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Peripheral blood but not synovial fluid natural killer T cells are biased towards a Th1-like phenotype in rheumatoid arthritis

Natural killer T (NKT) cells have been implicated in the regulatory immune mechanisms that control autoimmunity. However, their precise role in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The frequency, cytokine profile and heterogeneity of NKT cells were studied in peripheral blood mononuclear cells (PBMCs) from 23 RA patients and 22 healthy control individuals, including paired PBMC–synovial fluid samples from seven and paired PBMC–synovial tissue samples from four RA patients. Flow cytometry revealed a decreased frequency of NKT cells in PBMCs from RA patients. NKT cells were present in paired synovial fluid and synovial tissue samples. Based on the reactivity of PBMC-derived NKT cells toward α-galactosylceramide, RA patients could be divided into responders (53.8%) and nonresponders (46.2%). However, NKT cells isolated from synovial fluid from both responders and nonresponders expanded upon stimulation with α-galactosylceramide. Analysis of the cytokine profile of CD4+ and CD4- PBMC derived NKT cell lines from RA patients revealed a significantly reduced number of IL-4 producing cells. In contrast, synovial fluid derived NKT cell lines exhibited a Th0-like phenotype, which was comparable to that in healthy control individuals. This suggests that synovial fluid NKT cells are functional, even in patients with nonresponding NKT cells in their blood. We conclude that, because the number of Vα24+Vβ11+CD3+ NKT cells is decreased and the cytokine profile of blood-derived NKT cells is biased toward a Th1-like phenotype in RA patients, NKT cells might be functionally related to resistance or progression of RA. Providing a local boost to the regulatory potential of NKT cells might represent a useful candidate therapy for RA.

Prognostic value of circulating cytokines on overall survival and disease-free survival in cancer patients

Through their tumor-promoting and/or tumor-suppressive properties, cytokines can influence progression of cancer. We systematically reviewed the current literature on the prognostic value of the circulating cytokines IL-1α/β, IL-6, IL-8, IL-10, IL-12, TNF-α, TGF-β and IFN-γ to predict overall and disease-free survival in any type of cancer patients. PubMed was systematically searched and based on eligibility assessment using our five criteria of the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) checklist, six unique studies were reviewed. Elevated IL-6 and IL-10 levels seem independently associated with worse prognosis in terms of overall and disease-free survival. The prognostic value of IL-1α/β, IL-8, IL-12, TNF-α, TGF-β and IFN-γ could not be demonstrated. The small number of selected studies underlines the need for large well-designed prospective studies, using the REMARK checklist as a guideline, to determine which cytokines have prognostic value on survival in cancer patients.

Study protocol of KLIMOP: a cohort study on the wellbeing of older cancer patients in Belgium and the Netherlands

BackgroundCancer is mainly a disease of older patients. In older cancer patients, additional endpoints such as quality of survival and daily functioning might be considered equally relevant as overall or disease free survival. However, these factors have been understudied using prospective designs focussing on older cancer patients. Therefore, this study will focus on the impact of cancer, ageing, and their interaction on the long-term wellbeing of older cancer patients.Methods/DesignThis study is an observational cohort study. We aim to recruit 720 cancer patients above 70 years with a new diagnosis of breast, prostate, lung or gastrointestinal cancer and two control groups: one control group of 720 patients above 70 years without a previous diagnosis of cancer and one control group of 720 cancer patients between 50 - 69 years newly diagnosed with breast, prostate, lung or gastrointestinal cancer. Data collection will take place at inclusion, after six months, after one year and every subsequent year until death or end of the study. Data will be collected through personal interviews (consisting of socio-demographic information, general health information, a comprehensive geriatric assessment, quality of life, health locus of control and a loneliness scale), a handgrip test, assessment of medical records, two buccal swabs and a blood sample from cancer patients (at baseline). As an annex study, caregivers of the participants will be recruited as well. Data collection for caregivers will consist of a self-administered questionnaire examining depression, coping, and burden.DiscussionThis extensive data collection will increase insight on how wellbeing of older cancer patients is affected by cancer (diagnosis and treatment), ageing, and their interaction. Results may provide new insights, which might contribute to the improvement of care for older cancer patients.

Clinical-scale in vitro expansion preserves biological characteristics of cardiac atrial appendage stem cells

Cardiac atrial appendage stem cells (CASCs) have recently emerged as an attractive candidate for cardiac regeneration after myocardial infarction. As with other cardiac stem cells, CASCs have to be expanded ex vivo to obtain clinically relevant cell numbers. However, foetal calf serum (FCS), which is routinely used for cell culturing, is unsuitable for clinical purposes, and influence of long‐term in vitro culture on CASC behaviour is unknown.

The value of fatigue severity to rule out depression in older adult patients with cancer

PURPOSE/OBJECTIVES To evaluate whether fatigue severity can serve as a cue to investigate the presence of depression in older adult patients with cancer. DESIGN Cross-sectional observational cohort study. SETTING Seven hospitals and general practices in Belgium and the Netherlands. SAMPLE 205 older adult patients with cancer and 436 older adults without cancer (aged 70 years or older). METHODS The diagnostic accuracy of fatigue as a proxy for depression was evaluated using sensitivity, specificity, and predictive values. MAIN RESEARCH VARIABLES Fatigue was measured with a visual analog scale, and depression was measured with the 15-item Geriatric Depression Scale. FINDINGS Fifty-six percent of the population experienced fatigue, and 13% were depressed. For fatigue as a cue for depression, sensitivity was 82%, specificity was 47%, positive predictive value was 18%, and negative predictive value was 95%. CONCLUSIONS The data confirm that fatigue is a valuable cue to investigate the presence of depression because 82% of depressed participants were correctly identified by fatigue. The assessment of fatigue severity is intuitive, quick, straightforward, and usually already implemented. IMPLICATIONS FOR NURSING Identification of depression is difficult in older adult patients with cancer. Instead of experiencing affective symptoms of depression, older adult patients are more likely to disclose somatic symptoms, such as fatigue, which often overlap with cancer-related symptoms. Nurses should be aware of this problem and should be alert for the possibility of depression in older adult patients presenting with fatigue.

Magnitude of muscle wasting early after on‐pump coronary artery bypass graft surgery and exploration of aetiology

What is the central question of this study? It remains uncertain whether significant fat‐free mass wasting occurs early after coronary artery bypass graft surgery, and the aetiology of this wasting in these particular conditions is unexplored. What is the main finding and its importance? Significant fat‐free mass wasting is present after coronary artery bypass graft surgery, and this wasting effect is greater in younger patients and in patients with greater increments in blood cortisol‐to‐testosterone ratios after surgery.