This study is primarily aimed at assessing serum changes on a large panel of proteins in patients with chronic back pain following spa therapy, as well as evaluating different spa therapy regimens as a preliminary exploratory clinical study. Sixty-six patients with chronic back pain secondary to osteoarthritis were randomly enrolled and treated with daily mud packs and bicarbonate-alkaline mineral water baths, or a thermal hydrotherapy rehabilitation scheme, the combination of the two regimens or usual medication only (control group), for two weeks. Clinical variables were evaluated at baseline, after 2 and 12 weeks. One thousand serum proteins were tested before and after a two-week mud bath therapy. All spa treatment groups showed clinical benefit as determined by improvements in VAS pain, Roland Morris disability questionnaire and neck disability index at both time points. The following serum proteins were found greatly increased (≥2.5 fold) after spa treatment: inhibin beta A subunit (INHBA), activin A receptor type 2B (ACVR2B), angiopoietin-1 (ANGPT1), beta-2-microglobulin (B2M), growth differentiation factor 10 (GDF10), C-X-C motif chemokine ligand 5 (CXCL5), fibroblast growth factor 2 (FGF2), fibroblast growth factor 12 (FGF12), oxidized low density lipoprotein receptor 1 (OLR1), matrix metallopeptidase 13 (MMP13). Three proteins were found greatly decreased (≤0.65 fold): apolipoprotein C-III (Apoc3), interleukin 23 alpha subunit p19 (IL23A) and syndecan-1 (SDC1). Spa therapy was confirmed as beneficial for chronic back pain and proved to induce changes in proteins involved in functions such as gene expression modulation, differentiation, angiogenesis, tissue repair, acute and chronic inflammatory response.

Purpose Longitudinal studies specifically addressed to describe the development of systemic autoimmune diseases in antiphospholipid (aPL) positive healthy subjects are not available. Thus, we longitudinally followed a single-center aPL carriers cohort to evaluate the rate of disease evolution, focusing on anti-phospholipid syndrome (APS) and Systemic Lupus Erythematosus (SLE). Methods Healthy subjects positive for aPL in at least two consecutive determinations were enrolled. Medical history was recorded and laboratory evaluation was performed [aCL and anti-b2GPI IgG/IgM, lupus anticoagulant (LA), antinuclear antibody (ANA), C3/C4 levels, genetic thrombophilia screening]. All subjects were evaluated every six months to register the occurrence of clinical and laboratory features suggestive of APS or SLE. Results Ninety-five subjects (M/F 20/75, median age at first determination 46 years, IQR 19) were enrolled; aCL were identified in 75 carriers (78.9%), ab2GPI in 60 (62.5%) and LA in 45 (47.3%). We prospectively followed our cohort for a median period of 72 months (IQR 84). In detail, eight aPL carriers (8.4%) were lost to follow up. At the last visit, 6 (6.3%) subjects became persistently negative after a median interval of 21 months (IQR 43.5); all of them were female with aCL positivity at low titer in 83.3% of cases. During a total follow-up of 7692 person-months, we found an absolute risk for systemic autoimmune diseases development equal to 0.9%. In detail, four patients (4.2%) developed a thrombotic event and were classified as affected by APS. Notably, all of these subjects shared a laboratory phenotype, characterized by LA and ANA positivity. Interestingly, this phenotype was observed only in two out of the remaining persistently positive carriers (2.7%, p= 0.0001). Furthermore, three patients could be classified as affected by SLE according to the 2019 ACR/EULAR classification criteria. All these patients were then treated by HCQ 5 mg/Kg/daily. Conclusions In the present study, we evaluated the progression from asymptomatic aPL positivity condition to clinically manifested autoimmune disease. The tight and prolonged monitoring of our cohort allowed to observe the evolution to APS or SLE in almost 7% of cases. To the best of our knowledge, this is the first longitudinal cohort study specifically addressing the transition to systemic autoimmune diseases in aPL positive healthy individuals. Of note, it should be considered not only the expected APS development, but also the progression to SLE.

were randomly divided in 4 groups: in 1st and 2nd grs. 10 animals received 3 intra-articular injections of PAP (on 5th,7th,14th day after knee trauma) as a control (gr.3 and 4) 10 rabbits received 3 intra-articular injections of 0,9% NaCl at the same days after trauma; histopathology was performed at 45th (1st and 3rd gr.) & at 90th day (2nd and 4th gr.) after trauma. 146 patients-58 men (39.7%) & 88 women (60.3%), were divided into 2 grs. Gr.1 included 68 patients who consented to receive standard OA treatment and 3 weekly intra-articular injections of PAP (total 2 courses in 12 months) (plasma volume 12-15ml/course, total platelets number per injection 1260,24±22,1x10 9); Gr.2 consisted of 78 patients with the same diagnosis who received only standard OA treatment (non-steroidal anti-inflammatory drugs, physiotherapy, exercises). Both groups were of comparable age, gender and initial WOMAC data (Gr.1 40,9±0,7 Gr.2 39,7±0,9, p>0,05). WOMAC scale parameters were analyzed before treatment and after 3 weeks; 6 & 12 months after course of treatment in both groups. Results: In animals histopathology has found better repair, ↓ inflammation, better structure of the knee cartilage after PAP injections comparing with the control groups animals; in addition in 3rd group of rabbits ↓ signs of early posttraumatic osteoarthritis were found (comparing to 4th gr.). Clinical study demonstrated better changes in pain, stiffness and function in 3 weeks after treatment in patients of Gr.1 comparing to Gr.2 (WOMAC had decreased by 35.8% in Gr.2 and by 74.1% in Gr.1), p<0,05. After 6 months of follow-up (before 2 course of PAP treatment), the mean number of OA exacerbations was (0,7±0,02) in Gr.1 & (1,6±0,04) in Gr.2 (p<0,05) and general WOMAC index in Gr.1 was significantly lower than in Gr.2 (accordingly (22,8±0,3) and (36,5±0,8); p<0,05). In the next 6 months again patients in Gr.1 had less exacerbations (0,51±0,03) then patients in Gr.