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Introduction Chloroquine and hydroxychloroquine are widely used in the long-term treatment of connective tissue disease and usually considered safe. However, chloroquine- or hydroxychloroquine-related cardiac disorder is a rare but severe adverse event, which can lead to death. This systematic review investigates cardiac complications attributed to chloroquine and hydroxychloroquine. Methods PubMED, EMBASE, and Cochrane database searches were conducted using keywords derived from MeSH terms. Reports published prior to 31 July, 2017 were eligible for inclusion, without restriction to study design. Searches were also conducted on reference lists of included studies. Results Eighty-six articles were identified, reporting individual cases or short series, providing information on 127 patients (65.4% female). A majority of patients were treated with chloroquine (58.3%), with the remaining treated with hydroxychloroquine (39.4%), or both in succession. Most patients had been treated for a long time (median 7 years, minimum 3 days; maximum 35 years) and with a high cumulative dose (median 1235 g for hydroxychloroquine and 803 g for chloroquine). Conduction disorders were the main side effect reported, affecting 85% of patients. Other non-specific adverse cardiac events included ventricular hypertrophy (22%), hypokinesia (9.4%), heart failure (26.8%), pulmonary arterial hypertension (3.9%), and valvular dysfunction (7.1%). For 78 patients reported to have been withdrawn from treatment, some recovered normal heart function (44.9%), while for others progression was unfavorable, resulting in irreversible damage (12.9%) or death (30.8%). Limitations The risk of cardiac complications attributed to chloroquine/hydroxychloroquine was not quantified because of the lack of randomized controlled trials and observational studies investigating the association. Conclusions Clinicians should be warned that chloroquine- or hydroxychloroquine-related cardiac manifestations, even conduction disorders without repercussion, may be initial manifestations of toxicity, and are potentially irreversible. Therefore, treatment withdrawal is required when cardiac manifestations are present.

This phase I clinical trial evaluated the safety and clinical efficacy of adipose‐derived stromal cells (ASCs) in osteoarthritis. Eighteen patients with severe knee osteoarthritis were treated with a single intra‐articular injection of autologous ASCs at low (2 × 106 cells), medium (10 × 106), or high (50 × 106) doses (n = 6 each). After 6 months, no serious adverse events were reported, and patients treated with low‐dose ASCs significantly improved in pain and function. Osteoarthritis (OA) is the most widespread musculoskeletal disorder in adults. It leads to cartilage damage associated with subchondral bone changes and synovial inflammation, causing pain and disability. The present study aimed at evaluating the safety of a dose‐escalation protocol of intra‐articular injected adipose‐derived stromal cells (ASCs) in patients with knee OA, as well as clinical efficacy as secondary endpoint. A bicentric, uncontrolled, open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries. From April 2012 to December 2013, 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra‐articular injection of autologous ASCs. The study design consisted of three consecutive cohorts (six patients each) with dose escalation: low dose (2 × 106 cells), medium dose (10 × 106), and high dose (50 × 106). The primary outcome parameter was safety evaluated by recording adverse events throughout the trial, and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index. After 6 months of follow‐up, the procedure was found to be safe, and no serious adverse events were reported. Four patients experienced transient knee joint pain and swelling after local injection. Interestingly, patients treated with low‐dose ASCs experienced significant improvements in pain levels and function compared with baseline. Our data suggest that the intra‐articular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients. A placebo‐controlled double‐blind phase IIb study is being initiated to assess clinical and structural efficacy. Significance Although this phase I study included a limited number of patients without a placebo arm, it showed that local injection of autologous adipose‐derived stem cells was safe and well tolerated in patients with knee osteoarthritis. This study also provides encouraging preliminary evidence of efficacy. Larger and controlled long‐term studies are now mandatory to confirm whether this new strategy of cell therapy can improve pain and induce structural benefit in osteoarthritis.

ObjectiveTo evaluate the efficacy of tocilizumab, an antibody against IL-6 receptor, in patients with hand osteoarthritis.MethodsThis was a multicentre, 12-week, randomised, double-blind, placebo-controlled study from November 2015 to October 2018. Patients with symptomatic hand osteoarthritis (pain ≥40 on a 0–100 mm visual analogue scale (VAS) despite analgesics and non-steroidal anti-inflammatory drugs; at least three painful joints, Kellgren-Lawrence grade ≥2) were randomised to receive two infusions 4 weeks apart (weeks 0 and 4) of tocilizumab (8 mg/kg intravenous) or placebo. The primary endpoint was changed in VAS pain at week 6. Secondary outcomes included the number of painful and swollen joints, duration of morning stiffness, patients’ and physicians’ global assessment and function scores.ResultsOf 104 patients screened, 91 (45 to tocilizumab and 46 to placebo; 82% women; mean age 64.4 (SD 8.7) years) were randomly assigned and 79 completed the 12-week study visit. The mean change between baseline and week 6 on the VAS for pain (primary outcome) was −7.9 (SD 19.4) and −9.9 (SD 20.1) in the tocilizumab and placebo groups (p=0.7). The groups did not differ for any secondary outcomes at weeks 4, 6, 8 or 12. Overall, adverse events were slightly more frequent in the tocilizumab than placebo group.ConclusionTocilizumab was no more effective than placebo for pain relief in patients with hand osteoarthritis.

Mesenchymal stromal cells (MSCs) are the most commonly tested adult progenitor cells in regenerative medicine. They stimulate tissue repair primarily through the secretion of immune-regulatory and pro-regenerative factors. There is increasing evidence that most of these factors are carried on extracellular vesicles (EVs) that are released by MSCs, either spontaneously or after activation. Exosomes and microvesicles are the most investigated types of EVs that act through uptake by target cells and cargo release inside the cytoplasm or through interactions with receptors expressed on target cells to stimulate downstream intracellular pathways. They convey different types of molecules, including proteins, lipids and acid nucleics among which, miRNAs are the most widely studied. The cargo of EVs can be impacted by the culture or environmental conditions that MSCs encounter and by changes in the energy metabolism that regulate the functional properties of MSCs. On the other hand, MSC-derived EVs are also reported to impact the metabolism of target cells. In the present review, we discuss the role of MSC-EVs in the regulation of the energy metabolism and oxidative stress of target cells and tissues with a focus on the role of miRNAs.

The emergence and spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the resulting COVID-19 disease, have had a tremendous impact on public health and the world economy. Thus far, COVID-19 does not appear to be more severe in immunocompromised patients, but relevant data are scarce.

Proinflammatory cytokines play an important role in the systemic and focal bone loss associated with chronic inflammatory diseases. Targeting these cytokines with biologics and small molecules has led to a major improvement of the bone health of patients with inflammatory arthritis. Cytokines from the IL-17 family have been shown to be involved in the pathogenesis of several diseases such as spondyloarthritis, psoriatic arthritis, or psoriasis. IL-17A has been the first described and the most studied. The recent development of targeted therapies against IL-17A or its receptor and their efficacy has confirmed the importance of this cytokine in the development of inflammatory diseases. The aim of this review was to describe the effects of the IL-17 family and more particularly of IL-17A on bone and cartilage tissues. At the cellular level, IL-17A is proosteoclastogenic whereas its effects on osteoblasts depend on the stage of differentiation of these cells. In vivo, IL-17A is not required for normal bone homeostasis but plays an important role in bone loss notably in an ovariectomized mouse model of osteoporosis. Preliminary data from clinical trials showed a stabilisation of bone density in patients treated with anti-IL-17A antibodies. IL-17A plays a central role in the cartilage damage through the induction of collagenases and by decreasing the expression of their inhibitors in synergy with the other proinflammatory cytokines. The prevention of structural damage by anti-IL-17A therapies has been demonstrated in several pivotal clinical trials. Overall, blocking the IL-17A pathway seems to have a positive effect on the bone and cartilage damage observed in inflammatory arthritis. Differences and specificity of these effects compared to those already described with other biologics such as anti-TNF therapies remain to be explored.

Introduction The Chronic Disease Self‐Management Programme (CDSMP) has resulted in improved health outcomes for patients. However, research has focused mainly on those with chronic conditions and has not extensively explored prevention programmes targeting individuals with specific vulnerability profiles. Aim This study aimed to understand the effects of the CDSMP on the lived experience of vulnerable patients included in the EFFICHRONIC project in France, based on their needs and expectations before and after participation. Methods We conducted a qualitative phenomenological semio‐pragmatic study based on 37 in‐depth interviews with 20 patients (20 before/17 after CDSMP). Results By transforming existential dimensions (identity, relationship with others and bodily experience), chronic illness generates new needs in the vulnerable person. By resonating with the expectations and needs of participants, the CDSMP induces motivation and a sense of belonging to a community of peers. It has enabled the participants to become actors of their own health until empowerment. Although some limitations are reported, the programme has awakened a desire in the participants to take better care of their health and to develop personal skills with, for some, a desire to become involved in health education. Conclusion Our phenomenological approach highlighted the resonance between the programme (its design and implementation) and the lived experience of patients, as an effective element of empowerment. This necessitates training the facilitators to elicit the lived experience of patients. Furthermore, as a patient‐centred approach is required, the facilitators need to learn how to adapt the design of the programme to the singularity of the patient. Patient or Public Contribution Patients provided the data that were collected through in‐depth interviews, and their experiences before and after the programme were analysed.

Introduction Objective Structured Clinical Examinations (OSCEs) are critical for assessing clinical competencies in medical education. While traditional teaching methods remain prevalent, this study introduces an innovative approach by evaluating the effectiveness of an OSCE preparation podcast in improving medical students’ OSCE performance using nephrology as a proof of concept. This novel method offers a flexible and accessible format for supplementary learning, potentially revolutionizing medical education. Methods A mono-centric randomized controlled trial was conducted among 50 fourth-year medical students. Participants were randomly assigned to either the podcast intervention group or a control group. Both groups completed six nephrology-specific OSCE stations on DocSimulator, a generative AI-powered virtual patient platform. Scores from three baseline and three post-intervention OSCE stations were compared. The primary outcome was the change in OSCE scores. Secondary outcomes included interest in nephrology and students’ self-reported competence in nephrology-related skills. Results The baseline OSCE scores did not differ between the two groups (23.8 ± 3.9 vs. 23.3 ± 5.3; p  = 0.77). After the intervention, the podcast group demonstrated a significantly higher OSCE score compared to the control group (27.6 ± 3.6 vs. 23.6 ± 5.0; p  = 0.002) with a greater improvement in OSCE scores (+ 3.52[0.7,6.5] vs. -1.22[-3,5.5]; p  = 0.03). While the podcast did not increase students’ intention to specialize in nephrology (4.2% vs. 4.0%; p  = 0.99), it significantly improved their confidence in nephrology-related clinical skills (41.7% vs. 16%, p  = 0.04). 68% of students in the podcast group found OSCE training podcast useful for their OSCE preparation, and 96% reported they would use it again. Conclusions The use of an OSCE preparation podcast significantly enhanced students’ performance in AI-based simulations and confidence in nephrology clinical competencies. Podcasts represent a valuable supplementary tool for medical education, providing flexibility and supporting diverse learning styles. Trial Registration Not applicable.

Background The regenerative potential of mesenchymal stromal/stem cells (MSCs) has been extensively studied in clinical trials in the past decade. However, despite the promising regenerative properties documented in preclinical studies, for instance in osteoarthritis (OA), the therapeutic translation of these results in patients has not been fully conclusive. One factor contributing to this therapeutic barrier could be the presence of senescent cells in OA joints. Methods This study evaluated a novel approach to OA treatment by combining adipose tissue-derived MSCs (AD-MSCs) with rapamycin, a clinically approved immunosuppressive drug with anti-senescence properties. First, rapamycin effects on senescence and fibrosis markers were investigated in freshly isolated OA chondrocytes by immunostaining. Next, the in vitro differentiation capacities of AD-MSCs, their regulatory immune functions on activated immune cells and their regenerative effects on OA chondrocyte signature were assessed in the presence of rapamycin. Results In OA chondrocytes, rapamycin reduced the senescence marker p15 INK4B and the fibrosis marker COL1A1 without affecting the expression of the master chondrogenic markers SOX9 and COL2. Rapamycin also enhanced AD-MSC differentiation into chondrocytes and reduced their differentiation into adipocytes. In addition, rapamycin improved AD-MSC immunoregulatory functions by promoting the expression of immunosuppressive factors, such as IDO1 , PTGS2 and also CD274 (encoding PD-L1). Finally, RNA sequencing analysis showed that in the presence of rapamycin, AD-MSCs displayed improved chondroprotective regenerative effects on co-cultured OA chondrocytes. Conclusions Our findings suggest that the rapamycin and AD-MSC combination enhances the therapeutic efficacy of these cells in senescence-driven degenerative diseases such as OA, notably by improving their anti-fibrotic and anti-inflammatory properties. Graphical abstract

During the past 20 years, the development of telemedicine has accelerated due to the rapid advancement and implementation of more sophisticated connected technologies. In rheumatology, e-health interventions in the diagnosis, monitoring and mentoring of rheumatic diseases are applied in different forms: teleconsultation and telecommunications, mobile applications, mobile devices, digital therapy, and artificial intelligence or machine learning. Telemedicine offers several advantages, in particular by facilitating access to healthcare and providing personalized and continuous patient monitoring. However, some limitations remain to be solved, such as data security, legal problems, reimbursement method, accessibility, as well as the application of recommendations in the development of the tools.