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Article ; Online: Serum markers of gut permeability and endotoxemia in patients with osteoarthritis of the knee associated with metabolic syndrome.

Shirinsky, Ivan / Kalinovskaya, Natalia / Filatova, Katerina / Shirinsky, Valery

International journal of rheumatic diseases

2023 Volume 26, Issue 11, Page(s) 2344–2346

MeSH term(s)	Humans ; Endotoxemia/diagnosis ; Endotoxemia/complications ; Metabolic Syndrome/diagnosis ; Metabolic Syndrome/complications ; Osteoarthritis, Knee/diagnosis ; Osteoarthritis, Knee/complications ; Biomarkers ; Permeability
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-06-22
Publishing country	England
Document type	Letter
ZDB-ID	2426924-4
ISSN	1756-185X ; 1756-1841
ISSN (online)	1756-185X
ISSN	1756-1841
DOI	10.1111/1756-185X.14794
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Zs.A 6098: Show issues

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Article ; Online: H

Shirinsky, Ivan / Shirinsky, Valery

Arthritis research & therapy

2018 Volume 20, Issue 1, Page(s) 116

Abstract: Background: There is growing evidence that mast cells (MCs) play a role in knee osteoarthritis (OA). H: Methods: Baseline data from the Osteoarthritis Initiative cohort were analysed cross-sectionally. Unadjusted and adjusted logistic regression ... ...

Abstract	Background: There is growing evidence that mast cells (MCs) play a role in knee osteoarthritis (OA). H Methods: Baseline data from the Osteoarthritis Initiative cohort were analysed cross-sectionally. Unadjusted and adjusted logistic regression models were performed to compare the prevalence of knee OA in H Results: The analysed sample consisted of 8545 knees (664 knees of H Conclusions: H
MeSH term(s)	Aged ; Cross-Sectional Studies ; Data Analysis ; Female ; Histamine Antagonists/therapeutic use ; Histamine H1 Antagonists/therapeutic use ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Osteoarthritis, Knee/diagnostic imaging ; Osteoarthritis, Knee/epidemiology ; Osteoarthritis, Knee/prevention & control ; Prevalence
Chemical Substances	Histamine Antagonists ; Histamine H1 Antagonists
Language	English
Publishing date	2018-06-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2107602-9
ISSN	1478-6362 ; 1478-6354
ISSN (online)	1478-6362
ISSN	1478-6354
DOI	10.1186/s13075-018-1619-7
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Zs.A 5490: Show issues

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Article: Serum Cytokines as Biomarkers in Heart Failure with Preserved Ejection Fraction and Sleep Apnea: A Prospective Cohort Study.

Yakovlev, Alexey / Teplyakov, Alexander / Grakova, Elena / Shilov, Sergey / Yakovleva, Natalia / Kopeva, Kristina / Shirinsky, Valery / Shirinsky, Ivan

Life (Basel, Switzerland)

2023 Volume 13, Issue 3

Abstract: Heart failure with preserved ejection fraction (HFpEF) and obstructive sleep apnea (OSA) frequently co-occur and this comorbidity represents a separate phenotype of HFpEF. While many research attempts are focused on biomarkers of HFpEF, currently, there ... ...

Abstract	Heart failure with preserved ejection fraction (HFpEF) and obstructive sleep apnea (OSA) frequently co-occur and this comorbidity represents a separate phenotype of HFpEF. While many research attempts are focused on biomarkers of HFpEF, currently, there is a lack of validated biomarkers of HFpEF and OSA. In this study, we aimed to evaluate prognostic significance of several serum cytokines in patients with HFpEF and OSA. The patients with HFpEF and OSA were recruited from the Sleep Apnea Center of Novosibirsk, Russian Federation and followed up for 12 months. The main analyzed outcomes were five-point major adverse cardiovascular events (MACE) and the 6-min walk test (6MWT). The analyzed cytokines were circulating IL-6, IL-10, and VEGF measured at baseline. We recruited 77 male patients with HFpEF and OSA, the data of 71 patients were available for analyses. Patients who developed MACE had four-fold elevated concentrations of serum IL-10. There was no association between baseline cytokine levels and longitudinal changes in 6MWT. Circulating IL-10 levels are positively associated with MACE in men with HFpEF and OSA and thus may be a potential prognostic biomarker in this subgroup of patients. These results should be confirmed in larger studies encompassing both males and females.
Language	English
Publishing date	2023-02-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life13030628
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Article ; Online: Effects of medication-treated diabetes on incidence and progression of knee osteoarthritis: a longitudinal analysis of the Osteoarthritis Initiative data.

Shirinsky, Ivan V / Shirinsky, Valery S

Rheumatology international

2017 Volume 37, Issue 6, Page(s) 983–991

Abstract: Diabetes has been proposed as a factor involved in the pathogenesis of osteoarthritis (OA). Currently, there is a lack of research evaluating the prospective impact of diabetes on OA structural outcomes. In this study, we assessed the effects of ... ...

Abstract	Diabetes has been proposed as a factor involved in the pathogenesis of osteoarthritis (OA). Currently, there is a lack of research evaluating the prospective impact of diabetes on OA structural outcomes. In this study, we assessed the effects of medication-treated diabetes on incidence and progression of knee OA. We analysed longitudinal data from the multi-center, longitudinal, prospective observational Osteoarthritis Initiative (OAI) study. The main outcomes were radiographic OA incidence (development of Kellgren-Lawrence grade 2 with joint space narrowing, JSN) and progression (increase in semiquantitative JSN or a new knee replacement). For the study of incidence, we selected participants with KL <2 or /KL = 2 without JSN at baseline (incidence sample). To evaluate progression, we selected participants with baseline JSN <3 (progression sample). We used generalized estimating equations (GEE) logistic regression with adjustment for potential confounders to evaluate the effects of medication-treated diabetes on knee OA incidence and progression. We studied 3725 knees (3498 non-diabetic and 228 diabetic) in the incidence sample and 3594 knees (3335 non-diabetic and 259 diabetic) in the progression sample. Medication-treated diabetes did not have an effect on knee OA incidence (odds ratio, OR 0.53, 95% confidence interval, CI 0.23-1.5). There was an independent association between medication-treated diabetes and reduced progression of knee OA [OR 0.66, 95% CI (0.44-0.98)]. Medication-treated diabetes has no effect on knee OA incidence but reduces knee OA progression. The role of diabetes and anti-diabetic drugs in knee OA progression needs further exploration.
MeSH term(s)	Aged ; Chi-Square Distribution ; Diabetes Mellitus/diagnosis ; Diabetes Mellitus/drug therapy ; Diabetes Mellitus/epidemiology ; Disease Progression ; Female ; Humans ; Hypoglycemic Agents/therapeutic use ; Incidence ; Logistic Models ; Longitudinal Studies ; Male ; Middle Aged ; Odds Ratio ; Osteoarthritis, Knee/diagnostic imaging ; Osteoarthritis, Knee/epidemiology ; Prognosis ; Prospective Studies ; Protective Factors ; Risk Factors ; Time Factors ; United States/epidemiology
Chemical Substances	Hypoglycemic Agents
Language	English
Publishing date	2017-02-28
Publishing country	Germany
Document type	Journal Article ; Multicenter Study ; Observational Study
ZDB-ID	8286-7
ISSN	1437-160X ; 0172-8172
ISSN (online)	1437-160X
ISSN	0172-8172
DOI	10.1007/s00296-017-3676-7
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Article: Pleiotropic Effects of Comarum palustre L. in Patients with Osteoarthritis and Diabetes Mellitus with High Comorbidity Burden: An Exploratory Study.

Shirinsky, Ivan V / Kalinovskaya, Natalia Y / Filatova, Katerina / Shirinsky, Valery S

Alternative therapies in health and medicine

2020 Volume 27, Issue S1, Page(s) 80–84

Abstract: Background: Patients with osteoarthritis (OA) and diabetes mellitus (DM) are at increased risk of polypharmacy. A potential approach to this group of patients could be the use of herbal treatments influencing multiple biological pathways and aiming ... ...

Abstract	Background: Patients with osteoarthritis (OA) and diabetes mellitus (DM) are at increased risk of polypharmacy. A potential approach to this group of patients could be the use of herbal treatments influencing multiple biological pathways and aiming simultaneously at both OA and related comorbid conditions. Comarum palustre L. is widely used in traditional medicine but there is a lack of studies evaluating its pleiotropic effects in OA and DM. Primary study objective: To investigate pleiotropic effects of Comarum palustre L. in patients with OA and diabetes mellitus (DM). Methods: This was open-label, single-arm exploratory study on patients with knee OA and DM. Setting: Single-center study. Participants: Fifteen adult patients (mean age 68.6 years, fourteen women, one man) with knee OA and DM. Intervention: The patients received Comarum palustre L.tablets 500 mg twice daily for 28 days. Primary outcome measure: Changes from baseline in Visual Analogue Scale (VAS) for Pain. Results: At the end of treatment there were significant reductions in VAS pain (effect size (ES) 1.45, 95% confidence interval (CI) 0.61 to 2.3), OA symptoms (ES 1.1 95% CI (-1.9 to -0.29), and disability (ES -0.88 95% CI -1.66 to -0.09). Treatment with Comarum palustre L. resulted in decrease in total cholesterol (TC), cholesterol ratio, and an increase in HDL-C. There was decrease of circulating TNF-α concentrations, and increase in circulating IL-10 and adiponectin levels. Conclusion: Treatment with Comarum palustre L.is associated with pleiotropic effects in patients with OA and comorbid DM. These results provide a rationale for larger randomized controlled studies.
MeSH term(s)	Adult ; Aged ; Comorbidity ; Diabetes Mellitus ; Female ; Humans ; Male ; Osteoarthritis, Knee/complications ; Osteoarthritis, Knee/drug therapy ; Osteoarthritis, Knee/epidemiology ; Pain ; Pain Measurement
Language	English
Publishing date	2020-10-10
Publishing country	United States
Document type	Clinical Trial ; Journal Article
ZDB-ID	1225073-9
ISSN	1078-6791
ISSN	1078-6791
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Zs.A 4504: Show issues

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Article ; Online: Tear cytokines as potential biomarkers in non-infectious uveitis: post hoc analysis of a randomised clinical trial.

Shirinsky, Ivan V / Biryukova, Anastasia A / Kalinovskaya, Natalia Y / Shirinsky, Valery S

Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie

2020 Volume 258, Issue 8, Page(s) 1813–1819

Abstract: Purpose: The study aimed to evaluate cytokines in tears as potential biomarkers in non-infectious uveitis.: Methods: Tear samples were obtained using Schirmer strips from 50 patients enrolled in a randomised controlled study of simvastatin in non- ... ...

Abstract	Purpose: The study aimed to evaluate cytokines in tears as potential biomarkers in non-infectious uveitis. Methods: Tear samples were obtained using Schirmer strips from 50 patients enrolled in a randomised controlled study of simvastatin in non-infectious uveitis and from a control group of 30 healthy participants. The concentrations of IL-6, IL-8, IL-10, and IFN-γ in tears were measured at the study's baseline and again after 8 weeks of treatment using commercial enzyme-linked immunosorbent assay kits. Results: The concentrations of tears IL-6 and IL-10 were increased in patients with non-infectious uveitis in comparison with the healthy participants. Longer disease duration was associated with elevated levels of IL-6. The concentrations of the studied cytokines in tears did not correlate with the extent of eye inflammation at baseline. No link between the changes in cytokine levels and changes in clinical parameters during treatment was observed. Baseline IL-10 concentrations independently predicted the development of the clinical response to treatment at weeks 4 and 8. Conclusion: Although elevated in non-infectious uveitis patients, tear cytokine levels do not correlate with eye inflammation and are not sensitive to change after treatment. However, the level of IL-10 may be a predictive biomarker of response to the treatment of uveitis. Trial registration: NCT04183387.
MeSH term(s)	Adult ; Biomarkers/metabolism ; Cytokines/metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Prognosis ; Severity of Illness Index ; Tears/chemistry ; Uveitis/metabolism
Chemical Substances	Biomarkers ; Cytokines
Language	English
Publishing date	2020-05-06
Publishing country	Germany
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	8435-9
ISSN	1435-702X ; 0721-832X
ISSN (online)	1435-702X
ISSN	0721-832X
DOI	10.1007/s00417-020-04707-7
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Ul I Zs.15: Show issues

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Article ; Online: Simvastatin as an Adjunct to Conventional Therapy of Non-infectious Uveitis: A Randomized, Open-Label Pilot Study.

Shirinsky, Ivan V / Biryukova, Anastasia A / Shirinsky, Valery S

Current eye research

2017 , Page(s) 1–6

Abstract: Purpose: Statins have been shown to reduce ocular inflammation in animal models of uveitis and to prevent development of uveitis in observational studies. There have been no experimental human studies evaluating statins' efficacy and safety in uveitis. ... ...

Abstract	Purpose: Statins have been shown to reduce ocular inflammation in animal models of uveitis and to prevent development of uveitis in observational studies. There have been no experimental human studies evaluating statins' efficacy and safety in uveitis. In this study, we aimed to investigate efficacy and safety of simvastatin in patients with uveitis. Methods: For this single-center, open-label, randomized study, we enrolled patients with acute non-infectious uveitis. The patients were randomized to receive 40 mg simvastatin per day for 2 months in addition to conventional treatment or conventional treatment alone. The studied outcomes were the rate of steroid-sparing control of ocular inflammation, measures of ocular inflammation, intraocular pressure, and visual acuity. Results: Fifty patients were enrolled in the study. Twenty-five patients were randomly assigned to receive simvastatin with conventional treatment and 25 to conventional treatment alone. Simvastatin was associated with significantly higher rates of steroid-sparing ocular inflammation control, decrease in anterior chamber inflammation, and improvement in visual acuity. The treatment was well tolerated, no serious adverse effects were observed. Conclusions: Our findings suggest that statins may have therapeutic potential in uveitis. These results need to be confirmed in double-blind, randomized, controlled studies.
Language	English
Publishing date	2017-09-22
Publishing country	England
Document type	Journal Article
ZDB-ID	82079-9
ISSN	1460-2202 ; 0271-3683
ISSN (online)	1460-2202
ISSN	0271-3683
DOI	10.1080/02713683.2017.1355468
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Article ; Online: Treatment of erosive osteoarthritis with peroxisome proliferator-activated receptor alpha agonist fenofibrate: a pilot study.

Shirinsky, Ivan V / Shirinsky, Valery S

Rheumatology international

2013 Volume 34, Issue 5, Page(s) 613–616

Abstract: Hand osteoarthritis (HOA) is a common condition associated with high disease burden and frequently accompanied by comorbidities including dyslipidemia, atherosclerosis and obesity. The most debilitating HOA phenotype is erosive HOA (EHOA), characterized ... ...

Abstract	Hand osteoarthritis (HOA) is a common condition associated with high disease burden and frequently accompanied by comorbidities including dyslipidemia, atherosclerosis and obesity. The most debilitating HOA phenotype is erosive HOA (EHOA), characterized by synovial inflammation, formation of erosions, and substantial decline in hand function. Currently, there is no proven symptomatic treatment for the EHOA. Due to their broad spectrum effects directed on lipid metabolism, inflammation and pain, the agonists of peroxisome proliferator-activated receptor alpha or fibrates are a candidate class of drugs for the treatment of EHOA. In this study, we assessed the influence of fenofibrate treatment on clinical efficacy parameters, in vivo cytokine and adipokine production and concentrations of endothelial progenitor cells (EPC) in patients with EHOA. Fourteen patients received treatment with 145 mg of fenofibrate/day for 12 weeks. Fenofibrate treatment was associated with significant decreases in pain score, tender joint count, duration of morning stiffness, disease activity score, Cochin index, and ESR. Eight (57.14 %) patients developed Outcome Measures in Rheumatology Clinical Trials-Osteoarthritis Research Society response at the end of treatment. Paracetamol consumption did not change during the treatment course. There was a significant reduction in triglyceride levels. No changes were detected in serum pro-inflammatory cytokine and adipokine concentrations while circulating IL-10 levels significantly decreased. There were no differences in circulating EPC numbers before and after the treatment. Fenofibrate was well tolerated, no patient experienced disease flare during the treatment. In conclusion, in EHOA patients, fenofibrate is associated with pleiotropic effects on pain, inflammation, and lipid profile. Larger, controlled studies are needed to confirm these results.
MeSH term(s)	Analgesics, Non-Narcotic/therapeutic use ; Anti-Inflammatory Agents/therapeutic use ; Biomarkers/blood ; Female ; Fenofibrate/therapeutic use ; Hand Joints/drug effects ; Hand Joints/metabolism ; Hand Joints/pathology ; Hand Joints/physiopathology ; Humans ; Inflammation Mediators/blood ; Middle Aged ; Osteoarthritis/blood ; Osteoarthritis/diagnosis ; Osteoarthritis/drug therapy ; Osteoarthritis/physiopathology ; PPAR alpha/agonists ; PPAR alpha/metabolism ; Pilot Projects ; Recovery of Function ; Time Factors ; Treatment Outcome
Chemical Substances	Analgesics, Non-Narcotic ; Anti-Inflammatory Agents ; Biomarkers ; Inflammation Mediators ; PPAR alpha ; Fenofibrate (U202363UOS)
Language	English
Publishing date	2013-04-26
Publishing country	Germany
Document type	Journal Article
ZDB-ID	8286-7
ISSN	1437-160X ; 0172-8172
ISSN (online)	1437-160X
ISSN	0172-8172
DOI	10.1007/s00296-013-2766-4
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Article ; Online: Observed efficacy and clinically important improvements in participants with osteoarthritis treated with subcutaneous tanezumab: results from a 56-week randomized NSAID-controlled study.

Neogi, Tuhina / Hunter, David J / Churchill, Melvin / Shirinsky, Ivan / White, Alexander / Guermazi, Ali / Omata, Masanari / Fountaine, Robert J / Pixton, Glenn / Viktrup, Lars / Brown, Mark T / West, Christine R / Verburg, Kenneth M

Arthritis research & therapy

2022 Volume 24, Issue 1, Page(s) 78

Abstract: Background: A recent phase 3 study demonstrated that treatment with tanezumab, a nerve growth factor inhibitor, or nonsteroidal anti-inflammatory drugs (NSAIDs) improves pain and physical function in participants with moderate-to-severe osteoarthritis ( ... ...

Abstract	Background: A recent phase 3 study demonstrated that treatment with tanezumab, a nerve growth factor inhibitor, or nonsteroidal anti-inflammatory drugs (NSAIDs) improves pain and physical function in participants with moderate-to-severe osteoarthritis (OA) of the hip or knee. Here, we evaluated the time course and clinical importance of these initial efficacy findings using a mixture of primary, secondary, and post hoc endpoints. Methods: Participants on stable NSAID therapy and with a history of inadequate response to other standard OA analgesics were enrolled in an 80-week (56-week treatment/24-week safety follow-up), randomized, NSAID-controlled, phase 3 study primarily designed to assess the safety of tanezumab for moderate-to-severe OA of the knee or hip. Participants received oral NSAID (twice daily naproxen, celecoxib, or diclofenac) or subcutaneous tanezumab (2.5mg or 5mg every 8 weeks). Non-responders were discontinued at week 16. Changes from baseline in WOMAC Pain and Physical Function, Patient's Global Assessment of Osteoarthritis (PGA-OA), and average pain in the index joint were compared between tanezumab and NSAID groups over the 56-week treatment period. Clinically meaningful response (e.g., ≥30% and ≥50% improvement in WOMAC Pain and Physical Function), rescue medication use, and safety were also assessed. Results: All groups improved WOMAC Pain, WOMAC Physical Function, PGA-OA, and average pain in the index joint over the 56-week treatment period relative to baseline. Across all groups, improvements generally occurred from the time of first assessment (week 1 or 2) to week 16 and then slightly decreased from week 16 to 24 before stabilizing from weeks 24 to 56. The magnitude of improvement and the proportion of participants achieving ≥30% and ≥50% improvement in these measures was greater (unadjusted p≤0.05) with tanezumab than with NSAID at some timepoints on or before week 16. Adverse events of abnormal peripheral sensation, prespecified joint safety events, and total joint replacement surgery occurred more frequently with tanezumab than with NSAID. Conclusions: Tanezumab and NSAID both provided early and sustained (up to 56 weeks) efficacy relative to baseline. Improvements in pain and function were clinically meaningful in a substantial proportion of participants. Adverse events of abnormal peripheral sensation and joint safety events occurred more frequently with tanezumab than with NSAID. Trial registration: ClinicalTrials.gov NCT02528188 . Registered on 19 July 2015.
MeSH term(s)	Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Dose-Response Relationship, Drug ; Double-Blind Method ; Humans ; Osteoarthritis, Hip/drug therapy ; Osteoarthritis, Knee/complications ; Osteoarthritis, Knee/drug therapy ; Pain Measurement/methods ; Treatment Outcome
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Antibodies, Monoclonal, Humanized ; tanezumab (EQL0E9GCX1)
Language	English
Publishing date	2022-03-29
Publishing country	England
Document type	Clinical Trial, Phase III ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2107602-9
ISSN	1478-6362 ; 1478-6354
ISSN (online)	1478-6362
ISSN	1478-6354
DOI	10.1186/s13075-022-02759-0
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Article ; Online: Targeting Nuclear Hormone Receptors: PPARα Agonists as Potential Disease-Modifying Drugs for Rheumatoid Arthritis.

Shirinsky, Ivan V / Shirinsky, Valery S

International journal of rheumatology

2011 Volume 2011, Page(s) 937843

Abstract: In recent years, peroxisome proliferator-activated receptors (PPARs) have received growing interest due to the broad spectrum of their biological activities. PPARα, an isoform of PPAR, plays an important role in lipid homeostasis and inflammation, which ... ...

Abstract	In recent years, peroxisome proliferator-activated receptors (PPARs) have received growing interest due to the broad spectrum of their biological activities. PPARα, an isoform of PPAR, plays an important role in lipid homeostasis and inflammation, which makes it a potential target for the treatment of chronic inflammatory disorders, including RA. This paper reviews studies on the properties of PPARα agonists which may be pertinent to the treatment of RA. These properties include effects on lipid metabolism, inflammation, and angiogenesis, as well as interference with glucocorticoid effects, and a potential role in gender dimorphism of autoimmune disorders. However, current clinical experience with this class of drugs in RA is limited. New studies are needed to elucidate whether PPARα agonism may be an effective treatment strategy for RA patients.
Language	English
Publishing date	2011-06-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2503284-7
ISSN	1687-9279 ; 1687-9260
ISSN (online)	1687-9279
ISSN	1687-9260
DOI	10.1155/2011/937843
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