importantly, we found that ATM activation was impaired in monocyte of the SSc patients with ILD. These results collectively suggest that the loss of ATM activation in monocytes may contribute to the disease process of SSc, and is possibly due to DNA damage and oxidative stress. References [1] Guo Z, et al. Science. 2010;330:517–521. [2] Sambo P, et al. J Invest Dermatol. 1999;112:78–84. [3] Gabrielli A, et al. Open Rheumatol J. 2012;6:87–95. Disclosure of Interest None declared

Background In advanced non-small cell lung cancer (NSCLC), small biopsy specimens from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are often the only available material from cancer tissue for the analysis of programmed death ligand-1 (PD-L1) expression. We aim to assess the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PD-L1 expression at ≥ 1% and ≥ 50% on EBUS-TBNA samples compared with their corresponding surgically resected tumor. Methods We retrospectively reviewed all patients who underwent EBUS-TBNA followed by surgical resection of NSCLC between July 2006 and September 2016. Demographic information and periprocedural/surgical data were collected. The archived specimens were retrieved and assessed for PD-L1. A positive PD-L1 stain was defined using two separate cutoff points: ≥ 1% and ≥ 50% of tumor cell positivity. EBUS-TBNA aspirates were compared with the surgically resected specimen to calculate the sensitivity, specificity, PPV, and NPV. Results Sixty-one patients were included. For PD-L1 ≥ 1%, the sensitivity, specificity, PPV, and NPV were 72%, 100%, 100%, and 80%, respectively. For PD-L1 ≥ 50%, the sensitivity, specificity, PPV, and NPV were 47%, 93%, 70%, and 84%, respectively. The concordance rates for PD-L1 ≥ 1% and ≥ 50% were 87% and 82%, respectively. Conclusions A PD-L1 cutoff of ≥ 1% on EBUS-TBNA has a strong correlation with resected tumor specimen. For PD-L1 ≥ 50%, there is a significant decrease in the sensitivity and PPV of EBUS-TBNA specimen when compared with resected tumor. When analyzing for PD-L1 expression using a cutoff of ≥ 50%, EBUS-TBNA specimens may misclassify the status of PD-L1.

Background. The FilmArray Respiratory Panel (FARP) (BioFire Diagnostics, Inc.) is a multiplex, polymerase chain reaction (PCR) technique that can detect 17 respiratory viruses and 3 bacterial targets in a single reaction. Immunocompromised hosts (ICH) with respiratory illnesses often undergo bronchoscopy with bronchoalveolar lavage (BAL). This prospective study aimed to evaluate the yield and concordance of NP and BAL FARP testing when performed on the same patient concurrently. Methods. From February to December 2016, 125 patients (100 ICH and 25 non-ICH) were enrolled. NP swabs and BAL samples were sent for FARP testing. Results. The yield of the BAL FARP among ICH and non-ICH was 24% (24/100) and 8% (2/25), respectively. The yield of positive NP swabs in ICH was 27% (27/100) versus 4% (1/25) in non-ICH. The majority of patients (89%; 111/125) had concordant results between NP and BAL specimens. Of the 24 ICH patients who had a positive BAL FARP, the majority (79%) had the same pathogen detected from the NP swab. Conclusion. The FARP may be useful in the ICH. Given the high concordance, in patients whom a pathogen is identified on the NP FARP, a FARP performed on BAL will likely yield the same result. However, if the NP FARP is negative, performing the test on a BAL sample may have an incremental yield.

A persistent air leak (PAL) can be caused by either an alveolar-pleural fistula (APF) or bronchopleural fistula (BPF). Complications from PAL lead to an increase in morbidity and mortality, prolonged hospital stay, and higher resource utilization. Pulmonary physicians and thoracic surgeons are often tasked with the difficult and often times frustrating diagnosis and management of PALs. While most patients will improve with chest tube thoracostomy, many will fail requiring alternative bronchoscopic or surgical strategies. Herein, we review the bronchoscopic and surgical diagnostic and treatment options for PAL as it pertains to the field of interventional pulmonology and thoracic surgery.

Objective. To determine whether results of the nasopharyngeal FilmArray respiratory panel (NP-FARP) influenced antibiotic decisions. Methods. We reviewed the medical records of nonintensive care unit (ICU) inpatients that had an NP-FARP performed at our institution between June 2013 and June 2014. The inpatient records were reviewed 48 hours after the NP-FARP for the following data: demographic information; NP-FARP, serum procalcitonin, and methicillin-resistant Staphylococcus aureus nasal swab (MRSA NS) results; antibiotics prior and post-48 hours of the NP-FARP result; and the current immunosuppression status. Clinical outcome data were not obtained. Patients were categorized into those who had a positive (+) or a negative (−) NP-FARP. We further subdivided these two categories into groups A, B, and C based on the antibiotic modifications 48 hours after their NP-FARP result. Group A included patients who were never initiated on antimicrobial therapy. Patients whose antibiotics were discontinued or deescalated were placed in group B. Patients with antibiotic escalation or continuation without change constituted group C. We compared and analyzed groups A, B, and C in the (+) and (−) NP-FARP cohorts. Results. A total of 545 patients were included. There were 143 (26%) patients with positive and 402 (74%) patients with negative NP-FARPs. Comparison of groups A, B, and C between those with a (+) and (−) NP-FARP were as follows: (+) A and (−) A, 28/143 (20%) and 84/402 (21%); (+) B and (−) B, 59/143 (41%) and 147/402 (37%); and (+) C and (−) C, 56/143 (39%) and 171/402 (43%), respectively. We found no statistically significant differences between groups (+) A versus (−) A, (+) B versus (−) B, and (+) C versus (−) C with respect to age, gender, MRSA NS result, procalcitonin result, or concurrent immunosuppression. Conclusion. In non-ICU inpatients, NP-FARP alone or in combination with procalcitonin or MRSA NS did not influence antibiotic decisions during the study period.

Pyoderma gangrenosum is a chronic sterile skin disorder that is frequently seen in association with systemic disorders such as inflammatory bowel disease. Extracutaneous pyoderma gangrenosum is rare and most commonly occurs in the lungs. It is particularly unusual for extracutaneous pyoderma gangrenosum to manifest prior to skin findings and without an associated systemic disorder. A 19-year-old white man presented with shortness of breath and a productive cough. His skin exam was normal. Unenhanced chest computed tomography showed peripheral consolidations, areas of cavitation, nodules and bilateral pleural effusions. A bronchoalveolar lavage and an autoimmune panel were unremarkable. Right lung wedge biopsies via thoracostomy was performed and showed pulmonary pyoderma gangrenosum. He was treated with corticosteroids and has returned back to his baseline. This is the first case of pulmonary pyoderma gangrenosum without any associated underlying systemic disorder and without any cutaneous manifestations to date. Serial follow-ups are necessary to assess for the development of an associated systemic disorder or skin lesions.

There is various potentially hazardous aerosol suspended in atmospheric air, such as virus, exhaust gas, PM 0.1 and 2.5, endospore of bacteria, etc. One of the important issue is a monitoring technology to protect from such the hazardous aerosol from out living sphere. For this purpose, we have tried to develop a sampling mechanism, which is suitable for longtime continuous monitoring purpose. In this work, we have proposed and experimentally demonstrated new sampling method, which was utilized with liquid-gat. By testing the device using a carbon toner as a model of carbon particulate in atmospheric air, we confirmed that the liquid-gate sampling worked successfully.

Background In systemic sclerosis (SSc), systemic remodeling, microvascular injuries and production of autoantibodies are well known as disease hallmarks. However, the master regulator of these characteristics is still unclear. Microparticle (MP) is a small membrane vesicle, released from various kinds of cells, and distributes systemically through circulation1). Recent reports revealed that MP contains various growth factors, proteases and cytokines including TGF-b2), suggesting that MP can contribute to immune and mesenchymal responses as a conveyor3). and involve with disease process of SSc. Although, the possible involvement of MPs in the pathogenesis of SSc is indicated, the detailed association of MPs including MP subsets with SSc is not well clarified. Objectives To elucidate the association between circulating MP subsets and patients9 characteristic of SSc. Methods Thirty-six patients with SSc and 13 healthy controls were involved in this study. Platelet-rich plasma containing microparticles was isolated from whole blood using gradient centrifugation and analyzed using flow cytometer. MP was defined as particles smaller than 1.0 μm diameter using Megamix®, and identified each MP subsets based on expression of cell type-specific surface markers; platelet (CD31+CD41+), endothelial cell (CD31+CD41-) and monocyte (CD14+CD45+) using fluorescence-tagged antibodies. Clinical information was retrospectively collected from patients9 records, and the correlation with the number of each MP subset was analyzed. Results Mean age of 36 patients with SSc was 60.9±1.8 years, 94% was female, and mean disease duration was 11.2±9.5 years. Patients with diffuse cutaneous SSc (dcSSc) was 6 (17%). As for the proportion of MP subsets, platelet-derived MP (PMP) was the largest subset, followed by endothelial cell-derived MP (EMP) and monocyte-derived MP (MoMP) in all samples. In patients with SSc, the number of total MP and all MP subsets were higher than those in healthy controls (p Conclusions These results suggest that MP subsets are associated with extended fibrotic phenotype in patients with SSc, and might be utilized as novel biomarkers. References Bayer C et al. Nat Rev Rheumatol. 6:21–9, 2010. Antonyak MA et al. Method Mol Biol. 1165:147–73, 2014. Budoni M et al. Cell Transplant. 22:369–79, 2013. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) is a systemic connective tissue disease and characterized by inflammation of synovium of multiple joints, however, its pathogenesis is still unclear (1). Physiologically, microparticle (MP) is categorized as a membrane microvesicle which contains various humoral factors such as cytokines or growth factors and 0.1–1 μm in size (2). And MPs can distribute systemically through circulation. MP is released from almost all cell types and induced by stimulation, stress or apoptosis (3). Thus, we hypothesized that MPs derived from various cells can distribute to the lesion of RA and be associated with systemic disease process of RA. Objectives To clarify the source of MPs in circulation of RA and elucidate their role in the pathogenesis and the possibility for application as a novel disease marker. Methods Twenty patients with RA and 13 healthy controls were involved. Using gradient centrifugation, platelet-rich plasma was isolated from whole blood and applied to flow cytometry. MP is defined as a vesicle less than 1 mm in diameter and Megamix® was used to set a gating condition to detect microparticles (4). Sources of MP (MP subsets) were identified by the expression of cell-specific markers using flow cytometry with fluorescence-conjugated antibodies as follows; platelets MP: CD41 + CD31 + MP, endothelial cell MP: CD41 - CD31 + MP, immune cell MP: CD45 + CD41 - MP, MP derived other cells: CD41 - CD31 - CD45 - MP. Correlation between clinical information and proportion of MP subsets was also analyzed. Comparisons between two groups were examined by Mann-Whitney U-test with Bonferroni correction. Significant difference was defined as corrected p value ( Pc ) Results Mean age of 20 patients with RA was 56±14 years, 95% was female, disease duration was 8.5±8.0 years, and DAS28-ESR was 2.0±1.1. Methotrexate was administered to 75% and average dose was 8.0±2.4 mg/week. Platelet-derived MP covered the largest proportion in all groups. Interestingly, proportion of immune-cell-derived MP was higher ( Pc Pc Conclusions Proportion of circulating immune-cell-derived MPs, especially monocyte-derived MPs, increased in RA and correlate with disease activity. These results suggest that monocyte-derived MPs can be measured as a novel biomarker and involved in the disease process of RA. References Smolen JS et al. Lancet 388: 2023–2038, 2016. van der Pol E et al. 64: 676–705, 2012. Buzas EI et al. Nat Rev Rheumatol 10: 356–364, 2014. Chandler WL et al. J Thromb Haemost 9:1216–1224, 2011. Disclosure of Interest None declared

Background Ultrasonography (US) is a useful modality that can directly visualize RA joint inflammation. Recently, brightness of thickened synovium is considered to associate with local synovitis. However the accuracy of US findings with the local pathophysiology remains uncertain since synovial biopsy could be heterogeneous depending on the biopsy site and can be influenced by various medications. On another front, synovial fluid (SF) is homogenous, easy to access and contains abundant inflammatory cytokines and growth factors, which play an important role in the local pathogenesis of RA. However, the association between SF proteins and joint US findings is not clear. Objectives To clarify whether synovitis detected by US including synovial hypertrophy, vascularity and brightness reflect local joint molecular pathophysiology. Methods Forty-four RA patients were recruited. All patients were performed standardized US examination of knee joint. US images were evaluated by semi-quantitative scoring (synovial hypertrophy; grey scale (GS) US, vascularity; power Doppler (PD) US) and quantitative analysis by using Image J (National Institutes of Health, MD, Maryland USA). The average of the pixels of synovial tissue area (GS quant), PD signal area (PD quant) and mean gray values of synovium (Brightness) in 3 areas of the knee joint were calculated. US guided SF aspiration was performed on the same day and concentrations of cytokines and growth factors were measured by Cytometric Beads Array. (BD Biosciences, NJ, USA) Results Median age, disease duration and DAS28-ESR were 64 years, 1.5 years and 5.2 respectively. Mean GSUS and PDUS were 2.3 and 2.0. Nineteen patients were untreated. US inflammatory findings especially PD quant were well correlated with corresponding SF IL-6, IL-8, IL-1β and IL-10.(range of rho;0.40–0.72, p Conclusions Our results suggest that not only US PD signals but also synovial brightness is a useful indicator for joint inflammation rather than synovial hypertrophy itself in treated RA patients. References Naredo E et al. Arthritis Rheum 2008; 58: 2248–56. Kelly S et al. Arthritis Res Ther. 2015 Mar 13;17:58. Disclosure of Interest None declared

Background and Aims CD4 + T cells play a crucial role in pathological process of Systemic Lupus Erythematosus (SLE). Recently, we found that T-bet is an important factor for shift to glycolysis in activated CD4 + T cells in vitro . In this study, we examined the mechanism by which T-bet in CD4 + T cells involved in pathogenesis of SLE. Methods Peripheral blood mononuclear cells were obtained from 19 healthy controls (HCs), 30 patients with bio-naive active RA and 60 patients with SLE. The expression of CXCR3, T-bet, mTORC1 phosphorylation and IFN-γ production in CD4 + T cells were measured by flow cytometry, and assessed the association with clinical characteristics. Results We found that the ratio of CD28 - CXCR3 int T-bet hi cells in patients with SLE was significantly higher compared to HCs. CD4 + CD28 - CXCR3 int T-bet hi cells mainly consisted of CD45RA - CCR7 - effector memory cells and were significantly activated with pronounced IFN-γ production. Interestingly, the ratio of CD4 + CD28 - CXCR3 int T-bet hi cells was significantly correlated with the number of immunosuppressants previously used for the SLE patients, that is treatment-resistant. Phosphorylation of mTORC1, which is important for shift to glycolysis, in CD4 + T cells from patients with SLE was significantly increased compared to HCs. T-bet expression was significantly correlated with mTOC1 phosphorylation and IFN-γ production in CD4 + T cells from patients with SLE. Conclusions These results indicated that CD4 + CD28 - CXCR3 int T-bet hi cells might be related to refractory to established therapies in patients with SLE. In addition, these cells are constitutively activated accompanied with shift to glycolysis through IFN-γ-mTORC1-T-bet pathway, which is a potential target for patients with SLE.

Background and aims To elucidate the diversity of systemic lupus erythematosus (SLE), we stratified SLE patients based on immunophenotyping. Methods Peripheral blood mononuclear cells were obtained from 80 active SLE patients (with one or more BILAG category A, or two or more BILAG category B). Circulating B, T and dendritic cells were defined based on flow cytometric analysis for human immune system termed ”the Human Immunology Project”. Based on these results, the immunophenotype was visualised by principal component analysis and SLE patients classified into subgroups by cluster analysis. Results Principal component analysis indicated that the immunophenotype of active SLE patients was consistent with T and B cell axes. Among these correlations, Th17 and Treg cells were statistically close, and showed positive correlation (p Conclusions Our study indicates that SLE patients can be divided into three subgroups based on T cell heterogeneity. This heterogeneity should be taken into consideration not only in basic research but also in patient selection in clinical trials for development of new drugs.

Background and aims The aim of this study was to assess the peripheral immune cell phenotypes in a correlation with clinical findings in patients with systemic lupus erythematosus (SLE). Methods Peripheral blood mononuclear cells were obtained from 143 SLE patients and 26 healthy donors (HD). Circulating B, T and dendritic cells were defined based on flow cytometric analysis for human immune system termed “the Human Immunology Project” proposed by the National Institutes of Health (NIH) and the Federation of Clinical Immunology Societies (FOCIS). Results The proportions of CD3 + CD4 + CXCR5 + ICOS + T follicular helper (Tfh) cells, but not CD3 + CD4 + CXCR3 + CCR6 - Th1 and CD3 + CD4 + CXCR3 - CCR6 + Th17 cells, were higher in SLE than the HD. The proportions of CD19 + CD20 + IgD + CD27 + central memory B cells and CD19 + CD20 + IgD - CD27 - effector B cells were higher in SLE. The largest difference relative to the HD was observed in the proportion of CD19 + CD20 - CD27 + CD38 + plasmablasts, which was higher in SLE and correlated with BILAG index. The proportion of Tfh cells correlated with serum IgG level, and the proportion of activated Tfh cells correlated with serum anti-Sm antibody level. Among helper T cell subsets (Th1, Th17, Treg and Tfh), Tfh cells only showed positive correlation with the proportion of plasmablast (r=0.24, p=0.02). Conclusions Peripheral immuno-phenotyping confirmed the importance of Tfh-plasmablasts axis in patients with SLE, i.e. activation of Tfh cells correlated with autoantibody production while plasmablast did with disease activity of SLE. Our findings supported the relevance of Tfh-plasmablasts axis as a potential therapeutic target for SLE.

Background and aims Aberrant and persistent production of type I interferon (IFN) is known to play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE), and plasmacytoid dendritic cells (pDCs) are the major source of type I IFN upon toll-like receptor 7 (TLR7) and TLR9 stimulation. However the respective impacts of TLR7 and TLR9 responses on type I IFN production in SLE has not been addressed.To investigate the precise function of pDCs in SLE patients, we shed light upon the differential regulation of TLR7/9 responses during type I IFN production from pDCs. Methods PBMCs from SLE patients and healthy controls were analysed in the presence of a TLR7 agonist loxoribine and a TLR9 agonist CpG2216. The IFN-α production in Lin-HLA-DR+CD123+CD11c- pDCs was detected by flow cytometry. Results We demonstrated that TLR7-mediated IFN-α production were up-regulated and were positively correlated with disease activity, conversely, TLR9-mediated IFN-α production were down-regulated in SLE. The differential regulation of TLR7/9 responses of pDCs was not dependent on expression levels of TLR7/9. Furthermore, in vitro experiments revealed that up-regulation of TLR7 response was caused by pre-treatment with type I IFNs, conversely, down-regulation of TLR9 response was caused by pre-treatment with type II IFN. Conclusions This is the first report demonstrated the differential regulation of TLR7- and TLR9- mediated IFN-α production from pDCs in SLE, namely, caused by priming effects of type I and type II IFNs. Taken together, TLR7-, but not TLR9-, mediated IFN-α production contributes the pathogenesis of SLE, and TLR7 could be a potential therapeutic target for SLE.

No abstract available. Article truncated at 150 words. History of Present Illness A 69 year old man was admitted to the intensive care unit with shortness of breath and atrial fibrillation with a rapid ventricular response. PMH, FH, SH He has a history of peripheral vascular disease, end-stage renal disease and is receiving chronic hemodialysis. Physical Examination Afebrile. Pulse 135 and irregular. BP 105/65 mm Hg. SpO2 96% while receiving oxygen at 2L/min by nasal cannula. HEENT: Unremarkable. Neck: Jugular venous distention to the angle of the jaw while the head is elevated at 45 degrees. Lungs: Decreased breath sounds at the right base. Cardiovascular: Irregularly, irregular rhythm. 2-3+ pretibial edema. Abdomen: no hepatosplenomegaly. Radiography The admission chest x-ray is shown in figure 1. Which of the following is the best interpretation of the chest x-ray given the clinical situation? 1. Hepatomegaly elevating the right diaphragm 2. Large right pleural effusion 3. Paralyzed right diaphragm 4. Right lower ...