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Non-steroidal anti-inflammatory drugs, diclofenac (DCF) and naproxen (NPX), represent a group of environmental contaminants often detected in various water and soil samples. This work aimed to assess possible phytotoxic effects of DCF and NPX in concentrations 0.1, 1 and 10 mg/L, both individually and in binary mixtures, on the seed germination and primary root elongation of crops, monocots Allium porrum and Zea mays, and dicots Lactuca sativa and Pisum sativum. Results proved that the seed germination was affected by neither individual drugs nor their mixture. The response of primary root length in monocot and dicot species to the same treatment was different. The Inhibition index (%) comparing the root length of drug-treated plants to controls proved to be approximately 10% inhibition in the case of dicots lettuce and pea, and nearly 20% inhibition in monocot leek, but almost 20% stimulation in monocot maize. Assessment of the binary mixture effect confirmed neither synergistic nor antagonistic interaction of DCF and NPX on early plant development in the applied concentration range.

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Background: Headache disorders, particularly primary headaches like migraine and tension-type headache, still remain underdiagnosed and undertreated despite their high prevalence and significant impact on quality of life. In recent years, several specific medications targeting key pathways in the pathophysiology of migraine have been developed. Despite this advancement, numerous studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics remain the most commonly used drugs. This study focused on the use of NSAIDs and simple analgesics as acute treatments for migraine among patients at a tertiary headache center. Methods: A retrospective observational study was conducted at the Fondazione Policlinico Universitario Campus Bio-Medico throughout 2022. Data were collected on the type and frequency of headaches, the usage and dosage of NSAIDs and other medications, and changes in their use at follow-up visits. Statistical analyses were performed to evaluate the efficacy and determinants of NSAID consumption and headache frequency changes. Results: Two hundred and eightythree patients diagnosed with migraine undergoing their first examination at our center were enrolled. Initially, 58.7% of patients used NSAIDs or simple analgesics, which decreased to 46.6% 3 months after, while triptan use increased from 65.1 to 72.8%. Changes in prophylactic therapies were significantly associated with a decrease in NSAID intake (W = 834.000, p = 0.004) and in headache frequency (W = 5960.5, p = 0.003). Specifically, the addition of topiramate or amitriptyline was associated with a reduction in NSAID use and headache frequency. Even pain freedom after the intake of NSAIDs improved from 55.2 to 79.4% of cases at follow-up. Conclusion: The study highlights the importance of appropriate diagnosis and tailored treatment strategies in the management of primary headaches. It underscores the need for specialized care to enhance treatment efficacy and patient outcomes, demonstrating that adjustments in prophylactic therapy can significantly reduce NSAID intake and improve headache care. This reinforces the role of tertiary headache centers in providing specialized care that can adapt treatments to individual patient needs and improve overall headache management.

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BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended for the management of acute postoperative pain as part of a multimodal strategy to reduce opioid use, relieve pain, and reduce chronic pain in non-cardiac surgery. However, significant concerns arise in cardiac surgery due to the potential adverse effects of NSAID including increased bleeding and acute kidney injury (AKI). We hypothesized that NSAIDs are effective against pain and safe in the early postoperative period following cardiac surgery, taking contraindications into account. METHODS: The KETOPAIN trial is a prospective, double blind, 1:1 ratio, versus placebo multicentric trial, randomizing 238 patients scheduled for cardiac surgery. Written consent will be obtained for all participants. The inclusion criterion is patients more than 18 years old undergoing for elective cardiac surgery under cardiopulmonary bypass (CPB). Patients will be allocated to the intervention (ketoprofen) group (n = 119) or the control (placebo) group (n = 119). In the intervention group, in addition to the standard treatment, patients will receive NSAIDs (ketoprofen) at a dose of 100 mg each 12 h 48 h after. The control group, in addition to the standard treatment, will receive a placebo of NSAIDs every 12 h for 48 h after surgery. An intention-to-treat analysis will be performed. The primary endpoint will be the intensity of acute postoperative pain at rest at 24 h from the end of surgery. Pain will be assessed using the numerous rating scale. The secondary endpoints will be postoperative pain on coughing during chest physiotherapy, postoperative pain until day 7, the pain trajectory between day 3 and day 7, cumulative opioid consumption within 48 h after surgery, nausea and vomiting, the occurrence of postoperative pulmonary complications within the first 7 days after surgery, neuropathic pain at 3 months, and quality of life at 3 months. DISCUSSION: NSAIDs function as non-selective, reversible inhibitors of the cyclooxygenase enzyme and play a role in a multimodal pain management approach. While there are recommendations supporting the use of NSAIDs in major non-cardiac surgery, recent guidelines do not favor their use in cardiac surgery. However, this is based on low-quality evidence. Major concerns regarding NSAID use in cardiac surgery patients are potential increase in postoperative bleeding or AKI. However, few studies support the possible use of NSAIDs without the risk of bleeding and/or AKI. Also, in a recent French survey, many anesthesiologists reported using NSAIDs in cardiac surgery. To date, no large randomized study has been conducted to evaluate the efficacy of NSAIDs in the management of postoperative pain in cardiac surgery. The expected outcome of this study is an improvement in the management of acute postoperative pain in cardiac surgery with a multimodal strategy including the use of NSAIDs. TRIAL REGISTRATION: ClinicalTrials.gov NCT06381063. Registered on April 24, 2024.

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INTRODUCTION: Heterotopic ossification (HO) is a relatively common complication after total hip arthroplasty (THA) and can range from a radiographic observation only to severely disabling and requiring revision surgery. Prophylaxis is recommended for high-risk patients, though the ideal method and targeted population are open to debate. Tranexamic acid (TXA) is a medication increasingly being used to reduce blood loss associated with orthopaedic surgeries, including THA. METHODS: A retrospective review of 357 patients undergoing THA from November 2020 through December 2023 was conducted. The patients were grouped based on whether they received intravenous TXA perioperatively or not, and their propensity score matched 2:1 TXA to no TXA on age, body mass index, sex, the Charlson Comorbidity Index, and perioperative celecoxib use. Univariate and multivariate analyses were performed. RESULTS: After propensity score matching, the only significant differences between groups were American Society of Anesthesiologists scores and preoperative celecoxib use between groups, as the TXA group had fewer patients who had an ASA of 3 or more (38.9 versus 58.5%, P < 0.001) and more patients who had taken celecoxib preoperatively (16.3 versus 5.9%, P = 0.010). Perioperatively, patients were more likely to undergo THA using the anterior approach (74.5 versus 57.6%, P = 0.002) and were more likely to receive postoperative celecoxib prescriptions (44.8 versus 31.4%, P = 0.021), but there was no difference in other nonsteroidal anti-inflammatory drug usage postoperatively. Postoperatively, patients who received TXA had a lower rate of heterotopic ossification on the last postoperative x-ray (20.1 versus 33.9%, P = 0.007). Multivariable logistic regression, to assess predictors of HO, found that patients who had TXA were 42% less likely to have visible HO (OR [odds ratio] = 0.58, P = 0.047) while holding surgical approach, ASA score, preoperative and postoperative celecoxib use, and postoperative other NSAID use constant. CONCLUSION: The use of tranexamic acid in patients undergoing primary total hip arthroplasty results in a decreased likelihood of heterotopic ossification formation on postoperative x-rays.

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BACKGROUND: Topical non-steroidal anti-inflammatory drugs have the potential to reduce treatment burden and improve outcomes of anti-VEGF therapy for a number of retinal disorders, including neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. In this review, we focused on the advantages of topical bromfenac as an adjunct to intravitreal anti-VEGF therapy in VEGF-driven maculopathies. METHODS: Cochrane Library, PubMed, and EMBASE were systematically reviewed to identify the relevant studies of neovascular age-related macular degeneration, diabetic macular edema, macular edema associated with retinal vein occlusion, myopic choroidal neovascularization, and radiation maculopathy which reported changes in central retinal thickness, visual acuity, and the number of anti-VEGF injections needed when anti-VEGF therapy was combined with topical bromfenac. RESULTS: In total, ten studies evaluating bromfenac as an adjunct to anti-VEGF therapy were identified. Five studies were included in meta-analysis of the number of injections and five studies were included in the analysis of changes in central retinal thickness. A statistically significantly lower number of intravitreal injections (p = 0.005) was required when bromfenac was used as an adjunct to anti-VEGF therapy compared to anti-VEGF monotherapy with pro re nata regimen. At the same time, eyes receiving bromfenac as an adjunct to anti-VEGF therapy demonstrated non-inferior outcomes in central retinal thickness (p = 0.07). Except for one study which reported better visual outcomes with combined treatment, no difference in visual acuity or clinically significant adverse effects were reported. CONCLUSIONS: This literature review and meta-analysis showed that topical bromfenac can be considered as a safe adjunct to anti-VEGF therapy with a potential to reduce the treatment burden with anti-VEGF drugs requiring frequent injections without compromising improvement of central retinal thickness or visual acuity.

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Background: Parkinson's disease (PD) is a neurological condition that typically shows up with aging. It is characterized by generalized slowness of movement, resting tremor or stiffness, and bradykinesia. PD patients' brains mostly exhibit an increase in inflammatory mediators and microglial response. Nevertheless, a variety of non-steroidal anti-inflammatory medications (NSAIDS) offered neuroprotection in animal models and preclinical trials. Aim: The current systematic review and meta-analysis were designed to try to resolve the debate over the association of NSAID use with the development of PD because the results of several studies were somehow contradictory. Methods: An intense search was performed on Scopus, PubMed, and Web of Science databases for articles relating the incidence of PD to the use of NSAIDs. Statistical analysis of the included studies was carried out using Review Manager version 5.4.1 by random effect model. The outcome was identified as the development of PD in patients who were on NSAIDs, ibuprofen only, aspirin only, and non-aspirin NSAIDs. This was analyzed using pooled analysis of odds ratio (OR) at a significance level of ≤0.05 and a confidence level of 95%. A statistically significant decreased risk of PD was observed in patients taking NSAIDs, Ibuprofen, and non-aspirin NSAIDs. Results: The ORs of PD occurrence in patients who took NSAIDs, Ibuprofen, and non-aspirin NSAIDs were 0.88 [95% CI (0.8-0.97), p = 0.01], 0.73 [95% CI (0.53-1), p = 0.05] and 0.85 [95% CI (0.75-0.97), p = 0.01]. Meanwhile, the risk of PD in patients who took aspirin was not statistically significant. Conclusion: In conclusion, Ibuprofen, non-aspirin NSAIDs, and other types of NSAIDs could be associated with a reduction in PD risk. However, there was no association between aspirin intake and the development of PD.

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Non-steroidal anti-inflammatory drugs (NSAIDs) are crucial components of multimodal analgesia for musculoskeletal injuries, targeting cyclooxygenase (COX) enzymes (COX-1 and/or COX-2 isoenzymes). Concerns exist regarding their potential interference with bone healing and orthopaedic device-related infections (ODRI), where data are limited. This study aimed to investigate whether the COX-selectivity of NSAIDs interfered with antibiotic efficacy and bone changes in the setting of an ODRI. In vitro testing demonstrated that combining celecoxib (a COX-2 inhibitor) with cefazolin significantly enhanced antibacterial efficacy compared to cefazolin alone (p < 0.0001). In vivo experiments were performed using Staphylococcus epidermidis in the rat proximal tibia of an ODRI model. Long and short durations of celecoxib treatment in combination with antibiotics were compared to a control group receiving an antibiotic only. The long celecoxib treatment group showed impaired infection clearance, while the short celecoxib treatment showed increased bone formation (day 6, p < 0.0001), lower bone resorption (day 6, p < 0.0001), and lower osteolysis (day 6, BV/TV: p < 0.0001; BIC: p = 0.0005) compared to the control group, without impairing antibiotic efficacy (p > 0.9999). Given the use of NSAIDs as part of multimodal analgesia, and considering these findings, short-term use of COX-2 selective NSAIDs like celecoxib not only aids pain management but also promotes favorable bone changes during ODRI.

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Upper gastrointestinal bleeding (UGIB) is a significant concern in children, contributing to 6-20% of cases in pediatric intensive care units. This study evaluates the roles of Helicobacter pylori (H. pylori) infection and non-steroidal anti-inflammatory drug (NSAID) usage in the etiology of UGIB in children, with a particular focus on trends observed during the COVID-19 pandemic. We conducted a retrospective analysis of 103 pediatric patients who underwent esophagogastroduodenoscopy (EGD) for UGIB between January 2015 and December 2023. Of these, 88 patients were included in the final analysis, where the source of bleeding was successfully identified. Hematemesis was the most common presentation, and the source of bleeding was identified in 85.43% of cases. The prevalence of H. pylori infection remained stable across the pre-pandemic (39.7%) and post-pandemic (36.7%) periods. However, NSAID usage increased nearly threefold during the pandemic, with 36.7% of post-pandemic UGIB cases associated with NSAID use, compared to 12.1% pre-pandemic. These findings underscore the significant roles of H. pylori and NSAID use in pediatric UGIB, with a notable increase in NSAID-related cases during the pandemic.

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Non-steroidal anti-inflammatory drugs (NSAIDs) are largely used for controlling various pain conditions and are widely available in community pharmacies, with and without prescription. Despite their effectiveness, NSAIDs can pose significant risks due to potential side effects and drug interactions, particularly in polypharmacy and comorbidity contexts and for vulnerable users. This study investigated whether and how NSAIDs deprescribing can be conducted at the community pharmacy level by assessing pharmacists' confidence, attitudes, and potential barriers and facilitators. Additionally, we aimed to identify any deprescribing guidelines that pharmacists could use. A literature search and a cross-sectional digital questionnaire targeting community pharmacists in Norway were conducted. Results showed that study participants (N = 73) feel confident in identifying needs for deprescribing NSAIDs but barriers such as time constraints, lack of financial compensation, and communication challenges were noted. Participants reported positive attitudes toward deprescribing but highlighted a need for better guidelines and training. This study highlights a gap in specific guidelines for deprescribing NSAIDs and a potential for enhancing pharmacists' roles in the deprescribing process, for example, through training and improved financial incentives. Further research is encouraged to develop concrete strategies for an effective implementation where community pharmacists can be involved in the deprescribing of NSAIDs.

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Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for various conditions but are associated with numerous adverse drug reactions (ADRs). Understanding these ADRs is necessary to reduce morbidity and mortality. NSAID-induced angioedema, although rare, can be life-threatening and is often due to increased leukotriene production from COX pathway inhibition. Mast cells and basophil degranulation play vital roles in its pathogenesis. Prompt recognition and immediate cessation of the culprit drug, along with the administration of corticosteroids and antihistamines, are essential. Here, we report a case of angioedema caused by diclofenac administration, which needs prompt vigilance and a rapid therapeutic response.

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BACKGROUND: It has been documented that NSAIDs (nonsteroidal anti-inflammatory and antirheumatic drugs) reduce the effectiveness of some antihypertensive drugs. OBJECTIVE: Analyze the prescription of NSAID and the variables associated in outpatients with hypertension and explore some characteristics of the physicians. MATERIAL AND METHODS: Cross-sectional study, included patients with hypertension from the Family Medicine Unit No. 24 in Mante, Tamaulipas. From the patients, sociodemographic data, clinical history and pharmacological treatments were obtained. From the physicians, sociodemographic and academic information were collected. RESULTS: Mean age of the patients was 63 ± 11 years and 31.7% were prescribed NSAIDs. When compare exposed versus non-exposed to NSAIDs, being in uncontrolled high blood pressure, uncontrolled hypertension, multimorbidity and polypharmacy. The variables associated to the prescription of NSAIDs were: uncontrolled hypertension, multimorbidity and polypharmacy. The 56.7% of the physicians were women, 83.3% with experience >10 years and 33.3% with current certification by the Council in Family Medicine. CONCLUSIONS: The inappropriate prescription of NSAIDs revealed the need to implement actions to mitigate the potential risk for the hypertension patients to present a complication.

ANTECEDENTES: Los antiinflamatorios y los antirreumáticos no esteroideos (AINE) disminuyen la eficacia de algunos antihipertensivos. OBJETIVO: Analizar el patrón de prescripción de AINE y las variables asociadas en pacientes ambulatorios con diagnóstico de hipertensión arterial, así como explorar algunas características de los médicos prescriptores. MATERIAL Y MÉTODOS: Estudio transversal de pacientes con hipertensión de la Unidad de Medicina Familiar 24 en Ciudad Mante, Tamaulipas. De los pacientes se registraron datos sociodemográficos, antecedentes patológicos y tratamientos farmacológicos; y de los médicos, información sociodemográfica y académica. RESULTADOS: La edad promedio de los pacientes fue de 63 ± 11 años, 31.7 % recibía AINE y al contrastarlos con quienes no los recibían, se identificó mayor proporción de obesidad, presión arterial más elevada, más casos en descontrol de la hipertensión arterial, multimorbilidad y polimedicación. Las variables asociadas a la prescripción de AINE fueron estar en descontrol de la hipertensión arterial, multimorbilidad y polimedicación; 56.7 % de los médicos prescriptores fue del sexo femenino, 83.3 % con antigüedad superior a 10 años y 33.3 % con certificación vigente. CONCLUSIONES: La prescripción inapropiada de AINE reveló la necesidad de implementar acciones para mitigar el riesgo potencial de los pacientes hipertensos de presentar una complicación.

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Background: Neuroinflammation is postulated as a potential mechanism underlying postoperative delirium. This study aimed to investigate the impact of non-steroidal anti-inflammatory drug (NSAID) use on postoperative delirium. Methods: We conducted a literature search in electronic databases, including PubMed, EMBASE, CENTRAL, and Web of Science, to identify eligible randomized controlled studies. The primary outcome was the incidence of postoperative delirium, and the secondary outcomes included pain scores and the amounts of opioid used at 24 h postoperatively. We estimated the effect size through calculating the odds ratios (ORs) or mean differences (MDs) with 95% CIs, as appropriate. Results: In the analysis of eight studies involving 1,238 participants, the incidence of postoperative delirium was 11% and 19% in the NSAID and control groups, respectively, with a significant reduction in the NSAID group (OR, 0.54; 95% CI, 0.38 to 0.76; P = 0.0001; I2 = 0%). NSAID use had a significant effect on postoperative pain reduction (MD, -0.75; 95% CI, -1.37 to -0.13; P = 0.0172; I2 = 88%). Significant lower postoperative opioid consumption was observed in the NSAID group (MD, -2.88; 95% CI, -3.54 to -2.22; P = 0.000; I2 = 0%). Conclusions: NSAID administration reduced the incidence of postoperative delirium, severity of pain, and opioid dose used.

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Musculoskeletal infections (MIs) are among the most difficult-to-treat staphylococcal diseases due to antibiotic resistance. This has encouraged the development of innovative strategies, such as combination therapy, to combat MI. The aim of this study was to investigate the in vitro antistaphylococcal activity of anti-inflammatory drugs and the combined antimicrobial effect of celecoxib and oxacillin. The minimum inhibitory concentrations (MICs) of 17 anti-inflammatory drugs against standard strains and clinical isolates of S. aureus, including methicillin-resistant strains (MRSAs), were determined using the broth microdilution method. The fractional inhibitory concentration indices (FICIs) were evaluated using checkerboard assays. Celecoxib produced the most potent antistaphylococcal effect against all tested strains (MICs ranging from 32 to 64 mg/L), followed by that of diacerein against MRSA3 and MRSA ATCC 33592 (MIC 64 mg/L). Several synergistic effects were observed against the tested S. aureus strains, including MRSA (FICI ranging from 0.087 to 0.471). The strongest synergistic interaction (FICI 0.087) was against MRSA ATCC 33592 at a celecoxib concentration of 2 mg/L, with a 19-fold oxacillin MIC reduction (from 512 to 26.888 mg/L). This is the first report on the combined antistaphylococcal effect of celecoxib and oxacillin. These findings suggest celecoxib and its combination with oxacillin as perspective agents for research focused on the development of novel therapies for MI caused by S. aureus. This study further indicates that celecoxib could resensitize certain MRSA strains, in some cases, to be susceptible to ß-lactams (e.g., oxacillin) that were not previously tested. It is essential to mention that the in vitro concentrations of anti-inflammatory drugs are higher than those typically obtained in patients. Therefore, an alternative option for its administration could be the use of a drug delivery system for the controlled slow release from an implant at the infection site.

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BACKGROUND: Proton pump inhibitors (PPIs) are reported to decrease the efficacy of immune checkpoint inhibitors (ICIs), but there are few reports on the association between ICI efficacy and antacids other than PPIs, and simultaneous examination of the effects of antacids, corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs) on ICI therapy. METHODS: We conducted a retrospective study of 381 patients with non-small cell lung cancer who received ICI therapy from January 1, 2016 to December 31, 2022. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). Antacids included histamine type 2 receptor antagonists (H2RAs), PPIs, and potassium-competitive acid blockers (P-CABs). RESULTS: Antacids were administered to 218 patients, including 168 with PPIs, 37 with P-CABs, and 13 with H2RAs. Patients with antacids had worse median PFS and OS than those without antacids (PFS, 2.9 vs. 6.2 months; OS, 12.3 vs. 24.0 months), and those with PPIs, P-CABs, or H2RAs had similar results. However, there were no significant differences between patients with and without antacids when stratified by corticosteroid and NSAID use. Multivariate analyses showed that corticosteroids and NSAIDs administered for cancer-associated symptoms were related to poor prognosis, but antacids including PPIs, P-CABs, or H2RAs were not related. CONCLUSIONS: Antacids were not related to ICI efficacy when NSAIDs or corticosteroids were taken into consideration. This may be because the most frequent reason for administering NSAIDs and corticosteroids was cancer-associated symptoms, which are a poor prognostic factor, and most of the patients treated with these medications also received antacids.

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An acute abdomen that is tender to palpation often represents a life-threatening emergency requiring immediate surgical or medical management. We present a case of acute abdomen with peritoneal signs and symptoms due to epiploic appendagitis (EA) that resolved with a single dose of ibuprofen. EA often mimics appendicitis, diverticulitis, and rarely cholecystitis based on its location. It arises due to ischemic infarction of an epiploic appendage, typically caused by torsion or spontaneous thrombosis of the central draining vein. Despite its rarity, clinicians need to recognize the characteristic imaging findings of EA on CT and ultrasound to avoid unnecessary surgical interventions and to manage the condition conservatively.

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Although phytochemicals are plant-derived toxins that are primarily produced as a form of defense against insects or microbes, several lines of study have demonstrated that the phytochemical, quercetin, has several beneficial biological actions for human health, including antioxidant and inflammatory effects without side effects. Quercetin is a flavonoid that is widely found in fruits and vegetables. Since recent studies have demonstrated that quercetin can modulate neuronal excitability in the nervous system, including nociceptive sensory transmission via mechanoreceptors and voltage-gated ion channels, and inhibit the cyclooxygenase-2-cascade, it is possible that quercetin could be a complementary alternative medicine candidate; specifically, a therapeutic agent against nociceptive and pathological pain. The focus of this review is to elucidate the neurophysiological mechanisms underlying the modulatory effects of quercetin on nociceptive neuronal activity under nociceptive and pathological conditions, without inducing side effects. Based on the results of our previous research on trigeminal pain, we have confirmed in vivo that the phytochemical, quercetin, demonstrates (i) a local anesthetic effect on nociceptive pain, (ii) a local anesthetic effect on pain related to acute inflammation, and (iii) an anti-inflammatory effect on chronic pain. In addition, we discuss the contribution of quercetin to the relief of nociceptive and inflammatory pain and its potential clinical application.

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Objectives: This systematic review was designed to summarize randomized controlled trials of intra-articular administration of non-steroidal anti-inflammatory drugs (NSAIDs) for temporomandibular disorders. Methods: Randomized controlled trials regarding intra-articular injections of non-steroidal anti-inflammatory drugs for temporomandibular disorders were included in the review. The final search was conducted on 16 June 2024 in the Bielefeld Academic Search Engine, PubMed, and Scopus databases. Results: Of the 173 identified studies, 6 were eligible for review. In trials comparing arthrocentesis alone to arthrocentesis with NSAIDs, slight differences in joint pain were noted. For tenoxicam, differences were under 1 point on a 0-10 scale after 4 weeks, with inconsistent results. Piroxicam showed no significant difference, and pain levels were minimal in both groups. For maximum mouth opening (MMO), tenoxicam showed no significant difference. Piroxicam increased MMO by nearly 5 mm, based on one small trial with bias concerns. Conclusions: Currently, there is no strong scientific evidence supporting the injection of NSAIDs into the temporomandibular joint to relieve pain or increase jaw movement. Preliminary reports on piroxicam with arthrocentesis and tenoxicam or diclofenac without rinsing justify further research.

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Ketoprofen (KTF) and ketorolac (KTL) are among the most primarily used non-steroidal anti-inflammatory drugs (NSAIDs) in humans to alleviate moderate pain and to treat inflammation. Their binding affinity with albumin (the main globular protein responsible for the biodistribution of drugs in the bloodstream) was previously determined by spectroscopy without considering some conventional pitfalls. Thus, the present work updates the biophysical characterization of the interactions of HSA:KTF and HSA:KTL by 1H saturation-transfer difference nuclear magnetic resonance (1H STD-NMR), ultraviolet (UV) absorption, circular dichroism (CD), steady-state, and time-resolved fluorescence spectroscopies combined with in silico calculations. The binding of HSA:NSAIDs is spontaneous, endothermic, and entropically driven, leading to a conformational rearrangement of HSA with a slight decrease in the α-helix content (7.1% to 7.6%). The predominance of the static quenching mechanism (ground-state association) was identified. Thus, both Stern-Volmer quenching constant (KSV) and binding constant (Kb) values enabled the determination of the binding affinity. In this sense, the KSV and Kb values were found in the order of 104 M-1 at human body temperature, indicating moderate binding affinity with differences in the range of 0.7- and 3.4-fold between KTF and KTL, which agree with the previously reported experimental pharmacokinetic profile. According to 1H STD-NMR data combined with in silico calculations, the aromatic groups in relation to the aliphatic moiety of the drugs interact preferentially with HSA into subdomain IIIA (site II) and are stabilized by interactions via hydrogen bonding and hydrophobic forces. In general, the data obtained in this study have been revised and updated in comparison to those previously reported by other authors who did not account for inner filter corrections, spectral backgrounds, or the identification of the primary mathematical approach for determining the binding affinity of HSA:KTF and HSA:KTL.

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Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD) is a distinct clinical syndrome characterized by nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity, asthma, and nasal polyposis. Its diagnosis is challenging owing to variable presentations and a lack of simple tests, leading to diagnostic delays. Recent research has revealed its genetic predispositions, environmental triggers, and associations with atopy and second-hand tobacco smoke exposure or smoking cessation. Despite its severity, diagnostic awareness remains low, leading to the delay in effective management. Therapeutically, NSAID-ERD necessitates multidisciplinary approaches, often combining surgical interventions with medical management, including aspirin desensitization and biologic agents. However, predictive biomarkers for treatment response remain elusive. Understanding the underlying mechanisms driving NSAID-ERD pathogenesis and identifying reliable biomarkers are crucial for enhancing diagnostic accuracy and refining targeted therapeutic strategies for this debilitating condition. This review aims to provide a thorough understanding of NSAID-ERD, covering its history, clinical features, epidemiology, diagnosis, systemic and molecular biomarkers, available treatment options, and avenues for future research.