Use Of Anti-inflammatory Drugs Research Articles

Investigation of risk factors in the development of recurrent urethral stricture after internal urethrotomy

BACKGROUND Urethral stricture is a condition that often develops with trauma and results in narrowing of the urethral lumen. Although endoscopic methods are mostly used in its treatment, it has high recurrence rates. Therefore, open urethroplasty is recommended after unsuccessful endoscopic treatments. AIM To investigate the risk factors associated with urethral stricture recurrence. METHODS The data of male patients who underwent internal urethrotomy for urethral stricture between January 2017 and January 2023 were retrospectively analyzed. Demographic data, comorbidities, preoperative haemogram, and biochemical values obtained from peripheral blood and operative data were recorded. Patients were divided into two groups in terms of recurrence development; recurrence and non-recurrence. Initially recorded data were compared between the two groups. RESULTS A total of 303 patients were included in the study. The mean age of the patients was 66.6 ± 13.6 years. The mean duration of recurrence development was 9.63 ± 9.84 (min-max: 1-39) months in the recurrence group. Recurrence did not occur in non-recurrence group throughout the follow-up period with an average time of 44.15 ± 24.07 (min-max: 12-84) months. In the comparison of both groups, the presence of diabetes mellitus (DM), hypertension (HT), and multiple comorbidities were significantly higher in the recurrence (+) group (P = 0.038, P = 0.012, P = 0.013). Blood group, postoperative use of non-steroidal anti-inflammatory drugs, preoperative cystostomy, cause of stricture, iatrogenic cause of stricture, location and length of stricture, indwelling urinary cathater size and day of catheter removal did not differ between the two groups. No statistically significant difference was observed between the two groups in terms of age, uroflowmetric maximum flow rate value, hemogram parameters, aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting blood sugar, creatinine, glomerular filtration rate, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio, monocyte-lymphocyte ratio and AST/ALT ratios. CONCLUSION In patients with urethral stricture recurrence, only the frequency of DM and HT was high, while inflammation marker levels and stricture-related parameters were similar between the groups.

Exploring the association between microscopic colitis and celiac disease: A comprehensive analysis using the national in-patient data (2016-2019).

Several investigations suggested correlation between microscopic colitis (MC) and celiac disease (CD). This study aimed to examine this relationship using large-sized, population-based data with adequate control for confounding factors. This study employed the National Inpatient Sample (NIS) database over 4 years (2016-2019). Patients with/without MC in the presence/absence of CD were identified through ICD-10 codes. Univariate and multi-variate analyses involving odds ratios (OR) and 95% confidence intervals (CI) were performed. Overall, 26,836,118 patients were analyzed. Of whom, 6,836 patients had MC (n = 179 with CD and n = 6,657 without CD). The mean hospital stay was not significantly different between both groups (5.42 ± 5.44 days vs. 4.95 ± 4.66 days, P = 0.202). The univariate analysis revealed a significant association between MC and CD (OR = 22.69, 95% [19.55, 26.33], P < 0.0001). In the multi-variate analysis, which adjusted for potential confounders including age, race, hospital region, hospital teaching status, ZIP income, smoking status, alcohol overuse, hypertension, diabetes mellitus, lipidemia-related disorders, non-steroidal anti-inflammatory drug use, and selected auto-immune diseases, the association remained significant (OR = 15.71, 95% CI [13.52, 18.25], P < 0.0001). Moreover, in patients with MC, the presence of CD emerged as a significant, independent variable of in-hospital mortality in univariate (OR = 2.87, 95% [1.14, 7.21], P = 0.025) and multi-variate (OR = 3.37, 95% CI [1.32, 8.60], P = 0.011) analyses. This study establishes a probable link between MC and CD, backed by both univariate and multi-variate analyses, while also identifying CD as an independent risk factor for increased mortality among MC patients. These findings need to be validated in real-world clinical studies.

Low back pain: justification of treatment standards (literature review)

The American Association of Neurological Surgeons reported that approximately 75–85 % of Americans experience low back pain (LBP) during their lifetime. There is considerable heterogeneity among epidemiologic studies of LBP, which limits the ability to compare and generalize the data. One-year incidence of the first episode of LBP ranges from 6.3 to 15.4 %, while 1-year incidence of any episode of low back pain is from 1.5 to 36 %. In hospital-based studies, episode remission after one year ranges from 54 to 90 %. Experts from Europe, Australia and Latin America identified 15 clinical practice guidelines for the treatment of low back pain in primary care settings. The authors pay attention to the fact that the data on the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the mentioned guidelines are contradictory. Enzymatic oxidation of arachidonic acid has been shown to lead to the formation of potent pathological agents by two main pathways. Those in the prostaglandin (PG) pathway, particularly PGE2, have been considered inflammatory mediators for many years. The discovery of the biological activity of thromboxane A2 and prostacyclin, as well as the destructive oxygen-centered radical as additional products of this biosynthetic pathway now require their consideration as potential inflammatory mediators. Like PGE2, their biosynthesis is inhibited by nonsteroidal anti-inflammatory drugs. There is also an alternative lipoxygenase pathway that yields arachidonic acid oxygenation products called leukotrienes and eicosanoids, which have also been shown to be important inflammatory mediators resistant to NSAIDs. It was shown that dexamethasone suppresses the release of arachidonate from human epithelial cells by inducing the synthesis of the p11 protein and inhibiting the activity of phospholipase A2, that is, it affects the pathological mechanisms of inflammation that are lacking in NSAIDs, namely, it blocks the release of arachidonic acid salts. Dexamethasone has been shown to affect both exudative and proliferative phases of inflammation. Inflammatory mediators block active sulfhydryl groups of proteins, enzymes, receptors, and ion channels. The positive role of donors of such groups in the treatment of LBP is shown in the literature. In the treatment of allodynia, bisphosphonates, which normalize calcium metabolism and reduce calcification of cartilage and ligaments, have proven themselves to be the best: they cause a decrease in the intensity of pain and swelling and improve nerve function. Racetams have been shown to be useful for the treatment of not only neuropathic pain, but also cognitive impairment. Racetams are especially active in combination with choline donors. Peripheral neuropathy (PN) is a common disease with an incidence of approximately 8 % in the elderly. Neuropathic pain has a high prevalence in the general population and affects more than half of all patients with PN. The pathophysiology of PN is characterized by damage to myelin-producing Schwann cells in peripheral nerves. Regeneration/protection of the myelin sheath after nerve injury is a fundamental element of recovery in PN. Nucleotides such as uridine monophosphate have been shown to be effective in treating the cause of myelin damage in several experimental and clinical models. B vitamins such as В12, В6, В3, В1 are essential for nerve health. These vitamins can aid in the healing of damaged nerves and relieve symptoms of nerve damage like numbness and tingling, that is why they are called neurotropic vitamins. In confirmation of the clinical value of these arguments, a clinical case is presented, when the patient was managed with a combination of the discussed drugs and felt significantly better.

Analysis of the Consumption of Medicinal Products Associated with a High Risk of Drug-Induced Liver Injury in Patients with COVID-19

INTRODUCTION. The risk of liver damage correlates with the severity of COVID-19. However, a growing number of studies have shown an association between liver function impairment and combinations of medicinal products used to treat COVID-19.AIM. The study aimed to analyse the annual consumption of medicinal products associated with a high risk of drug-induced liver injury (DILI) used as part of combination therapy in COVID-19 patients and to review a number of medication administration records in order to develop measures to prevent DILI.MATERIALS AND METHODS. The study used the ATC/DDD methodology to study consumption data for 2020, 2021, and 2022 and analysed a sample of 1250 inpatient medical records and medication administration records of COVID-19 patients treated in a Volgograd region hospital converted into a COVID-19 care centre. For genetically engineered biologicals and cyclophosphamide, which were lacking DDDs, the authors calculated the volume of consumption using the average dose per treatment course. The authors identified medicines capable of causing clinically apparent liver damage (according to the LiverTox database and Russian clinical practice guidelines) and/or elevated liver enzymes in ≥1% of patients (according to safety reports).RESULTS. The study found that 28% of the medicinal products used in combination for inpatient treatment of COVID-19 were associated with a high risk of DILI. In 2020, 2021, and 2022, the total consumption of medicinal products associated with a high risk of DILI was 342.3, 425.3, and 402.3 DDDs per 100 bed days, and the total consumption of genetically engineered biologicals (administered as a single dose) and cyclophosphamide was 3.5, 16.9, and 29.7 average course doses per 100 patients, respectively. According to the selective analysis of medical records, 19.8% (247/1250) reported concomitant use of 5 or more medicinal products associated with a high risk of DILI, which increased the risk of adverse drug interactions leading to DILI. In 2022, the most prescribed medicinal products with a high risk of DILI were omeprazole (188.7 DDDs per 100 bed days), non-steroidal anti-inflammatory drugs and paracetamol (54.4 DDDs per 100 bed days), atorvastatin (46.2 DDDs per 100 bed days), levofloxacin (26.4 DDDs per 100 bed days), ceftriaxone (20.5 DDDs per 100 bed days), favipiravir (17.3 DDDs per 100 bed days), and genetically engineered biologicals (24.0 DDDs per 100 bed days).CONCLUSIONS. To reduce the risk of DILI in COVID-19 patients admitted to infectious disease units, including the risk of DILI due to drug interactions, it is necessary to limit the use of hepatotoxic antibacterial agents, proton-pump inhibitors, and non-steroidal anti-inflammatory drugs, or consider alternative medicinal products with a lower risk of hepatotoxicity.

Predictors of adherence to direct oral anticoagulants after cardiovascular or bleeding events in Medicare Advantage Plan enrollees with atrial fibrillation.

Direct oral anticoagulants (DOACs) are recommended for patients with atrial fibrillation (AF) given their improved safety profile. Suboptimal adherence to DOACs remains a significant concern among individuals with AF. However, the extent of adherence to DOACs following a cardiovascular or bleeding event has not been fully evaluated. To evaluate the pattern of adherence trajectories of DOACs after a cardiovascular or bleeding event and to investigate the sociodemographic and clinical predictors associated with each adherence trajectory by using claims-based data. This retrospective study was conducted among patients with AF prescribed with DOACs (dabigatran/apixaban/rivaroxaban) between July 2016 and December 2017 and who were continuously enrolled in the Texas-based Medicare Advantage Plan. Patients who experienced a cardiovascular or bleeding event while using the DOACs were further included in the analysis. The sample was limited to patients who experienced a clinical event such as a cardiovascular or bleeding event while using the DOACs. The clinical events considered in this study were cardiovascular (stroke, congestive heart failure, myocardial infarction, systemic embolism) and bleeding events. To assess adherence patterns, each patient with a DOAC prescription was followed up for a year after experiencing a clinical event. The monthly adherence to DOACs after these events was evaluated using the proportion of days covered (PDC). A group-based trajectory model incorporated the monthly PDC to classify groups of patients based on their distinct patterns of adherence. Predictors associated with each trajectory were assessed using a multinomial logistic regression model, with the adherent trajectory serving as the reference group in the outcome variable. Among the 694 patients with AF who experienced clinical events after the initiation of DOACs, 3 distinct adherence trajectories were identified: intermediate nonadherent (30.50%), adherent (37.7%), and low adherent (31.8%); the mean PDC was 0.47 for the intermediate nonadherent trajectory, 0.93 for the adherent trajectory, and 0.01 for low adherent trajectory. The low-income subsidy was significantly associated with lower adherence trajectories (odds ratio [OR] = 4.81; 95% CI = 3.07-7.51) and with intermediate nonadherent trajectories (OR = 1.57; 95% CI = 1.06-2.34). Also, nonsteroidal anti-inflammatory drug use was significantly associated with lower adherence trajectories (OR = 5.10; 95% CI = 1.95-13.36) and intermediate nonadherent trajectories (OR = 3.17; 95% CI = 1.26-7.93). Other predictors significantly associated with both nonadherent trajectories are type of DOACs (OR = 0.53; 95% CI = 0.35-0.79), presence of coronary artery disease (OR = 1.89; 95% CI = 1.01-3.55), and having 2 or more clinical events (OR = 1.65; 95% CI = 1.09-2.50). Predictors identified provide valuable insights into the suboptimal adherence of DOACs among Medicare Advantage Plan enrollees with AF, which can guide the development of targeted interventions to enhance adherence in this high-risk patient population.

Recent clinical practice guidelines for the management of low back pain: a global comparison.

Low back pain (LBP) is a significant health problem worldwide, with a lifetime prevalence of 84% in the general adult population. To rationalise the management of LBP, clinical practice guidelines (CPGs) have been issued in various countries around the world. This study aims to identify and compare the recommendations of recent CPGs for the management of LBP across the world. MEDLINE, EMBASE, CINAHL, PEDro, and major guideline databases were searched from 2017 to 2022 to identify CPGs. CPGs focusing on information regarding the management and/or treatment of non-specific LBP were considered eligible. The quality of included guidelines was evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Our analysis identified a total of 22 CPGs that met the inclusion criteria, and were of middle and high methodological quality as assessed by the AGREE II tool. The guidelines exhibited heterogeneity in their recommendations, particularly in the approach to different stages of LBP. For acute LBP, the guidelines recommended the use of non-steroidal anti-inflammatory drugs (NSAIDs), therapeutic exercise, staying active, and spinal manipulation. For subacute LBP, the guidelines recommended the use of NSAIDs, therapeutic exercise, staying active, and spinal manipulation. For chronic LBP, the guidelines recommended therapeutic exercise, the use of NSAIDs, spinal manipulation, and acupuncture. Current CPGs provide recommendations for almost all major aspects of the management of LBP, but there is marked heterogeneity between them. Some recommendations lack clarity and overlap with other treatments within the guidelines.

Association between perioperative non-steroidal anti-inflammatory drug use and cardiovascular complications after non-cardiac surgery in older adult patients.

We investigated in older adult non-cardiac surgical patients whether receipt of perioperative non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased incidence of postoperative cardiovascular complications. We retrospectively extracted the information for patients with age ≥ 65years who had inpatient non-cardiac surgery with a duration of ≥ 1h from the American College of Surgeons-National Surgical Quality Improvement Program registry data acquired at the University of Washington Medical Center. We compared patients who received NSAIDs perioperatively to those who did not receive NSAIDs, on the two composite outcomes: (1) the incidence of postoperative cardiovascular complications within 30days of the surgery, and (2) the incidence of combined postoperative gastrointestinal and renal complications, and length of postoperative hospital stay. We used separate multivariable logistic regression models to analyze the two composite outcomes and a Poisson regression model for the length of hospital stay. The receipt of perioperative NSAIDs was not associated with postoperative cardiovascular complications (estimated odds ratio (OR), 1.78; 95% confidence interval (CI), 0.97 to 3.25; P = 0.06), combined renal and gastrointestinal complications (estimated OR, 1.30; 95% CI, 0.53 to 3.20; P = 0.57), and length of postoperative hospital stay in days (incidence rate ratio, 1.06; 95% CI, 0.93 to 1.21; P = 0.39). In older adult non-cardiac surgical patients, receipt of perioperative NSAIDs was not associated with increased incidences of postoperative cardiovascular complications, and renal and gastrointestinal complications within 30days after surgery, or length of postoperative hospital stay.

The impact of skeletal muscle index at the third lumbar spine on nosocomial deterioration and short-term prognosis in acute pancreatitis: a retrospective observational study.

To investigate the impact of the third lumbar skeletal muscle index (L3-SMI) assessed by CT on the in-hospital severity and short-term prognosis of acute pancreatitis. A total of 224 patients with severe acute pancreatitis admitted to Yantaishan Hospital from January 2021 to June 2022 were selected as the subjects. Based on the in-hospital treatment outcomes, they were divided into a mortality group of 59 cases as well as a survival group of 165 cases. Upon admission, general information such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, along with the abdominal CT images of each patient, were analyzed. The L3-SMI was calculated, and the Modified CT Severity Index (MCTSI) and Balthazar CT grade were used to assess the severity of in-hospital complications of acute pancreatitis. The evaluation value of L3-SMI for the prognosis of severe acute pancreatitis was analyzed, as well as the factors influencing the prognosis of severe acute pancreatitis. No statistically significant differences in gender, age, BMI, etiology, duration of anti-inflammatory drug use, and proportion of surgical patients between the survival and mortality groups were observed. But the mortality group showed higher proportions of patients with an elevated APACHE II score upon admission, mechanical ventilation, and renal replacement therapy, compared to the survival group, with statistically significant differences (P < 0.001). Furthermore, the mortality group had higher MCTSI scores (6.42 ± 0.69) and Balthazar CT grades (3.78 ± 0.45) than the survival group, with statistically significant differences (P < 0.001). The mortality group also had a lower L3-SMI (39.68 ± 3.25) compared to the survival group (42.71 ± 4.28), with statistically significant differences (P < 0.001). L3-SMI exhibited a negative correlation with MCTSI scores and Balthazar CT grades (r = -0.889, -0.790, P < 0.001). Logistic regression analysis, with mortality of acute pancreatitis patients as the dependent variable and MCTSI scores, Balthazar CT grades, L3-SMI, APACHE II score upon admission, mechanical ventilation, and renal replacement therapy as independent variables, revealed that MCTSI scores and L3-SMI were risk factors for mortality in acute pancreatitis patients (P < 0.001). Logistic regression analysis using the same variables confirmed that all these factors were risk factors for mortality in acute pancreatitis patients. This study confirmed that diagnosing muscle depletion using L3-SMI is a valuable radiological parameter for predicting in-hospital severity and short-term prognosis in patients with acute pancreatitis.

To study the Helicobacter pylori infection in peptic ulcer

Helicobacter pylori is a gram negative bacterium which causes chronic gastritis and plays important roles in peptic ulcer disease, gastric carcinoma, and gastric lymphoma. Its major in the human pathogen that produces inflammation of the stomach and etiologically related to the duodenal ulcer, gastric ulcer, gastric cancer and mucosa-lymphoid tissue. It is weakens the protective mucous coating of the stomach and duodenum, thus allowing acid to get through to the sensitive lining beneath. Both the acid and the bacteria irritate the lining and cause a sore, or ulcer. Helicobacter treated with a combination of antibiotics plus a proton pump inhibitor. Peptic ulcer is characterized by discontinuation in the inner lining of the gastrointestinal tract because of the gastric acid secretion or pepsin. It extends into muscularis propria layer of the gastric epithelium. It usually occurs in the stomach and proximal duodenum. Peptic means that cause of the problem is due to the acid. It is most common causes in the peptic ulcers are infection with the bacterium and causes the long-term use of the non-steroidal anti-inflammatory drugs. Gastric ulcer occurs in the stomach. Duodenal ulcer occurs in the first part of the small intestine. The interplay of gastritis phenotype related to the bacterium colonization and resulting acid secretion.

Characteristics of Nonunion Fractures in Patients with Antebrachial Fractures at dr. Mohamad Soewandhie General Hospital Surabaya 2021-2022: A Retrospective Study

Background: Nonunion, a complication of fracture healing, can lead to patient morbidity. Contributing factors include age, gender, fracture type, multiple fractures, infection, prolonged nonsteroidal anti-inflammatory drug (NSAID) use, smoking, nutritional status, and history of chronic disease. This study aims to determine the prevalence and characteristics of nonunion antebrachial fractures at dr. Mohamad Soewandhie General Hospital Surabaya. Methods: This retrospective descriptive study involved 111 patients. Data was gathered from medical records treated at dr. Mohamad Soewandhie General Hospital Surabaya for antebrachial fracture during 2021-2022. The study protocol obtained approvals from two local ethical committees. Data included demographics, fracture characteristics, fracture type, multiple fractures, infection, NSAID use, hypertension and diabetes history, smoking habits, and nutritional status by BMI calculation. Results: This study found a 24.3% prevalence of antebrachial nonunion fractures at dr. Mohamad Soewandhie General Hospital Surabaya in 2021-2022, mostly in males (66.7%) aged 17-25 years (22.2%). Nonunion in antebrachial fractures is marked by high rates in closed (92.6%) and single fractures (92.6%). Notably, infections (22.2%), smoking (7.4%), and hypertension history (7.4%) are common contributors. Despite ideal BMI in many cases (44.4%), nonunion still occurred. Conclusions: The study conducted at Dr. Mohamad Soewandhie General Hospital in Surabaya revealed a high prevalence of antebrachial nonunion fractures at 24.3%, particularly among young males. It was found that closed, single fractures were the most common type, with infections, smoking, and a history of hypertension being significant contributing factors. Interestingly, even individuals with an ideal BMI were still at risk for nonunion.

[Wound healing after trabeculectomy : What and when in postoperative aftercare?]

Excessive wound healing in filtering glaucoma surgery is akey factor for a failed surgery. After the introduction of trabeculectomy in the 1960s many factors associated with an increased fibrotic reaction were recognized and methods were developed to influence postoperative wound healing. These range from the perioperative use of anti-inflammatory drugs and antimetabolites to the use of newer chemical compounds that influence the morphology of postoperative fibroblast growth. In the routine clinical practice, the fine tuning of therapeutic decisions plays adecisive role in the success or failure of filtration surgery.

Pouchitis: pathophysiology and management.

Pouchitis is an acute or chronic inflammatory disease of the ileal reservoir. It is common after restorative proctocolectomy with ileal pouch-anal anastomosis, and treatment of chronic antibiotic-refractory pouchitis has proven challenging. Most cases of acute pouchitis evolve into chronic pouchitis. The aetiology of acute pouchitis is likely to be partly related to the gut microbiota, whereas the pathophysiology of chronic pouchitis involves abnormal interactions between genetic disposition, faecal stasis, the gut microbiota, dysregulated host immunity, surgical techniques, ischaemia and mesentery-related factors. Pouchoscopy with biopsy is the most valuable modality for diagnosis, disease monitoring, assessment of treatment response, dysplasia surveillance and delivery of endoscopic therapy. Triggering or risk factors, such as Clostridioides difficile infection and use of non-steroidal anti-inflammatory drugs, should be modified or eradicated. In terms of treatment, acute pouchitis usually responds to oral antibiotics, whereas chronic antibiotic-refractory pouchitis often requires induction and maintenance therapy with integrin, interleukin or tumour necrosis factor inhibitors. Chronic pouchitis with ischaemic features, fistulae or abscesses can be treated with hyperbaric oxygen therapy.

A Minority of Childhood Disorders of Gut-Brain Interaction Persist Into Adulthood: A Risk-Factor Analysis.

Disorders of gut-brain interaction (DGBIs) may originate in childhood. There are currently limited data on persistence of DGBI into adulthood and risk factors for persistence. Furthermore, there are no data on this question from general practice, where the majority of DGBIs are diagnosed and managed. This study documents the proportion of childhood-diagnosed DGBIs that persisted into adulthood and what factors were associated with persistence. General practice records were obtained for more than 60,000 patients whose medical record spanned both childhood and adulthood years. Patients with diagnosed organic gastrointestinal disorder were excluded. Medical records were also interrogated for potential risk factors. Eleven percent of patients with irritable bowel syndrome (IBS) and 20% of patients with functional dyspepsia (FD) diagnosed in childhood had repeat diagnoses of the same condition in adulthood. Female sex (odds ratio [OR] 2.02) was associated with persistence for IBS, while a childhood diagnosis of gastritis (OR 0.46) was risk-protective. Childhood non-steroidal anti-inflammatory drug use (OR 1.31, 95% confidence interval [CI] 1.09-1.56) was a risk factor for persistence in IBS. For FD, a childhood diagnosis of asthma (OR 1.30, 95% CI 1.00-1.70) was a risk factor, as was anxiety for both IBS (OR 1.24, 95% CI 1.00-1.54) and FD (OR 1.48 95% CI 1.11-1.97) with a similar finding for depression for IBS (OR 1.34, 95% CI 1.11-1.62) and FD (OR 1.88 95% CI 1.47-2.42). Childhood DGBIs persist into adulthood in 10%-20% of patients, suggesting that management monitoring should continue into adulthood. Those diagnosed with anxiety or mood disorders in childhood should receive particular attention, and prescription of non-steroidal anti-inflammatory drugs in children should be made judiciously.

P064 It’s a long time to wait: exploring the support needs of people with rheumatoid arthritis starting methotrexate

Abstract Background/Aims Methotrexate (MTX) is recommended as initial Disease Modifying Anti-Rheumatic Drug (DMARD) therapy for people with Rheumatoid Arthritis (RA) but often takes several months to become effective. Little is known about the support needs of people with RA whilst MTX takes effect. Methods 76 adults with RA referred for MTX counselling attending two rheumatology units in the West Midlands were invited to take part in qualitative semi-structured interviews (either by phone or video). Research partners with RA helped to develop interview topic guides. Interviews were digitally recorded, transcribed and analysed using reflexive thematic analysis. Results 19 participants, (11 male, 8 Female, White British, age 45-75 years, disease duration (6 weeks - 35 years) took part in telephone (n = 17) and video (n = 2) interviews (duration 34-82 minutes). Three themes were identified; Concerns regarding time to effect, Learning to cope with the impact of RA, A need for support to self-manage RA. Concerns regarding time to effect: most people expressed concerns about coping with active symptoms of RA whilst waiting for MTX to take effect. Few recalled receiving information about nonpharmacological symptom management. Many experienced initial benefit following intramuscular bridging steroids, often wearing off as MTX commenced, and did not recall plans for further steroids. Conflicting advice about the use of analgesia and non-steroidal anti-inflammatory drugs (NSAIDs) to manage pain and joint stiffness sometimes created confusion. A few recollected advice to stop taking analgesia or NSAIDs when starting MTX. Several reported difficulties accessing help with symptom control and obtaining analgesia and NSAIDs in primary care. Learning to cope with the impact of RA: Participants reported limitations to physical function, restricting their independence with daily living activities with an impact on social, relational and work roles. Most, however, reported finding ways to manage these limitations. Several described negative impacts on mental health. A need for support to self-manage RA: Most identified unmet needs regarding self-management whilst waiting for MTX to take effect. Few recalled receiving education or support regarding self-management for RA. Some received leaflets regarding managing flares of RA that were seen to provide practical advice and reassurance. Several reported not reading leaflets and coping with flares without education or support. Positive support was sometimes received from relatives and others with RA, whereas few used the internet to find additional help. Rheumatology advice lines were often perceived as a useful source of support, but some people were reticent to seek help and others had concerns about delayed responses. Conclusion Many people with RA report unmet needs to support self-management whilst waiting for MTX to take effect. Appropriate signposting and referral to support provided by RA patient associations may offer useful solutions for some. Disclosure S.J. Logan: None. S. Hider: None. J. Green: None. S. Ryan: None.

Celecoxib and sulindac sulfide elicit anticancer effects on PIK3CA-mutated head and neck cancer cells through endoplasmic reticulum stress, reactive oxygen species, and mitochondrial dysfunction

Gain-of-function mutation in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit alpha gene (PIK3CA) is a significant factor in head and neck cancer (HNC). Patients with HNC harboring PIK3CA mutations receive therapeutic benefits from the use of non-steroidal anti-inflammatory drugs (NSAIDs). However, the molecular mechanisms underlying these effects remain unknown. Here, we examined the Detroit562 and FaDu cell lines as HNC models with and without a hyperactive PIK3CA mutation (H1047R), respectively, regarding their possible distinct responses to the NSAIDs celecoxib and sulindac sulfide (SUS). Detroit562 cells exhibited relatively high PI3K/Akt pathway-dependent cyclooxygenase-2 (COX-2) expression, associated with cell proliferation. Celecoxib treatment restricted cell proliferation and upregulated endoplasmic reticulum (ER) stress-related markers, including GRP78, C/EBP-homologous protein, activating transcription factor 4, death receptor 5, and reactive oxygen species (ROS). These effects were much stronger in Detroit562 cells than in FaDu cells and were largely COX-2-independent. SUS treatment yielded similar results. Salubrinal (an ER stress inhibitor) and N-acetyl-L-cysteine (a ROS scavenger) prevented NSAID-induced ROS generation and ER stress, respectively, indicating crosstalk between ER and oxidative stress. In addition, celecoxib and/or SUS elevated cleaved caspase-3 levels, Bcl-2-associated X protein/Bcl-2-interacting mediator of cell death expression, and mitochondrial damage, which was more pronounced in Detroit562 than in FaDu cells. Salubrinal and N-acetyl-L-cysteine attenuated celecoxib-induced mitochondrial dysfunction. Collectively, our results suggest that celecoxib and SUS efficiently suppress activating PIK3CA mutation-harboring HNC progression by inducing ER and oxidative stress and mitochondrial dysfunction, leading to apoptotic cell death, further supporting NSAID treatment as a useful strategy for oncogenic PIK3CA-mutated HNC therapy.

Paradoxical effect of anti-inflammatory drugs on IL-6 mRNA expression in patients with PTSD during treatment.

The pathophysiology of posttraumatic stress disorder (PTSD) is associated with the activation of the innate immune system, including cytokines like interleukin 6 (IL-6). However, the role of IL-6 in the etiology and treatment of PTSD still remains elusive. We conducted a prospective controlled trial to investigate the development of IL-6 during psychosomatic treatment in individuals with PTSD in comparison with individuals without PTSD. We assessed IL-6 mRNA expression before and after 2 months of psychosomatic treatment in individuals with and without PTSD. Severities of PTSD and depressive symptoms were assessed in parallel. Linear mixed regression was applied for statistical analysis, including the factors diagnosis PTSD and pre-post treatment after subgrouping for intake of anti-inflammatory drugs. The development of IL-6 mRNA expression during treatment was affected by the use of anti-inflammatory drugs. In the subgroup without intake of anti-inflammatory drugs, no significant statistical treatment effect in individuals with and without PTSD emerged. In the subgroup of individuals taking anti-inflammatory drugs, a significant interaction effect of the factors pre-post treatment and diagnosis PTSD was observed. Whereas IL-6 mRNA expression in individuals without PTSD decreased according to amelioration of symptoms, IL-6 mRNA expression in individuals with PTSD increased significantly during treatment, in opposite direction to symptom severity. Anti-inflammatory drugs might affect IL-6 mRNA expression in individuals with PTSD in a paradoxical way. This study offers a further piece of evidence that IL-6 could be involved in the pathophysiology of PTSD and PTSD-specific immunologic molecular mechanisms.

Risk of cardiovascular disease with high-dose versus low-dose use of non-steroidal anti-inflammatory drugs in ankylosing spondylitis

ObjectiveTo investigate the risk of cardiovascular disease (CVD) associated with increasing dose of a non-steroidal anti-inflammatory drug (NSAID) in patients with ankylosing spondylitis (AS).MethodsUsing the Korean National Health Insurance database,...

Aspirin Does Not Inhibit Platelet-Rich Plasma Releasate Efficacy in a Murine Model of Rotator Cuff Tendinopathy

Background: Platelet-rich plasma (PRP) has been shown to be a promising treatment for subacromial impingement, and although its interaction with aspirin (ASA) is controversial, many providers ask patients to stop non–steroidal anti-inflammatory drug use before PRP administration. Purpose: This studied aimed to identify the effect of PRP in a murine model of subacromial impingement and to explore the effect of ASA on PRP treatment. Methods: A murine model of subacromial impingement was used, incorporating 48 wild-type C57BL/6 mice. After impingement surgery, mice received either human PRP activated via calcium chloride or saline injected into the subacromial space. The mice received either drinking water with ASA or standard drinking water, creating 4 groups: saline injection, saline injection + ASA, PRP injection, and PRP injection + ASA. All injections occurred at 3 weeks after impingement surgery, and mice were evaluated at 6 weeks. Each mouse underwent gait analysis, biomechanical analysis (N = 10 shoulders), histological analysis (N = 6), and gene expression analysis (N = 8). Results: Biomechanical testing showed increased load to failure in the PRP group compared to the ASA group, and increased stiffness in PRP vs saline, PRP vs ASA, and PRP vs ASA + PRP. Gene expression analysis identified 17 downregulated genes between the ASA + PRP and saline groups. Eight of these differentially expressed genes contribute to collagen biosynthesis and modification, 4 to extracellular matrix (ECM) synthesis, and 4 to ECM degradation. Conclusions: In this preliminary analysis, PRP injections in a murine model of subacromial impingement demonstrated mixed effects on tendon quality and pain, and ASA did not have a consistent effect on the response to PRP.

RISK FACTORS AND CLINICAL CORRELATIONS OF URINARY TGF-Β1 IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS AND EARLY KIDNEY FIBROSIS

The course of juvenile idiopathic arthritis (JIA) is associated with a long-term infl ammatory process and the use of nonsteroidal anti-infl ammatory drugs (NSAIDs), which can cause nephrotoxicity with fi brotic kidney damage in patients with JIA. Regardless of the etiology of joint damage, prolonged infl ammation promotes the progression of fi brosis, and renal fi brosis is the fi nal common stage of chronic kidney disease (CKD). Kidney biopsy, which is invasive, risky and underutilized, is generally considered the only clinical method to detect fi brosis. Over the past decade, some progress has been made in the search for minimally invasive biomarkers of early kidney fi brosis, with transforming growth factor-β1 (TGF-β1) playing a key role in the progression of kidney fi brosis, but the signifi cance of TGF-β1 in children with JIA is unknown.Material and Methods: 80 children with JIA were examined. Urinary TGF-β1 levels were determined using a TGF-β1 ELISA kit(DRG International, Inc., Germany, EIA-1864) according to the manufacturer’s instructions. Methods of variation statistics were used. Informed consent was obtained from all patients. The study has a positive conclusion of the Commission on Biomedical Ethics of Dnipro State Medical University (Minutes of the meeting of the Commission No. 12 dated December 19, 2002), which decided that the scientifi c research can be considered in accordance with generally accepted moral standards, the requirements of respecting the rights, interests and personal dignity of study participants, bioethical standards for work with pediatric patients. There is no risk to the research subjects in the performance of the work. The legal representatives of the children involved in the research are informed about all aspects related to the purpose, objectives, methods and expected benefi ts of the research. Laboratory and instrumental research methods are generally accepted; the drugs to be used are approved for use. No human experiments were performed.Methods of variation statistics were used. Statistical analysis was performed using the STATISTICA 6.1 software package(StatSoft Inc., serial no. AGAR909E415822FA). The work was carried out as part of the research work of the Department of Propaedeutic of Childhood Diseases and Pediatrics 2 of the Dnipro State Medical University «Development of criteria for early diagnosis and prediction of comorbid kidney damage in children with somatic and infectious diseases» (state registration No. 0119U100932, implementation period 01.2019-12.2023).Results. The mean TGF-β1 level in our study was 20.26±16.34 (14.02, 12.5-17.98) pg/ml. Polyarthritis almost quadrupledthe probability of pathological changes in TGF-β1. The overwhelming majority of children with elevated TGF-β1 suff ered from polyarthritis (80.0 %) – one and a half times more often than those with relatively normal TGF-β1 concentration, p&lt;0.04.If the active stage of the disease lasted at least 4 years, the probability of elevated TGF-β1 increased more than sixfold. Thetendency of signifi cant nephrotoxic eff ect of prolonged active JIA was confi rmed by the results of correlation analysis, according to which, in general, the duration of active JIA was directly related to the increase of TGF-β1 (ρ=0.38, p&lt;0.001), and the duration of remission and the total duration of JIA had no signifi cant correlation with it (ρ= –0.19 and ρ=0.18, respectively, p&gt;0.05). The direct dependence of elevated urinary TGF-β1 levels on clinical features such as polyarthritis and the duration of the active phase of JIA has been demonstrated. These clinical features in children with JIA can be considered as risk factors for the development of early renal fi brosis. Against the background of elevated TGF-β1, a reduced GFR according to the Hoek formula (&lt;90 ml/min/1.73 m2) was found in 95 % of cases, i. e. the estimates of the functional state of the kidneys obtained by two diff erent methods were quite clearly the same. In the sample with TGF-β1&lt;17.98 pg/ml, 22.76 % of children received immunobiologic therapy, while in the sample to increase TGF-β1 – only 14.76 %. Immunobiological therapy reduced the risk of increasing this urinary marker by 5.5 times.Conclusions. Elevated levels of the TGF-β1 biomarker were found in 25 % of children with JIA. An association of early renalfi brosis with duration of active phase of JIA ≥ 4 years, increased ESR, polyarthritis, arterial hypertension, and dental carieswas observed. Elevated urinary TGF-β1 levels are associated with reduced eGFR and are observed in almost all children witheGFR&lt;90 ml/min/1.73 m2, confi rming the importance of early renal fi brosis in the development of renal dysfunction.

Characterization of Plasmids Isolated from Bacterial Flora of CRC Patients – Proof of Concept

Abstract Introduction Colorectal cancer (CRC) is one of the leading oncogenic disorders, both in terms of incidence and mortality. The etiology of the disease is certainly multifactorial. Various risk factors like alcohol consumption, smoking, CRC family history, inflammatory bowel disease, hormone therapy, aspirin/nonsteroidal anti-inflammatory drugs use, higher body mass index, consumption of red and/or processed meat, insufficient physical activity, and decreased intake of fruit and vegetables have been pointed out; however, there is not enough support evidence for a single particular causative mechanism. Recently, gut bacterial microbiota has been shown to influence significantly the pathogenesis of CRC. However, little attention is paid to the putative impact of plasmids in gut flora. Material and methods We have designed and tested the workflow for semi-selective isolation and amplification of random circular sequences. The exploitation of rolling circle amplification (RCA) with a random hexamers protocol is crucial for the outcome. Results Our results suggest that it is possible to isolate and amplify plasmid DNA from gut flora and further process, sequence, and identify them. Discussion Little is known about the interactions between bacterial plasmids and human cells. The collection of plasmid sequencing data and the comparison of CRC patients and healthy control sequences can be the first step to elucidating this phenomenon.