Use Of Nonsteroidal Anti-inflammatory Drugs Research Articles

The effect of nonsteroidal anti-inflammatory drug use on soft tissue and bone healing in the knee: a systematic review.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to mitigate pain and inflammation associated with musculoskeletal conditions; however, there is conflicting data on the adverse effects of these drugs on tissue and bone healing. The objective of this study was to investigate the effect of NSAIDs on the healing of knee, soft tissue, and bone. A systematic literature search was conducted across PubMed/MEDLINE, Excerpta Medical Database (Embase)/Ovid, and the Cochrane Central Register of Controlled Trials databases. Clinical, animal, and in vitro studies on the effect of NSAIDs on knee healing were included. Risk of bias assessment was performed using the Cochrane bias assessment tool and Methodological Index for Non-Randomized Studies scoring system for included clinical studies, and the Systematic Review Center for Laboratory Animal Experimentation assessment tool for all included animal studies. General study population characteristics, interventions used, NSAIDs utilized, outcome measures, and study results were analyzed using descriptive statistics. Fifteen articles met the inclusion criteria. Of the 15 studies, there were three clinical, ten animal, and two in vitro studies. In clinical studies, nonselective cyclooxygenase (COX) inhibitors and selective COX-2 inhibitors did not cause a significant increase in failure of anterior cruciate ligament (ACL) reconstructions or meniscal repairs with NSAID administration pre-, peri-, or post-operatively in comparison to placebo or no NSAID administration. Among animal studies assessing COX-2 inhibitor effects on soft tissue, healing was impaired (2/4), delayed but unaffected (1/4), or unaffected (1/4). In animal studies assessing COX-1 inhibitors, ligament healing was either increased (1/4), unaffected (2/4), or impaired (1/4). Meanwhile, administration of non-selective COX inhibitors in animals did not affect soft tissue (3/3) and cartilage (1/1) healing. Two in vitro studies identified a negative outcome on patellar tendon and ACL cell proliferation or viability after non-selective COX inhibition and variable results after selective COX-2 inhibition. Animal studies on postoperative NSAID use after knee surgery suggest that administration of selective and nonselective COX-2 inhibitors may impair healing of soft tissue, bone and tendon-to-bone; however, further clinical studies are needed to better characterize dose and duration dependent risks of NSAIDs.

Clinical Benefits of Oral Anticoagulants for Elderly Patients With Cardioembolic Stroke at High Bleeding Risk.

The relationship between the severity of cardioembolic stroke (CES) and oral anticoagulant (OAC) treatment before stroke onset in very elderly (≥80 years) patients with nonvalvular atrial fibrillation (NVAF) at high bleeding risk remains unknown. A total of 364 consecutive patients (≥80 years) with CES and NVAF within 48 h following stroke onset were investigated. High bleeding risk was defined as follows: Bleeding history, renal dysfunction (creatinine clearance <30 ml/min), low body weight (≤45 kg), and antiplatelet or nonsteroidal anti-inflammatory drug use. Patients were divided into two groups: High bleeding risk (n=214) and non-high bleeding risk (n=150). We assessed stroke severity and functional outcome between the two groups, and evaluated the effect of therapy with direct OAC (DOAC) on stroke severity in the high-risk group. The high-risk group had a worse modified Rankin Scale (mRS) at discharge than the non-high-risk group [median: 4 (range=2-5) vs. 3 (range=1-4); p=0.02]. Patients in the high-risk group were categorized according to OAC treatment before stroke onset: No OAC (n=148), warfarin (n=46), and DOAC (n=20). The numbers of patients with National Institutes of Health Stroke Scale score (NIHSS) ≥8 on admission in these groups were 104 (70%), 30 (65%), and 8 (40%) (p=0.03), respectively. Multivariate analysis confirmed that DOAC therapy had a lower odds ratio (OR) for severe stroke (NIHSS ≥8) on admission (OR relative to no OAC=0.22, 95% confidence interval=0.08-0.62; p=0.005) and poor functional outcome (mRS ≥4) at discharge (OR=0.31, 95% confidence interval=0.11-0.90; p=0.03). Very elderly patients with CES at high bleeding risk have unfavorable functional outcomes. DOAC administration may be associated with reduced stroke severity.

Coexistence of multiple causes in patients with iron deficiency.

The etiology of disorders may be attributable to multiple causal factors simultaneously. This study sought to investigate how frequently, and which causes coexist in patients with iron deficiency. All patients who applied to the Iron Deficiency Outpatient Clinic between January and December 2021 were included in this cross-sectional study. The causes of iron deficiency were extracted from patient files. Analyses were conducted on the entire population as well as three subgroups: women of reproductive age, postmenopausal women, and males. Numbers and frequencies of causes of iron deficiency were calculated. The subgroups were compared using the Jamovi software. The study sample comprised a total of 331 patients. Women of reproductive age were the majority of patients admitted to the clinic (86.7%, n=287). Men represented 6.3% of the sample (n=21), and postmenopausal women accounted for 7.0% (n=23). The mean ages were 37.6±9.05, 49.2±15.49 and 57.8±10.84 years, respectively. The overall sample's rate of multiple iron deficiency causes coexisting was 33.5% (n=111) and the subgroups showed similar frequencies for the coexistence of multiple causes. Statistically, the number of simultaneous multiple causes varied between subgroups (χ2=118, df=10, p<0.001). Heavy menstrual bleeding and nonsteroidal anti-inflammatory drug use were the most common dual causes of multiple coexisting conditions (n=46, 41.4%). In terms of the number of causes, the coexistence of two causes of iron deficiency in women was notable, whereas the coexistence of three causes in males was remarkable. Furthermore, it has been found that some patients have up to five coexisting causes of iron deficiency. Some iron deficiency causes may coexist, and this must be taken into account for the effective management of iron deficiency.

Farmakoterapija hroničnog nekancerskog bola kod odraslih

Chronic non-cancer pain (CNCP) in adults is one of the most common reasons for which patients seek medical help. Chronic pain is present in about 20% of the world's adult population and as a global health problem requires greater attention from every society. Chronic pain has a negative impact not only on the individual but by increasing costs, directly on the health system and indirectly on the economy of the whole society. Its adequate treatment is a human right, and every healthcare system must ensure it. In this regard, great progress has been made with the implementation of chronic pain in the revised ICD-11, which will contribute to changing health policy and focusing more attention on the prevention and treatment of chronic pain worldwide. Integrative pharmacological and nonpharmacological therapeutic approaches with the patient in focus (patient-centric approach) have the strongest evidence of effectiveness; because they reduce not only the intensity of pain but also improve physical, psychological, and social functionality and increase patient satisfaction. Individually tailored balanced pharmacological approaches for different phenotypes of chronic pain (nociceptive, neuropathic, nociplastic) involve the use of nonselective and selective non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, antidepressants, anticonvulsants, other adjuvant therapies and opioid analgesics. These pharmacological approaches based on mechanisms, intensity of pain, and comorbidities, contribute to the optimization of individual therapeutic goals and the maximization of safety and quality of life of persons being treated. Liberalization of opioid prescription in CNCP and inadequate selection and follow-up of patients have contributed to opioid prescription reaching epidemic proportions in the USA, Canada, and some Western European countries and led to the phenomenon of medicalization, iatrogenesis, and fatal outcomes, i.e. opioid crisis. The U.S. Centers for Disease Control (CDC, 2022) guideline for opioid prescribing is summarized in 12 key recommendations based on strong evidence and related to initiation of opioid therapy, opioid selection, dose determination, duration of therapy, monitoring, and assessment of potential side effects from the use of opioids.

Integrated Care Model by the Village Health Volunteers to Prevent and Slow down Progression of Chronic Kidney Disease in a Rural Community, Thailand.

Chronic kidney disease (CKD) is a major health problem in Thailand and health behaviors are central to its risk and progression. Because of the shortage of healthcare personnel, village health volunteers (VHVs) have been collaborating in the primary health care system. However, the contribution of VHVs to CKD reduction has not been evaluated yet. This study aimed to evaluate the efficacy of the VHV-integrated model in preventing and slowing down CKD and its risk factors. The population-based cohort study was conducted in a rural community of Thailand between 2017 and 2019. Baseline clinical and behavioral characteristics including CKD, diabetes, hypertension, and other high-risk factors of the participants were collected. The integrated care model was initiated by the multidisciplinary care team that facilitated, empowered, and trained VHVs targeting risk factors of CKD, health literacy, and health promotion. Then the participants were educated and trained for lifestyle modification and were monitored continuously for 18 months by VHVs. Changes in the CKD risk factors, and kidney functions before and after the application of integrated care model were compared. A total of 831 subjects participated in the study with an average age of 57.5 years, and 69.5% were female. Among them, 222 participants (26.7%) were diagnosed as having CKD, the vast majority (95%) of which were in the early stages (G1-G3 and A1-A2). CKD risk factors such as high salt intake, smoking, alcohol consumption, self-NSAID (non-steroidal anti-inflammatory drugs) use were significantly decreased after application of the care model. Also, hemoglobin A1c was significantly reduced in diabetic patients, and blood pressure was controlled better than before in the hypertensive patients. Most importantly, a decline of estimated glomerular filtration rate of the CKD group was improved and lower than the non-CKD group. The integrated care model through VHV significantly attenuated the risk factors associated with CKD in the general and high-risk population and effectively slowed down the progression of CKD.

Top 4 Research Studies of the month for Italian Primary Care Physicians: December 2023.

This monthly article provides a collection of summaries of the most relevant studies identified as POEMs (patient-oriented evidence that matters) for Italian primary care physicians. 1) According to a high-quality network meta-analysis, oral isotretinoin is the most effective therapy for decreasing the number of inflammatory and non-inflammatory skin lesions in patients with acne vulgaris. 2) Non-steroidal anti-inflammatory drug (Nsaid) use is associated with a small increase (0.004%) in the risk of venous thromboembolism. Combining Nsaid use with a medium-risk hormonal contraceptive increases the risk to 0.011%; the addition of a high-risk hormonal contraceptive increases the risk to 0.023%. 3) For adults who wish to quit smoking, nicotine delivery via e-cigarettes, plus counseling, may be more effective than other means of nicotine replacement, or counseling alone for long-term smoking cessation. 4) We can reassure our patients that nonerosive gastroesophageal reflux disease (Gerd) does not increase the likelihood of esophageal cancer. Erosive Gerd, however, is associated with a doubled - but still low - risk of developing cancer, with the likelihood increasing over time.

Pola Penggunaan Obat Analgetik Antiinflamasi Nonsteroid di Pelayanan Farmasi IGD RSUD. Dr. Pirngadi Medan

Background: Pain is the main reason why patients come to the Emergency Room (IGD) with a prevalence of 78-86%. Non-steroidal anti-inflammatory Drugs (NSAIDs) are widely used to treat mild to moderate inflammatory pain. This study looked at the use of NSAIDs in the emergency room pharmacy services at Dr. Pirngadi Medan. Methods: This non-experimental, retrospective descriptive study was conducted at the Emergency Room Pharmacy Service at Dr. RSUD. Pirngadi Medan from January to June 2019. Results: Of the 11,257 NSAIDs used, mefenamic acid 500 mg three times a day (28.69%), diclofenac sodium 50 mg twice a day (24.96%), meloxicam 75 mg twice a day (2.29%), ketorolac injection 30 mg if needed (42.20%), meloxicam 15 mg suppository (0.07%), and proton suppository (1.79%) were given as needed. Conclusion: The use of NSAIDs in the emergency room at Dr. Pirngadi Medan in the January-June 2019 period had the correct indications, doses, drugs and patients.

Gastric perforation in neonates: Our experience

Background: Neonatal gastric perforation (NGP) is a life-threatening condition with a high mortality rate. It accounts for 7% of all gastrointestinal tract (GIT) perforations. The number of NGP cases has been increasing due to the rise in premature and low birth weight neonates. In this study, we present our experience with gastric perforation in neonates. Methods: This retrospective study analyzed all cases of gastric perforation in neonates that were treated at Loma Linda University Medical Center's Neonatal Intensive Care Unit (NICU) between the years 2000 and 2023. The study looked at several variables including patient demographics, birth weight, age at admission and surgery, comorbidities, use of non-steroidal anti-inflammatory drugs (NSAIDs) and steroids, and mortality rate. Results: We treated 15 patients with neonatal gastric perforation (NGP) during the study tenure. The median age at admission was 2 days, with 67% admitted within that timeframe. Surgery occurred at a median age of 5.5 days, and the median birth weight was 2.075 kg, with 26.67% below 1 kg. Males comprised 67%, and 60% had patent ductus arteriosus. Steroids were given to 46.66%, and 30-day mortality was 26.67%, with higher rates among males. Idiopathic cases were common, with notable etiologies including ischemia, necrosis, and congenital anomalies. Primary surgical repair was the main modality, and perforations occurred at various locations. Two cases had necrotizing enterocolitis. Six patients had favorable outcomes, while others experienced mild to moderate complications. Conclusion: Our research supports the idea that males have a worse outcome in terms of both prevalence and survival rates in neonatal gastric perforation (NGP) patients. However, our findings did not confirm the notion that NGP mortality risk is higher in neonates with low birth weight. We also discovered that the median time between admission and surgery in our study group was 1.5 days, emphasizing the importance of early detection of NGP in neonates. Early diagnosis can lead to better decision-making regarding treatment options and surgical intervention.

RECENT ACHIEVEMENTS IN THE STUDY OF PATHOMECHANISMS OF RHYNOSINUSITIS ASSOCIATED WITH NON-STEROID ANTI-INFLAMMATORS INTOLERANCE (literature review)

Background. The pathomechanism of rhinosinusitis associated with the use of non-steroidal anti-inflammatory drugs is complex and still not fully understood. They are now known to be associated with genetic predisposition and environmental triggers that lead to dysregulation of fatty acid and lipid metabolism, cell transmetabolism, and chronic inflammation in the airways.&#x0D; Aim: analysis of recent advances in the study of aspirin-associated respiratory disease (AERD), summarization of already known information about the pathomechanisms of the disease.&#x0D; Materials and methods. The analysis of literary sources included publications in the international electronic scientometric databases PubMed, Scopus, Web of Science by keywords for the period 2013-2023. 46 sources were selected for analysis, of which 24 were used that met the search criteria.&#x0D; Results. The results showed that researchers are actively studying the role of immunological factors, particularly IgG4 and IgE in the pathogenesis of the disease. IgG4 was detected in nasal polyp tissue and associated with poor postoperative outcome, which may indicate its important role in chronic sinusitis. In addition, cytokines such as thymic stromal lymphopoietin, IL-4, IL-10, IL-5, IL-13, and IL-33 have been detected in eosinophilic nasal polyps in patients with aspirin intolerance, suggesting their possible role in the development AERD.&#x0D; Conclusion. The cause of severe nasal polyposis in AERD has not been definitively determined. Further research may lead to the development of more personalized treatments. Dietary modification and development of new monoclonal antibody drugs lead to reduction of AERD symptoms and improvement of patients' quality of life.

NSAID: Current limits to prescription

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed to alleviate pain and inflammation in conditions like arthritis, migraines, and post-operative recovery. Their mechanism involves inhibiting prostaglandins that contribute to inflammation. NSAIDs are categorized based on their structure, selectivity for COX-1 and COX-2 enzymes, and plasma half-life. They are effective in treating osteoarthritis, spondyloarthritis, and rheumatoid arthritis but might carry an elevated risk of adverse events. Despite their effectiveness, NSAIDs have limitations and risks that warrant cautious consideration. Extensive research has investigated their side effects, and this review aims to examine the current limitations of oral NSAID therapy, including safety profiles, specific scenarios where their use may not be appropriate, and gaps in knowledge. By critically evaluating these aspects, healthcare practitioners can make informed decisions about prescribing NSAIDs, optimizing patient outcomes while minimizing potential risks. This narrative review summarizes existing knowledge and underscores the importance of risk-benefit assessments in NSAID prescribing. Ultimately, the goal is to enhance the rational use of NSAIDs, maximizing benefits while mitigating adverse effects.

Mitochondrial H2O2 Is a Central Mediator of Diclofenac-Induced Hepatocellular Injury.

Nonsteroidal anti-inflammatory drug (NSAID) use is associated with adverse consequences, including hepatic injury. The detrimental hepatotoxicity of diclofenac, a widely used NSAID, is primarily connected to oxidative damage in mitochondria, which are the primary source of reactive oxygen species (ROS). The primary ROS responsible for inducing diclofenac-related hepatocellular toxicity and the principal antioxidant that mitigates these ROS remain unknown. Peroxiredoxin III (PrxIII) is the most abundant and potent H2O2-eliminating enzyme in the mitochondria of mammalian cells. Here, we investigated the role of mitochondrial H2O2 and the protective function of PrxIII in diclofenac-induced mitochondrial dysfunction and apoptosis in hepatocytes. Mitochondrial H2O2 levels were differentiated from other types of ROS using a fluorescent H2O2 indicator. Upon diclofenac treatment, PrxIII-knockdown HepG2 human hepatoma cells showed higher levels of mitochondrial H2O2 than PrxIII-expressing controls. PrxIII-depleted cells exhibited higher mitochondrial dysfunction as measured by a lower oxygen consumption rate, loss of mitochondrial membrane potential, cardiolipin oxidation, and caspase activation, and were more sensitive to apoptosis. Ectopic expression of mitochondrially targeted catalase in PrxIII-knockdown HepG2 cells or in primary hepatocytes derived from PrxIII-knockout mice suppressed the diclofenac-induced accumulation of mitochondrial H2O2 and decreased apoptosis. Thus, we demonstrated that mitochondrial H2O2 is a key mediator of diclofenac-induced hepatocellular damage driven by mitochondrial dysfunction and apoptosis. We showed that PrxIII loss results in the critical accumulation of mitochondrial H2O2 and increases the harmful effects of diclofenac. PrxIII or other antioxidants targeting mitochondrial H2O2 could be explored as potential therapeutic agents to protect against the hepatotoxicity associated with NSAID use.

Acute Corneal Melting Induced by the Concomitant Use of a Non-steroidal Anti-inflammatory Agent with an Antiseptic Eye Drop.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed perioperatively to reduce intraoperative prostaglandin release, diminishing pain, preventing miosis, modulating postoperative inflammation, and reducing the incidence of cystoid macular edema (CME). A 70-year-old female patient without previous history of ocular or systemic disease was urgently referred to our hospital because of a sudden corneal perforation concerning her left eye (OS). The patient had instilled bromfenac eye drops and antiseptic eye drops twice and four times daily, respectively, for 2days only, in preparation of scheduled cataract surgery. Slit-lamp examination revealed diffuse inferior corneal melting with a 1 × 2 mm area of full-thickness perforation and a very shallow anterior chamber. Both topical agents were immediately discontinued. Cyanoacrylate glue was applied to seal the perforation and a bandage contact lens was applied together with a topical antibiotic given hourly. Two hours later, the anterior chamber started to reform. The following day, the anterior chamber was fully reformed with a negative Seidel test. At her next follow-up appointment, 1month later, the glue was detached and the cornea was seen to have successfully healed with only some corneal thinning remaining inferiorly. Perioperative use of topical NSAIDs in combination with antiseptic eye drops may rarely elicit corneal perforation in certain susceptible elderly individuals. Their use should therefore be carefully monitored.

Post-endoscopic retrograde cholangiopancreatography pancreatitis: a review

Endoscopic retrograde cholangiopancreatography (ERCP) has continued to develop over recent decades with regard to both indications for its use and improvements in technique. The most common complication is post-ERCP pancreatitis (PEP) with incidence rates being reported at ~10%. The exact mechanism of PEP is unknown but is likely multifactorial with papillary edema contributing to the activation of the inflammatory cascade playing an important role. Selected risk factors include patient-related factors (female sex, younger age, sphincter of Oddi dysfunction, and history of PEP) and procedure-related factors (difficult cannulation, multiple pancreatic duct guidewire passes, pancreatic acinarization, multiple pancreatic duct contrast injections, and precut sphincterotomy). Several preventative prophylactic strategies have been posited; however, current guidelines recommend the use of rectal non-steroidal anti-inflammatory drugs (NSAIDs), aggressive intravenous (IV) fluid hydration, and pancreatic duct stents. Appropriate patient selection and the use of noninvasive imaging modalities for diagnosis of pancreaticobiliary abnormalities is a key aspect in prevention. Future studies continue to explore various pharmacologic, procedure-related, and combination strategies for prevention and will be important as the use of ERCP continues to grow.

Mitochondrial Stress Links Environmental Triggers with Pro-Inflammatory Signaling in Crohn's Disease.

Inflammatory Bowel Diseases (IBD) are a group of chronic, inflammatory disorders of the gut. The incidence and activity of IBD are determined by both genetic and environmental factors. Among these factors, polymorphisms in genes related to autophagy and the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) have been consistently associated with IBD. We show that NSAIDs induce mitochondrial stress and mitophagy in intestinal epithelial cells. In an altered mitophagy context simulating that observed in IBD patients, NSAID-induced mitochondrial stress leads to the release of mitochondrial components, which act as Danger Associated Molecular Patterns with pro-inflammatory potential. Furthermore, colonic organoids from Crohn's disease patients and healthy donors show activation of the mitochondrial Unfolded Protein Response (UPRmt) upon treatment with ibuprofen. Finally, colon biopsies from Crohn's disease patients in remission or with low-to-moderate activity also show expression of genes involved in UPRmt, while patients with severe activity show no increase compared to healthy donors. Our results suggest the involvement of mitochondria in the mechanisms triggering inflammation in IBD after NSAID use. Moreover, our results highlight the clinical relevance of mitochondrial stress and activation of the UPRmt pathway in the pathophysiology of Crohn's disease.

Investigation of the association of long-term NSAID use with radiographic hip osteoarthritis over four to five years: Data from the OAI and CHECK studies

ObjectiveTo examine the relationship between long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence and progression of radiographic hip osteoarthritis (RHOA), as well as the degeneration of individual radiographic features. MethodsWe analyzed data from the Osteoarthritis Initiative (OAI) and the Cohort Hip and Cohort Knee (CHECK) study. Our exposure was the number of years of NSAID use over a 4-to-5-year follow-up period. Our outcomes were the incidence and progression of RHOA over a 4-to-5-year follow-up as assessed using a modified Croft grade in OAI and the Kellgren-Lawrence (K/L) grade in CHECK. The incidence of RHOA was defined as having RHOA (grade ≥2) at follow-up and investigated in “incidence cohorts” of hips without RHOA at baseline (grade <2). The progression of RHOA was defined as an increase of ≥1 grade at follow-up from baseline and investigated in “progression cohorts” of hips with RHOA at baseline (grade ≥2). Additionally, we assessed the degeneration of nine specific radiographic features, such as joint space narrowing and osteophytes, defined by a grade increase of ≥1 ​at follow-up from baseline, in all cohorts. ResultsIn the incidence cohorts, there were 5153 hips in OAI and 1011 in CHECK; in the progression cohorts, there were 285 and 106 hips, respectively. There was no association between NSAID use and the outcomes investigated. ConclusionOver 4-to-5 years, long-term NSAID use showed no association with the incidence or progression of RHOA, or with the degeneration of individual radiographic features.

Causal effect of gut microbiota on Gastroduodenal ulcer: a two-sample Mendelian randomization study.

Gastroduodenal ulcers are associated with Helicobacter pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). However, the causal relationship between gastroduodenal ulcers and gut microbiota, especially specific gut microbiota, remains unclear. We conducted an analysis of published data on the gut microbiota and Gastroduodenal ulcer using genome-wide association studies (GWAS). Two-sample Mendelian randomization (MR) analysis was performed to determine the causal relationship between gut microbiota and Gastroduodenal ulcer. Sensitivity, heterogeneity, and pleiotropy analyses were conducted to confirm the accuracy of the research findings. Our study showed that the abundance of Enterobacteriaceae, Butyricicoccus, Candidatus Soleaferrea, Lachnospiraceae NC2004 group, Peptococcus, and Enterobacteriales was negatively correlated with the risk of Gastroduodenal ulcer. Conversely, the abundance of Streptococcaceae, Lachnospiraceae UCG010, Marvinbryantia, Roseburia, Streptococcus, Mollicutes RF9, and NB1n was positively correlated with the risk of Gastroduodenal ulcer. MR analysis revealed causal relationships between 13 bacterial genera and Gastroduodenal ulcer. This study represents a groundbreaking endeavor by furnishing preliminary evidence regarding the potentially advantageous or detrimental causal link between the gut microbiota and Gastroduodenal ulcer, employing Mendelian Randomization (MR) analysis for the first time. These discoveries have the potential to yield fresh perspectives on the prevention and therapeutic approaches concerning Gastroduodenal ulcer, with a specific focus on the modulation of the gut microbiota.

Use of non-steroidal anti-inflammatory drugs in renal transplant patients: A retrospective study.

Renal transplanted patients are often prescribed non-steroidal anti-inflammatory drugs (NSAIDs) for analgesic purposes. Considering the dearth of data, we carried out the present study to evaluate the use of various NSAIDs and the incidence of acute kidney injury (AKI) in transplant patients. A retrospective study amongst renal transplant patients prescribed at least one dose of NSAID was carried between January and December 2020 at the Department of Nephrology, Salmaniya Medical Complex, Kingdom of Bahrain. The patients' demographic details, serum creatinine values, and drug-related details were obtained. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used for defining AKI. Eighty-seven patients were included. Forty-three patients were prescribed diclofenac, 60 received ibuprofen, six received indomethacin, 10 were administered mefenamic acid, and 11 received naproxen. Due to multiple courses of NSAID prescription, a total of 70 prescriptions were identified for diclofenac, 80 for ibuprofen, six for indomethacin, 11 for mefenamic acid, and 16 for naproxen. No significant differences were observed in the absolute (p =0.08) and percent changes in serum creatinine (p =0.1) between the NSAIDs. Twenty-eight (15.2%) courses of NSAID therapy met the KDIGO criteria for AKI. Age (OR: 1.1, 95% CI: 1.007, 1.2; p =0.02), concomitant everolimus (OR: 483, 95% CI: 4.3, 54407; p =0.01), and mycophenolate + cyclosporine + azathioprine (OR: 63.4E+006, 95% CI: 203.2157 to 19.8E+012; p =0.005) administration were observed with significant risk of NSAID-induced AKI. We observed possible NSAID-induced AKI to an extent of around 15.2% in our renal transplant patients. No significant differences were observed in the incidence of AKI between various NSAIDs and none of them had either graft failure or death.

Phenotypic and metabolic adaptations of Rhodococcus cerastii strain IEGM 1243 to separate and combined effects of diclofenac and ibuprofen.

The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) has raised concerns regarding their environmental impact. To address this, understanding the effects of NSAIDs on bacteria is crucial for bioremediation efforts in pharmaceutical-contaminated environments. The primary challenge in breaking down persistent compounds lies not in the biochemical pathways but in capacity of bacteria to surmount stressors. In this study, we examined the biodegradative activity, morphological and physiological changes, and ultrastructural adaptations of Rhodococcus cerastii strain IEGM 1243 when exposed to ibuprofen, diclofenac, and their mixture. Our findings revealed that R. cerastii IEGM 1243 exhibited moderate biodegradative activity towards the tested NSAIDs. Cellular respiration assay showed higher metabolic activity in the presence of NSAIDs, indicating their influence on bacterial metabolism. Furthermore, catalase activity in R. cerastii IEGM 1243 exposed to NSAIDs showed an initial decrease followed by fluctuations, with the most significant changes observed in the presence of DCF and the NSAID mixture, likely influenced by bacterial growth phases, active NSAID degradation, and the formation of multicellular aggregates, suggesting potential intercellular synergy and task distribution within the bacterial community. Morphometric analysis demonstrated alterations in size, shape, and surface roughness of cells exposed to NSAIDs, with a decrease in surface area and volume, and an increase in surface area-to-volume ratio (SA/V). Moreover, for the first time, transmission electron microscopy confirmed the presence of lipid inclusions, polyphosphates, and intracellular membrane-like structures in the ibuprofen-treated cells. These results provide valuable insights into the adaptive responses of R. cerastii IEGM 1243 to NSAIDs, shedding light on the possible interaction between bacteria and pharmaceutical compounds in the environment.

Randomized Comparative Study of Analgesic Effects of Ilioinguinal and Iliohypogastric Nerve Block with Levobupivacaine (0.25%) versus Diclofenac Suppository in Pediatric Patients Undergoing Inguinal Herniotomy under General Anesthesia

Context: Pain management intraoperatively and postoperatively in the pediatric age group is a matter of concern. On the one hand, children are poorer at precisely conveying the extent of pain all the while being more susceptible to pain-related complications such as laryngospasm. On the other hand, children are less suited to use of potent opioids due to associated complications which can often lead to catastrophe. Therefore, a multimodal approach is desirable to optimize pain management in children. A nerve block is a highly effective and popular modality nowadays. In this single-blinded, parallel group, monocentric, and randomized protocol study, we have compared the efficacy of pain control achieved in the use of nonsteroidal anti-inflammatory drugs as analgesic versus iliohypogastric ilioinguinal (IIIH) nerve block in herniotomy in pediatric age group. Materials and Method: The parallel-group prospective study recruited 104 participants who were randomly allocated into two groups of 52 each, such that both groups received 1 mcg/kg fentanyl and sevoflurane during induction of GA. For analgesia, Group 2 was given diclofenac suppository intraoperative after induction of GA. Group 1 was given IIIH nerve block under nerve stimulator guidance for perioperative analgesia. Both groups were studied for the following parameters which included: time to get the 1st dose of rescue analgesic, total dose of rescue analgesic, visual analog scale (VAS) score, and hemodynamic parameters. Results: We observed that Group 1 showed a statistically significant difference in the form of longer duration of analgesia after surgery (9.67 ± 1.80 h vs. 6.35 ± 0.84 h) and lower total dose of rescue analgesic requirement (69.23 ± 2 [22.77] vs. 106.23 ± 2 [21.49]) while having a better hemodynamic profile and lower cumulative VAS score (7.71 ± 1.39 vs. 12.04 ± 1.72). Conclusion: Based on the above findings, we deduce that preincisional nerve stimulator-guided IIIH block by levobupivacaine (0.25%, 0.3 ml/kg) and rectal diclofenac (2 mg/kg) is both safe approaches to provide postoperative analgesia in pediatric inguinal herniotomy under general anesthesia. However, nerve stimulator-guided IIIH nerve block by levobupivacaine is a safe and better choice as it provides more intense analgesia for a longer duration compared to diclofenac suppository in the immediate postoperative period.

Novel sulindac derivatives for colorectal cancer chemoprevention that target cGMP phosphodiesterases to suppress Wnt/β-catenin transcriptional activity

&lt;p class="MsoNormal" style="margin-top: 6pt; line-height: 13pt; text-align: justify;"&gt;&lt;span lang="EN-US" style="font-size: 10pt; font-family: arial, helvetica, sans-serif;"&gt;Approximately 28 million individuals in the United States face the risk of developing precancerous colonic adenomas (polyps) and potentially progressing to colorectal cancer (CRC). While a promising strategy for CRC prevention involves pharmacological intervention, such as cancer chemoprevention or interception, currently, there are no FDA-approved drugs capable of preventing the formation or progression of adenomas to adenocarcinoma. Numerous clinical, epidemiological, and preclinical studies have offered compelling evidence supporting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in CRC chemoprevention. However, the prolonged use of NSAIDs is not FDA-approved due to potential life-threatening toxicities resulting from cyclooxygenase (COX) inhibition and the depletion of physiological prostaglandins. Despite indications that the COX inhibitory activity of NSAIDs may not be essential for their antineoplastic effects, the absence of a well-defined target impeded the development of derivatives that do not inhibit COX. Earlier research suggests that the inhibition of cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) may be responsible, at least in part, for the antineoplastic activity of the NSAID sulindac. This could potentially offer a novel target for CRC chemoprevention. To identify the cGMP PDE isozyme(s) contributing to the antineoplastic activity of sulindac, we synthesized a chemically diverse library of over 1500 compounds, all sharing the indene scaffold of sulindac. Subsequently, we screened these compounds for their impact on cancer cell growth and PDE inhibitory activity. From this screening, a series of lead compounds emerged. These compounds lacked COX-1 and COX-2 inhibitory activity, surpassing sulindac in potency to inhibit CRC cell growth. Importantly, they demonstrated greater selectivity by not affecting normal cell growth. Through chemical optimization, we identified several development candidates that selectively inhibit PDE5 and/or PDE10. These compounds activate cGMP/PKG signaling, suppressing Wnt/&amp;beta;-catenin transcription. This action counters the growth advantages resulting from APC or CTNNB1 mutations, which are responsible for most human CRCs. This review delves into the scientific literature supporting PDE5 and/or PDE10 as potential targets for CRC chemoprevention or interception. Our findings suggest a promising avenue for developing drugs that may effectively intervene in the progression of colorectal cancer, offering hope for improved preventive strategies in the future.&lt;/span&gt;&lt;/p&gt;