SAT0018 THE THERAPEUTIC EFFECT OF STIMULATION OF THE SPLENIC NEUROVASCULAR BUNDLE IN MICE WITH COLLAGEN-INDUCED ARTHRITIS IS ENHANCED BY CONCOMITANT ANTI-TNF TREATMENT

Background:Vagus nerve (VN) stimulation has shown the potential to improve the disease development in animal models of arthritis and in patients with RA. However, the VN can affect respiratory, cardiovascular, endocrine and gastro-intestinal physiology. The splenic nerve (SpN) has been confirmed to be the principal effector nerve for the VN-mediated immune control. Previous studies have shown that stimulating the splenic nerve resulted in an increase of norephiniphrine in the spleen, as well as a significant reduction in LPS-induced TNF (1).Objectives:To test the therapeutic efficiency of splenic nerve stimulation (SNS) in collagen-induced arthritis (CIA) in mice alone or in combination with anti-TNF treatment.Methods:CIA was induced in DBA1/J mice by immunization with bovine type II collagen at days 0 and 21. At day 11, mice were implanted with micro-cuff electrode (CorTec) onto the SpN or VN. From day 16 to day 45, SNS were applied as rectangular charged-balanced biphasic pulses with 650 μA pulse amplitude, 200 µs pulse width at 10 Hz frequency for 2 min 1 or 6 times a day using a Plexon stimulator. In order to investigatedthe mechanism of action in more detail, propranolol, a beta-adrenergic receptor (β-AR) antagonist, was added to the drinking water of mice receiving SNS. In addition, a control group was treated with anti-TNF (etanercept, 3 times/week; 10mg/kg i.p.). In curative settings, SNS and/or anti-TNF treatment was applied starting when mice scored positive for 3 consecutive days. Clinical arthritis was determined by visual examination of swelling and redness of the paws and measurement of paw thickness. Sham mice were undergoing the same procedure but did not receive stimulation.Results:In CIA in mice all sham animals developed arthritis, compared to only 14% following six times per day SNS (p <0.001) in a prophylactic setting. In contrast, 85% of the animals developed arthritis (p = 0.35) when SNS was applied only once a day. In both stimulated groups a significant decrease in clinical scores and paw thickness was observed compared to unstimulated group (p < 0.01 and p < 0.05, respectively). While etanercept treatment reduced clinical scores (p <0.001) an immediate rebound in clinical score was seen following treatment arrest, while mice with SNS were still partially protected 35 days after treatment discontinuation (p = 0.013, compared to sham). Propranolol inverted the effect of SNS in CIA mice. Finally, when SNS was applied as a curative treatment, clinical scores were significantly reduced (p < 0.001). Importantly, these clinical scores even further decreased when anti-TNF treatment was given to mice receiving SNS.Conclusion:These studies demonstrate that SNS suppresses pro-inflammatory cytokine production, and reduces clinical symptoms in mice with CIA which is at least partially mediated by the β-AR. The additive effect of anti-TNF in reducing the clinical scores demonstrates that that mechanism of action of SNS is not primarilys mediated by reducing TNF levels. Moreover, anti-TNF potentiating the inhibitory effect of SNS is supporting a combined use of these treatments, or even a combination of SNS with other biologicals, to treat RA, potentially getting more patients closer to remission. In conclusion, the data is providing compelling scientific rationale and pre-clinical evidence that splenic neuromodulation might be a new treatment modality for RA.References:[1] Guyot M et al, Brain Behav Immun. 2019;80:238.Disclosure of Interests:Thomas Simon Grant/research support from: research grant from Galvani Bioelectronics, Clara Panzolini Grant/research support from: Working on research grant Galvani bioelectronics, Julien Lavergne Grant/research support from: working on research grant Galvani Bioelectrocnics, Nicolas Hypolite Grant/research support from: Working on research grant Galvani Bioelectronics, Nicolas Glaichenhaus: None declared, Margriet Vervoordeldonk Employee of: I am an employee of Galvani Bioelectronics, Philippe Blancou Grant/research support from: Received research grant from Galvani Bioelectronics

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Clinical Usefulness of Monitoring Expression Levels ofCCL24(Eotaxin-2) mRNA on the Ocular Surface in Patients with Vernal Keratoconjunctivitis and Atopic Keratoconjunctivitis

Journal of Ophthalmology ◽

10.1155/2016/3573142 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 8

Author(s):

Yukiko Shiraki ◽

Jun Shoji ◽

Noriko Inada

Keyword(s):

Mrna Expression ◽

Ocular Surface ◽

Clinical Score ◽

Clinical Severity ◽

Vernal Keratoconjunctivitis ◽

Control Group ◽

Expression Levels ◽

Atopic Keratoconjunctivitis ◽

Clinical Scores ◽

Mrna Expression Levels

Purpose. This study aimed to evaluate the clinical efficacy of using expression levels ofCCL24(eotaxin-2) mRNA on the ocular surface as a biomarker in patients with vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC).Methods. Eighteen patients with VKC or AKC (VKC/AKC group) and 12 control subjects (control group) were enrolled in this study. The VKC/AKC clinical score was determined by objective findings in patients by using the 5-5-5 exacerbation grading scale. All subjects underwent modified impression cytology and specimens were obtained from the upper tarsal conjunctiva. Expression levels ofCCL24(eotaxin-2) mRNA on the ocular surface were determined using real-time reverse transcription polymerase chain reaction.Results. The VKC group was divided into two subgroups, depending on the clinical score: the active stage subgroup with 100 points or more of clinical scores and the stable stage subgroup with 100 points or less.CCL24(eotaxin-2) mRNA expression levels in the active VKC/AKC stage subgroup were significantly higher than those in the stable VKC/AKC subgroup and the control group. Clinical scores correlated significantly withCCL24(eotaxin-2) mRNA expression levels in the VKC group.Conclusions.CCL24(eotaxin-2) mRNA expression levels on the ocular surface are a useful biomarker for clinical severity of VKC/AKC.

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Attenuation of Collagen-Induced Arthritis in Rat by Nicotinic Alpha7 Receptor Partial Agonist GTS-21

BioMed Research International ◽

10.1155/2014/325875 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 9

Author(s):

Yiping Hu ◽

Ruoxi Liu ◽

Jinchao Li ◽

Ye Yue ◽

Wenxiang Cheng ◽

...

Keyword(s):

Clinical Symptoms ◽

Partial Agonist ◽

Control Group ◽

Tartrate Resistant Acid Phosphatase ◽

Collagen Induced Arthritis ◽

Bone Degradation ◽

Histological Score ◽

Hematoxylin And Eosin ◽

Alpha7 Receptor ◽

Phosphate Buffered Saline

This research was performed to observe the effect of GTS-21 on Collagen Induced Arthritis (CIA). CIA model was used and after the onset of arthritis, the rats were divided into three groups based on their clinical symptoms score. Two groups were intraperitoneally (IP) injected daily with GTS-21 (1 mg/kg, 2.5 mg/kg) for a week, whereas phosphate buffered saline (PBS) was used for the control group. Cytokine titers, radiological, and histological examinations were performed at different time points after treatment with GTS-21. Compared with those of the control, the levels of TNF-α, IL-1, and IL-6 in the serum were significantly reduced after GTS-21 management. In addition, radiological results show that bone degradation was inhibited as well. Moreover, the hematoxylin and eosin (H&E) staining indicated that the histological score was significantly alleviated in the therapeutic group. Tartrate-resistant acid phosphatase (TRAP) stain-positive cells were also detected in the destruction of the articular cartilage, which was significantly reduced compared with the control group. This study provides the first evidence on the effect of GTS-21 as a potential treatment for RA.

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Possibilities of correction of menopausal disorders in women with the use of medicine Menopace

HEALTH OF WOMAN ◽

10.15574/hw.2016.111.95 ◽

2016 ◽

pp. 95-100

Author(s):

G.I. Reznichenko ◽

◽

N.Yu. Reznichenko ◽

V.Yu. Potebnya ◽

K.I. Kovalenko ◽

...

Keyword(s):

General Condition ◽

Clinical Symptoms ◽

Average Score ◽

Control Group ◽

Climacteric Syndrome ◽

Basic Subgroup ◽

Menopausal Syndrome ◽

Natural Menopause ◽

Surgical Menopause ◽

Observation Period

The objective: to determine the efficacy of medicine «Menopace» in treatment of women with natural and surgical menopause. Patients and methods. 20 women (I group) with a natural menopause were examined (basic subgroup consisted of 10 patients who used Menopace for 3 months; control subgroup consisted of 10 patients). 20 women (II group) with surgical menopause were examined (basic subgroup consisted of 10 patients who received Menopace for 3 months; control subgroup consisted of 10 patients). Results. The average score of neurovegetative and emotional manifestations of climacteric syndrome during the observation period decreased in women with natural and surgical menopause who used Menopace, compared with subgroups of patients who had not used the medicine. Conclusions. 1. The use of the medicine Menopace in women with natural menopause after 3 months showed the disappearance of clinical symptoms of climacteric syndrome in 70% of the cases, and significant improvement in general condition in 30% of cases. 2. During surgical menopause after 1 month of treatment with Menopace manifestations of sweating were observed 4.5 times less often than in control group, tides were observed 7 times less often than in control group. Neurovegetative and psychoemotional symptoms of menopause were absent in 80% of women after 3 months of treatment and in 20% of cases significant improvement was shown. 3. The obtained results give grounds to recommend wide use of Menopace in practical work for the treatment of menopausal syndrome during natural and surgical menopause. Key words: menopause, therapy, Menopace.

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57. Evaluating the Utility of a Penicillin Allergy Reconciliation Program within an Infectious Diseases Consult Population in a Community Health System

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.102 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S49-S50

Author(s):

Bruce M Jones ◽

Emily Plauche ◽

Susan E Smith ◽

Christopher M Bland

Keyword(s):

Infectious Diseases ◽

Health System ◽

Community Health ◽

Intervention Program ◽

Primary Outcome ◽

Panel Member ◽

Penicillin Allergy ◽

Secondary Outcome ◽

Research Support ◽

Research Grant

Abstract Background Penicillin allergy reconciliation is an important aspect of antimicrobial stewardship with ~10% of the population reporting a penicillin allergy. Our facility utilizes a Penicillin Allergy Reconciliation Program (PARP) led by an Infectious Diseases (ID) Pharmacist and pharmacy students to identify patients with penicillin allergies to reconcile and intervene when necessary. Information is collected by interview, electronic medical record (EMR) review, prescription outpatient fill history. This study evaluated reconciliations with and without a PARP in patients in a community health system. Methods This was a retrospective study that compared reconciliations performed on adult patients admitted at least once in 2019 with a self-reported penicillin allergy and ID physician consult at a hospital with a PARP (Institution 1) and one without a formal evaluation and intervention program (Institution 2) within the same community health system with same ID physicians. The primary outcome was documented reconciliation of a patient’s penicillin allergy during an inpatient visit in 2019. Reconciliation was defined as an edit or clarification (updating the severity, reaction, or comments section, as well as deleting) to a patient’s penicillin allergy in the EMR. The secondary outcome evaluated the percentage of total and ID consult patients with a penicillin allergy. Results There were 245 patients who met criteria and were included in the study, 113 from Institution 1 and 132 from Institution 2. For the primary outcome, there were 82 (72.6%) reconciliations at Institution 1 and 15 (11.4%) reconciliations at Institution 2 (p < 0.001). Interventions at Institution 1 and 2 resulted in 74 EMR updates and 8 removals and 14 EMR updates and 1 removal, respectively. Reconciliation was performed on the same visit as the ID consult in 59/82 patients (72%) at Institution 1 and 11/15 patients (73.3%) at Institution 2. All reconciliations at Institution 2 were made by pharmacist (10) or nurses (5). For the secondary outcome, 10.9% of patients with an ID consult and 12.6% of all patients admitted in 2019 had a penicillin allergy (p=0.027). Conclusion A PARP led by an ID pharmacist and students was an effective method to perform penicillin allergy reconciliations, even in the presence of active ID consultation. Disclosures Bruce M. Jones, PharmD, BCPS, ALK-Abello (Research Grant or Support)Allergan/Abbvie (Speaker’s Bureau) Christopher M. Bland, PharMD, FCCP, FIDSA, BCPS, ALK Abello, Inc. (Grant/Research Support)Biomerieux (Consultant)Merck (Consultant, Grant/Research Support, Advisor or Review Panel member, Speaker’s Bureau)Tetraphase (Speaker’s Bureau)

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The Effect of Immunosuppression on Selected Antioxidant Parameters in Patients with Graves’ Disease with Active Thyroid-Associated Orbitopathy

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-1274-0998 ◽

2020 ◽

Author(s):

Magdalena Londzin-Olesik ◽

Beata Kos-Kudla ◽

Jacek Karpe ◽

Aleksandra Nowak ◽

Mariusz Nowak

Keyword(s):

Oxidative Stress ◽

Clinical Symptoms ◽

Immunosuppressive Treatment ◽

Serum Vitamin ◽

Serum Levels ◽

Paraoxonase 1 ◽

Control Group ◽

Graves Disease ◽

Methylprednisolone Treatment ◽

Antioxidant Parameters

Abstract Background and Study Aims Thyroid-associated orbitopathy, the most common extrathyroidal manifestation of Graves’ disease, is an autoimmune inflammation of orbital soft tissue. We report the study assessing the effect of immunosuppressive treatment with methylprednisolone on selected antioxidant parameters in patients with Graves’ disease with active thyroid-associated orbitopathy. Patients and Methods Activity and serum levels of selected antioxidant parameters as well as lipid peroxidation products were determined in a group of 56 patients with active thyroid-associated orbitopathy at three time-points: at baseline, after the discontinuation of intravenous methylprednisolone treatment and at 3 months after the discontinuation of additional oral methylprednisolone treatment. A control group consisted of 20 healthy age- and sex-matched volunteers. Results We found an increased activity of superoxide dismutase and glutathione peroxidase and increased serum levels of uric acid, malondialdehyde and conjugated dienes, as well as a reduced activity of paraoxonase-1 and reduced serum vitamin C level in the study group at baseline. Systemic intravenous and oral methylprednisolone therapy led to normalization of activity and concentration of the most studied parameters. Conclusion Results of our study confirmed that oxidative stress is one of the factors involved in the pathogenesis of thyroid-associated orbitopathy and the methyloprednisolone treatment is effective in reducing both clinical symptoms and oxidative stress in patients with this disease.

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AB1346-HPR REAL-WORLD EFFECTIVENESS AND PERCEIVED USEFULNESS OF SYMPTOM CHECKERS IN RHEUMATOLOGY: INTERIM REPORT FROM THE PROSPECTIVE MULTICENTER BETTER STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1604 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1961.1-1961

Author(s):

J. Knitza ◽

J. Mohn ◽

C. Bergmann ◽

E. Kampylafka ◽

M. Hagen ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Real World ◽

Search Engines ◽

Correct Diagnosis ◽

Perceived Usefulness ◽

Symptom Duration ◽

Research Support ◽

Link Type ◽

The Mean ◽

Research Grant

Background:Symptom checkers (SC) promise to reduce diagnostic delay, misdiagnosis and effectively guide patients through healthcare systems. They are increasingly used, however little evidence exists about their real-life effectiveness.Objectives:The aim of this study was to evaluate the diagnostic accuracy, usage time, usability and perceived usefulness of two promising SC, ADA (www.ada.com) and Rheport (www.rheport.de). Furthermore, symptom duration and previous symptom checking was recorded.Methods:Cross-sectional interim clinical data from the first of three recruiting centers from the prospective, real-world, multicenter bETTeR-study (DKRS DRKS00017642) was used. Patients newly presenting to a secondary rheumatology outpatient clinic between September and December 2019 completed the ADA and Rheport SC. The time and answers were recorded and compared to the patient’s actual diagnosis. ADA provides up to 5 disease suggestions, Rheport calculates a risk score for rheumatic musculoskeletal diseases (RMDs) (≥1=RMD). For both SC the sensitivity, specificity was calculated regarding RMDs. Furthermore, patients completed a survey evaluating the SC usability using the system usability scale (SUS), perceived usefulness, previous symptom checking and symptom duration.Results:Of the 129 consecutive patients approached, 97 agreed to participate. 38% (37/97) of the presenting patients presented with an RMD (Figure 1). Mean symptom duration was 146 weeks and a mean number of 10 physician contacts occurred previously, to evaluate current symptoms. 56% (54/96) had previously checked their symptoms on the internet using search engines, spending a mean of 6 hours. Rheport showed a sensitivity of 49% (18/37) and specificity of 58% (35/60) concerning RMDs. ADA’s top 1 and top 5 disease suggestions concerning RMD showed a sensitivity of 43% (16/37) and 54% (20/37) and a specificity of 58% (35/60) and 52% (31/60), respectively. ADA listed the correct diagnosis of the patients with RMDs first or within the first 5 disease suggestions in 19% (7/37) and 30% (11/37), respectively. The average perceived usefulness for checking symptoms using ADA, internet search engines and Rheport was 3.0, 3.5 and 3.1 on a visual analog scale from 1-5 (5=very useful). 61% (59/96) and 64% (61/96) would recommend using ADA and Rheport, respectively. The mean SUS score of ADA and Rheport was 72/100 and 73/100. The mean usage time for ADA and Rheport was 8 and 9 minutes, respectively.Conclusion:This is the first prospective, real-world, multicenter study evaluating the diagnostic accuracy and other features of two currently used SC in rheumatology. These interim results suggest that diagnostic accuracy is limited, however SC are well accepted among patients and in some cases, correct diagnosis can be provided out of the pocket within few minutes, saving valuable time.Figure:Acknowledgments:This study was supported by an unrestricted research grant from Novartis.Disclosure of Interests:Johannes Knitza Grant/research support from: Research Grant: Novartis, Jacob Mohn: None declared, Christina Bergmann: None declared, Eleni Kampylafka Speakers bureau: Novartis, BMS, Janssen, Melanie Hagen: None declared, Daniela Bohr: None declared, Elizabeth Araujo Speakers bureau: Novartis, Lilly, Abbott, Matthias Englbrecht Grant/research support from: Roche Pharma, Chugai Pharma Europe, Consultant of: AbbVie, Roche Pharma, RheumaDatenRhePort GbR, Speakers bureau: AbbVie, Celgene, Chugai Pharma Europe, Lilly, Mundipharma, Novartis, Pfizer, Roche Pharma, UCB, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, Timo Meinderink: None declared, Wolfgang Vorbrüggen: None declared, Cay-Benedict von der Decken: None declared, Stefan Kleinert Shareholder of: Morphosys, Grant/research support from: Novartis, Consultant of: Novartis, Speakers bureau: Abbvie, Novartis, Celgene, Roche, Chugai, Janssen, Andreas Ramming Grant/research support from: Pfizer, Novartis, Consultant of: Boehringer Ingelheim, Novartis, Gilead, Pfizer, Speakers bureau: Boehringer Ingelheim, Roche, Janssen, Jörg Distler Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Paid instructor for: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim, Peter Bartz-Bazzanella: None declared, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Martin Welcker Grant/research support from: Abbvie, Novartis, UCB, Hexal, BMS, Lilly, Roche, Celgene, Sanofi, Consultant of: Abbvie, Actelion, Aescu, Amgen, Celgene, Hexal, Janssen, Medac, Novartis, Pfizer, Sanofi, UCB, Speakers bureau: Abbvie, Aescu, Amgen, Biogen, Berlin Chemie, Celgene, GSK, Hexal, Mylan, Novartis, Pfizer, UCB

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FRI0052 INFLUENCE OF RHEUMATOID ARTHRITIS ON THE CLINICAL AND BIOLOGICAL PROFILE OF TYPE-2 DIABETES MELLITUS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5408 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 601.2-602

Author(s):

J. Avouac ◽

M. Elhai ◽

M. Forien ◽

J. Sellam ◽

F. Eymard ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Insulin Requirement ◽

Multivariate Logistic Regression ◽

Biological Profile ◽

Research Support ◽

Insulin Resistant ◽

Research Grant

Background:Type-2 diabetes and rheumatoid arthritis (RA) are two chronic diseases characterized by tissue inflammation and insulin resistance. To date, no data have evaluated the influence of RA-induced joint and systemic inflammation on the course of type-2 diabetes.Objectives:To study the impact of RA on type-2 diabetesMethods:Observational, multicenter, cross-sectional usual-care study, including 7 rheumatology centers. This study included over a 24-month period consecutive patients with type-2 diabetes and RA, fulfilling the 2010 ACR / EULAR criteria, and diabetic controls with osteoarthritis (OA). The following data were collected: demographics, disease activity and severity indices, current treatment for RA and diabetes, history and complications of diabetes. A systematic blood test was performed, assessing inflammatory (CRP levels) and metabolic (fasting glycemia and insulin levels, HbA1c) parameters. The HOMA2%B (insulin secretion) and HOMA2%S (tissue insulin sensitivity) indices (HOMA calculator, © Diabetes Trials Unit, University of Oxford) were used to assess insulin resistance. Ra and OA patients were compared using parametric tests after adjusting for age and BMI. A multivariate logistic regression was performed ti identify factors independently associated with insulin resistance.Results:We included 122 RA patients (74% women, mean age 64+/-11 years, mean disease duration 15+/-11 11 years, 75% with positive ACPA antibodies and 64% with erosive disease) and 54 controls with OA. 64% of RA patients were treated with oral corticosteroids <10 mg/day, 65% received methotrexate and 53% received targeted biological therapies.The characteristics of type-2 diabetes in the 54 OA patients corresponded to severe insulin-resistant diabetes: age> 65 years, high BMI> 30 kg/m2, mean HbA1c 7.3%+/-11 1.3%, 30% of insulin requirement, high frequency of other cardiovascular risk factors, macroangiopathy found in almost half of patients and biological criteria of insulin resistance (elevation of HOMA2%B and decrease of HOMA2%S).RA patients with type-2 diabetes had a younger age (64+/-11 years vs. 68+/-12 years, p=0.031) and lower BMI (27.7+/-11 5.5 vs. 31.5+/-11 6.3, p<0.001). These patients also had severe diabetes (HbA1c 7.0%+/-11 1.2%, 29% of insulin requirement, 43% of macroangiopathy) with an insulin resistance profile identical to OA controls. After adjusting for age and BMI, RA patients had a significantly increased insulin secretion compared to OA patients (HOMA2%B: 83.1+/-11 65.2 vs. 49.3+/-11 25.7, p=0.023) as well as a significant reduction of insulin sensitivity (HOMA2%S: 61.1+/-11 31.6 vs. 92.9+/-11 68.1, p=0.016). This insulin resistance was associated with the inflammatory activity of RA, with a negative correlation between the HOMA2%S and the DAS28 (r=-0.28, p=0.027). The multivariate logistic regression confirmed the independent association between the HOMA2%S index and DAS28 (OR: 3.93, 95% CI 1.02-15.06), as well as high blood pressure (OR: 1.29, 95% CI 0.33-1.99 CI).Conclusion:RA patients with type-2 diabetes displayed severe, poorly controlled diabetes, highlighting the burden of comorbidities associated with RA. The clinical-biological profile of diabetic RA patients was severe insulin-resistant diabetes, with a biological profile of insulin resistance linked to the inflammatory activity of the disease. These findings may have therapeutic implications, with the potential targeting of insulin resistance through the treatment of joint and systemic inflammation.Acknowledgments:Société Française de Rhumatologie (research grant)Bristol Myers Squibb (research grant)Disclosure of Interests:Jérôme Avouac Grant/research support from: Pfizer, Bristol Myers Squibb, Consultant of: Sanofi, Bristol Myers Squibb, Abbvie, Boerhinger, Nordic Pharma, Speakers bureau: Sanofi, Bristol Myers Squibb Abbvie, MSD, Pfizer, Nordic Pharma, Muriel ELHAI: None declared, Marine Forien: None declared, Jérémie SELLAM: None declared, Florent Eymard Consultant of: Regenlab, Anna Moltó Grant/research support from: Pfizer, UCB, Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, UCB, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Frédéric Banal: None declared, Joel Daminano: None declared, Philippe Dieudé: None declared, Yannick Allanore Shareholder of: Sanofi, Roche, Consultant of: Actelion, Bayer, BMS, Boehringer Ingelheim, Inventiva, Sanofi

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Longitudinal assessment of S100B serum levels and clinical factors in youth patients with mood disorders

Scientific Reports ◽

10.1038/s41598-021-91577-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Aleksandra Rajewska-Rager ◽

Monika Dmitrzak-Weglarz ◽

Pawel Kapelski ◽

Natalia Lepczynska ◽

Joanna Pawlak ◽

...

Keyword(s):

Mood Disorders ◽

Calcium Binding ◽

Clinical Symptoms ◽

Small Sample Size ◽

Serum Levels ◽

Small Sample ◽

Drop Out ◽

Control Group ◽

Longitudinal Assessment ◽

Depressed Group

AbstractMood disorders have been discussed as being in relation to glial pathology. S100B is a calcium-binding protein, and a marker of glial dysfunctions. Although alterations in the S100B expression may play a role in various central nervous system diseases, there are no studies on the potential role of S100B in mood disorders in adolescents and young adults . In a prospective two-year follow-up study, peripheral levels of S100B were investigated in 79 adolescent/young adult patients (aged 14–24 years), diagnosed with mood disorders and compared with 31 healthy control subjects. A comprehensive clinical interview was conducted which focused on clinical symptoms and diagnosis change. The diagnosis was established and verified at each control visit. Serum S100B concentrations were determined. We detected: lower S100B levels in medicated patients, compared with those who were drug-free, and healthy controls; higher S100B levels in a depressed group with a family history of affective disorder; correlations between age and medication status; sex-dependent differences in S100B levels; and lack a of correlation between the severity of depressive or hypo/manic symptoms. The results of our study indicate that S100B might be a trait-dependent rather than a state-dependent marker. Due to the lack of such studies in the youth population, further research should be performed. A relatively small sample size, a lack of exact age-matched control group, a high drop-out rate.

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1104. Risk Factors and Outcomes of Refractory and/or Resistant Cytomegalovirus (CMV) Infection after Allogeneic Hematopoietic Stem Cell Transplantation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1290 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S582-S583

Author(s):

Eleni Karantoni ◽

Yiqi Su ◽

Anat Stern ◽

Phaedon D Zavras ◽

Sergio Giralt ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

T Cell ◽

Panel Member ◽

Multivariable Model ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Advisory Boards ◽

Research Grant

Abstract Background The epidemiology of CMV end-organ disease (EOD) after Hematopoietic Cell Transplant (HCT) in the era of preemptive therapy (PET) is defined. In contrast, less data exists on refractory and/or resistant (R/R) CMV. We report on 1) the incidence; 2) risk factors and outcomes of R/R CMV by 1-year post HCT. Methods Retrospective review of 167 CMV seropositive (R+) recipients of first marrow or peripheral blood HCT from 1/2014 - 12/2017 managed by PET. Refractory CMV was defined as failure to achieve >1 log10 decrease in CMV viral load (VL) and having VL >1,000 IU/mL after ≥14 day of PET. Resistant CMV required genotypic confirmation of resistance mutation(s) in UL54 and/or UL97 genes. End organ disease (EOD) was defined by standard criteria. Patients (pts) were followed through 1-year post HCT and were categorized in two mutually exclusive groups as R/R and no R/R. Demographics, clinical characteristics and outcomes were extracted from medical records and hospital databases. Univariable and multivariable logistic models were used to identify risk factors for R/R CMV. Results Of 167 PET recipients, 91 (54.5%) received ex vivo T cell depleted (TCD) HCT; 40 (24.0%) had mismatched donor; and 26 (15.6%) had multiple myeloma. 66/167 (39.5%) pts developed refractory CMV (6 pts also had resistant CMV). Time from HCT to CMV viremia was shorter in R/R group: median (IQR) 21.5 (17.2-27.8) days compared to no R/R group: 26 (19-32) days (p=0.031). Maximum VL was higher for R/R compared to no R/R: median (IQR) 9,118 (2,849-18,456) and 868 (474-1,908), respectively (p< 0.001). In multivariable model, risk factors for R/R included TCD HCT (p< 0.0001) and higher VL at PET initiation (p=0.0002). In contrast, CMV seropositive donor (p=0.035) was protective (Figure 1). CMV EOD developed in 28.2% of R/R and 16.2% of no R/R groups (p=0.085) (Figure 2). Overall survival at 1 year was 59.1% for R/R compared to 83.1% for no R/R group (p=0.00027) (Figure 3). Figure 1. Adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable model evaluating risk factors of refractory/resistant (R/R) CMV. Figure 2. Cumulative incidence curves of CMV end-organ disease (EOD) at 1-year post HCT Figure 3. Kaplan-Meier survival curves of overall survival (OS) at 1-year post HCT Conclusion 1) Refractory and/or resistant CMV occurred in 39,5% of PET recipients. 2) T-cell depletion and higher CMV VL at PET initiation were risk factors for R/R CMV in multivariable models. 3) R/R CMV was associated with more EOD and worse overall survival. Disclosures Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

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Implementation of NAVIGATE Coordinated Specialty Care for First Episode Psychosis: the Michigan Experience

CNS Spectrums ◽

10.1017/s1092852920002928 ◽

2021 ◽

Vol 26 (2) ◽

pp. 177-178

Author(s):

Eric D. Achtyes ◽

Kari Kempema ◽

Zhehui Luo ◽

Katharine N. Thakkar ◽

Catherine Adams ◽

...

Keyword(s):

Mental Health ◽

Clinical Symptoms ◽

The United States ◽

First Episode Psychosis ◽

Specialty Care ◽

First Episode ◽

Control Group ◽

Evidence Based ◽

Block Grant ◽

Episode Psychosis

AbstractStudy ObjectivesCoordinated specialty care (CSC) is widely accepted as an evidence-based treatment for first episode psychosis (FEP). The NAVIGATE intervention from the Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) study is a CSC intervention which offers a suite of evidence-based treatments shown to improve engagement and clinical outcomes, especially in those with shorter duration of untreated psychosis (DUP). Coincident with the publication of this study, legislation was passed by the United States Congress in 2014–15 to fund CSC for FEP via a Substance Abuse and Mental Health Services Administration (SAMHSA) block grant set-aside for each state. In Michigan (MI) the management of this grant was delegated to Network180, the community mental health authority in Kent County, with the goal of making CSC more widely available to the 10 million people in MI. Limited research describes the outcomes of implementation of CSC into community practices with no published accounts evaluating the use of the NAVIGATE intervention in a naturalistic setting. We describe the outcomes of NAVIGATE implementation in the state of MI.MethodsIn 2014, 3 centers in MI were selected and trained to provide NAVIGATE CSC for FEP. In 2016 a 4th center was added, and 2 existing centers were expanded to provide additional access to NAVIGATE. Inclusion: age 18–31, served in 1 of 4 FEP centers in MI. Data collection began in 2015 for basic demographics, global illness (CGI q3 mo), hospital/ED use and work/school (SURF q3 mo) and was expanded in 2016 to include further demographics, diagnosis, DUP, vital signs; and in 2018 for clinical symptoms with the modified Colorado Symptom Inventory (mCSI q6 mo), reported via an online portal. This analysis used data until 12/31/19. Mixed effects models adjusted by age, sex and race were used to account for correlated data within patients.ResultsN=283 had useable demographic information and were included in the analysis. Age at enrollment was 21.6 ± 3.0 yrs; 74.2% male; 53.4% Caucasian, 34.6% African American; 12.9 ± 1.7 yrs of education (N=195). 18 mo retention was 67% with no difference by sex or race. CGI scores decreased 20% from baseline (BL) to 18 mo (BL=3.5, N=134; 15–18 mo=2.8, N=60). Service utilization via the SURF was measured at BL (N=172) and 18 mo (N=72): psychiatric hospitalizations occurred in 37% at BL and 6% at 18 mo (p<0.01); ER visits occurred in 40% at BL and 13% at 18 mo (p<0.01). 44% were working or in school at BL and 68% at 18 mo (p<0.01). 21% were on antipsychotics (AP) at BL (N=178) and 85% at 18 mo (N=13) with 8% and 54% on long acting injectable-AP at BL and 18 mo, respectively. Limitations include missing data and lack of a control group.ConclusionThe implementation of the NAVIGATE CSC program for FEP in MI resulted in meaningful clinical improvement for enrollees. Further support could make this evidence-based intervention available to more people with FEP.FundingSupported by funds from the SAMHSA Medicaid State Block Grant set-aside awarded to Network180 (Achtyes, Kempema). The funders had no role in the design of the study, the analysis or the decision to publish the results.

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