Tratamiento de una lesión primaria por loxoscelismo cutáneo, complicada por infección, con solución electrolizada de superoxidación con pH neutro (SES). Informe de un caso / Treatment of a Primary Lesion of Cutaneous Loxoscelismo, Complicated by Infection, with Neutral Electrolyzed Water (SES). A Case Report

Resumen Las lesiones por loxoscelismo cutáneo pueden complicarse con infecciones concomitantes debido a que el diagnóstico es presuntivo y no existe un esquema de tratamiento específico. Las soluciones electrolizadas de superoxidación de pH neutro (SES) han mostrado ser eficaces en el tratamiento de lesiones cutáneas severas por sus efectos antisépticos y de regeneración del tejido, por lo que podrían ser un método de curación para las lesiones por loxoscelismo cutáneo. Presentamos el caso de un paciente del sexo masculino, de 73 años, cardiópata, diagnosticado con loxoscelismo cutáneo en el tobillo izquierdo que recibió tratamiento convencional de antibióticos, antiinflamatorios, antihistamínicos y analgésicos, y fue dado de alta. Sin embargo, la lesión evolucionó y fue tratada de manera casera con remedios tradicionales; esta se extendió 360° y presentaba exudado fétido al momento en que decidió regresar al hospital. En la clínica de heridas se optó por manejar la lesión en primera instancia con lavados con SES y desbridamiento, seguido de lavados con SES y apósitos de gel SES 3 veces al día, por 3 días, logrando el control de la infección en este tiempo. Posteriormente, con el régimen basado en la aplicación de SES cada 48 horas, se observó la aparición del tejido de granulación al día 7, y la reepitelización en el día 45 de iniciado el abordaje con SES; el cierre total de la lesión se logró el día 67. El esquema de tratamiento basado en el uso de soluciones electrolizadas de superoxidación de pH neutro mostró ser eficaz en el control de la infección y en la inducción del proceso de regeneración del tejido que llevó al cierre de la herida sin complicaciones para el paciente.

Abstract Cutaneous loxoscelism wounds can be complicated by concomitant infections because the diagnosis is presumptive and there is no specific treatment scheme. Neutral electrolyzed water (SES) has been shown to be effective in the treatment of severe skin lesions due to their antiseptic and tissue regeneration effects and could therefore be a healing method for skin loxoscelism lesions. We present the case of a 73-year-old male patient with heart disease, diagnosed with cutaneous loxoscelism in the left ankle, who received conventional treatment of antibiotics, anti-inflammatories, antihistaminics, and analgesics. He was discharged. However, the injury developed and was treated at home with traditional remedies. It extended 360° and presented a fetid exudate at the time he decided to return to the hospital. In the clinic it was decided to manage the lesion in the first instance with washes with SES and debridement, followed by washes with SES and SES gel dressings three times a day for 3 days, achieving control of the infection at that moment. Subsequently, with the regimen based on the application of SES every 48 hours, the appearance of granulation tissue was observed on day 7, and re-epithelialization on day 45 after starting the SES approach, the total closure of the lesion was achieved on day 67. The treatment scheme based on the use of neutral electrolyzed water proved to be effective in controlling the infection and in inducing the tissue-generation process that led to the closure of the wound without complications for the patient.

Protective Effect of Neutral Electrolyzed Saline on Gentamicin-Induced Nephrotoxicity: Evaluation of Histopathologic Parameters in a Murine Model.

Background and Objectives: Gentamicin (GM) is a nephrotoxic aminoglycoside. Neutral electrolyzed saline (SES) is a compound with anti-inflammatory, antioxidant, and immunomodulatory properties. The objective of the present study was to evaluate whether kidney damage by GM can be prevented and/or reversed through the administration of SES. Materials and Methods: The study was carried out as a prospective, single-blind, five-arm, parallel-group, randomized, preclinical trial. The nephrotoxicity model was established in male BALB/c mice by administering GM at a dose of 100 mg/kg/day intraperitoneally for 30 days, concomitantly administering (+) SES or placebo (physiologic saline solution), and then administering SES for another 30 days after the initial 30 days of GM plus SES or placebo. At the end of the test, the mice were euthanized, and renal tissues were evaluated histopathologically. Results: The GM + placebo group showed significant tubular injury, interstitial fibrosis, and increased interstitial infiltrate of inflammatory cells compared with the group without GM. Tubular injury and interstitial fibrosis were lower in the groups that received concomitant GM + SES compared with the GM + placebo group. SES administration for 30 days after the GM administration periods (GM + placebo and GM + SES for 30 days) did not reduce nephrotoxicity. Conclusions: Intraperitoneal administration of SES prevents gentamicin-induced histologic nephrotoxicity when administered concomitantly, but it cannot reverse the damage when administered later.

Clinical Characteristics in the Acute Phase of COVID-19 That Predict Long COVID: Tachycardia, Myalgias, Severity, and Use of Antibiotics as Main Risk Factors, While Education and Blood Group B Are Protective.

BACKGROUND: Risk factors for developing long COVID are not clearly established. The present study was designed to determine if any sign, symptom, or treatment of the acute phase, or personal characteristics of the patient, is associated with the development of long COVID. METHODS: A cohort study was carried out, randomly selecting symptomatic COVID-19 patients and not vaccinated. The severity of the acute illness was assessed through the number of compatible COVID-19 symptoms, hospitalizations, and the symptom severity score using a 10-point visual analog scale. RESULTS: After multivariate analysis, a severity score ≥8 (RR 2.0, 95%CI 1.1-3.5, p = 0.022), hospitalization (RR 2.1, 95%CI 1.0-4.4, p = 0.039), myalgia (RR 1.9, 95%CI 1.08-3.6, p = 0.027), tachycardia (RR 10.4, 95%CI 2.2-47.7, p = 0.003), and use of antibiotics (RR 2.0, 95%CI 1.1-3.5, p = 0.022), was positively associated with the risk of having long COVID. Higher levels of education (RR 0.6, 95%CI 0.4-0.9, p = 0.029) and type positive B blood group (B + AB, RR 0.44, 95%CI 0.2-0.9, p = 0.044) were protective factors. The most important population attributable fractions (PAFs) for long COVID were myalgia (37%), severity score ≥8 (31%), and use of antibiotics (27%). CONCLUSIONS: Further studies in diverse populations over time are needed to expand the knowledge that could lead us to prevent and/or treat long COVID.

Systemic Administration of Neutral Electrolyzed Saline as a Novel Treatment for Rheumatoid Arthritis Reduces Mechanical and Inflammatory Damage to the Joints: Preclinical Evaluation in Mice.

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.

Nasopharyngeal and oropharyngeal rinses with neutral electrolyzed water prevents COVID-19 in front-line health professionals: A randomized, open-label, controlled trial in a general hospital in Mexico City.

The worldwide efforts that healthcare professionals are making in the COVID-19 pandemic is well known, and the high risk of illness and death that front-line staff experience on a daily basis is a reality, despite well-defined protocols for the use of personal protective equipment. In addition, it is well known that vaccination is still faraway to be achieved worldwide and that new variants are emerging, thus additional protective measures must be explored. A prospective open-label randomized controlled clinical trial was performed on front-line medical staff from the Dr. Enrique Cabrera General Hospital in México City to evaluate the effectiveness of nasopharyngeal and oropharyngeal rinses with a neutral electrolyzed water, known as SES, to reduce the risk of COVID-19 disease among front-line, not vaccinated medical staff. A total of 170 volunteers were enrolled and equally divided in a control group and SES group. All members of the trial wore the adequate personal protection equipment at all times while performing their duties, as required by standard COVID-19 safety protocols. Additionally, the SES group participants followed a prophylactic protocol with SES (oral and nasal rinses, three times a day for 4 weeks). All participants were monitored for COVID-19 symptoms and disease in a time-frame of 4 weeks and the incidence of illness per group was registered. The relative risk of disease, associated with each treatment was calculated. The presence of COVID-19-positive cases, in the group that received the nasal and oral rinses with SES was 1.2%, while in the group that did not do the SES rinses (control group), it was 12.7% (P=0.0039 and RR=0.09405; 95% CI of 0.01231-0.7183). The prophylactic protocol was demonstrated as a protective factor, in more than 90%, for developing the disease, and without adverse effects. Nasal and oral rinses with SES may be an efficient alternative to reinforce the protective measures against COVID-19 disease and should be further investigated. The present clinical trial was retrospectively registered in the Cuban public registry of clinical trials (RPCEC) database (March 16, 2021; PREVECOVID-19: RPCEC00000357).

Efficacy of the use of mefenamic acid combined with standard medical care vs. standard medical care alone for the treatment of COVID­19: A randomized double­blind placebo­controlled trial.

Mefenamic acid is a non­steroidal anti­inflammatory drug exhibiting a wide range of anti­inflammatory, antipyretic, analgesic and probable antiviral activities. The present study evaluated the efficacy of treatment with mefenamic acid combined with standard medical care vs. standard medical care plus a placebo in ambulatory patients with coronavirus disease 2019 (COVID­19; nasal/oropharyngeal swabs reverse transcription­PCR test results positive for severe acute respiratory syndrome coronavirus 2). The present study is a phase II prospective, two­arm, parallel­group, randomized, double­blind placebo­controlled clinical trial which analyzed 36 patients. Two aspects were evaluated during the 14­day follow­up period: i) The time for reaching a patient acceptable symptom state (PASS), and ii) the last day of each COVID­19 symptom presentation. Adverse effects were evaluated. The clinical severity for all the patients in the study was mild (88.9%) and moderate (11.1%). The control (placebo) group achieved PASS on day 8.0±1.3, compared with day 4.4±0.8 in the mefenamic acid group (P=0.020, Kaplan­Meier analyses using log­rank tests). Patients that received mefenamic acid plus standard medical care had a ~16­fold higher probability of achieving PASS on day 8 (adjusted RR, 15.57; 95% CI, 1.22­198.71; P=0.035), compared with the placebo plus standard medical care group. All symptoms lasted for fewer days in the mefenamic acid group, compared with the placebo group; however, only the symptoms of headache (P=0.008), retro­orbital eye pain (P=0.049), and sore throat (P=0.029) exhibited statistically significant differences. The experimental treatment produced no severe adverse effects. On the whole, the present study demonstrates that the administration of mefenamic acid markedly reduced the symptomatology and time to reach PASS in ambulatory patients with COVID­19. Due to its probable antiviral effects and potent anti­inflammatory mechanisms, mefenamic acid may prove to be useful in the treatment of COVID­19, in combination with other drugs, including the new antivirals (remdesivir, molnupiravir, or favipiravir). However, future studies are also required to confirm these findings.

Safety and efficacy of a COVID-19 treatment with nebulized and/or intravenous neutral electrolyzed saline combined with usual medical care vs. usual medical care alone: A randomized, open-label, controlled trial.

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. The experimental treatment decreased the risk of hospitalization by 89% [adjusted relative risk (RR)=0.11, 95% confidence interval (CI): 0.03-0.37, P<0.001] and the risk of death by 96% (adjusted RR=0.04, 95% CI: 0.01-0.42, P=0.007) and also resulted in an 18-fold higher probability of achieving an acceptable symptom state on day 5 (adjusted RR=18.14, 95% CI: 7.29-45.09, P<0.001), compared with usual medical care alone. Overall, neutral electrolyzed saline solution was better than usual medical care alone. Of the patients analyzed, >50% were negative for the virus as detected by RT-qPCR in naso/oro-pharyngeal samples on day 4, with only a small number of positive patients on day 6. Clinical improvement correlated with a decrease in C-reactive protein, aberrant monocytes and increased lymphocytes and platelets. Cortisol and testosterone levels were also evaluated and a decrease in cortisol levels and an increase in the testosterone-cortisol ratio were observed on days 2 and 4. The experimental treatment produced no serious adverse effects. In conclusion, neutral electrolyzed saline solution markedly reduced the symptomatology and risk of progression in ambulatory patients with COVID-19. The present clinical trial was registered in the Cuban public registry of clinical trials (RPCEC) database (May 5, 2020; no. TX-COVID19: RPCEC00000309).

Improve cognitive impairment using mefenamic acid non-steroidal anti-inflammatory therapy: additional beneficial effect found in a controlled clinical trial for prostate cancer therapy.

Inflammation is an essential component of prostate cancer (PCa), and mefenamic acid has been reported to decrease its biochemical progression. The current standard therapy for PCa is androgen deprivation therapy (ADT), which has side effects such as cognitive dysfunction, risk of Alzheimer's disease, and dementia. Published results of in vitro tests and animal models studies have shown that mefenamic acid could be used as a neuroprotector. Objective: Examine the therapeutic potential of mefenamic acid in cognitive impairment used in a controlled clinical trial. Clinical trial phase II was conducted on patients undergoing ADT for PCa. Two groups of 14 patients were included. One was treated with a placebo, while the other received mefenamic acid 500 mg PO every 12hrs for six months. The outcome was evaluated through the Mini-Mental State Examination (MMSE) score at six months. At the beginning of the study, both groups had similar MMSE scores (mefenamic acid vs. placebo: 26.0±2.5 vs. 27.0±2.6, P=0.282). The mefenamic acid group improved its MMSE score after six months compared with the placebo group (27.7±1.8 vs. 25.5±4.2, P=0.037). Treatment with mefenamic acid significantly increases the probability of maintained or raised cognitive function compared to placebo (92% vs. 42.9%, RR=2.2, 95% CI: 1.16-4.03, NNT=2.0, 95% CI: 1.26-4.81, P=0.014). Furthermore, 42.9% of the placebo group patients had relevant cognitive decline (a 2-point decrease in the MMSE score), while in patients treated with mefenamic acid, cognitive impairment was not present. This study is the first conducted on humans that suggests that mefenamic acid protects against cognitive decline.

Patient-Reported Health Outcomes After Treatment of COVID-19 with Nebulized and/or Intravenous Neutral Electrolyzed Saline Combined with Usual Medical Care Versus Usual Medical care alone: A Randomized, Open-Label, Controlled Trial.

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.

A novel cell-free formulation for the treatment of knee osteoarthritis generates better patient-reported health outcomes in more severe cases.

BACKGROUND: The bioactive cell-free formulation (BIOF2) for cartilage regeneration has shown a major therapeutic response in severe knee osteoarthritis. However, its effect on patients with mild or moderate stages of the disease has not been studied. OBJECTIVE: To evaluate the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, minimal clinically important improvement (MCII) and sleep disturbances in mild, moderate, and severe stages of knee osteoarthritis (OA) with the novel cell-free formulation treatment (BIOF2). METHODS: An open-label, nonrandomized, baseline-controlled, parallel group study on patients with mild, moderate, and severe knee OA was conducted to evaluate the effect of intra-articular administration of BIOF2. Clinical improvement was determined through the WOMAC score and MCII, whereas sleep disturbances were measured through a Likert scale questionnaire. RESULTS: At 6 months post-treatment, the mean decrease in the total WOMAC score was 16.4 +/- 4.7%, 49.9 +/- 6.4%, and 62.7 +/- 4.5% in the patients with mild, moderate, and severe disease, respectively (p < 0.001, analysis of variance test). MCII at 6 months was 18%, 78%, and 100% for mild, moderate, and severe disease, respectively (p < 0.001, likelihood-ratio χ2 test). Concerning sleep disturbances, 60% of the patients with severe OA had important sleep problems before beginning treatment, and those difficulties were overcome 6 months after treatment. Only 18% of the patients with mild disease and 16% with moderate disease had serious sleep disturbances at the beginning of the study, and there was slight improvement after treatment. No adverse events were recorded during follow-up. CONCLUSION: BIOF2 generates better patient-reported health outcomes (on pain, stiffness, function, and sleep) in the more severe cases of knee OA.

Patient-reported health outcomes for severe knee osteoarthritis after conservative treatment with an intra-articular cell-free formulation for articular cartilage regeneration combined with usual medical care vs. usual medical care alone: A randomized controlled trial.

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.

Adenovirus 5 produces obesity and adverse metabolic, morphological, and functional changes in the long term in animals fed a balanced diet or a high-fat diet: a study on hamsters.

Adenovirus 5 (Ad-5) infection is a common cause of acute respiratory infections and the main vector used in gene therapy. There are few studies on the relationship of Ad-5 to obesity. In the present study, we evaluated the chronic effects of Ad-5 infection on golden (Syrian) hamsters fed either a balanced diet (BD) or a high-fat diet (HFD). After a single inoculation with Ad-5 (1 × 107 pfu), the body weight of the animals was measured weekly. Medium-term (22 weeks) serum biochemical analyses and long-term (44 weeks) liver morphology, adiposity, and locomotive functionality (movement velocity) assessments were carried out. In the animals fed the BD, adenovirus infection produced hyperglycemia and hyperlipidemia. In the long term, it produced a 57% increase in epididymal pad fat and a 30% body weight gain compared with uninoculated animals. In addition, morphological changes related to non-alcoholic fatty liver disease (NAFLD) were observed. The animals fed the HFD had similar but more severe changes. In addition, the hamsters presented an obesity paradox: at the end of the study, the animals that had the most morphological and functional changes (significantly reduced movement velocity) had the lowest body weight. Despite the fact that an HFD appears to be a more harmful factor in the long term than adenovirus infection alone, infection could increase the severity of harmful effects in individuals with an HFD. Epidemiological studies are needed to evaluate the effect of adenovirus as a precursor of chronic liver and cardiovascular diseases, including the chronic effects of gene therapy.

Evaluación de un gel antiséptico de aplicación intravaginal para pacientes con infecciones cervicovaginales multitratadas / Evaluation of an antiseptic gel of intravaginal application for multitreated patients for infectious cervicovaginitis

Resumen OBJETIVO: Evaluar la efectividad y seguridad de un gel intravaginal antiséptico, elaborado con agua electrolizada, en el tratamiento de infecciones cervicovaginales bacterianas, fúngicas, parasitarias o mixtas, y en el control de los síntomas típicos en pacientes multitratadas. MATERIALES y MÉTODOS: Estudio clínico, comparativo con el tratamiento convencional, de dos brazos, multicéntrico, al azar, con escalamiento de dosis efectuado en pacientes atendidas entre mayo de 2017 y mayo de 2018 en el servicio de Ginecología y Obstetricia del Hospital General de Ecatepec Las Américas, en el Estado de México y en el Centro Hospitalario Unión, de Colima. Grupo control: esquema convencional, antibiótico-antifúngico (7 días); grupos experimentales, gel antiséptico durante 3, 5 o 10 días. Seguimiento del pH vaginal, agente etiológico y síntomas. RESULTADOS: Se incluyeron 62 pacientes, con límites de edad de 18 y 42 años, con vaginitis bacteriana en 25 de 62, candidiasis 10 de 62, tricomoniasis 6 de 62 o infección mixta en 21 de 62, multitratadas. La aplicación del gel durante 5 o 10 días erradicó el agente etiológico en 14 de 15 y en 18 de 20 pacientes; con el tratamiento control lo lograron 8 de 14 pacientes (p = 0.021 y 0.030, respectivamente). El gel antiséptico aplicado durante 5 o 10 días fue casi 3 veces más eficaz que el tratamiento control para erradicar el agente infeccioso, eliminar los síntomas y normalizar el pH vaginal. CONCLUSIONES: El tratamiento durante 5 o 10 días con el gel antiséptico intravaginal fue casi 3 veces más efectivo que el convencional (antibiótico-antimicótico) en pacientes con cervicovaginitis infecciosa multitratada, útil en la eliminación de los síntomas típicos y bien tolerado.

Abstract OBJECTIVE: To evaluate the efficacy and safety of an intravaginal antiseptic gel, made of electrolyzed water, against bacterial, yeast, parasitic and mixed cervical infections, and to control typical symptoms in multi-treated patients. MATERIALS AND METHODS: Clinical study, comparative with conventional treatment, two arms, multicentric, randomized, with dose escalation carried out in patients attended between May 2017 and May 2018 in the gynecology and obstetrics service of the Hospital General de Ecatepec La Américas, in the Estado de Mexico and the Centro Hospitalario Unión, of Colima. Control group: conventional scheme, antibiotic-antifungal (7 days); Experimental groups, antiseptic gel for 3, 5 or 10 days. Monitoring of vaginal pH, etiologic agent and symptoms. RESULTS: 62 multi-treated patients (18-42 years old) were enrolled, presenting bacterial vaginosis 25/62, yeast infection 10/62, trichomoniasis 6/62 or mixed infection 21/62; bacteria and yeast). Treatment with antiseptic gel during 5 or 10 days eradicated etiological agent, respectively in 14/15 patients and 18/20 patients; control treatment did it in 8/14 patients (p = 0.021, p = 0.026, respectively). Additionally, gel treatment for 5 or 10 days was 3 times more effective than control treatment to eradicate the infection, control symptoms and to normalize vaginal pH. CONCLUSIONS: Intravaginal antiseptic gel (5-10 days) was almost 3 times more effective than conventional therapy (antibiotics/antimycotics) against multi-treated cervical infections; as well as useful to control typical symptoms and well tolerated.

A phase I-II controlled randomized trial using a promising novel cell-free formulation for articular cartilage regeneration as treatment of severe osteoarthritis of the knee.

BACKGROUND: A 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. METHODS: A 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. RESULTS: The 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. CONCLUSIONS: The 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 .

Smoking and female sex as key risk factors associated with severe arthralgia in acute and chronic phases of Chikungunya virus infection.

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.

Dengue virus-1 NS5 genetic variant associated with a severe clinical infection: Possible reduction of the innate immune response by inhibition of interferon type 1 and the Janus kinase-signal transducer and activator of transcription signaling pathway.

Dengue virus (DENV) is currently considered as one of the most important mosquito-borne viral pathogens affecting humans. Genetic variations in viruses are likely to be a condition for more effective evasion of the immune system and resulting in severe clinical consequences. The DENV­1 NS5 gene was sequenced to establish whether during an epidemic burst there were genetic variations of the virus and whether any variant was associated (through a case­control design) with severe clinical behavior. A total of 31 patients positive for DENV­1 were enrolled. Among the nucleotide differences between the sequences, only two generated amino acid changes. The variants 124Met/166Ser (amino acid positions according to the report GenBank AJL35015.1), were associated with a severe clinical course of the disease. Via in silico tests, it was identified that the variations generate changes in the protein probably affecting the function of type­1 interferon, either at the level of its receptor or by interfering with the Janus kinase­signal transducer and activator of transcription signaling pathway.

A promising novel formulation for articular cartilage regeneration: Preclinical evaluation of a treatment that produces SOX9 overexpression in human synovial fluid cells.

Osteoarthritis (OA) is a chronic disorder of synovial joints, in which there is progressive softening and disintegration of the articular cartilage. OA is the most common form of arthritis, and is the primary cause of disability and impaired quality of life in the elderly. Despite considerable medical necessity, no treatment has yet been proven to act as a disease­modifying agent that may halt or reverse the structural progression of OA. The replacement of the joint with a prosthesis appears to be the best option in the advanced stages of the disease. A formulation (BIOF2) for cartilage regeneration has been recently developed. The present study evaluated the effects of BIOF2 on gene expression in human cell cultures, followed by efficacy trials in three OA animal models. Human synovial fluid cells that were exposed to the formulation exhibited increased transcription factor SOX­9 (SOX9; chondrogenic factor) expression, and decreased mimecan (mineralization inducer) and macrophage­stimulating protein receptor (osteoclastogenic factor) expression. The intra­articular application of BIOF2 in the animal models significantly increased cartilage thickness from 12 to 31% at 28 days, compared with articular cartilage treated with saline solution. The articular area and number of chondrocytes additionally increased significantly, maintaining an unaltered chondrocyte/mm2 proportion. Evaluation of the histological architecture additionally displayed a decrease in the grade of articular damage in the groups treated with BIOF2. In conclusion, BIOF2 has proven to be effective for treating OA in animal models, most likely due to SOX9 overexpression in articular cells.