BackgroundA promising novel cell-free bioactive formulation for articular cartilage regeneration, called BIOF2, has recently been tested in pre-clinical trials. The aim of the present study was to evaluate the efficacy and safety of BIOF2 for intra-articular application in patients with severe osteoarthritis of the knee.MethodsA prospective, randomized, 3-arm, parallel group clinical trial was conducted. It included 24 patients with severe osteoarthritis of the knee (WOMAC score 65.9 ± 17). Before they entered the study, all the patients were under osteoarthritis control through the standard treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), prescribed by their family physician. Patients were distributed into three groups of 8 patients each (intra-articular BIOF2, total joint arthroplasty, or conservative treatment with NSAIDs alone). The WOMAC score, RAPID3 score, and Rasmussen clinical score were evaluated before treatment and at months 3, 6, and 12. BIOF2 was applied at months 0, 3, and 6. Complete blood count and blood chemistry parameters were determined in the BIOF2 group before treatment, at 72 h, and at months 1, 3, 6, and 12. In addition, articular cartilage volume was evaluated (according to MRI) at the beginning of the study and at month 12.ResultsThe NSAID group showed no improvement at follow-up. Arthroplasty and BIOF2 treatments showed significant improvement in all the scoring scales starting at month 3. There were no statistically significant differences between the BIOF2 group and the arthroplasty group at month 6 (WOMAC score: 19.3 ± 18 vs 4.3 ± 5; P = 0.24) or month 12 (WOMAC score: 15.6 ± 15 vs 15.7 ± 17; P = 1.0). Arthroplasty and BIOF2 were successful at month 12 (according to a WOMAC score: ≤ 16) in 75% of the patients and the daily use of NSAIDs was reduced, compared with the group treated exclusively with NSAIDs (RR = 0.33, 95% CI 0.12–0.87, P = 0.02. This result was the same for BIOF2 vs NSAIDs and arthroplasty vs NSAIDs). BIOF2 significantly increased the articular cartilage by 22% (26.1 ± 10 vs 31.9 ± 10 cm2, P < 0.001) and produced a significant reduction in serum lipids. BIOF2 was well tolerated, causing slight-to-moderate pain only upon application.ConclusionsThe intra-articular application of the new bioactive cell-free formulation (BIOF2) was well tolerated and showed no significative differences with arthroplasty for the treatment of severe osteoarthritis of the knee. BIOF2 can regenerate articular cartilage and is an easily implemented alternative therapy for the treatment of osteoarthritis.Trial registration Cuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000250. Registered 08/15/2017—Retrospectively registered, http://rpcec.sld.cu/en/trials/RPCEC00000250-En.Electronic supplementary materialThe online version of this article (10.1186/s40001-018-0349-2) contains supplementary material, which is available to authorized users.

Background: Coronavirus disease (COVID-19) is currently the main public health problem worldwide. The administration of neutral electrolyzed saline, a solution that contains reactive species of chlorine and oxygen (ROS), may be an effective therapeutic alternative due to its immunomodulating characteristics, in systemic inflammation control, as well as in immune response improvement, promoting control of the viral infection. The present study evaluated the efficacy of treatment with intravenous and/or nebulized neutral electrolyzed saline combined with usual medical care versus usual medical care alone, in ambulatory patients with COVID-19.Methods: A prospective, 2-arm, parallel group, randomized, open-label, phase I-II clinical trial included 39 patients in the control group (usual medical care alone) and 45 patients in the experimental group (usual medical care + intravenous and/or nebulized electrolyzed saline, with dose escalation). Two aspects were evaluated during the twenty-day follow-up: i) the number of patients with disease progression (hospitalization or death); and ii) the Patient Acceptable Symptom State (PASS), a single-question outcome that determines patient well-being thresholds for pain and function. Biochemical and hematologic parameters, as well as adverse effects, were evaluated in the experimental group. Results: The experimental treatment decreased the risk for hospitalization by 92% (adjusted RR=0.08, 95% CI: 0.01-0.50, P=0.007), with a 43-fold increase in the probability of achieving an acceptable symptom state on day 5 (adjusted RR= 42.96, 95% CI: 9.22-200.0, P<0.001). Intravenous + nebulized administration was better than nebulized administration alone, but nebulized administration was better than usual medical care alone. Clinical improvement correlated with a decrease in C-reactive protein, and aberrant monocytes and an increase of lymphocytes, and platelets. Cortisol and testosterone levels were also evaluated, observing a decrease in cortisol levels and an increment of testosterone-cortisol ratio, on days 2 and 4. Conclusions: The experimental treatment produced no serious adverse effects. In conclusion, intravenous and/or nebulized neutral electrolyzed saline importantly reduced the symptomatology and risk of progression (hospitalization and death), in ambulatory patients with COVID-19.Trial registration: Cuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000309. Registered: 05. May 2020. https://rpcec.sld.cu/en/trials/RPCEC00000309-En

Coronavirus disease 2019 (COVID-19) is currently the major public health problem worldwide. Neutral electrolyzed saline solution that contains reactive chlorine and oxygen species may be an effective therapeutic. In the present study, the treatment efficacy of intravenous and/or nebulized neutral electrolyzed saline combined with usual medical care vs. usual medical care alone was evaluated in ambulatory patients with COVID-19. A prospective, 2-arm, parallel-group, randomized, open-label, multi-center, phase I-II clinical trial including 214 patients was performed. The following two outcomes were evaluated during the 20-day follow-up: i) The number of patients with disease progression; and ii) the patient acceptable symptom state. Serial severe acute respiratory syndrome coronavirus 2 naso/oro-pharyngeal detection by reverse transcription-quantitative (RT-q) PCR was performed in certain patients of the experimental group. Biochemical and hematologic parameters, as well as adverse effects, were also evaluated in the experimental group.

Osteoarthritis (OA) is a major public health problem characterized by joint pain, fatigue, functional limitation and decreased quality of life of the patient, which results in increased use of healthcare services and high economical costs. A promising novel bioactive cell-free formulation (BIOF2) for cartilage regeneration has recently been tested in pre-clinical and clinical trials, and has demonstrated a success rate similar to that of total joint arthroplasty for the treatment of severe knee OA. The present study evaluated the efficacy of treatment with BIOF2, by including it within a conservative regimen of ‘usual medical care’ of knee OA, and whether its efficacy was affected in subgroups of patients presenting with comorbidities that exacerbate OA. A prospective, randomized, 2-arm parallel group phase III clinical trial was conducted, which included 105 patients in the ‘usual medical care’ group (paracetamol/NSAIDs and general care provided by the family physician) and 107 patients in the BIOF2 group (usual medical care + intra-articular BIOF2 application at 0, 1 and 2 months). Two aspects were evaluated at 0, 6 and 12 months: i) Minimal clinically important improvement (MCII), based on 30% improvement of pain from the baseline; and ii) the Patient Acceptable Symptom State (PASS), a questionnaire that determines patient well-being thresholds for articular pain and function. Adverse effects and regular NSAID use were registered. At 12 months, BIOF-2 treatment produced MCII in 70% of the patients and >50% achieved PASS. Excluding the patients with class 2 obesity or malalignment conditions ( genu varum or genu valgum >20 degrees), the experimental treatment produced MCII and PASS in 100 and 92% of patients, respectively, compared with 25 and 8% in the group of usual medical care (P<0.001). No patient with malalignment and treatment with BIOF2 achieved PASS. Notably, there were no serious adverse effects. To conclude, BIOF2 is a safe therapeutic alternative that is easy to implement together with usual medical care for knee OA. Trial registration: Cuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000277. Retrospectively registered June, 2018.

Rheumatoid arthritis is globally present in about 1% of the population. This autoinflammatory disease modifies the connective tissue, causing pain and inflammation of the joints. Over time, it causes the loss of joint cartilage and bone mass, decreasing the patient's quality of life. Treatment options now available either give symptomatic alleviation or alter the disease process. Nonetheless, adherence to chronic treatment is typically limited due to adverse effects. As a result, new therapy approaches, such as systemic administration of neutral electrolyzed saline to improve patients’ quality of life, are being investigated. The study is a randomized prospective preclinical trial with a single-blind and a 4-arm parallel group using a collagen-induced mice model to generate rheumatoid arthritis. It was carried out on 36 male BALB/c mice, with the primary outcome measure being a scoring system for histopathologic assessment. When all groups are compared, there are significant differences. In addition, the animal model was validated by the healthy group. The animals treated with neutral electrolyzed saline had much less cartilage degradation, bone erosion, pannus development, and inflammation than the placebo-treated mice. Serum IL-6 levels were evaluated in parallel with disease severity expressed as synovitis grading of the affected joints. Spearman’s rank correlation coefficient (Rs) = 0.399 ( P = 0.016 ) between serum IL-6 levels and the synovitis grading suggests a direct correlation between IL-6 production and disease severity. An additional trial of 20 male BALB/c mice (10 treated with placebo and 10 with neutral electrolyzed saline for 30 days) showed no clinical nor histopathological evidence of adverse effects. According to histopathological and blood test results, we conclude that neutral electrolyzed saline minimizes mechanical and inflammatory damage to the joint and may be helpful as an alternative to rheumatoid arthritis therapy.