Systemic and local antiinflammatory effect of magnesium chloride in experimental arthritis.

OBJECTIVE: Despite some knowledge gaps in scientific evidence, MgCl2 is largely used for pain relief in musculoskeletal diseases. Mg salts were shown to provide analgesia postoperatively in orthopedic surgery and low Mg levels were linked to arthritis development and severity. We determined the anti-inflammatory activity of MgCl2 in an acute arthritis model. METHODS: Mice received 0.1 mg/25µL Zymosan (Zy) or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, and interleukin (IL)-1 level were assessed in joint lavage at 6 h. Synovia were excised for histopathology and analysis of immunoexpression of nuclear factor kappa B (NFκB) and tumor necrosis factor (TNF)-α. Groups (n = 6/group) received either 90 mg/kg MgCl2/100 µL or saline per os (systemic) or 500 µg/25 µL MgCl2 or saline intra-articularly (i.a.) 30 min prior to Zy. RESULTS: MgCl2 given either systemically or locally significantly reduced cell influx (p = 0.0012 and p = 0.0269, respectively), pain (p = 0.0005 and p = 0.0038, respectively), and intra-articular IL-1 level (p = 0.0391), as compared to saline. Systemic MgCl2 significantly decreased NFκB (p < 0.05) immmunoexpression, as compared to saline. CONCLUSION: MgCl2 given systemically or locally displayed anti-inflammatory activity in a severe acute arthritis model reducing cell influx, pain, and cytokine release. MgCl2 operates at least partially via inhibiting NFκB activation. This is the first in vivo demonstration that MgCl2 decreases cytokine release in arthritis, prompting reduction of inflammation and pain relief.

Having chronic back pain did not impact COVID-19 outcome in a low-income population - a retrospective observational study.

INTRODUCTION: Chronic back pain (CBP) is a major cause of years lived with disability. Social inequalities increase the prevalence and burden of CBP. Management of CBP was affected by restricted access to non-pharmacological treatments and outdoor activities during COVID-19 pandemic. OBJECTIVE: To determine the prevalence of CBP among patients with COVID-19 as well as the impact of having CBP in COVID-19 outcome in our low-income population. METHODS: Retrospective cohort of individuals with confirmed COVID diagnosis from May 2020 - March 2021, at Hospital Regional UNIMED (HRU) in Fortaleza, Ceará, Brazil. Data included comorbidities and household income. RESULTS: Among 1,487 patients, 600 (40.3%) were classified as having CBP. Mean age as well as income were similar in CBP and non-CBP groups, with more women in the CBP group. Hypertension and asthma, but not diabetes, were more prevalent in those with CBP. Need for emergency care, hospitalization, and admission to intensive care unit were similar regardless of having CBP. Dyspnea was more common in CBP vs. non-CBP groups, with 48.8% vs. 39.4% percentages, respectively (p = 0.0004). CONCLUSION: Having CBP prior to COVID did not impact the acute clinical outcome of COVID individuals of a low-income population.

Systemic and local antiinflammatory effect of magnesium chloride in experimental arthritis

Abstract Objective Despite some knowledge gaps in scientific evidence, MgCl2 is largely used for pain relief in musculoskeletal diseases. Mg salts were shown to provide analgesia postoperatively in orthopedic surgery and low Mg levels were linked to arthritis development and severity. We determined the anti-inflammatory activity of MgCl2 in an acute arthritis model. Methods Mice received 0.1 mg/25μL Zymosan (Zy) or saline into the knees. Joint pain was evaluated using von Frey test; cell influx, and interleukin (IL)-1 level were assessed in joint lavage at 6 h. Synovia were excised for histopathology and analysis of immunoexpression of nuclear factor kappa B (NFκB) and tumor necrosis factor (TNF)-α. Groups (n = 6/group) received either 90 mg/kg MgCl2/100 μL or saline per os (systemic) or 500 μg/25 μL MgCl2 or saline intra-articularly (i.a.) 30 min prior to Zy. Results MgCl2 given either systemically or locally significantly reduced cell influx (p = 0.0012 and p = 0.0269, respectively), pain (p = 0.0005 and p = 0.0038, respectively), and intra-articular IL-1 level (p = 0.0391), as compared to saline. Systemic MgCl2 significantly decreased NFκB (p < 0.05) immmunoexpression, as compared to saline. Conclusion MgCl2 given systemically or locally displayed anti-inflammatory activity in a severe acute arthritis model reducing cell influx, pain, and cytokine release. MgCl2 operates at least partially via inhibiting NFκB activation. This is the first in vivo demonstration that MgCl2 decreases cytokine release in arthritis, prompting reduction of inflammation and pain relief.

Having chronic back pain did not impact COVID-19 outcome in a low-income population - a retrospective observational study

Abstract Introduction Chronic back pain (CBP) is a major cause of years lived with disability. Social inequalities increase the prevalence and burden of CBP. Management of CBP was affected by restricted access to non-pharmacological treatments and outdoor activities during COVID-19 pandemic. Objectives To determine the prevalence of CBP among patients with COVID-19 as well as the impact of having CBP in COVID-19 outcome in our low-income population. Methods Retrospective cohort of individuals with confirmed COVID diagnosis from May 2020 - March 2021, at Hospital Regional UNIMED (HRU) in Fortaleza, Ceará, Brazil. Data included comorbidities and household income. Results Among 1,487 patients, 600 (40.3%) were classified as having CBP. Mean age as well as income were similar in CBP and non-CBP groups, with more women in the CBP group. Hypertension and asthma, but not diabetes, were more prevalent in those with CBP. Need for emergency care, hospitalization, and admission to intensive care unit were similar regardless of having CBP. Dyspnea was more common in CBP vs. non-CBP groups, with 48.8% vs. 39.4% percentages, respectively (p = 0.0004). Conclusion Having CBP prior to COVID did not impact the acute clinical outcome of COVID individuals of a low- income population.

Montelukast as a treatment for refractory cutaneous lupus: A case series.

INTRODUCTION: There are no drugs specifically approved to treat cutaneous lupus. Inflammatory cells in lupus skin lesions can produce leukotrienes (LT), which promote tissue damage. In addition to hypersensitivity reactions, LT are also associated with cardiovascular diseases and elevated serum LT levels have been linked to worse atherosclerotic disease in lupus. Targeting LT could thus be an alternative to treat lupus. We present 4 cases of cutaneous lupus successfully treated with montelukast (MLK), a Cys-LT antagonist. METHODS: Four consecutive female systemic lupus erythematosus (SLE) patients with refractory skin lesions were treated with MLK (10 mg/d) in the Hospital Universitário Walter Cantídio of the Universidade Federal do Ceará. Skin lesions were scored using Revised Cutaneous LE Disease Area and Severity Index (RCLASI). Relative expression of the 5-lipoxigenase (ALOX5) and 15-lipoxigenase (ALOX15) genes was determined in peripheral blood cells (PBC) from lupus patients and 4 age-matched female controls. RESULTS: All patients experienced improvement of skin lesions measured using RCLASI scores within 2-12 weeks following initiation of MLK. The response was sustained for at least 3 months follow-up and no adverse events were recorded. ALOX5 but not ALOX15 gene expression was significantly (P = 0.0425) increased in PBC from SLE patients vs controls. CONCLUSION: This is the first report of a fast and sustained successful response of cutaneous lupus to MLK. Given its acceptable safety profile, our data encourage development of a randomized trial as an attempt to reposition MLK as a safe, affordable alternative to treat cutaneous lupus.

Análise de intoxicação por medicamentos / Analysis of drug intoxication / Análisis de intoxicaciones medicamentosas

Os Centros de Assistência Toxicológica possuem uma importância relevante na promoção, prevenção e controle de agravos à saúde em casos de intoxicação, pois fornece um serviço de orientação e atendimento especializado para lidar com essas situações e para minimizar os prejuízos causados pelos agentes tóxicos. Diante disso, o objetivo do estudo foi analisar o perfil epidemiológico de intoxicações por medicamento, no período de 2017 a 2021, no estado do Ceará. Este estudo está caracterizado como epidemiológico exploratório- descritivo, de abordagem quantitativa, em que serão analisados os dados secundários do registro de casos de intoxicações por medicamento, registrados no Sistema Nacional de Agravos de Notificação, entre os anos de 2017 e 2021. Os dados foram coletados no período de março a abril de 2022. As variáveis levantadas são faixa etária, sexo, circunstâncias das intoxicações, óbito. Nas análises epidemiológicas foi feito o cálculo dos registros de intoxicação por medicamentos coletados no SINAN-TABNET. Resultados: Os resultados desse estudo no período de 2017 a 2021 permitiram a identificação do perfil de intoxicações medicamentosas no Estado do Ceará. Observamos que dentre as variáveis estudadas houve uma prevalência do sexo feminino, faixa etária entre 20-39 anos, e dentre as circunstâncias demostradas, a tentativa de suicídio apresentou dados mais alarmantes. Conclusão: Verificamos a necessidade de medidas efetivas no combate ao uso incorreto dos medicamentos, com ações sociais para conscientizar a população para o uso racional dos medicamentos e orientação para os riscos apresentados por medicamentos devido seu abuso intencional ou não intencional, e uma reavaliação do perfil das pessoas com alta prevalência de intoxicações.

The Toxicological Assistance Centers are relevant in promoting, preven- tion, and control of health aggravations in cases of poisoning, as it provides a specialized guidance and assistance service to deal with such situations and to minimize the damage caused by toxic agents. Therefore, the aim of the study was to analyze the epidemiolog- ical profile of medication poisonings in the period from 2017 to 2021 in the state of Ceará. This study is characterized as an exploratory-descriptive epidemiological study, with a quantitative approach, in which secondary data from the record of drug poisoning cases, registered in the National System of Notifiable Diseases, registered in the years 2017 to 2021 will be analyzed. collected from March to April 2022. The variables are age group, sex, circumstances of poisoning, death. In the epidemiological analyses, the calculation of the records of intoxication by drugs collected in SINAN-TABNET was performed. Results: The results of this study in the period from 2017 to 2021 allowed the identification of the profile of drug poisoning in the State of Ceará. We observed that among the variables studied, there was a prevalence of females, the age group is 20-39 years, and among the circumstances, suicide attempt presented the most alarming data. Conclusion: We verified the need for effective measures to combat the misuse of medi- cine, with social actions to make the population aware about the rational use of medi- cines and guidance for the risks presented by medicines due to their intentional or unin- tentional abuse, and a reassessment of the profile of the people with a high prevalence of poisoning.

Los Centros de Asistencia Toxicológica son relevantes en la promoción, prevención y control de los agravamientos de la salud en casos de intoxicación, ya que proporciona un servicio especializado de orientación y asistencia para hacer frente a es- tas situaciones y minimizar los daños causados por los agentes tóxicos. Por lo tanto, el objetivo del estudio fue analizar el perfil epidemiológico de las intoxicaciones medica- mentosas en el período de 2017 a 2021 en el estado de Ceará. Este estudio se caracteriza por ser un estudio epidemiológico exploratorio-descriptivo, con enfoque cuantitativo, en el que se analizarán datos secundarios del registro de casos de intoxicación medicamentosa, inscritos en el Sistema Nacional de Enfermedades de Declaración Obli- gatoria, registrados en los años 2017 a 2021. recogidos de marzo a abril de 2022. Las variables son grupo de edad, sexo, circunstancias de la intoxicación, muerte. En los aná- lisis epidemiológicos se ha realizado el cálculo de los registros de intoxicaciones por drogas recogidos en SINAN-TABNET. Resultados: Los resultados de este estudio en el período de 2017 a 2021 permitieron identificar el perfil de las intoxicaciones por drogas en el Estado de Ceará. Observamos que entre las variables estudiadas, hubo una preva- lencia de fe- varones, el grupo de edad es de 20-39 años, y entre las circunstancias, el intento de suicidio pre-sentó los datos más alarmantes. Conclusiones: Verificamos la necesidad de medidas eficaces para combatir el uso indebido de medicamentos, con ac- ciones sociales de concienciación de la población sobre el uso racional de medicamentos y orientación sobre los riesgos que presentan los medicamentos por su abuso intencional o no intencional, y una reevaluación del perfil de las personas con alta prevalencia de intoxicaciones.

Potent anti-inflammatory activity of the lectin-like domain of TNF in joints.

In view of the crucial role of tumor necrosis factor (TNF) in joint destruction, TNF inhibitors, including neutralizing anti-TNF antibodies and soluble TNF receptor constructs, are commonly used therapeutics for the treatment of arthropathies like rheumatoid arthritis (RA). However, not all patients achieve remission; moreover, there is a risk of increased susceptibility to infection with these agents. Spatially distinct from its receptor binding sites, TNF harbors a lectin-like domain, which exerts unique functions that can be mimicked by the 17 residue solnatide peptide. This domain binds to specific oligosaccharides such as N'N'-diacetylchitobiose and directly target the α subunit of the epithelial sodium channel. Solnatide was shown to have anti-inflammatory actions in acute lung injury and glomerulonephritis models. In this study, we evaluated whether the lectin-like domain of TNF can mitigate the development of immune-mediated arthritis in mice. In an antigen-induced arthritis model, solnatide reduced cell influx and release of pro-inflammatory mediators into the joints, associated with reduction in edema and tissue damage, as compared to controls indicating that TNF has anti-inflammatory effects in an acute model of joint inflammation via its lectin-like domain.

Quantitative evaluation of very early cartilage damage in experimental osteoarthritis using scanning electron microscopy.

OBJECTIVE: To describe parametric changes observed using scanning electron microscopy (SEM) in very early stages in posttraumatic osteoarthritis (OA) models in mice. METHODS: Mice (5/group) had their knees subjected to anterior cruciate ligament transection (ACLT), ACLT plus meniscectomy (MNCT) or sham surgery, sacrificed after 3, 7 or 14 days, had the articular cartilage evaluated under optical microscopy using Osteoarthritis Research Society International (OARSI) parameters as well as cartilage thickness, roughness, and a damage index using SEM. RESULTS: Alterations of the cartilage under optical microscopy were not significantly relevant among groups. SEM analysis revealed reduction of femoral and tibial cartilage thickness in ACLT and MNCT groups at 7 and 14 days, with increased cartilage roughness in MNCT group as early as 3 days postsurgery, being sustained up to 14 days. Articular damage index was significantly higher at 14 days post surgery in ACLT and MNCT vs control groups. CONCLUSION: This is the first demonstration of very early quantitative changes in the cartilage of mice subjected to posttraumatic experimental OA using SEM, revealing increased roughness and thickness as early as 3 days post surgery. These changes may be used as early surrogates for later joint damage in experimental OA.

Prevalence of Inflammatory Back Pain in a Low-Income Population.

BACKGROUND: Inflammatory back pain (IBP) is a major criterion in identifying axial spondyloarthritis. Whether socioeconomic issues impact prevalence of IBP assessed using standardized questionnaires has not been assessed. We determined IBP prevalence and performance of IBP questionnaires in a low-income, low-literacy population. METHODS: Individuals were interviewed in Fortaleza, Brazil, for the prevalence of IBP using Calin's, Berlin, and ASAS IBP questionnaires; monthly family income (US dollars), literacy (>/≤8 school years [SYs]), and smoking habit (present/absent) were registered. RESULTS: Two hundred nineteen individuals were included (mean age, 38.2 ± 12.9 years), 110 (50.2%) men, 58 (26.4%) White, and 38 (17.3%) smokers. Overall, 152 (69.4%) declared

Ease in Emergency Hospital Visits Due to Covid-19 Following Implementation of a Telemedicine Service in Ceará, Brazil.

Background: We assessed the impact of implementing a virtual emergency room (VER) in easing emergency room (ER) visits in patients suspected of having COVID-19. Materials and Methods: Retrospective observational cohort study conducted in May 2020 and in March 2021, during the first and second waves in Brazil. Patients could choose to either visiting ER or using the VER (implemented in March 2021). Medical records were revised for demographic and clinical data. The primary outcome was the number of visits. Results: A total of 32,822 visits were evaluated. HR was more than three times less in the VER group with <10% VER clients going to ER. The trend and volume of use of the emergency sector in the periods did not show a statistically significant difference, despite the higher number of cases in the second period. Conclusion: This telemedicine strategy led to a reduction in visits to the ER. Also, our results suggest the safety of this intervention.

Translation, cultural adaptation and reproducibility of a Portuguese version of the Functional Index for Hand OsteoArthritis (FIHOA).

BACKGROUND: The Functional Index for Hand Osteoarthritis (FIHOA) is a simple, reliable, and reproducible specific instrument to evaluate hand OA that can be applied both in clinical practice and research protocols. In order to be used in Brazil, FIHOA has to be translated into Portuguese, culturally adapted and have the reliability of the translated FIHOA version tested, which is the purpose of this study. METHODS: The FIHOA was translated into Brazilian Portuguese and administered to 68 patients with hand OA recruited between May 2019 and February 2020. The test-retest was applied to 32 patients and the reliability was assessed using Spearman's correlation coefficient and intraclass correlation coefficient (ICC). The internal consistency reliability was evaluated using Cronbach's alpha. External construction validity was assessed using the Spearman's correlation test between FIHOA and pain, assessed with a Visual Analogue Scale (VAS), the Cochin Hand Functional Scale (CHFS) and Health Assessment Questionnaire (HAQ). RESULTS: The 30 participants that initially answered the translated version of the FiHOA did not report difficulties in understanding or interpreting the translated version. The test-retest reliability for the total score was strong (r = 0.86; ICC = 0.89). Mean differences (1.37 ± 0.68) using Bland Altman's analysis did not significantly differ from zero and no systematic bias was observed. Cronbach's alpha was also high (0.89) suggesting a strong internal coherence in the test items. There were also correlations between FIHOA and the CHFS (r = 0.88), HAQ (r = 0.64) and pain in the hands both at rest (r = 0.55) and in motion (r = 0.44). CONCLUSION: The translation of the FIHOA into Brazilian Portuguese proved a valid instrument for measuring the functional capacity of patients with hand OA who understand Brazilian Portuguese.

Decreased Sulfate Content and Zeta Potential Distinguish Glycosaminoglycans of the Extracellular Matrix of Osteoarthritis Cartilage.

We aimed to determine the characteristics that distinguish glycosaminoglycans (GAGs) from osteoarthritis (OA) and normal cartilage and from men and women. Cartilage samples from 30 patients subjected to total joint arthroplasty secondary to OA or fracture (control) were evaluated, and the GAG content (µg/mg dry cartilage) after proteolysis was determined by densitometry, using agarose-gel electrophoresis. Relative percentages of carbon (C), nitrogen (N), and sulfur (S) in GAGs were determined by elemental microanalysis, as well as the zeta potential. Seventeen samples (56.6%) were from patients >70 years old, with 20 (66.6%) from women, and most [20 (66.6%)] were from the hip. The GAG content was similar regardless of patients being >/≤ 70 years old with 96.5 ± 63.5 and 78.5 ± 38.5 µg/mg (P = 0.1917), respectively. GAG content was higher in women as compared to men, with 89.5 ± 34.3 and 51.8 ± 13.3 µg/mg, respectively (P = 0.0022), as well as in OA than fracture samples, with 98.4 ± 63.5 and 63.6 ± 19.6 µg/mg, respectively (P = 0.0355). The GAG extracted from the cartilage of patients >70 years old had increase in N, and there were no gender differences regarding GAG elemental analysis. GAG from OA had a highly significant (P = 0.0005) decrease in S% (1.79% ± 0.25%), as compared to fracture samples (2.3% ± 0.19%), with an associated and significant (P = 0.0001) reduction of the zeta potential in the OA group. This is the first report of a reduced S content in GAG from OA patients, which is associated with a reduced zeta potential.

Tumor necrosis factor inhibitors prevent structural damage in hips in ankylosing spondylitis-time to reconsider treatment guidelines? A case series and review of literature.

Tumor necrosis factor inhibitors (TNFi) are indicated to treat ankylosing spondylitis (AS), also termed radiographic axial spondyloarthritis (axSpA). The main indication for TNFi is symptom relief, and whether they retard spinal structural damage as assessed by radiography is debated. Hips are the most common "non-spinal" joints involved in AS patients leading to major incapacitation. No major treatment guidelines mention measures to prevent peripheral joint damage, especially hips, in individuals with AS. We present our experience of prevention of structural damage in hips by TNFi in 4 AS patients from our practice. We conducted a literature review looking for articles describing prevention of structural damage progression in hips by TNFi. Over a 10-year period, three out of four patients were treated with TNFi and had no progression in hip damage as assessed by imaging. Only one patient that withdrew the TNFi due to infectious complications developed rapid worsening and required hip arthroplasty. Our literature review showed multiple case series with similar results suggesting that use of TNFi in patients with AS may prevent structural damage and at least postpone a hip replacement at a young age. Based on our experience, as well as from the literature review, we believe that treatment guidelines in axSpA should recommend prompt institution of TNFi following identification of hip involvement in patients to prevent a major source of disability. Whether interleukin (IL)-17 inhibitors or targeted synthetic anti-rheumatic drugs have hip sparing effects in patients with AS should also be investigated. Key Points • Hip involvement in ankylosing spondylitis is a major source of disability. • TNFi prevent hip damage in ankylosing spondylitis. • Prompt institution of TNFi should follow suspicion of hip involvement in ankylosing spondylitis.