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Revista Da Associacao Medica Brasileira... 2024Patients with rheumatic diseases have an increased risk of infections, especially tuberculosis. In this study, we aimed to recognize the positivity rate of tuberculosis...
OBJECTIVE
Patients with rheumatic diseases have an increased risk of infections, especially tuberculosis. In this study, we aimed to recognize the positivity rate of tuberculosis skin test in patients with rheumatoid arthritis and spondyloarthritis and the characteristics of the patients with positive results.
METHODS
Retrospective study of tuberculosis skin test results in patients followed from 2004 to 2021 in a single rheumatology unit. Data related to clinical and epidemiological features, along with treatment information referring to the period in which the tuberculosis skin test was performed, were collected from patients' charts.
RESULTS
A total of 723 tests were identified (448 tests in 269 rheumatoid arthritis patients and 275 in 174 spondyloarthritis patients). In the rheumatoid arthritis sample, 31/275 (11.5%) individuals had positive tests, and in the spondyloarthritis, 38/174 (21.8%) had positive tests. In the rheumatoid arthritis sample, patients with positive tuberculosis skin tests used a higher dose of methotrexate than those with negative results (median of 25 mg/week versus median of 20 mg/week respectively; p=0.02). In the spondyloarthritis sample, tuberculosis skin test positivity was associated with alcohol ingestion (13.1% versus 2.9% in users and non-users respectively; p=0.02) and sulfasalazine use (15.7% of positivity in users versus 5% in non-users; p=0.01).
CONCLUSION
The tuberculosis skin test-positive prevalence in rheumatoid arthritis was lower than in the spondyloarthritis sample. Patients with rheumatoid arthritis using a higher dosage of methotrexate or with spondyloarthritis using sulfasalazine had more frequency of tuberculosis skin test positivity and should be carefully followed by the attending physician in order to avoid the appearance of full-blown tuberculosis.
Topics: Humans; Methotrexate; Sulfasalazine; Tuberculin Test; Brazil; Prevalence; Retrospective Studies; Arthritis, Rheumatoid; Spondylarthritis; Tuberculosis
PubMed: 38265349
DOI: 10.1590/1806-9282.20230725 -
Rheumatology and Therapy Apr 2024Randomized controlled trials have demonstrated tofacitinib efficacy for psoriatic arthritis (PsA); however, real-world effectiveness data are limited. This real-world...
INTRODUCTION
Randomized controlled trials have demonstrated tofacitinib efficacy for psoriatic arthritis (PsA); however, real-world effectiveness data are limited. This real-world analysis assessed baseline demographics/disease characteristics and tofacitinib effectiveness in patients with PsA in the CorEvitas PsA/Spondyloarthritis Registry.
METHODS
This study (NCT05195814) included patients with PsA initiating tofacitinib from December 2017-December 2021, as monotherapy or with oral small molecules (methotrexate/leflunomide/sulfasalazine/apremilast), pre-existing use, or initiated concurrently.
OUTCOMES
mean change from baseline in disease activity/patient-reported outcomes, proportion of patients achieving low disease activity (LDA)/remission at 6 ± 3 months, and discontinuation rates.
RESULTS
Of 222 patients with PsA who initiated tofacitinib (60.8% as monotherapy), 123 patients had 6 ± 3 months of follow-up. At initiation, 59.7% were female, 92.3% were White, mean age was 56.3 years, PsA duration since diagnosis was 8.2 years, and 25.7% were biologic disease-modifying antirheumatic drug (bDMARD)-naïve. Improvements to 6 ± 3 months were observed with tofacitinib for Clinical Disease Activity Index for PsA (cDAPSA), DAPSA, PsA Disease Activity Score (PASDAS), Clinical Disease Activity Index, body surface area (BSA), tender/swollen joint count, patient fatigue, pain, Patient Global Skin Assessment, and Health Assessment Questionnaire-Disability Index. At 6 ± 3 months, 25.0%/7.8% of patients treated with tofacitinib achieved cDAPSA-defined LDA/remission, 18.2% achieved minimal disease activity, 30.8% had PASDAS ≤ 3.2, 42.9%/29.4% had resolved enthesitis/dactylitis, and 22.5% achieved BSA = 0%. Tofacitinib discontinuation occurred in 51.2% of patients (51.6% of monotherapy initiators) at/prior to 6 ± 3 months (27.6%/23.6%), 57.1% of whom switched to tumor necrosis factor/interleukin-17 inhibitors. Reasons for discontinuation were not reported in 85.3%/79.3% of patients who discontinued at/prior to 6 ± 3 months.
CONCLUSIONS
This real-world US cohort analysis described patients with PsA newly initiating tofacitinib; most were bDMARD-experienced or receiving monotherapy treatment. In patients who remained on therapy (48.8%), tofacitinib was effective across multiple PsA domains at 6 ± 3 months. Limitations included small patient numbers at follow-up and potential selection bias.
TRIAL REGISTRATION
ClinicalTrials.gov identifier, NCT05195814.
PubMed: 38252211
DOI: 10.1007/s40744-023-00631-4 -
The International Journal of... Apr 2024Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has a high mortality rate and incidence of complications. The pathophysiology of ALI/ARDS is still not...
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) has a high mortality rate and incidence of complications. The pathophysiology of ALI/ARDS is still not fully understood. The lipopolysaccharide (LPS)-induced mouse model of ALI has been widely used to study human ALI/ARDS. Sulfasalazine (SASP) has antibacterial and anti-inflammatory effects and is used for treating inflammatory bowel and rheumatic diseases. However, the effect of SASP on LPS-induced ALI in mice has not yet been reported. Therefore, we aimed to investigate the effect of SASP on LPS-induced ALI in mice. Mice were intraperitoneally injected with SASP 2 h before or 4 h after LPS modeling. Pulmonary pathological damage was measured based on inflammatory factor expression (malondialdehyde and superoxide dismutase levels) in the lung tissue homogenate and alveolar lavage fluid. The production of inflammatory cytokines and occurrence of oxidative stress in the lungs induced by LPS were significantly mitigated after the prophylactic and long-term therapeutic administration of SASP, which ameliorated ALI caused by LPS. SASP reduced both the production of inflammatory cytokines and occurrence of oxidative stress in RAW264.7 cells, which respond to LPS. Moreover, its mechanism contributed to the suppression of NF-κB and nuclear translocation. In summary, SASP treatment ameliorates LPS-induced ALI by mediating anti-inflammatory and antioxidant effects, which may be attributed to the inhibition of NF-κB activation and promotion of antioxidant defenses. Thus, SASP may be a promising pharmacologic agent for ALI therapy.
Topics: Mice; Humans; Animals; NF-kappa B; Lipopolysaccharides; Sulfasalazine; Acute Lung Injury; Lung; Oxidative Stress; Anti-Inflammatory Agents; Cytokines; Antioxidants; Respiratory Distress Syndrome
PubMed: 38246263
DOI: 10.1016/j.biocel.2024.106530 -
Scientific Reports Jan 2024To construct a model of the antibody response to COVID-19 vaccination in patients with rheumatoid arthritis (RA), and to identify clinical factors affecting the antibody...
To construct a model of the antibody response to COVID-19 vaccination in patients with rheumatoid arthritis (RA), and to identify clinical factors affecting the antibody response. A total of 779 serum samples were obtained from 550 COVID-19-naïve RA patients who were vaccinated against COVID-19. Antibody titers for the receptor binding domain (anti-RBD) and nucleocapsid (anti-N) were measured. The time from vaccination, and the log-transformed anti-RBD titer, were modeled using a fractional polynomial method. Clinical factors affecting antibody responses were analyzed by a regression model using generalized estimating equation. The anti-RBD titer peaked at about 2 weeks post-vaccination and decreased exponentially to 36.5% of the peak value after 2 months. Compared with the first vaccination, the 3rd or 4th vaccinations shifted the peaks of anti-RBD antibody response curves significantly upward (by 28-fold [4-195] and 32-fold [4-234], respectively). However, there was no significant shift in the peak from the 3rd vaccination to the 4th vaccination (p = 0.64). Multivariable analysis showed that sulfasalazine increased the vaccine response (by 1.49-fold [1.13-1.97]), but abatacept or JAK inhibitor decreased the vaccine response (by 0.13-fold [0.04-0.43] and 0.44-fold [0.26-0.74], respectively). Age was associated with lower ln [anti-RBD] values (coefficient: - 0.03 [- 0.04 to - 0.02]). In conclusion, the anti-RBD response of RA patients peaked at 2 weeks after COVID-19 vaccination, and then decreased exponentially, with the maximum peak increase observed after the 3rd vaccination. The antibody response was affected by age and the medications used to treat RA.
Topics: Humans; Antibody Formation; COVID-19 Vaccines; COVID-19; Arthritis, Rheumatoid; Vaccination; Antibodies, Viral
PubMed: 38228736
DOI: 10.1038/s41598-024-51535-4 -
Materials Today. Bio Feb 2024Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by the infiltration of inflammatory cells and proliferation of synovial cells. It can cause...
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by the infiltration of inflammatory cells and proliferation of synovial cells. It can cause cartilage and bone damage as well as disability and is regarded as an incurable chronic disease. Available therapies cannot prevent the development of diseases due to the high toxicity of the therapeutic agents and the inefficient drug delivery. Ferroptosis, an iron-dependent manner of lipid peroxidative cell death, indicates great potential for RA therapy due to ability to damage the infiltrated inflammatory cells and proliferated fibroblast-like synoviocytes. Here, we use macrophages as vector to deliver FeO nanoparticles and sulfasalazine (SSZ) for ferroptosis and photothermal therapy of RA. The inherent property of migration towards the inflamed joints under the guidance of inflammatory factors enables macrophages to targetedly deliver the payload into the RA. Upon the irradiation of the near infrared light, the FeO nanoparticles convert the light into heat to damage the proliferated synovium. Meanwhile, the iron released from FeO nanoparticles works with SSZ to generate synergetic ferroptosis effect. The resident inflammatory cells and proliferated synovium are efficiently damaged by the ferroptosis and photothermal effect, showing pronounced therapeutic effect for RA.
PubMed: 38226012
DOI: 10.1016/j.mtbio.2023.100925 -
BMC Cancer Jan 2024Glioblastoma is the most common and most aggressive malignant primary brain tumor in adults. Glioblastoma cells synthesize and secrete large quantities of the excitatory...
A phase Ib/II randomized, open-label drug repurposing trial of glutamate signaling inhibitors in combination with chemoradiotherapy in patients with newly diagnosed glioblastoma: the GLUGLIO trial protocol.
BACKGROUND
Glioblastoma is the most common and most aggressive malignant primary brain tumor in adults. Glioblastoma cells synthesize and secrete large quantities of the excitatory neurotransmitter glutamate, driving epilepsy, neuronal death, tumor growth and invasion. Moreover, neuronal networks interconnect with glioblastoma cell networks through glutamatergic neuroglial synapses, activation of which induces oncogenic calcium oscillations that are propagated via gap junctions between tumor cells. The primary objective of this study is to explore the efficacy of brain-penetrating anti-glutamatergic drugs to standard chemoradiotherapy in patients with glioblastoma.
METHODS/DESIGN
GLUGLIO is a 1:1 randomized phase Ib/II, parallel-group, open-label, multicenter trial of gabapentin, sulfasalazine, memantine and chemoradiotherapy (Arm A) versus chemoradiotherapy alone (Arm B) in patients with newly diagnosed glioblastoma. Planned accrual is 120 patients. The primary endpoint is progression-free survival at 6 months. Secondary endpoints include overall and seizure-free survival, quality of life of patients and caregivers, symptom burden and cognitive functioning. Glutamate levels will be assessed longitudinally by magnetic resonance spectroscopy. Other outcomes of interest include imaging response rate, neuronal hyperexcitability determined by longitudinal electroencephalography, Karnofsky performance status as a global measure of overall performance, anticonvulsant drug use and steroid use. Tumor tissue and blood will be collected for translational research. Subgroup survival analyses by baseline parameters include segregation by age, extent of resection, Karnofsky performance status, O-methylguanine DNA methyltransferase (MGMT) promotor methylation status, steroid intake, presence or absence of seizures, tumor volume and glutamate levels determined by MR spectroscopy. The trial is currently recruiting in seven centers in Switzerland.
TRIAL REGISTRATION
NCT05664464. Registered 23 December 2022.
Topics: Adult; Humans; Brain Neoplasms; Chemoradiotherapy; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Repositioning; Glioblastoma; Glutamates; Multicenter Studies as Topic; Quality of Life; Randomized Controlled Trials as Topic; Steroids
PubMed: 38225589
DOI: 10.1186/s12885-023-11797-z -
Clinical Case Reports Jan 2024
PubMed: 38223520
DOI: 10.1002/ccr3.8436 -
Dose-response : a Publication of... 2024The present study aims to evaluate the protective effect of berries decoction extract (CAB-DE) against acetic acid-induced ulcerative colitis as well as the mechanisms...
The present study aims to evaluate the protective effect of berries decoction extract (CAB-DE) against acetic acid-induced ulcerative colitis as well as the mechanisms implicated in such protection. Adult male rats were separated into seven groups: Control (HO), acetic acid (AA), AA + various doses of CAB-DE (100, 200, and 400 mg/kg, ), and AA + sulfasalazine (100 mg/kg, ) or gallic acid (50 mg/kg, ) during 10 days. All rats were kept fasting overnight and ulcerative colitis was induced by rectal infusion of AA (300 mg kg, ) (3%, v/v, 5 mL kg ), for 30 s. The colon was rapidly excised and macroscopically examined to measure ulcerated surfaces and the ulcer index. In vitro, we found that CAB-DE exhibited a high antioxidant activity against DPPH radical (IC = 164.17 ± 4.78 μg/mL). In vivo pretreatment with CAB-DE significantly protected the colonic mucosa against AA-induced damage by stimulating mucus secretion, reducing ulcer index as well as histopathological changes. Also, CAB-DE limited the oxidative status induced by AA in the colonic mucosa, as assessed by MDA and HO increased levels and the depletion of both enzymatic activities and non-enzymatic levels. In addition, AA intoxication increased iron and calcium levels in colonic mucosa and plasma, while CAB-DE pretreatment regulated all intracellular mediators deregulation and significantly reduced inflammatory markers such as CRP (1.175 ± .04 ─ .734 ± .06 μg/dl) and ALP (161.53 ± 5.02 ─ 98.60 ± 4.21 UI/L) levels. We suggest that CAB-DE protected against AA-induced ulcerative colitis due in part to its antioxidant and anti-inflammatory properties.
PubMed: 38223297
DOI: 10.1177/15593258241226890 -
Complementary Therapies in Medicine Mar 2024Chinese herbal medicine (CHM) has been shown to be effective in autoimmune rheumatic diseases, but harmful herb-drug interactions might be inherent. We aim to review the... (Review)
Review
OBJECTIVES
Chinese herbal medicine (CHM) has been shown to be effective in autoimmune rheumatic diseases, but harmful herb-drug interactions might be inherent. We aim to review the evidence regarding herb-drug interactions between immunosuppressive drugs used in autoimmune rheumatic diseases and CHM.
METHODS
We searched PubMed, EMBASE and CINAHL from inception till 30 April 2023 using keywords that encompassed 'herb-drug interactions', 'herbs' and 'immunosuppressants'. Articles were included if they contained reports about interactions between immunosuppressive drugs used in the treatment of rheumatic diseases with CHM. Level of evidence for each pair of interaction was graded using the algorithm developed by Colalto.
RESULTS
A total of 65 articles and 44 unique pairs of interactions were identified. HDIs were reported for cyclophosphamide, cyclosporine, tacrolimus, methotrexate, mycophenolic acid, glucocorticoids, sulfasalazine, tofacitinib and biologic disease-modifying antirheumatic drugs. Among these, cyclosporine (n = 27, 41.5%) and tacrolimus (n = 19, 29.2%) had the highest number of documented interactions. Hypericum perforatum had the highest level of evidence of interaction with cyclosporine and tacrolimus. Consumption reduced the bioavailability and therapeutic effects of the drugs. Schisandra sphenanthera had the highest level of evidence of interaction with tacrolimus and increased the bioavailability of the drug. Majority of the articles were animal studies.
CONCLUSION
Overall level of evidence for the included studies were low, though interactions between cyclosporine, tacrolimus, Hypericum perforatum and Schisandra sphenanthera were the most and well-documented. Healthcare professionals should actively enquire about the concurrent use of CHM in patients, especially when drugs with a narrow therapeutic index are consumed.
Topics: Animals; Humans; Tacrolimus; Drugs, Chinese Herbal; Immunosuppressive Agents; Herb-Drug Interactions; Plant Oils; Cyclosporins
PubMed: 38218549
DOI: 10.1016/j.ctim.2024.103017 -
Journal of Traditional Chinese Medicine... Feb 2024To evaluate the efficacy and safety of Qingchang suppository (, QCS), a preparation of Chinese herbal medicine, in the induction of remission in patients with... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the efficacy and safety of Qingchang suppository (, QCS), a preparation of Chinese herbal medicine, in the induction of remission in patients with mild-to-moderate ulcerative proctitis (UP).
METHODS
We performed a multicenter, prospective, randomized, parallel-controlled trial to evaluate the efficacy of QCS induction therapy in 140 adult patients with mild-to-moderate UP and TCM syndrome of dampness-heat in large intestine. The patients were randomized to receive QCS (study group) or Salicylazosulfapyridine (SASP) suppository (control group) one piece each time, twice a day, per anum for 12 weeks. Mayo score and main symptoms score were evaluated at weeks 0, 2, 4, 8 and 12, rectosigmoidscopy was taken at weeks 0, 4, 8 and 12, Geboes score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and safety indexes were assessed at weeks 0 and 12. The primary efficacy endpoint is clinical remission rate, the secondary efficacy endpoints are clinical response rate, mucosa healing rate, Geboes score, the remission rates of the main symptoms, the median day to the remission of the symptom, etc. RESULTS: There were no statistical difference in the clinical remission rates, the clinical response rates, the mucosa healing rates, Geboes score, ESR and CRP between the two groups. The remission rates of tenesmus and anal burning sensation of the study group were significantly higher than those of the control group (76.5% 25.0%, 0.009; 74.51% 29.63%, 0.003). The median day to the remission of purulent bloody stool of the study group was significantly less than that of control group [11 (1, 64) 19 (2, 67), 0.007]. The patients receiving QCS had a significantly higher mucosa healing rate at week 4 than the patients receiving SASP suppository (71.42% 52.85%, 0.023). No adverse event occurred in the study group while the adverse events incidence of the control group was 5.7% ( 0.049).
CONCLUSIONS
QCS could induce the remission of UP as effectively and safely as SASP suppository, and was superior to SASP suppository in relieving the symptoms of tenesmus, anal burning sensation and purulent bloody stool and the time to reach mucosa healing.
Topics: Adult; Humans; C-Reactive Protein; Colitis, Ulcerative; Pain; Proctitis; Prospective Studies; Remission Induction; Sulfasalazine; Treatment Outcome
PubMed: 38213250
DOI: 10.19852/j.cnki.jtcm.20231121.004