Objective The efficacy of balneotherapy in rheumatology remains unclear. We aimed to estimate its benefits and risks in rheumatology. Methods We conducted a systematic review of randomised trials assessing any European balneotherapy for a rheumatological indication in adults versus any control, on clinical outcomes. We searched PubMed, Cochrane Library, Embase and https://clinicaltrials.gov/ (up to 28 November 2023). We used the Cochrane risk of bias tool version 2, funnel plot and asymmetry tests. We used a random effects model with an inverse-variance weighting method for standardised mean difference (SMD) and risk ratio (RR). We used the Grading of Recommendations Assessment, Development and Evaluation approach for two primary outcomes, pain and quality of life (QoL) at 3 months, and two safety outcomes, withdrawal and any adverse event (AE). Results We included 29 trials in mechanical disorders, 9 in inflammatory diseases and 4 in fibromyalgia. The synthesis suggested a decrease in pain of a very low level of certainty (SMD: −0.72 (95% CI (−1.00; −0.44)), very serious risk of bias and of inconsistency, publication bias strongly suspected); an increase in QoL of a very low level of certainty (SMD: 0.56 (95% CI (0.37; 0.75)), very serious risk of bias and serious risk of inconsistency); inconclusive results regarding the risk of withdrawal (RR: 0.75 (95% CI (0.46; 1.20)), very serious risk of bias and serious risk of imprecision) and of AE (RR: 0.80 (95% CI (0.43; 1.50)), serious risk of bias and of inconsistency and very serious risk of imprecision). Conclusion The certainty of the effect of balneotherapy in rheumatology was very low. PROSPERO registration number CRD42023448206.
Bone metastasis is a significant concern in advanced solid tumors, contributing to diminished patient survival and quality of life due to skeletal-related events (SREs). Denosumab (DMAB), a monoclonal antibody targeting the receptor activator of nuclear factor kappa-B ligand (RANKL), is used to prevent SREs in such cases. The RANK/RANKL axis, crucial in immunological processes, has garnered attention, especially with the expanding use of immune checkpoint inhibitors (ICI) in modern oncology. Our study aims to explore the potential synergistic antitumor effects of combining immunotherapy with denosumab, as suggested by anecdotal evidence, small cohort studies, and preclinical research. We conducted a retrospective analysis using the IMMUCARE database, encompassing patients receiving ICI treatment since 2014 and diagnosed with bone metastases. We examined overall survival (OS), progression-free survival (PFS) and switch of treatment line based on denosumab usage. Patients were stratified into groups: without denosumab, ICI followed by denosumab, and denosumab followed by ICI. Survival curves and multivariate Cox regression analyses were performed. Among the 268 patients with bone metastases, 154 received treatment with ICI alone, while 114 received ICI in combination with denosumab at some point during their oncological history. No significant differences were observed in overall survival (OS) or progression-free survival (PFS) between patients receiving ICI monotherapy and those receiving ICI with denosumab (p = 0.29 and p = 0.79, respectively). However, upon analyzing patients who received denosumab following ICI initiation (17 patients), a notable difference emerged. The group receiving ICI followed by denosumab exhibited a significant advantage compared to those without denosumab (154 patients) or those receiving denosumab before ICI initiation (72 patients) (p = 0.022). This retrospective investigation supports the notion of potential benefits associated with sequential administration of ICI and denosumab, although statistical significance was not achieved. Future studies, including prospective trials or updated retrospective analyses, focusing on cancers treated with first-line immunotherapy, could provide further insights into this therapeutic approach.
Bone metastases are frequent complications of many solid tumors, leading to painful skeletal morbidities and increasing mortality for patients with advanced cancer. Once in bone, cancer cells deregulate bone homeostasis, altering the functions of bone-forming (osteoblasts) and bone-resorbing (osteoclasts) cells, which results in skeletal deconstruction. Aside from bone cells, cancer cells in the bone marrow interact with other cell populations, including immune cells that also play an integral part in the regulation of bone homeostasis. In this respect, immune checkpoint inhibitors (ICIs) have become a standard of care in immunotherapy for the treatment of patients with advanced cancer. Strikingly, however, those with bone metastases have a shorter survival when treated with ICIs than ICI-treated cancer patients without bone metastases. In this Review, after presenting the immune cells involved in bone metastasis, we review preclinical and clinical findings assessing ICI efficacy both in bone and extraosseous metastases, and we discuss the clinical utility of using bone-targeted agents -including denosumab and bisphosphonates- to improve anti-tumoral efficacy of ICI treatments in patients with cancer and bone metastases.
More than 35% of lung adenocarcinoma patients have bone metastases at diagnosis and have a poor survival. Periostin, a carboxylated matrix protein, mediates lung cancer cell dissemination by promoting epithelial-mesenchymal transition, and is involved in bone response to mechanical stress and bone formation regulation. This suggests that periostin may be used as a biomarker to predict survival in lung cancer patients.
Background: Legionella spp. is recognized as a common cause of community acquired pneumonia, with Legionella pneumophila serogroup 1 being the most prevalent. At least 70 species are described so far but few are identified in pathogenic conditions. Data on extrapulmonary infections are scarce. Case presentation: A 73-yar-old male with chronic lymphoid leukemia was hospitalized for an insidious wrist arthritis. Ultrasound of the wrist showed a carpal and radiocarpal fluid effusion with positive Doppler signal. While routine bacterial cultures remained sterile, 16S rRNA PCR identified Legionella anisa. Ciprofloxacin 500 mg twice a day for a period of six weeks improved arthritis with full recovery at the end of the treatment. Conclusion: Legionella non pneumophila are a rare cause of septic arthritis especially found in immunosuppressed patients and identification of species could help clinician to adapt antibiotherapy.