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.

Meclofenamic acid was shown to be a potential antineoplastic agent for both androgen-dependent and androgen-independent prostate cancer.

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.

Abstract. Arthralgia is a potentially incapacitating condition and a persistent symptom in chronic or acute episodes of Chikungunya fever caused by infection with the Chikungunya virus (CHIKV). To the best of our knowledge, there are no reports on risk factors associated with the intensity of arthralgias in typical acute episodes of the disease. Although a number of studies have reported on risk factors associated with the development of the chronic stage of the disease, smoking habits have not been analyzed. Smoking is an interesting factor to consider since it is the main environmental risk factor for the development of rheumatoid arthritis (RA), a similar disease to CHIKV in many aspects. In the present study, 140 patients infected with CHIKV were assessed for risk factors associated with severe arthralgia intensity in the acute phase (pain of 9/10 on the visual analog scale of 0-10) and moderate to severe intensity (according to the Routine Assessment of Patient Index Data 3) 3.5 months after infection in patients that experienced the chronic phase of the disease. Women and smokers were 2-to 3-times more likely to experience severe pain in the acute and chronic stages. Likewise, the presence of severe arthralgia during the acute disease phase resulted in a 4-fold increased risk for entering the chronic phase. Smoking was a more important risk factor in males compared with females. Smoking resulted in a 20-fold increased risk for severe arthralgia during the acute phase in men, as well as a 10-fold increased risk for developing chronic disease with moderate-to-severe pain 3.5 months after the acute stage. The presence of rash, headache, muscular weakness or conjunctivitis in the acute phase, the presence of diabetes and age >40 years were considered significant risk factors due to their influence on illness progression. In conclusion, smoking and female sex were the main risk factors associated with development of severe joint pain in the acute and chronic phases of Chikungunya fever. These risk factors are similar to those associated with the development and severity of RA, possibly because the two diseases share pathophysiological mechanisms, including elevated interleukin-6 levels.

Background: Breast cancer is a public health problem and it is the most common gynecologic neoplasia worldwide. The risk factors for its development are of both hereditary and environmental origin. Certain foods have been clearly associated with modifying the breast cancer risk. The aim of the present analysis was to evaluate the effects of cow's milk and meat consumption on the development of breast cancer in a population from Western Mexico (Colima). Material and Methods: We studied 97 patients presenting with a histopathologic diagnosis of breast cancer and 104 control individuals who did not present with the disease (Breast Imaging Report and Data System (BI-RADS) 1-2). 80% of the population belonged to a low socioeconomic stratum. The main clinical characteristics were analyzed along with the lifetime consumption of meat and milk. Results: High milk consumption increased the breast cancer risk by 7.2 times (p = 0.008) whereas the consumption of meat was not significantly associated with the disease. Conclusions: High consumption of cow's milk was a risk factor for the development of breast cancer. Further studies are needed to evaluate the effects of dietary patterns on the development of breast cancer in diverse populations with ethnic, cultural, and economic differences.

Background/Aims: Breast cancer is the most common gynecologic malignancy known worldwide. The consumption of certain foods may modify the risk for its development. Peanuts and other seeds have shown anticarcinogenic effects in vitro, but there are a few studies that evaluate the effect of their consumption on the development of breast cancer. The aim of the present study was to determine whether there is an association between the consumption of peanuts, walnuts, and almonds and the development of breast cancer. Methods: We analyzed 97 patients presenting with breast cancer and 104 control subjects that did not have the pathology (BIRADS 1-2). An analysis of the main clinical characteristics and lifelong seed consumption was carried out. The association between the consumption of these foods and the risk for breast cancer was estimated by odds ratios and 95% confidence intervals, controlling other risk factors, using the Mantel-Haenszel analysis. Results: The high consumption of peanuts, walnuts, or almonds significantly reduced the risk for breast cancer by 2-3 times. This protective effect was not found with low or moderate seed consumption when compared with null consumption. Conclusions: High consumption of peanuts, walnuts, and almonds appears to be a protective factor for the development of breast cancer.

Adenocarcinoma of the duodenum comprises 50-70% of duodenal tumors. There is an increase in extracellular matrix metalloproteinases in this disease and it has been suggested that they play an important role in the development and pathology. Therefore, new therapeutic recommendations based on inhibitors of these enzymes, such as doxycycline, are under investigation. The cytotoxic effect of doxycycline was evaluated in the HuTu-80 duodenal adenocarcinoma cell line and its antitumor effect was determined in an immunodeficient murine model. A 10-µM (4.4 µg/ml) concentration of doxycycline was capable of causing apoptosis in 90% of the culture cells. Doxycycline was also responsible for a decrease in tumor growth and an increase in the survival of the mice with HuTu-80-cell tumors. These results suggest that doxycycline is a potential cytotoxic and antitumor agent effective in the treatment of adenocarcinoma of the duodenum.