Immune checkpoint inhibitor-associated acute kidney injury and mortality: An observational study.

Background: Immune checkpoint inhibitors, approved for the treatment of various types of cancer, are known to cause a unique spectrum of side effects, including acute kidney injury (AKI). The aim of this study was to describe the incidence, risk factors, renal outcomes, and mortality of AKI in patients receiving checkpoint inhibitors.

Methods: Patients receiving checkpoint inhibitors between January 2013 and May 2020 at the University Medical Center Utrecht, the Netherlands, were identified using the Utrecht Patient Oriented Database.

Multiomics and Machine Learning Accurately Predict Clinical Response to Adalimumab and Etanercept Therapy in Patients With Rheumatoid Arthritis.

Objective: To predict response to anti-tumor necrosis factor (anti-TNF) prior to treatment in patients with rheumatoid arthritis (RA), and to comprehensively understand the mechanism of how different RA patients respond differently to anti-TNF treatment.

Methods: Gene expression and/or DNA methylation profiling on peripheral blood mononuclear cells (PBMCs), monocytes, and CD4+ T cells obtained from 80 RA patients before they began either adalimumab (ADA) or etanercept (ETN) therapy was studied. After 6 months, treatment response was evaluated according to the European League Against Rheumatism criteria for disease response.

Health-related quality of life in patients with immune mediated inflammatory diseases: A cross-sectional, multidisciplinary study.

Immune mediated inflammatory diseases (IMIDs) have similarities in pathophysiology and treatment. Not much is known, however, about health-related quality of life (HR-QoL) in IMIDs. We assessed and compared HR-QoL, using the validated EuroQoL 5-dimensions 5-levels questionnaire, in an observational cohort comprising 530 patients (67.

Similarities and discrepancies in subchondral bone structure in two differently induced canine models of osteoarthritis.

In osteoarthritis (OA), cartilage degradation is accompanied by subchondral bone changes. The pathogenesis and physiology of bone changes in OA are still unclear. The changes in subchondral bone architecture and cartilage damage were compared in differently induced experimental models of OA.

The canine bilateral groove model of osteoarthritis.

In studies aimed at local treatment of experimental osteoarthritis (OA) it is optimal to have an internal (untreated) OA control. Such an approach excludes interanimal variation, and allows paired statistical evaluation of treatment efficacy. For this purpose, we developed and characterized a bilateral version of the canine Groove model.

Degeneration, inflammation, regeneration, and pain/disability in dogs following destabilization or articular cartilage grooving of the stifle joint.

Objective: The most used model for joint instability is the canine anterior cruciate ligament transection (ACLT)-model. The ACLT-model can be extended with a medial meniscectomy (MX) (i.e.

The groove model of osteoarthritis applied to the ovine fetlock joint.

Objective: Until now there have been no appropriate models for metacarpophalangeal osteoarthritis (OA), even though OA in this joint is a significant medical and economic problem in horses. A good model would be useful to evaluate progression and treatment of OA, particularly in this joint. Therefore, we translated the canine Groove model to the ovine metacarpophalangeal (fetlock) joint.

Inhibition of COX-2 by celecoxib in the canine groove model of osteoarthritis.

Objective: In vitro studies showed a beneficial effect of celecoxib on proteoglycan turnover and content of osteoarthritic cartilage. In the present study we evaluated whether these favourable effects of celecoxib could also be demonstrated in vivo.

Methods: In 24 Beagle dogs, osteoarthritis (OA) was induced in one knee according to the groove model.

The canine 'groove' model of osteoarthritis is more than simply the expression of surgically applied damage.

Objective: Recently a new canine model of osteoarthritis (OA; the 'groove' model) has been described. This model is based on surgically applied mechanical damage of the articular cartilage followed by transient forced loading of the affected joint. Ten weeks after surgery this model shows characteristics of OA, mimicking human OA.

Initiation of degenerative joint damage by experimental bleeding combined with loading of the joint: a possible mechanism of hemophilic arthropathy.

Objective: To investigate the effect of a limited number of experimental joint bleedings, combined with loading of the affected joint, on the development of progressive degenerative joint damage.

Methods: The right knee of 8 mature beagle dogs was injected with freshly collected autologous blood 3 times per week for 4 weeks, to mimic a limited number of joint hemorrhages occurring over a short period. To ensure loading of the experimental joint, the contralateral control knee of the animals was fixed to the trunk 4 hours per day, 3 days per week.

Identification of self-epitopes recognized by T cells in rheumatoid arthritis demonstrates matrix metalloproteinases as a novel T cell target.

Objective: To identify novel arthritis-associated and/or cartilage-specific self-epitopes recognized by T cells in patients with rheumatoid arthritis (RA).

Methods: Human analogs of several self-epitopes recognized in the rat adjuvant arthritis (AA) model (n = 13) were tested for T cell recognition in patients with RA and healthy controls. Recognition was assessed by proliferative activity of peripheral blood mononuclear cells (PBMC).

Immature articular cartilage is more susceptible to blood-induced damage than mature articular cartilage: an in vivo animal study.

Objective: Cartilage of young but skeletally mature dogs is more susceptible to blood-induced damage than that of old dogs. The aim of the present study was to investigate whether cartilage of skeletally immature individuals is even more adversely affected by exposure to blood than that of mature individuals, as suggested by clinical practice experience with humans.

Methods: Right knees of 3 groups of 6 beagle dogs (skeletally immature, young mature, and old animals) were injected with autologous blood on days 0 and 2.

Blood-induced joint damage: longterm effects in vitro and in vivo.

Objective: We previously showed that 4-day in vitro exposure of human cartilage to blood, as well as a single experimental joint bleeding in dogs, resulted in a disturbed cartilage matrix turnover lasting at least 2 weeks. We now evaluate the longterm outcome of the adverse in vitro and in vivo effects of blood on cartilage matrix turnover.

Methods: Human and canine articular cartilage tissue was cultured in the presence of homologous whole blood during 4 days.

Interleukin 10 (IL-10), not IL-4 or interferon-gamma production, correlates with progression of joint destruction in rheumatoid arthritis.

Objective: Both interleukin 4 (IL-4) and IL-10, separately and in combination, and under in vitro and in vivo conditions in animals, have been reported to inhibit characteristics of rheumatoid arthritis (RA) and experimentally induced arthritis. We investigated if IL-10 and IL-4 production, as well as interferon-gamma (IFN-gamma) production, opposing IL-4, were related to RA disease variables. A method was chosen to exclude the influence of age and disease duration.

Articular cartilage is more susceptible to blood induced damage at young than at old age.

Objective: It has been shown that cartilage is damaged upon intraarticular hemorrhage. We investigated differences in the susceptibility of cartilage from young adult and old animals to blood induced joint damage in a canine in vivo model.

Methods: Right knees of 6 young adult beagles (aged 2.

Apocynin, a plant-derived, cartilage-saving drug, might be useful in the treatment of rheumatoid arthritis.

Objective: To investigate whether apocynin, 1-(4-hydroxy-3-methoxyphenyl)ethanone, is able to diminish inflammation-induced cartilage destruction in rheumatoid arthritis (RA), studied in a human in vitro model.

Methods: Apocynin was added to cultures of RA peripheral blood mononuclear cells (PBMNC). Cartilage-destructive activity was determined by addition of culture supernatant to tissue samples of human articular cartilage.

Lymphocyte stimulation by CD3-CD28 enables detection of low T cell interferon-gamma and interleukin-4 production in rheumatoid arthritis.

The analysis of cytokine production is increasingly important in defining the course of an immune response and in evaluating specific therapies of immune diseases. In rheumatoid arthritis (RA), a dysregulation in T1/T2 cell balance, as defined by the production of their specific cytokines, IFN-gamma and IL-4, respectively, is suggested. A predominance of T1-cell mediated macrophage activity in the joint plays a key role in the destruction of articular cartilage and subchondral bone, whereas local T2 cell activity, mitigating disease, fails.

The immune suppressive effect of dexamethasone in rheumatoid arthritis is accompanied by upregulation of interleukin 10 and by differential changes in interferon gamma and interleukin 4 production.

Objectives: The influence of dexamethasone on interleukin 10 (IL10) production and the type 1 (T1)/type 2 (T2) T cell balance found in rheumatoid arthritis (RA) was studied.

Methods: Peripheral blood mononuclear cells (PB MNC) were isolated from 14 RA patients both before and 7 and 42 days after high dose dexamethasone pulse therapy. The ex vivo production of IL10, interferon gamma (IFN gamma) (T1 cell), and IL4 (T2 cell) by PB MNCs was assessed, along with parameters of disease activity (erythrocyte sedimentation rate, C reactive protein, Visual Analogue Scale, Thompson joint score).

Blood-induced joint damage: a canine in vivo study.

Objective: To investigate the direct and indirect (via synovial inflammation) effects of intraarticular bleeding on cartilage in vivo.

Methods: Right knees of 14 beagle dogs were injected with autologous blood on days 0 and 2. Cartilage matrix proteoglycan turnover, collagen damage, and synovial inflammation of these knees, including the cartilage-destructive properties of the synovial tissue, were determined and compared with those of the left control knees on day 4 (short-term effects; n = 7) and day 16 (long-term effects; n = 7).

Blood-induced joint damage: a human in vitro study.

Objective: To investigate mechanisms underlying cartilage damage caused by brief exposure of cartilage to blood, such as that occurring during intraarticular bleeding.

Methods: Human articular cartilage was cultured for 4 days in the presence of blood (components; 7.5-50% volume/volume).

Haemophilic arthropathy resembles degenerative rather than inflammatory joint disease.

Aims: To investigate the pathogenetic mechanisms of haemophilic arthropathy (HA) by comparing end-stage arthropathy with osteoarthritis (OA; a degenerative joint disorder) and rheumatoid arthritis (RA; an inflammation-mediated joint disease).

Methods And Results: Cartilage and synovium from patients with HA (n=10), RA (n=8), OA (n=14) and normal control subjects (n=6) were examined morphologically, biochemically and histochemically. Cartilage in HA exhibited characteristics of degenerative joint disease (OA), as evidenced by morphological, histochemical (Safranin-O fast green-iron haematoxylin, Mankin grade) and biochemical (proteoglycan synthesis, glycosaminoglycan content and DNA content) changes, whereas synovium in HA showed characteristics of inflammation-mediated joint disease (RA), as evidenced by histochemical (inflammation, haematoxylin and eosin (H&E) and iron deposition, Perls' blue) and biochemical changes (interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)alpha and catabolic properties).

Experimentally induced stress in rheumatoid arthritis of recent onset: effects on peripheral blood lymphocytes.

Objective: To examine the effects of experimentally-induced stress on the mobilization of peripheral blood lymphocytes (PBL) in patients with rheumatoid arthritis (RA) of recent onset.

Methods: Twenty-two (16 F, 6 M) patients (mean age 57.6 yrs.

Mutual antagonism of rheumatoid arthritis and hay fever; a role for type 1/type 2 T cell balance.

Objectives: The balance between interferon gamma (IFN gamma) and interleukin 4 (IL4) producing T cells (T1 and T2 cells) seems to be of importance in many (auto)immune disorders. In general, T1 cell activity is important in cellular immunity whereas T2 cell activity plays a part in humoral responses. T1 cell activity predominates in joints of patients with rheumatoid arthritis (RA) whereas T2 cell activity is characteristic of atopic syndromes.

Iron deposits and catabolic properties of synovial tissue from patients with haemophilia.

Haemophilic arthropathy is characterised by iron deposits in synovial tissues. We investigated the suggestion that iron plays an important role in synovial changes. We obtained synovial tissue from six patients with haemophilia during arthroplasty, finding that brown haemosideritic tissue was often adjacent to tissue with a macroscopically normal appearance in the same joint.

Cartilage damage as a result of hemarthrosis in a human in vitro model.

Objective: To investigate the direct effect of blood and blood components on human cartilage in vitro.

Methods: Healthy human articular cartilage tissue was obtained post mortem and cultured according to standard procedures. The harmful effects of whole blood and various isolated blood components as well as the reversibility of these effects were assessed by means of proteoglycan synthesis and proteoglycan release.