Nonsteroidal Research Articles

Clinical practice for migraine treatment and characteristics of medical facilities and physicians treating migraine: Insights from a retrospective cohort study using a Japanese claims database

The real-world treatment patterns at medical facilities and their physicians’ specialties treating migraine have not been fully investigated in Japan. Therefore, a retrospective cohort study aimed to describe real-world clinical practice and treatment patterns in Japanese patients with migraine according to medical facilities and physicians’ specialties. Anonymized claims data of patients with migraine was obtained from JMDC Inc (January 2018-June 2023). Patient characteristics and treatment pattern according to medical facilities and physicians’ specialties treating migraine were evaluated. Of 231,156 patients with migraine (mean age [SD], 38.8 [11.8] years; females, 65.3%), 81.8% had the first prescription at clinics (CPs), 42.5% underwent imaging tests, 44.4% visited general internal medicine, and 25.9% consulted neurosurgery at initial diagnosis. Imaging tests were carried out at CPs with specialists (59.4%), hospitals (HPs) with specialists (59.1%), HPs (32.9%), and CPs (26.9%) without specialists. Overall, 95.6% received acute treatment while 21.8% received preventive treatment. At facilities with specialists compared to without specialists, triptans were more frequently prescribed (67.9% vs 44.9%) whereas acetaminophen and nonsteroidal anti-inflammatory drugs were less frequently prescribed (52.4% vs 69.2%). Preventive treatment use was higher at facilities with specialists (27.4%) than without specialists (15.7%) and increased annually regardless of the type of medical institution. In Japan, only half of patients with migraine visited facilities with specialists at their first diagnosis, and specialists are more likely use migraine-specific and preventive drugs than nonspecialists. Therefore, there is a need for awareness among migraine patients that they should consult specialists and for enhancement of medical collaboration between specialists and nonspecialists.

Drug-Induced Myocardial Infarction: A Review of Pharmacological Triggers and Pathophysiological Mechanisms

Myocardial infarction (MI) is a significant cardiovascular event caused by the decrease in or complete cessation of blood flow to a portion of the myocardium. It can arise from a variety of etiological factors, including pharmacological triggers. This review aims to explore the diverse drugs and substances that might lead to drug-induced myocardial infarction, focusing on their mechanisms of action and the pathophysiological processes involved. Various established and emerging pharmacological agents that could elevate the risk of myocardial infarction, such as nonsteroidal anti-inflammatory drugs, hormonal therapies, anticoagulants, and antipsychotic medications, are discussed. The role of drug-induced endothelial dysfunction, coronary artery spasm, and thrombosis are presented in order to highlight the underlying mechanisms. This review emphasizes the need for increased awareness among healthcare professionals to mitigate the risks associated with different pharmacological therapies to improve patient outcomes.

Anesthetic- and Analgesic-Related Drugs Modulating Both Voltage-Gated Na+ and TRP Channels

Nociceptive information is transmitted by action potentials (APs) through primary afferent neurons from the periphery to the central nervous system. Voltage-gated Na+ channels are involved in this AP production, while transient receptor potential (TRP) channels, which are non-selective cation channels, are involved in receiving and transmitting nociceptive stimuli in the peripheral and central terminals of the primary afferent neurons. Peripheral terminal TRP vanilloid-1 (TRPV1), ankylin-1 (TRPA1) and melastatin-8 (TRPM8) activation produces APs, while central terminal TRP activation enhances the spontaneous release of L-glutamate from the terminal to spinal cord and brain stem lamina II neurons that play a pivotal role in modulating nociceptive transmission. There is much evidence demonstrating that chemical compounds involved in Na+ channel (or nerve AP conduction) inhibition modify TRP channel functions. Among these compounds are local anesthetics, anti-epileptics, α2-adrenoceptor agonists, antidepressants (all of which are used as analgesic adjuvants), general anesthetics, opioids, non-steroidal anti-inflammatory drugs and plant-derived compounds, many of which are involved in antinociception. This review mentions the modulation of Na+ channels and TRP channels including TRPV1, TRPA1 and TRPM8, both of which modulations are produced by pain-related compounds.

Predicting responsiveness to GLP-1 pathway drugs using real-world data

BackgroundMedications targeting the glucagon-like peptide-1 (GLP-1) pathway are an important therapeutic class currently used for the treatment of Type 2 diabetes (T2D). However, there is not enough known about which subgroups of patients would receive the most benefit from these medications.ObjectiveThe goal of this study was to develop a predictive model for patient responsiveness to medications, here collectively called GLP-1 M, that include GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP4) inhibitors (that normally degrade endogenously-produced GLP-1). Such a model could guide clinicians to consider certain patient characteristics when prescribing second line medications for T2D.MethodsWe analyzed de-identified electronic health records of 7856 subjects with T2D treated with GLP-1 M drugs at Vanderbilt University Medical Center from 2003–2019. Using common clinical features (including commonly ordered lab tests, demographic information, other T2D medications, and diabetes-associated complications), we compared four different models: logistic regression, LightGBM, artificial neural network (ANN), and support vector classifier (SVC).ResultsOur analysis revealed that the traditional logistic regression model outperforms the other machine learning models, with an area under the Receiver Operating Characteristic curve (auROC) of 0.77.Our model showed that higher pre-treatment HbA1C is a dominant feature for predicting better response to GLP-1 M, while features such as use of thiazolidinediones or sulfonylureas is correlated with poorer response to GLP-1 M, as assessed by lowering of hemoglobin A1C (HbA1C), a standard marker of glycated hemoglobin used for assessing glycemic control in individuals with diabetes. Among female subjects under 40 taking GLP-1 M, the simultaneous use of non-steroidal anti-inflammatory drugs (NSAIDs) was associated with a greater reduction in HbA1C (0.82 ± 1.72% vs 0.28 ± 1.70%, p = 0.008).ConclusionThese findings indicate a thorough analysis of real-world electronic health records could reveal new information to improve treatment decisions for the treatment of T2D. The predictive model developed in this study highlights the importance of considering individual patient characteristics and medication interactions when prescribing GLP-1 M drugs.

Over-prescription of nonsteroidal anti-inflammatory drugs: a potential biological threat in South Asia

Over-prescription of nonsteroidal anti-inflammatory drugs: a potential biological threat in South Asia

Pain and cognitive functions – the battle for cognitive reserve

Back pain and headache are the most common pain syndromes and have a significant impact on patients' quality of life. In the process of pain chronification emotional-affective, cognitive and motivational components can be distinguished. Cognitive impairments (CI), such as attention deficits, memory loss, reduced learning and decision-making abilities, are observed in almost one third of patients with chronic pain. The spectrum of CI in patients with chronic back pain is age-dependent. Primary headaches are also associated with the development of CI. An important measure to prevent CI in chronic pain is effective pain relief. Lornoxicam is a non-steroidal anti-inflammatory drug that acts at different levels of pain formation. The mutual influence of back pain and headache on cognitive function and the maintenance of cognitive potential in the complex treatment of patients are discussed.

Complex treatment of patients with chronic non-specific back pain and comorbid disorders: a prospective clinical study

A complex approach including an educational program, ergonomics, kinesiotherapy and pharmacotherapy is effective in the treatment of patients with chronic non-specific back pain (CNBP). The efficacy of complex treatment with personalized kinesiotherapy in patients with CNBP and comorbid disorders has not yet been sufficiently investigated.Objective: to evaluate the efficacy of a complex treatment including special kinesiotherapy, standard pharmacological and non-pharmacological methods in patients with CNBP and comorbid disorders.Material and methods. The study included 60 patients (12 men and 48 women, mean age 38.3±8.7 years) with CNBS and comorbid disorders (neck pain, insomnia, tension type headaches, anxiety and/or depressive symptoms). Patients were randomized into two groups: group 1 received complex treatment, including special kinesiotherapy, standard therapy (educational program, standard kinesiotherapy, non-steroidal anti-inflammatory drugs, muscle relaxers, antidepressants in some patients), group 2 – standard therapy. The clinical and psychological parameters of all patients were analyzed at baseline, and after 1, 3 and 6 months of treatment.Results. After 1 month of treatment, the clinical effect (CE) in terms of CNBS (reduction of back pain (BP) intensity according to the numerical rating scale and Oswestry questionnaire by 30% or more) was achieved in 80% of patients in group 1, which is statistically significantly (p<0.05) higher than in group 2 (46.7% of patients). By month 3 of observation, the number of patients achieving CE increased to 86.7% in group 1 and decreased to 36.6% in group 2. After 6 months, all patients in group 1 maintained the achieved CE, while in group 2 only 30% of patients maintained CE. In group 1, a complete regression of BP was observed in more than one third of patients at month 3 and 6 of observation (33.3 and 36.6%, respectively). In group 2, no regression of BP was observed in any case. In group 1, in contrast to group 2, a statistically significant (p<0.05) decrease in scores on the Beck Pain Catastrophizing Scale, the Kinesiophobia Scale, Beck Anxiety and Depression Scale, the Insomnia Severity Index, Headache Impact Index and Neck Pain Disability Index was observed. The decrease continued until the 6th month of observation.Conclusion. A complex treatment comprising special kinesiotherapy, standard non-drug and drug therapy leads to a rapid (after 1 month) positive effect in patients with CNBP and comorbid disorders that lasts over a long period of time (6 months).

Cross-sectional observation of self-medication pattern among readymade garment workers in southern Bangladesh and their knowledge and practice towards antibiotic self-medication

ObjectivesThis study aimed to assess the prevalence of self-medication practices and explore knowledge and practices related to antibiotic use among readymade garment (RMG) workers in Bangladesh.Study designThis large-scale cross-sectional survey was conducted among garment workers in three different garment factories in Chattogram, Bangladesh.MethodsData were collected from 1743 participants, using a pretested semi-structured questionnaire. Descriptive and regression analyses were performed to examine sociodemographic factors, medication patterns, and antibiotic knowledge and practices among the workers.ResultsA significant proportion of the participants (42.4%) only had a primary level of education and majority (80.3%) were not engaged in lifestyle habits such as smoking, drinking alcohol, or chewing betel leaves (80.3%). Cough, cold, and fever were the most reported health complications (66.0%). Most of the participants obtained their medications from pharmacies (66.4%). Self-medication was reported by 93.4% of them, with 55.9% practiced it thinking the disease was not severe. Poor knowledge and practice levels about antibiotics were observed. Gender and educational background influenced the participants' knowledge, while the presence of common diseases affected the practice score.ConclusionThe study demonstrated a high prevalence of self-medication practices among garment workers in Bangladesh, particularly with nonsteroidal anti-inflammatory drugs (NSAIDs). The findings suggest developing interventions to improve knowledge and practices related to antibiotic use and promote responsible self-medication practices among garment workers to mitigate potential risks and adverse effects.

Association of Therapies for Axial Spondyloarthritis on the Risk of Hip and Spine Fractures.

People with axial spondyloarthritis (axSpA) have increased fracture risk relative to the general population, possibly related to chronic inflammation. We assessed the impact of treatment with tumor necrosis factor inhibitors (TNFi) and non-biologic conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on hip and spine fractures in axSpA, relative to nonsteroidal anti-inflammatory drugs (NSAIDs). We conducted a nested case-control study using 2006-2021 data from the MerativeTM MarketScan® Database. We included adults 18-65 years old with ≥1 inpatient or ≥2 outpatient axSpA ICD-9 or 10 diagnosis codes separated by ≥7 days. The primary outcome was hip and/or spine fracture, defined by ICD-9 or 10 diagnosis or procedure codes. For each fracture case, we selected up to 10 controls without fracture. We evaluated medication exposure (TNFi, csDMARDs, NSAIDs [referent], or none) hierarchically using pharmacy claims and procedure codes. We assessed the relation of medication exposure with hip and spine fracture risk using unconditional logistic regression with confounder adjustment. Our main analysis included 13,519 individuals with axSpA, comprising 1,229 cases and 12,290 controls. Individuals on TNFi had 29% lower odds of fracture compared to those on NSAIDs (OR 0.71, 95% CI 0.59-0.85), accounting for age, sex, and diagnosis year. Results were similar in the fully adjusted model (OR 0.75, 95% CI 0.62-0.91) and when stratified by sex. Using a large US insurance claims database, we found evidence for a protective effect of TNFi on fracture risk in axSpA underscoring a potential impact of TNFi in diminishing comorbidities linked with axSpA.

Manganese(II) Complexes with Non-Steroidal Anti-Inflammatory Drugs: Structure and Biological Activity

Nine manganese(II) complexes with a series of non-steroidal anti-inflammatory drugs (namely sodium diclofenac, diflunisal, flufenamic acid, sodium meclofenamate, mefenamic acid, and tolfenamic acid) were prepared in the presence of diverse nitrogen donors, i.e., pyridine, 1,10–phenanthroline, 2,2′–bipyridine and neocuproine, as co-ligands and were characterized with spectroscopic techniques and single-crystal X-ray crystallography. The biological profile of the resultant complexes was investigated regarding their antioxidant potency and their interaction with DNA and serum albumins. The complexes interact with calf–thymus DNA in an intercalative mode and bind tightly and reversibly to human and bovine serum albumins studied. In order to assess the antioxidant activity of the Mn(II) complexes, their ability to scavenge 2,2′–azinobis(3–ethylbenzothiazoline–6–sulfonic acid) free radicals was monitored.

Agarose Hydrogels Enriched by Humic Acids as a Functional Model for the Transport of Pharmaceuticals in Nature Systems

The presence of pharmaceuticals in nature systems poses a threat to the environment, plants, animals, and, last but not least, human health. Their transport in soils, waters, and sediments plays important roles in the toxicity and bioavailability of pharmaceuticals. The mobility of pharmaceuticals can be affected by their interactions with organic matter and other soil and water constituents. In this study, a model agarose hydrogel enriched by humic acid as a representative of organic matter is used as a transport medium for pharmaceuticals. Sulphapyridine (as a representative of sulphonamide antibiotics) and diclofenac (as a representative of widely used non-steroidal anti-inflammatory drugs) were chosen for experiments in diffusion cells. Pharmaceuticals were passed through the hydrogel from the donor solution to the acceptor compartment and could interact with humic acids incorporated in the hydrogel. The lag time was prolonged if the hydrogel was enriched by humic acids from 134 to 390 s for sulphapyridine and from 323 to 606 s for diclofenac. Similarly, the incorporation of humic acids in the hydrogel resulted in a decrease in the determined diffusion coefficients. The decrease was stronger in the first stage of the experiment when diffusing particles could interact with vacant binding sites.

Clinical characteristics and prognostic factors of COVID-19 in rheumatic patients and their family members: a retrospective study

BackgroundPatients with rheumatic diseases who receive long-term treatment with steroids, immunosuppressants, or biologics are more susceptible to infection with pathogens than the general population. In order to explore the differences in clinical features and prognosis of Corona Virus Disease 2019 (COVID-19) infection between patients with rheumatic diseases and the general population (family members), a retrospective investigative study was used to analyze the differences between the two populations.MethodsThe study was conducted in 13 Grade A Tertiary hospitals in China to investigate the clinical symptoms and prognostic factors of patients with rheumatic diseases who were infected with COVID-19 for the first time and their families.ResultsA total of 2,889 participants were included in this study, including 1,530 patients with rheumatic diseases and 1,359 family members. In terms of clinical symptoms, the complete recovery time from COVID-19 for patients with rheumatic disease patients was 13 days (8.00, 18.00), which was shorter than that of family members (16 days, 11.00, 20.00). The risk of developing moderate to severe cases of COVID-19 was lower in patients with rheumatic disease than in their family members (OR=0.511, P=0.0026). Compared with non-use of non-steroidal anti-inflammatory drugs (NSAIDs), the risk of developing mild cases of COVID-19 was 0.595 times greater with pre-infection use of NSAIDs (P = 0.0003). The use of glucocorticoids and Chinese herbal decoctions before infection increased the probability of developing mild cases of COVID-19 (OR=1.537, 1.773, P<0.05). The risk of developing moderate to severe cases with disease-modifying anti-rheumatic drugs (DMARDs) used before infection was 0.350 times that without such drugs (P<0.001). In terms of prognosis, compared with family members, the complete recovery time of patients with rheumatic diseases was reduced by 2.241 days on average (P<0.001), and the complete recovery time of patients with mild rheumatism was reduced by 4.178 days on average (P<0.001). There was no significant difference in the complete recovery time from COVID-19 in patients with severe rheumatism compared with their family members (P=0.1672). The use of NSAIDs, glucocorticoids, DMARDs, biologics, Chinese patent medicine, and Chinese herbal decoctions during the infection period could shorten the recovery time of COVID-19 symptoms (P<0.05).ConclusionsCompared with their family members, patients with rheumatic diseases had milder symptoms after infection with COVID-19, which was related to the use of glucocorticoids, DMARDs, and Chinese herbal decoctions before infection. During the COVID-19 infection phase, the use of NSAIDs, glucocorticoids, DMARDs, biologics, Chinese patent medicine, and Chinese herbal decoctions might shorten the recovery time from symptoms of COVID-19.Chinese clinical trial registryChiCTR2300072679

Optimizing acute pain management in oral surgery: Current strategies and emerging approaches

Effective pain management in oral surgery is crucial to improving patient outcomes and satisfaction. Acute pain, a common result of oral surgical procedures such as extractions, implant placements, and bone grafting, can significantly impact patient recovery. However, pain control remains a complex challenge due to individual variability in pain perception, pre-existing medical conditions, and the inherent invasiveness of certain procedures. This article reviews current approaches to acute pain management in oral surgery, focusing on multimodal analgesia, pharmacological interventions, and non-pharmacological techniques. Traditional strategies such as non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and local anesthetics are discussed alongside newer alternatives, including nerve blocks, patient-controlled analgesia, and adjunct therapies like mindfulness and cryotherapy. The role of personalized pain management plans, which consider patient-specific factors, is explored to minimize side effects and enhance recovery. Advances in minimally invasive techniques, laser therapy, and alternative methods for reducing post-operative pain are also examined. Recent research highlights the importance of reducing opioid dependency while balancing the need for effective pain control. Future directions for pain management, such as precision medicine approaches and the use of digital health technologies for pain monitoring, are also discussed. The article concludes by emphasizing the need for a balanced, patient-centered approach to acute pain management in oral surgery, integrating both traditional and emerging strategies.

Non-steroidal anti-inflammatory drugs for osteoarthritis and non-specific back pain: basic provisions for effective and safe use (Interdisciplinary consensus)

The interdisciplinary council of leading experts has presented recommendations for the effective and safe use of non-steroidal anti-inflammatory drugs in osteoarthritis and non-specific back pain in general outpatient practice.

Reusable Ni-immobilized MOF Catalyst for Dehydrogenation of N-heterocycles Under Milder Conditions.

Herein, we have demonstrated the design and synthesis of a novel Ni-immobilized MOF as heterogeneous catalyst for the dehydrogenation of N-heterocycles. A series of five and six-member N-heteroarenes bearing one or more heteroatoms were synthesized in up to 98% yield (> 33 examples). Late stage functionalization to the synthesis of b-glucuronides inhibitor, antimalarial drug quinine, and the nonsteroidal anti-inflammatory drug (NSAID) indomethacin were obtained under milder reactions conditions. A series of mechanistic studies revealed the detection of H2 and H2O2 during the progress of the reactions and suggested the involvement of enamine-imine intermediate species for sequential dehydrogenation. Detailed characterization of the fresh catalyst and reused catalyst were performed using SEM, TEM, BET, PXRD, and EDX elemental mappings. The catalyst could be recycled up to four-times without much loss in catalytic activities. In-situ formed defects, pore size enlargement and additional Lewis acid sites within catalyst nanocrystals assisted in attaining high activity and selectivity to N-heteroarenes.

In Vitro Protective Effects of a Standardized Extract of Opuntia ficus-indica (L.) Mill. Cladodes and Olea europaea L. Leaves Against Indomethacin-Induced Intestinal Epithelial Cell Injury

Nonsteroidal anti-inflammatory drugs (NSAIDs) can induce serious adverse effects in gastrointestinal (GI) mucosa, increasing intestinal permeability and leading to mitochondrial dysfunction, oxidative stress, apoptosis and inflammation. As proton pump inhibitors are effective in protecting against NSAID-induced gastropathy but not NSAID-induced enteropathy, current research is focused on natural products as protective substances for therapy and prevention of intestinal injury. Herein, through the use of an in vitro model based on intestinal epithelial cell (Caco-2) damage caused by indomethacin (INDO), we examined the protective activity of a commercially available standardized extract (OFI+OE) from Opuntia ficus-indica (L.) Mill. cladodes and Olea europaea L. leaves. Pre-treatment with OFI+OE prevented INDO-induced intestinal epithelial barrier damage, as demonstrated by TEER measurement, fluorescein permeability, and tight junction protein expression. The extract showed positive effects against INDO-induced oxidative stress and correlated activation of apoptosis, decreasing pro-apoptotic markers BAX and Caspase-3 and increasing anti-apoptotic factor Bcl-2. Moreover, the extract inhibited the NF-κB pathway and pro-inflammatory cascade. In conclusion, these data support the use of OFI+OE extract as a natural strategy for therapy and prevention of intestinal mucosal damage, demonstrating its beneficial effects against INDO-induced intestinal damage, through modulation of oxidative, apoptotic, and inflammatory pathways.

Canis lupus familiaris and diclofenac: understanding the potential risks of this association

In many homes worldwide, dogs are considered part of the family. Every possible care is given to animals, including drug treatments. However, many animal guardians, in an attempt to minimize pain or improve the quality of life of their dogs, provide drugs without a veterinarian’s prescription. Diclofenac, a non-steroidal anti-inflammatory drug that acts on cyclooxygenase-1 and cyclooxygenase-2 enzymes, is associated with several adverse events, especially related to the gastrointestinal tract, both in humans and pet animals. Therefore, the availability of information about the effects of this drug in different species is always essential. This narrative review aims to present adverse reactions the domestic dog (Canis lupus familiaris) can suffer when exposed to diclofenac. Scientific publications, books, and case reports were consulted, and inquiries were also carried out with regulatory agencies. Many reports of suspected adverse reactions, especially related to the gastrointestinal tract, were found. Other clinical manifestations and lesions were also identified in the cardiovascular system, liver, kidneys, and hematological examinations. Therefore, diclofenac may constitute a hazard to dogs, mainly due to possible damage to the gastrointestinal tract. This fact reinforces the need to seek veterinary advice before providing any drug to animals, in addition to recommendations on ensuring the correct storage of medications to avoid accidental exposure.

Arthroscopy combined with bone tunnel technique for treating Berndt and Harty stage III or IV osteochondral lesions of the talus.

To explore the efficacy and feasibility of arthroscopy combined with bone tunnel technique in treating Berndt and Harty stage III or IV osteochondral lesions of the talus (OLT). A retrospective analysis was conducted on the clinical data of 21 patients with Berndt and Harty stage III or IV OLT who underwent surgical treatment at our institution from September 2017 to September 2022. Under arthroscopy, the displaced talar osteochondral lesion was restored. A 2.0mm Kirschner wire (K-wire) was used to create a bone tunnel from the medial (or lateral) malleolus to the realigned osteochondral lesion. A 1.5mmK-wire was then used to drill through this tunnel into the osteochondral fragment, and a 1.5mm absorbable bone rod was inserted for fixation. Preoperative and final follow-up visual analogue scale (VAS) for pain and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale were recorded and compared. All 21 patients were followed up for an average of 23.95 ± 6.01months. All wounds healed by primary intention, with no nerve, blood vessel, or tendon injuries. All osteochondral lesions healed, with an average healing time of 3.71 ± 0.62months. The VAS score decreased from a preoperative average of 5.38 ± 0.59 to 0.48 ± 0.51 at the final follow-up. The AOFAS ankle-hindfoot scale increased from a preoperative average of 56.29 ± 5.98 to 88.43 ± 2.68 at the final follow-up (P < 0.05), showing statistically significant differences. Two cases experienced medial pain after 12months, which was tolerable with non-steroidal anti-inflammatory drugs. Arthroscopy combined with bone tunnel technique for treating Berndt and Harty stage III or IV OLT has the advantages of minimal injury, visualization of fracture reduction, and fewer complications.

Marginal ulcer causing anastomotic perforation and delayed penetration following one anastomosis gastric bypass

We report the rare clinical case of perforation and delayed penetration of an ulcer at the gastro-jejunal anastomosis following 14 months after laparoscopic one anastomosis gastric bypass in a young female patient. No significant ulcer predictors at baseline: a chronic ulcer formed within the first six months after one anastomosis gastric bypass against the background of continued proton pump inhibitor therapy, regardless of smoking, helicobacter infection or use of non-steroidal anti-inflammatory drugs. Initially the patient underwent the laparotomy with perforation suturing and Roux-jejunojejunostomy formation to exclude the bile reflux into the gastric pouch. The result of the first surgery (non-healing ulcer with the development of delayed penetration six months later) is agree with the recent literature about the possible overstatement of the role of biliary reflux in ulcer formation after one anastomosis gastric bypass. The follow-up surgery was performed by the laparoscopic approach in condition of pronounced adhesion process in abdominal cavity and included adhesiolysis, resection of the gastric pouch with the anastomosis and reconstructive Roux-Y-gastric bypass. Clinical and endoscopic evaluation of the result of the reconstructive surgery 10 months after indicates the patient's recovery.

Self-Cascade API Nanozyme for Synergistic Anti-Inflammatory, Antioxidant, and Ferroptosis Modulation in the Treatment of Corneal Neovascularization.

Corneal neovascularization is a common pathological ocular change that can severely impairs vision, potentially leading to blindness. Although steroids and non-steroidal anti-inflammatory drugs are the primary treatments, their side effects, such as ocular hypertension, eye irritation, and corneal lysis, limit their widespread use. In the present study, an active pharmaceutical ingredient (API) nanozyme (PC-DS NE) is developed through the metal-organic coordination of ferrous sulfate with the anti-inflammatory agent diclofenac sodium and the natural antioxidant proanthocyanidin. PC-DS NE exhibited a spheroid morphology with a particle size of 39.7 ± 5.2 nm, and could achieve the short-term release of diclofenac sodium and sustained release of proanthocyanidin. Notably, the PC-DS NE possessed favorable biocompatibility, self-cascade redox regulation capacity, and significant anti-inflammatory activity. In corneal alkali burn experiments, PC-DS NE effectively inhibited corneal neovascularization by scavenging reactive oxygen species, inhibiting the expression of inflammatory cytokines and pro-angiogenic factors, and down-regulating ferroptosis. These synergistic effects highlighted the potential of PC-DS NE as a promising treatment for ocular inflammatory diseases.