Care/nursing homes globally have been severely affected by the COVID-19 pandemic and have disproportionately experienced a high rate of mortality which led to the introduction of strict isolation ...policies. However, while there are studies on the mortality, epidemiology, staffing challenges, and mismanagement in long-term care homes as a result of COVID-19, there appears to be a paucity of information regarding the Quality of Life (QoL), happiness, and associated well-being of the elderly residents of these homes. Therefore, we examined if COVID-19 affected the happiness level, QoL, and financial condition of long-term care home residents in Croatia. To achieve this, a survey of 308 participants in eight long term care homes was conducted. Descriptive analysis was performed to describe the mean of all responses and the Bayesian Integrated Nested Laplace Approximation (INLA) was used to provide a detailed quantitative analysis of the results. We found that the QoL and happiness of residents remained relatively stable during the COVID-19 pandemic. However, the income level, financial outlook, marital status, and vaccination positivity influenced the QoL and happiness of care home residents to a considerable degree. We recommend that policy makers pay attention to these underlying factors.
Active immunization, or vaccination, with tumor necrosis factor (TNF)-Kinoid (TNF-K) is a novel approach to induce polyclonal anti-TNF antibodies in immune-mediated inflammatory diseases. This study ...was performed to transfer the proof of concept obtained in mice model of rheumatoid arthritis (RA) into human. We designed a pilot study to demonstrate the feasibility of therapeutic vaccination in RA.
This was a phase IIa, placebo-controlled, multicenter study in adults with RA who previously experienced secondary failure of TNF antagonists. Patients were immunized intramuscularly with 2 or 3 doses of placebo (n = 10) or 90 (n = 6), 180 (n = 12), or 360 µg TNF-K (n = 12). The primary objective was to identify the best dose and schedule based on anti-TNF antibody titers. Clinical symptoms and safety were assessed during 12 months and solicited reactions for 7 days after each injection.
The highest anti-TNF antibody response was detected in patients immunized with 360 µg TNF-K and with 3 injections, although this difference was not significant with all other groups. Similar proportions of patients receiving TNF-K and placebo reported adverse events up to month 12. Serious adverse events were reported by 4 patients treated with TNF-K (13.3%) and 3 treated with placebo (30.0%), all unrelated to treatment. At month 12, DAS28-CRP, tender and swollen joint counts, and HAQ scores decreased significantly more in patients who exhibited anti-TNF antibody response than in patients who did not.
TNF-K therapeutic vaccination induced dose- and schedule-dependent anti-TNF antibodies in RA patients and was well tolerated. Patients who developed anti-TNF antibodies showed a trend toward clinical improvement. Although the most aggressive dose and schedule, i.e. 360 mg dose administered 3 times, did show a strong trend of higher antibody response, further studies are warranted to examine even higher and more frequent doses in order to establish the best conditions for clinical improvement.
ClinicalTrials.gov NCT01040715.
Spondyloarthritis (SpA) is a group of autoinflammatory/autoimmune diseases that affects the spine and peripheral joints. Involvement of the cervical spine correlates with occurrence of ...temporomandibular disorders (TMDs). Proinflammatory cytokines, interleukin (IL)-23, IL-17A, and tumour necrosis factor-alpha (TNF-α) are significantly involved in the immunopathogenesis of SpA, and inflammation is one of the causes of TMDs. We hypothesised that internal derangement (ID) of temporomandibular joints (TMJs), as the most frequent TMDs in patients with SpA, could be associated with salivary pro-inflammatory markers and clinical activity of axial SpA, measured with laboratory methods or rheumatological indexes. If a statistically significant difference in the concentration of salivary IL-23, IL-17A or TNF-α exists between patients with symptomatic or asymptomatic ID and patients without TMDs, the diagnostic accuracy of certain cytokine(s) for ID can be calculated. The diagnostic accuracy of the cytokine(s) could emphasise the inflammatory background of ID and possibly broaden therapeutic approaches for symptomatic ID in patients with SpA with biological drugs in addition to the routine application of occlusal splint and/or physical therapy.
Psoriatic arthritis (PsA) is influenced by a complex genetic predisposition. In patients with PsA, interleukin (IL)-17A plays a key role in triggering a complex autoimmune/autoinflammatory immune ...response in conjunction with other pro-inflammatory cytokines (such as tumor necrosis factor-alpha, IL-23, monocyte chemotactic protein-1, and IL-6). PsA manifests with various clinical symptoms, including musculoskeletal diseases and extra-articular manifestations. In particular, mediated by the soluble IL-17A presents a higher cardiovascular risk, suggesting connection between inflammation and cardiovascular diseases beyond the traditional risk factors. Moreover, studies have shown that patients with psoriasis are ten times at higher risk of developing dilated cardiomyopathy than those without psoriasis. Therefore, owing to the prominent role of IL-17A and psoriasis in the pathogenesis of PsA and endothelial dysfunction, we hypothesized that IL-17A is crucial in the early development of diastolic dysfunction (DD) and could serve as a tool to identify patients with asymptomatic DD and PsA. Although transthoracic echocardiography is the primary evaluation method for DD, it requires skilled personnel, routine parameters assessment, such as mitral inflow, and tissue Doppler imaging. As a result, assessing parameters such as left atrial deformity using novel techniques could be valuable for a more specific evaluation and diagnosis of DD. Clinical characteristics and laboratory parameters of PsA activity, cardiac ultrasound parameters, or cardiac functional markers like N-terminal pro-brain natriuretic peptide (NT-pro-BNP) can be correlated with the concentration of serum IL-17A. Moreover, determining the diagnostic accuracy of circulating IL-17A for early DD can also serve as a laboratory biomarker for diagnosing DD in asymptomatic patients. Thus, if the diagnostic accuracy of IL-17A for DD can be proven, the identification of biological drugs that inhibit IL-17A could be advantageous in treating patients with PsA and echocardiography-verified asymptomatic DD.
To compare characteristics of temporomandibular disorders (TMDs) in patients with rheumatoid arthritis (RA) to controls without RA.
The sample included 80 subjects (aged 33 to 73 years; 88% women), ...40 in each group. An international diagnostic protocol for TMD was followed.
Arthralgia was the most prevalent TMD in the RA group. Orofacial pain was more common than in controls (42.5% vs 15%, P = .031), with higher chronic pain grade and pain intensity (P ≤ .005). Somatization and depression were also increased (P < .001). In multiple logistic regression analysis, arthralgia (OR: 6.4; 95% CI: 1.1 to 37.1; P = .038) and age ≥ 55 years were predictors of RA (OR 3.9; 95% CI: 1.4 to 10.8; P = .009) when controlling for the effects of gender and pain intensity. TMD was related to 7.4-times higher odds for presence of orofacial pain, while RA was related to 3.4-times higher odds for pain.
RA patients experienced more orofacial pain and higher pain intensity, somatization, and depression compared to healthy individuals. Pain is more influenced by TMD than by RA.
Acute myocardial infarction (AMI) occurs as a result of insufficient myocardial perfusion leading to cell necrosis. This is most commonly due to the obstruction of the coronary artery by ruptured ...atherosclerotic plaque and thrombosis. Damaged ischemic and necrotic myocardial cells release pro-inflammatory substances in tissue and plasma, leading to a systemic inflammatory response. Profound systemic inflammatory response during ischemia/reperfusion injury causes disruption of endothelial glycocalyx and detachment of endothelial cells that express von Willebrant factor (vWF). We hypothesize that circulating vWF+ endothelial cells could act as antigen presenting cells which interact with T and NK cells directly, by cell to cell contact and indirectly by cytokine and chemokine secretion, leading to the immune response towards inflammation. Analyzing the frequency, phenotype and pro-inflammatory substances produced in circulating vWF positive (+) cells in patients with AMI could be beneficial to determine the severity of the pro-inflammatory response, according to the level of endothelial dysfunction in the early period of AMI. To evaluate these hypotheses, we suggest to determine frequency, phenotype, and ability of cytokine/chemokine production in circulating vWF+ endothelial cells by simultaneous surface and intracellular cell staining, and flow cytometry analysis. Secretion of pro-inflammatory cytokines and chemokines, pro-atherogenic substances and the components of glycocalyx might be measured in supernatants of magnetically separated or sorted vWF+ endothelial cells, as well as in the serum of a patient with acute AMI by enzyme linked–immunoassay tests. The interaction of increasing concentrations of isolated circulating vWF+ endothelial cells and cognate T and NK cells might be investigated by lymphocyte proliferation rate, cytotoxic mediators’ expression, and cytokine production. If our hypothesis is correct, characterization of circulating vWF+ endothelial cells could grant us greater insight into their role in pathophysiology of AMI and the degree of myocardial damage.
Psoriasis is a chronic relapsing autoimmune disease with a multigenetic predisposition, which occurs in about 2% of patients in Croatia and shows variable occurrence in the world. Psoriasis can be ...associated with various diseases, including autoimmune diseases (pemphigus, pemphigoid, vitiligo), and slightly less with allergic diseases (atopic dermatitis, asthma, urticaria, allergic contact dermatitis). According to clinical manifestations, psoriasis appears as plaque psoriasis, erythrodermic form and pustular psoriasis. Provocative factors that encourage psoriasis are infections, endogenous factors, hypocalcemia, psychogenic factors and medications. Psoriasis may worsen other dermatoses such as contact dermatitis, inflammatory dermatoses and skin cancer, and the association of psoriasis with internal diseases is quite common (HIV, Crohn's disease, liver lesions, vascular diseases, amyloidosis and gout). Today, psoriasis is considered as a systemic inflammatory disease that can also affect the joints. Atypical localization of psoriasis, as well as resistant cases of psoriasis and other papulosquamous and eczematoid dermatoses require detailed work-up and confirming of diagnosis because of the possibility of the existence of other diseases. This paper discusses the association of psoriasis with rheumatic and other internal diseases.
Osteoarthritis (OA) is a chronic joint disease caused by both mechanical damage and metabolic factors, which intertwine in their pathogenetic pathways. We hypothesise that the oxidised cholesterol ...derivative, 7-ketocholesterol (7-KCh), represents a danger signal in the synovia of patients with OA and promotes low-grade inflammation. The study would aim to elucidate the possible immune mechanisms initiated by 7-KCh that contribute to oxidative stress and inflammation in the synovia and synovial CD68+ cells, which are mostly macrophages. The polarisation of synovial CD68+ cells, their tissue distribution in relation to T and natural killer (NK) cells, and the influence of 7-KCh on the phenotype and intracellular cytokine and chemokine production in suspension is worth analysing. We envisage that this research would contribute to a better understanding of the biology of CD68+ macrophages influenced by 7-KCh and encourage the development of therapeutic approaches based on directing macrophage polarisation.
Arteritis divovskih stanica Perković, Dijana; Grazio, Simeon; Kehler, Tatjana ...
Liječnički vjesnik,
04/2021, Letnik:
143, Številka:
3-4
Journal Article
Recenzirano
Odprti dostop
Arteritis divovskih stanica ili gigantocelularni arteritis (engl. Giant Cell Arteritis – GCA) najčešći je vaskulitis starije životne dobi. Obično zahvaća ogranke karotidnih arterija, poglavito ...temporalnu i oftalmičku arteriju. Nastanku bolesti uz genetsku predispoziciju doprinose i okolišni čimbenici. Interleukin 6 (IL-6), čija razina korelira s upalnom aktivnošću, jedan je od ključnih citokina u patogenezi bolesti. Sterilna upala stijenke arterije uz hiperplaziju intime i razvoj okluzije dovodi do ishemije koja je odgovorna za nastanak simptoma. U kliničkoj slici dominira glavobolja uz opće simptome. Može nastati i nagli gubitak vida zbog anteriorne ishemičke optičke neuropatije (engl. anterior ischemic optic neuropathy – AION). Nerijetko su prisutni i znakovi reumatske polimijalgije (polymyalgia rheumatica – PMR). U laboratorijskim nalazima tipična je izrazito ubrzana sedimentacija eritrocita (SE) i povišen C reaktivni protein (CRP). Dijagnoza se temelji na kliničkoj slici, laboratorijskim nalazima, patohistološkoj analizi bioptata temporalne arterije te radiološkim slikovnim prikazima. Brzo postavljanje dijagnoze ključno je za pravodobno i adekvatno liječenje i sprječavanje nastanka ranih i kasnih komplikacija (sljepoće, aneurizme i disekcije arterija). Liječenje je donedavno bilo ograničeno na primjenu glukokortikoida (GK) i konvencionalnih imunomodulatora. U ovom preglednom radu navedene su nove terapijske mogućnosti proizašle iz boljeg poznavanja patofiziologije bolesti. Recentna istraživanja rezultirala su korekcijama smjernica za liječenje GCA (što je 2018. godine učinilo i Hrvatsko reumatološko društvo) preporukom primjene IL-6 inhibitora, tocilizumaba u bolesnika s refraktornom ili relapsnom bolešću, a inicijalno u bolesnika s povišenim rizikom za razvoj komplikacija. U tijeku su klinička istraživanja koja otvaraju i druge terapijske opcije u skoroj budućnosti.
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