Multinuclear complexes are metal compounds featured by adjacent bound metal centers that can lead to unconventional reactivity. Some M2L4-type paddlewheel dinuclear complexes with monoanionic bridging ligands feature promising properties, including therapeutic ones. Molybdenum has been studied for the formation of multiple-bonded M2+ compounds due to their unique scaffold, redox, and spectroscopic properties as well as for applications in several fields including catalysis and biology. These latter are much less explored and only sporadic studies have been carried out. Here, a series of four dimolybdenum (II,II) carboxylate paddlewheel complexes were synthesized using different Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) as ligands. The reaction of (NH4)5[Mo2Cl9]·H2O with the selected NSAIDs in methanol produced the complexes Mo2(μ-O2CR)4 where RCO2 is ibuprofen (1), naproxen (2), aspirin (3) and indomethacin (4). The products were obtained in good yields and extensively characterized with integrated techniques. Stability and solution behaviour were studied using a mixed experimental and computational approach. Finally, the biological activity of 1 and 3 (i.e. the most reactive and the most stable compounds of the series, respectively) was preliminarily assessed confirming the disassembling of the molecules in the biological milieu. Overall, some very interesting results emerged for these unconventional compounds from a mechanistic point of view.

BACKGROUND: Headaches are a common condition seen in the Emergency Department (ED), with numerous trials focused on improving care for these patients. However, there is limited recent large-scale, robust data available on the incidence, admission rates, evaluation, and treatment in the ED setting.
METHODS: This was a cross-sectional study of ED presentations for headache from 1/1/2016 to 12/31/2023 using the Epic Cosmos national database. All ED visits with headache-relevant ICD-10 coding were included. Outcomes included percentage of total ED visits, admission rates, computed tomography (CT) brain imaging, lumbar puncture (LP) performance, and medication administration. Medications were analyzed by class (NSAIDs, acetaminophen, dopamine antagonists, diphenhydramine, opioids, intravenous fluids, caffeine, and magnesium sulfate). Subgroup analyses were performed by specific types of dopamine antagonists.
RESULTS: Of 188,482,644 ED encounters, 6,007,090 (3.2%) were due to headache. Of these, 246,082 (4.1%) were admitted. Nearly half (46.6%) of patients received at least one CT. Rates of CT head without contrast increased from 38.2% to 47.9% over time, while rates of CT angiography rose from 2.8% to 10.2%. 1.4% of all patients received an LP, with rates decreasing from 1.8% to 1.1% over time. The most common medication was NSAIDs (45.3%), followed by dopamine antagonists (44.8%), diphenhydramine (38.1%), acetaminophen (24.8%), opioids (16.3%), magnesium sulfate (0.2%), and caffeine (0.1%). 50.8% of patients received intravenous fluids. Rates of opioids declined over time, while dopamine antagonists, acetaminophen, and intravenous fluid administration increased.
CONCLUSIONS: Headaches represent a common reason for ED presentation, with approximately 4% of patients being admitted. Imaging is frequently performed, with rises in CT without contrast and CT angiography rates over time, while LP rates have been declining. NSAIDs remain the most common medication given, with opioids declining over time while non-opioid agents such as dopamine antagonists have increased. These findings can help inform health policy initiatives, such as those focused on radiologic imaging and evidence-based medication administration.

UNASSIGNED: Although abdominal pain is one of the major criteria to diagnose acute pancreatitis (AP), there are no standardized guidelines to treat this troublesome symptom in the hospital setting. The aims of the study are to conduct a meta-analysis and to assess the efficacy of nonopioids vs opioids for pain management in AP.
UNASSIGNED: We searched the medical literature through May 2021 to identify randomized controlled trials that examined the efficacy of opioids with nonopioids in AP pain management. Efficacy was reported as odds ratio (OR) with 95% confidence intervals (CIs) of each comparison tested.
UNASSIGNED: We identified 7 eligible randomized controlled trials, containing 389 patients. No significant difference in terms of pain intensity at day 1 (OR 0.82, 95% CI -2.55 to 4.19) was found between opioids and nonopioids. Nonopioids have a significantly high risk of supplementary analgesic use compared with opioids (OR 3.87, 95% CI 1.25-12.04). However, this significance is not seen when comparing nonsteroidal anti-inflammatory drugs and paracetamol with opioids (OR 1.67, 95% CI 0.73-3.82) after excluding trials with procaine. Opioids did not show a significant increase in the complications of pancreatitis, nausea and vomiting, sedation, and deaths when compared with nonopioids.
UNASSIGNED: We found nonopioids, especially nonsteroidal anti-inflammatory drugs and paracetamol, can provide adequate pain relief in patients with AP with no change in supplementary analgesic use and adverse events when compared with opioids. Further research is needed to optimize the use of nonopioids along or in combination with opioids for better pain control in patients with AP.

暂无摘要。

Background: Aspirin is a representative non-steroidal anti-inflammatory drug (NSAIDs) and has been commonly used for the treatment of tendinopathy in clinical practice. In this study, we aimed to evaluate the biomechanical and histological healing effects of aspirin on the healing of the tendon-to-bone interface after rotator cuff tear repair. Methods: A total of 20 male Sprague-Dawley rats were randomly divided into two groups of 10 rats each. Group-C performed repaironly, and group-aspirin treated with aspirin after tendon repair. Group-aspirin rat were intraperitoneally injected with aspirin at 10 mg/kg every 24 h for 7 days. Eight weeks after surgery, the left shoulder of each rat was used for histological analysis and the right shoulder for biomechanical analysis. Results: In the biomechanical analysis, there was no significant difference in load-to-failure (group-C: 0.61 ± 0.32 N, group-aspirin: 0.74 ± 0.91 N; p = .697) and ultimate stress (group-C: 0.05 ± 0.01 MPa, group-aspirin: 0.29 ± 0.43 MPa; p = .095). For the elongation (group-C: 222.62 ± 57.98%, group-aspirin: 194.75 ± 75.16%; p = .028), group-aspirin confirmed a lower elongation level than group-C. In the histological evaluation, the Bonar score confirmed significant differences in collagen fiber density (group-C: 1.60 ± 0.52, group-aspirin: 2.60 ± 0.52, p = .001) and vascularity (group-C: 1.00 ± 0.47, group-aspirin: 2.20 ± 0.63, p = .001) between the groups. Conclusions: Aspirin injection after rotator cuff tear repair may enhance the healing effect during the early remodeling phase of tendon healing.

Osmoprotectant osmolyte and nonsteroidal anti-inflammatory drug (NSAID) coadministration can work synergistically in cancer chemotherapy since most tumors are inflammatory and cancer cells experience osmotic stress. NSAIDs have been shown to inhibit cyclooxygenase (COX) enzymes, which in turn reduces prostaglandin synthesis and prevents inflammation. They also encourage cell death to prevent tumor growth and its spread to other tissues and prevent the construction of new blood vessels, which contributes to the growth of cancer. Taurine belongs to the class of osmolytes since it has been shown to stabilize macromolecular structures and maintain cellular osmotic balance when combined with betaine and glycine. When these drugs are taken together, as opposed to separately, the effectiveness of cancer treatment is increased by increasing cancer cell death and suppressing tumor growth. Notable therapeutic benefits include the reduction of local inflammatory milieu by NSAIDs, which promotes tumor development, and the protection of surviving, normal cells and tissues from treatment-induced damage caused by cancer. By enhancing this synergy, side-effect risk can be decreased and treatment outcomes improved in terms of quality. Put another way, peptides can increase the therapeutic index of NSAIDs in cancer patients by preventing cell damage, which may lessen the gastrointestinal (GI), cardiovascular (CV), and renal side effects of the drug. However, there are drawbacks because using NSAIDs for an extended period of time is linked to serious side effects that call for strict supervision. More research is required because the usefulness and significance of osmolytes in cancer therapy are still very unclear, if not fragmented. In addition, people who live in places with limited resources may find it difficult to afford the possible expenditures associated with osmolytes and selective cyclooxygenase-2 (COX-2) inhibitors. Only the molecular mechanisms of the two drugs\' interactions, the appropriate dosages for combination therapy, and clinical trials to validate the efficacy and safety of this dosage should be the focus of future research. The request is inviting because it presents hope for an extremely successful antiviral strategy; nevertheless, in order to implement this approach successfully, it is likely to be necessary to create affordable formulations and scalable solutions that do not necessitate excessive treatment regimen individualization. Due to their complementary capacities to demonstrate anti-inflammatory and cytoprotective effects, Akta and 5-aminosalicylic acid (5-ASA) administration may thus represent a significant advancement in the treatment of cancer.

OBJECTIVE: To describe the use of non-steroidal anti-inflammatory drugs (NSAID), opioids, and physiotherapy (PT) among persons with newly diagnosed knee or hip osteoarthritis (OA) with and without NSAID contraindications or precautions.
METHODS: We used population-based register data to identify adults aged ≥35 as of January 1, 2014, residing in Skåne region (Sweden) between 2004 and 2013, without a previous knee or hip OA diagnosis. Among this cohort, we identified people with incident knee or hip OA diagnosis between 2014 and 2018 and the presence of contraindications to or precautions for oral NSAIDs at the time of OA diagnosis. We estimated the risk of 1) regular oral NSAID use, 2) regular opioid use, and 3) PT during the first year after diagnosis among those with vs. without contraindications or precautions using confounder-adjusted logistic regression with standardization.
RESULTS: We identified 35,173 persons with newly diagnosed OA, of whom 3257 and 8351 had ≥1 contraindication to oral NSAIDs and ≥1 precaution, respectively. Overall, 27% of individuals used oral NSAIDs (with or without opioids or PT), 10% used opioids, and 57% attended PT. Among patients with contraindications, 21% used oral NSAIDs compared to 31% without (absolute adjusted difference -0.06 (95% CIs: -0.08, -0.05)), 53% vs 59% used PT (adjusted difference -0.03 (-0.05, -0.01)), while 14% vs. 8% had prescribed dispensed opioids (adjusted difference 0.02 (0.01, 0.03)). Similar results were observed for those with precautions.
CONCLUSIONS: We highlight the need for safer treatment options. People with OA and contraindications/precautions to NSAIDs have a higher risk of opioid use, slightly lower risk of PT use, and continue to be prescribed NSAIDs.

OBJECTIVE: Opioids remain the mainstay of analgesia for critically ill patients, but its exposure is associated with negative effects including persistent use after discharge. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be an effective alternative to opioids with fewer adverse effects. We aimed to describe beliefs and attitudes towards the use of NSAIDs in adult intensive care units (ICUs).
METHODS: Our survey of Canadian ICU physicians was conducted using a web-based platform and distributed through the Canadian Critical Care Society (CCCS) email distribution list. We used previously described survey development methodology including question generation and reduction, pretesting, and clinical sensibility and pilot testing.
RESULTS: We received 115 completed surveys from 321 CCCS members (36%). Nonsteroidal anti-inflammatory drugs use was most described as \"rarely\" (59 respondents, 51%) with the primary concern being adverse events (acute kidney injury [108 respondents, 94%] and gastrointestinal bleeding [92 respondents, 80%]). The primary preferred analgesic was acetaminophen (75 respondents, 65%) followed by opioids (40 respondents, 35%). Most respondents (91 respondents, 80%) would be willing to participate in a randomized controlled trial examining NSAID use in critical care.
CONCLUSIONS: In our survey, Canadian critical care physicians did not mention commonly using NSAIDs primarily because of concerns about adverse events. Nevertheless, respondents were interested in further studying ketorolac, a commonly used NSAID outside of the ICU, in critically ill patients.
RéSUMé: OBJECTIF: Les opioïdes restent le pilier de l’analgésie pour les patient·es gravement malades, mais l’exposition à ces agents est associée à des effets négatifs, notamment à leur utilisation persistante après le congé de l’hôpital. Les anti-inflammatoires non stéroïdiens (AINS) pourraient constituer une alternative efficace aux opioïdes avec moins d’effets indésirables. Nous avons cherché à décrire les croyances et les attitudes à l’égard de l’utilisation des AINS dans les unités de soins intensifs (USI) pour adultes. MéTHODE: Notre sondage auprès des médecins intensivistes au Canada a été mené à l’aide d’une plateforme Web et distribué aux personnes sur la liste de distribution électronique de la Société canadienne de soins intensifs (SCSI). Nous avons utilisé une méthodologie d’élaboration d’enquêtes décrite précédemment, y compris la génération et la réduction de questions, les tests préalables, la sensibilité clinique et les tests pilotes. RéSULTATS: Nous avons reçu 115 sondages remplis par 321 membres de la SCSI (36 %). L’utilisation d’anti-inflammatoires non stéroïdiens a été décrite comme « rare » (59 répondant·es, 51 %), la principale préoccupation étant les événements indésirables (insuffisance rénale aiguë [108 répondant·es, 94 %] et saignements gastro-intestinaux [92 répondant·es, 80 %]). Le principal analgésique préféré était l’acétaminophène (75 répondant·es, 65 %), suivi des opioïdes (40 répondant·es, 35 %). La plupart des répondant·es (91 répondant·es, 80 %) seraient prêt·es à participer à une étude randomisée contrôlée examinant l’utilisation des AINS en soins intensifs. CONCLUSION: Dans notre sondage, les médecins intensivistes au Canada n’ont pas mentionné l’utilisation courante d’AINS, principalement en raison de préoccupations concernant leurs effets indésirables. Néanmoins, les répondant·es étaient intéressé·es à étudier plus avant le kétorolac, un AINS couramment utilisé en dehors des soins intensifs, chez les patient·es gravement malades.

UNASSIGNED: The history of any allergy to the medications should be asked by physicians before administration of the medication. The coincidence of allergic and ACS symptoms after a short time of drug administration might be an indicator of Kounis syndrome. Allergic and coronary symptoms should be considered and treated.
UNASSIGNED: Ischemic heart disease is still the leading cause of death worldwide. Some medications, including NSAIDS and antibiotics, can cause allergic reactions with cardiac manifestations due to spasms of the coronary arteries. In this case, we present a patient with chest pain syndrome due to a hypersensitivity reaction caused by an intramuscular (IM) diclofenac injection. The patient was a 51-year-old male who presented to the emergency department complaining of retrosternal chest pain, breathlessness, and pruritis that started half an hour after an IM diclofenac injection he had because of low back pain. The allergic symptoms subsided with an antihistamine injection, but chest pain and dyspnea remained stable. He was admitted due to the presence of ST-segment depression in leads II, III, and AVF and underwent percutaneous coronary angiography, which was normal. The patient was discharged with the diagnosis of Kounis syndrome, and he had an uneventful follow-up 1 year later. Kounis hypersensitivity-associated acute coronary syndrome, especially type I variant coronary spasm due to endothelial dysfunction is a type of acute myocardial syndrome. The following report describes an uncommon case of anaphylaxis-associated Kounis type I syndrome manifesting ST-segment changes in a male patient following an intramuscular injection of diclofenac.

BACKGROUND: Alzheimer\'s disease (AD), the main cause of dementia, is characterized by synaptic loss and neurodegeneration. Amyloid-β (Aβ) accumulation, hyperphosphorylation of tau protein, and neurofibrillary tangles (NFTs) in the brain are considered to be the initiating factors of AD. However, this hypothesis falls short of explaining many aspects of AD pathogenesis. Recently, there has been mounting evidence that neuroinflammation plays a key role in the pathophysiology of AD and causes neurodegeneration by over-activating microglia and releasing inflammatory mediators.
METHODS: PubMed, Web of Science, EMBASE, and MEDLINE were used for searching and summarizing all the recent publications related to inflammation and its association with Alzheimer\'s disease.
RESULTS: Our review shows how inflammatory dysregulation influences AD pathology as well as the roles of microglia in neuroinflammation, the possible microglia-associated therapeutic targets, top neuroinflammatory biomarkers, and anti-inflammatory drugs that combat inflammation.
CONCLUSIONS: In conclusion, microglial inflammatory reactions are important factors in AD pathogenesis and need to be discussed in more detail for promising therapeutic strategies.