The purpose of this scoping review was to identify possible chondrotoxic effects caused by drugs usually used for intra-articular injections. PubMed, Scopus, Web of Science and Cochrane were searched. Inclusion criteria required randomized controlled trials written in English that evaluate the toxic effect that damages the cartilage. The literature search resulted in 185 unique articles. 133 full-text articles were screened for inclusion, of which 65 were included. Corticosteroids, with the exception of triamcinolone, along with local anaesthetics, potentially excluding ropivacaine and liposomal bupivacaine, and nonsteroidal anti-inflammatory drugs, exhibited insufficient safety profiles to warrant casual use in clinical settings. Hyaluronic acid, on the other hand, appears to demonstrate safety while also mitigating risks associated with concurrent compounds, thereby facilitating therapeutic combinations. Additionally, there remains a paucity of data regarding platelet-rich plasma, necessitating further evaluation of its potential efficacy and safety. Overall, it seems that results are significantly influenced by the dosage and frequency of injections administered, observed in both human and animal studies.

Rising melanoma rates have spurred interest in preventive strategies. Nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, show potential in reducing cancer risks. NSAIDs act on cyclooxygenase (COX) enzymes, impacting COX-2 associated with inflammation and cancer progression. This paper explores aspirin\'s role in cutaneous melanoma prevention, elucidating its mechanisms and acknowledging varying literature outcomes. Rather than providing conclusive recommendations, the review emphasizes the influence of individual factors, contributing to the ongoing dialogue on aspirin\'s complexities in melanoma prevention. A PubMed search using \"Aspirin\" AND \"Cutaneous melanoma\" yielded relevant English-language, peer-reviewed studies. Selection criteria focused exclusively on skin cancers, specifically cutaneous melanoma. Exclusions included studies covering various cancers, some non-dermatologic, and those not evaluating aspirin use independently but in conjunction with NSAIDs. The potential chemopreventive effects of aspirin and NSAIDs against melanoma have gained attention due to their association with a reduced risk of various cancers including gastric, colorectal, and breast. By inhibiting COX enzymes and the NF-κB pathway, these agents theoretically slow malignant cell activities, presenting a prospect for cancer prevention. Aspirin exhibits noteworthy effects, depleting growth-stimulating hormones, generating reactive oxygen species harmful to cancerous cells, and inhibiting COX-2 linked to cancer progression. Limited literature suggests survival benefits with aspirin use in stage II and III melanoma, possibly due to slowing disease progression, evident in smaller Breslow depths. Gender-specific responses to aspirin are notable, with some studies reporting a stronger chemopreventive correlation in females. It\'s crucial to note that geographic disparities, demographic cohorts, and individual-specific factors are confounding variables that may contribute to conflicting findings regarding aspirin\'s impact on melanoma. The association between aspirin use and melanoma risk is complex, with conflicting findings across diverse populations. Although it appears that more studies suggest a protective role for aspirin rather than not, evidence lacks consistency. Factors such as gender, geography, race, sun exposure, and health conditions play a role in shaping these varied outcomes, necessitating large-scale, prospective studies research and standardized parameters for more conclusive insights that may help guide tailored clinical strategies for melanoma prevention.

The use of non-steroidal anti-inflammatory drugs (NSAIDs) for a wide range of diseases is increasing, in part due to an increasing elderly population. Elderly patients are more vulnerable to adverse drug reactions, including side effects and adverse effects of drug-drug interactions, often occurring in this category of patients due to multimorbidity and polypharmacy. One of the most popular NSAIDs in the world is celecoxib. It is a selective cyclooxygenase (COX)-2 inhibitor with 375 times more COX-2 inhibitory activity than COX-1. As a result, celecoxib has a better gastrointestinal tract safety profile than non-selective NSAIDs. Gastrointestinal tolerance is an essential factor that physicians should consider when selecting NSAIDs for elderly patients. Celecoxib can be used in a wide range of diseases of the musculoskeletal system and rheumatological diseases, for the treatment of acute pain in women with primary dysmenorrhea, etc. It is also increasingly used as part of a multimodal perioperative analgesia regimen. There is strong evidence that COX-2 is actively involved in the pathogenesis of ischemic brain damage, as well as in the development and progression of neurodegenerative diseases, such as Alzheimer\'s disease. NSAIDs are first-line therapy in the treatment of acute migraine attacks. Celecoxib is well tolerated in patients with risk factors for NSAID-associated nephropathy. It does not decrease the glomerular filtration rate in elderly patients and patients with chronic renal failure. Many meta-analyses and epidemiological studies have not confirmed the increased risk of cardiovascular events reported in previous clinical studies and have not shown an increased risk of cardiovascular events with celecoxib, irrespective of dose. COX-2 activation is one of the key factors contributing to obesity-related inflammation. Specific inhibition of COX-2 by celecoxib increases insulin sensitivity in overweight or obese patients. Combination therapies may be a promising new area of treatment for obesity and diabetes.
Использование нестероидных противовоспалительных препаратов (НПВП) в качестве лекарственной терапии широкого спектра заболеваний растет, отчасти – из-за увеличения численности пожилого населения. Пациенты пожилого возраста отличаются повышенной уязвимостью для нежелательных реакций от лекарственных средств, включая побочные эффекты и неблагоприятные последствия межлекарственных взаимодействий, часто встречающихся у данной категории пациентов в связи с полиморбидностью и полипрагмазией. Одним из наиболее популярных в мире НПВП является целекоксиб. Это селективный ингибитор циклооксигеназы (ЦОГ)-2, ингибирующее действие которого на ЦОГ-2 в 375 раз сильнее, чем на ЦОГ-1. Благодаря этому целекоксиб имеет более высокий профиль безопасности для желудочно-кишечного тракта по сравнению с неселективными НПВП. Переносимость со стороны желудочно-кишечного тракта является важным фактором, который врачи должны учитывать при выборе НПВП для пациентов пожилого возраста. Целекоксиб можно применять при широком спектре заболеваний опорно-двигательного аппарата и ревматологических заболеваниях, для лечения острой боли у женщин при первичной дисменорее. Он также все чаще используется как часть мультимодального режима периоперационного обезболивания. Появляются убедительные доказательства того, что ЦОГ-2 активно участвует в патогенезе ишемического повреждения головного мозга, а также в развитии и прогрессировании нейродегенеративных заболеваний, таких как болезнь Альцгеймера. НПВП являются терапией 1-й линии при лечении острых приступов мигрени. Целекоксиб хорошо переносится пациентами, имеющими факторы риска развития НПВП-ассоциированной нефропатии. Данный препарат не вызывает снижения скорости клубочковой фильтрации у больных пожилого возраста и пациентов с хронической почечной недостаточностью. Многочисленные метаанализы и эпидемиологические исследования не подтвердили повышенный риск сердечно-сосудистых осложнений, наблюдавшийся в предыдущих клинических исследованиях, и не выявили повышения риска сердечно-сосудистых заболеваний при приеме целекоксиба независимо от дозировки. Активация ЦОГ-2 является одним из ключевых факторов, способствующих воспалению, связанному с ожирением. Специфическое ингибирование ЦОГ-2 целекоксибом повышает чувствительность к инсулину у пациентов с избыточной массой тела или ожирением. Использование комбинированной терапии может стать новой многообещающей областью лечения ожирения и сахарного диабета.

Corneal neovascularization can impair vision and result in a poor quality of life. The pathogenesis involves a complex interplay of angiogenic factors, notably vascular endothelial growth factor (VEGF). This review provides a comprehensive overview of potential therapies for corneal neovascularization, covering tissue inhibitors of metalloproteinases (TIMPs), transforming growth factor beta (TGF-β) inhibitors, interleukin-1L receptor antagonist (IL-1 Ra), nitric oxide synthase (NOS) isoforms, galectin-3 inhibitors, retinal pigment epithelium-derived factor (PEDF), platelet-derived growth factor (PDGF) receptor inhibitors, and surgical treatments. Conventional treatments include anti-VEGF therapy and laser interventions, while emerging therapies such as immunosuppressive drugs (cyclosporine and rapamycin) have been explored. Losartan and decorin are potential antifibrotic agents that mitigate TGF-β-induced fibrosis. Ocular nanosystems are innovative drug-delivery platforms that facilitate the targeted release of therapeutic agents. Gene therapies, such as small interfering RNA and antisense oligonucleotides, are promising approaches for selectively inhibiting angiogenesis-related gene expression. Aganirsen is efficacious in reducing the corneal neovascularization area without significant adverse effects. These multifaceted approaches underscore the corneal neovascularization management complexity and highlight ideas for enhancing therapeutic outcomes. Furthermore, the importance of combination therapies and the need for further research to develop specific inhibitors while considering their therapeutic efficacy and potential adverse effects are discussed.

Emerging evidence suggest that quantitative sensory testing (QST) may predict the treatment response to pain-relieving therapies. This systematic review and meta-analysis focus on the predictive value of QST for pain management of knee osteoarthritis (OA). MEDLINE and EMBASE were systematically searched for all studies from year 2000 to 2023 on pretreatment QST and treatment of OA including surgical, pharmaceutical, and nonsurgical and nonpharmaceutical therapies. Preclinical studies and reviews were excluded. The systematic review followed the PRISMA guidelines and was pre-registered on the Open Science Framework website (link: https://osf.io/4FETK/, Identifier: DOI 10.17605/OSF.IO/4FETK). Meta-analysis were conducted to demonstrate the strength of the pre-treatment QST predictions on pain outcomes after OA treatments. Sixteen surgical (all on total knee arthroplasty [TKA], N = 1967), 5 pharmaceutical (4 on non-steroidal anti-inflammatory drugs [NSAIDs], N = 271), and 4 exercise-based therapy studies (N = 232) were identified. Pretreatment QST parameters predicted pain-relieving treatment outcomes in 81% of surgical, 100% of pharmaceutical, and 50% of exercise-based therapy studies. Meta-analyses found pretreatment QST profiles to predicted pain outcomes after TKA (random effects: 0.309, 95% confidence interval [CI]: 0.206-0.405, P < 0.001), NSAIDs (random effects: 0.323, 95% CI: 0.194-0.441, P < 0.001), and exercise-based therapies (random effects: 0.417, 95% CI: 0.138-0.635, P = 0.004). The overall risk of bias for the included studies was low to moderate. This systematic review and meta-analysis demonstrate weak-to-moderate associations between pretreatment QST and pain outcomes after standard OA pain treatments. Based on this work, it is hypothesized that a subset of specific pain sensitive patients with OA exist and that these patients do not respond adequately to standard OA pain treatments.

Arthritis is a chronic inflammatory condition that affects millions of individuals worldwide. The conventional treatment options for arthritis often come with limitations and potential side effects, leading to increased interest in herbal plants as alternative therapies. This article provides a comprehensive overview of the use of herbal plants in arthritis treatment, focusing on their traditional remedies, active components, mechanisms of action, and pharmaceutical approaches for enhancing their delivery. Various herbal plants, including turmeric, ginger, Boswellia, and willow bark, have shown anti-inflammatory and analgesic properties, making them valuable options for managing arthritis symptoms. The active components of these herbal plants, such as curcumin, gingerols, and boswellic acids, contribute to their therapeutic effects. To enhance the delivery of herbal medicines, pharmaceutical approaches like nanoparticle-based drug delivery systems, liposomes, polymeric nanoparticles, nanoemulsions, microneedles, and inhalation systems have been explored. These approaches aim to improve bioavailability, targeted delivery, and controlled release of herbal compounds. Safety considerations, including potential interactions with medications and the risk of allergic reactions, are also discussed. Future perspectives for this field involve conducting well-designed clinical studies, enhancing standardization and quality control measures, exploring novel drug delivery systems, and fostering collaborations between traditional medicine practitioners and healthcare professionals. Continued research and development in these areas will help unlock the full potential of herbal plants in arthritis treatment, offering personalized and effective care for affected individuals.

Ketorolac is one of the most potent nonsteroidal anti-inflammatory drugs commonly used in spine surgery. The purpose of this study is to examine the impact of ketorolac utilization with or without other medications on a patient\'s postoperative course after lumbar surgery.
A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed using PubMed, CINAHL, MEDLINE, and Web of Science in July 2023. Inclusion criteria were RCTs that used ketorolac for lumbar surgery.
Thirteen RCTs were included (N = 997; mean age, 54.6 ± 7.8 years; n = 535 in the ketorolac group) in this systematic review. There was no significant difference in the 24-hour and total postoperative morphine utilization (P = 0.185 and P = 0.109, respectively), 24-hour and final postoperative pain scores (0-10 scale) (P = 0.065 and P = 0.582, respectively), and length of stay at the hospital (P = 0.990) between patients in the ketorolac group and patients in the non-ketorolac group who underwent lumbar surgery. Overall, patients had similar rates of major complications (3.7% vs. 5.4%) and minor complications (42.1% vs. 51.7%) between groups after lumbar surgery. However, patients in the ketorolac group had a significantly lower rate of nausea and/or vomiting compared with the non-ketorolac group after lumbar surgery (21.6% vs. 37.1%, respectively; P = 0.018).
There is no significant difference in 24-hour and total postoperative morphine utilization, pain scores, or length of stay, with similar complication rates after lumbar surgery between patients receiving ketorolac and patients not receiving ketorolac via meta-analysis of RCTs.

Several studies have suggested that the mucosal protective effects of proton pump inhibitors (PPIs) do not extend beyond the duodenum; however, PPIs may cause lower gastrointestinal (LGI) injury, although these relationships have not yet been fully elucidated.
We searched all the relevant studies published until September 2022 that examined the risk of PPIs for LGI bleeding. We performed a meta-analysis of the risk of LGI bleeding (small bowel (SB) or colorectal bleeding) between PPI users and non-users. A subgroup analysis of patients consuming aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) was also performed.
Twelve studies with 341,063 participants were included in this meta-analysis. The use of PPIs was associated with the risk of LGI bleeding (odds ratio [OR] [95% confidence interval [CI]] = 1.42 [1.16-1.73]; hazard ratio [HR] [95% CI] = 3.23 [1.56-6.71]). An association between PPI use and the risk of LGI bleeding was also identified in the subgroup of aspirin or NSAID users (OR [95% CI] = 1.64 [1.49-1.80]; HR [95% CI] = 6.55 [2.01-21.33]). In the bleeding site-specific analyses, the risk of SB bleeding was associated with PPI use (OR [95% CI] = 1.54 [1.30-1.84]).
PPI use was associated with an increased risk of LGI bleeding, particularly SB bleeding. This association was particularly pronounced among aspirin and NSAID users. Inappropriate PPI prescriptions should be avoided in patients with LGI bleeding and a low risk of upper gastrointestinal disease.

While opioids are part of usual care for analgesia in the ICU, there are concerns regarding excess use. This is a systematic review of nonsteroidal anti-inflammatory drugs (NSAIDs) use in postoperative critical care adult patients.
METHODS: We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, trial registries, Google Scholar, and relevant systematic reviews through March 2023.
METHODS: Titles, abstracts, and full texts were reviewed independently and induplicate by two investigators to identify eligible studies. We included randomized control trials (RCTs) that compared NSAIDs alone or as an adjunct to opioids for systemic analgesia. The primary outcome was opioid utilization.
METHODS: In duplicate, investigators independently extracted study characteristics, patient demographics, intervention details, and outcomes of interest using predefined abstraction forms. Statistical analyses were conducted using Review Manager software Version 5.4. (The Cochrane Collaboration, Copenhagen, Denmark).
RESULTS: We included 15 RCTs (n = 1,621 patients) for admission to the ICU for postoperative management after elective procedures. Adjunctive NSAID therapy to opioids reduced 24-hour oral morphine equivalent consumption by 21.4 mg (95% CI, 11.8-31.0 mg reduction; high certainty) and probably reduced pain scores (measured by Visual Analog Scale) by 6.1 mm (95% CI, 12.2 decrease to 0.1 increase; moderate certainty). Adjunctive NSAID therapy probably had no impact on the duration of mechanical ventilation (1.6 hr reduction; 95% CI, 0.4 hr to 2.7 reduction; moderate certainty) and may have no impact on ICU length of stay (2.1 hr reduction; 95% CI, 6.1 hr reduction to 2.0 hr increase; low certainty). Variability in reporting adverse outcomes (e.g., gastrointestinal bleeding, acute kidney injury) precluded their meta-analysis.
CONCLUSIONS: In postoperative critical care adult patients, systemic NSAIDs reduced opioid use and probably reduced pain scores. However, the evidence is uncertain for the duration of mechanical ventilation or ICU length of stay. Further research is required to characterize the prevalence of NSAID-related adverse outcomes.

BACKGROUND: The oral route of drug delivery is the most widespread and preferred route of administration, but it has several limitations, including variable pharmacokinetics (PK), reduced dissolution and absorption, and gastrointestinal irritation. Further, many compounds have low aqueous solubility, which also limits intestinal absorption.
METHODS: For this narrative review, we conducted a literature search of PubMed until August 2022, focusing on emulsions, microemulsions, nanoemulsions, and self-emulsifying drug delivery systems.
RESULTS: The self-microemulsifying drug delivery system (SMEDDS) overcomes these limitations of hydrophobic compounds to enhance their bioavailability. A SMEDDS formulation is a clear, thermodynamically stable, oil-in-water emulsion of lipid, solubilized drug, and two surfactants, which spontaneously forms droplets < 100 nm in diameter. These components help deliver presolubilized drugs to the gastrointestinal tract, while protecting them from degradation in gastric acid or first-pass hepatic metabolism. SMEDDS formulations have improved oral drug delivery in the treatment of cancer (paclitaxel), viral infections (ritonavir), and migraine headache (ibuprofen and celecoxib oral solution). The American Headache Society recently updated their consensus statement for the acute treatment of migraine and included a selective cyclo-oxygenase-2 selective inhibitor formulated in SMEDDS, celecoxib oral solution. This SMEDDS formulation showed pronounced improvement in bioavailability compared with celecoxib capsules, allowing for a low dose of celecoxib in the oral solution to provide safe and effective acute migraine treatment. Here, we will focus on SMEDDS formulations, what differentiates them from other analogous emulsions as vehicles for poorly soluble drugs, and their clinical application in the acute treatment of migraine.
CONCLUSIONS: Oral drugs reformulated in SMEDDS have shown accelerated times to peak plasma drug concentrations and increased maximum plasma concentrations, compared with capsules, tablets, or suspensions. SMEDDS technology increases both drug absorption and bioavailability of lipophilic drugs, compared with other formulations. Clinically, this allows the use of lower doses with improved PK profiles without compromising efficacy, as shown with celecoxib oral solution for the acute treatment of migraine.