Administration Of Nonsteroidal Anti-inflammatory Drugs Research Articles

Role of Potassium-competitive Acid Blockers in the Treatment of Gastric Acid-related Disorders

Owing to their superior pharmacokinetic and pharmacodynamic profiles, potassium-competitive acid blockers (P-CABs) score over proton pump inhibitors (PPIs) in the treatment of gastric acid-related disorders and may provide clinical benefit in the management of these conditions. Previous studies have compared P-CABs with PPIs for treatment of gastric acid-related disorders, and current data show that P-CABs are non-inferior to PPIs in the treatment of erosive esophagitis and as maintenance therapy. P-CABs are useful for effective healing and as maintenance medications in patients with severe esophagitis. These drugs also aid with healing of peptic ulcers and artificial ulcers secondary to gastric endoscopic submucosal dissection (ESD). Few studies have discussed prevention of delayed ulcer bleeding after gastric ESD and ulcers associated with long-term nonsteroidal anti-inflammatory drug administration. Well-controlled, large-scale prospective studies are warranted in future to compare P-CABs with PPIs.

Desensitization for the Prevention of Drug Hypersensitivity

Drug desensitization is a treatment strategy for patients with hypersensitivity to essential drugs without alternatives. The gradual increase in the drug dosage from low doses to therapeutic levels induces a transient immune tolerance to the culprit drug. Although desensitization has traditionally been recommended for IgE-mediated immediate hypersensitivity, this indication has recently been expanded to include non-IgE-mediated immediate responses, nonimmunological responses, and T-cell mediated delayed hypersensitivity reactions. Although the exact mechanism behind desensitization remains unclear, the process is thought to attenuate various intracellular signals in target cells through the high-affinity IgE receptor (FcɛRI) internalization, alteration in signaling pathways in mast cells and basophils, reduction in Ca2+ influx, and production of anti-drug IgG4 blocking antibody. Desensitization can be used for the safe administration of anti-neoplastic agents, antibiotics, aspirin, and nonsteroidal anti-inflammatory drugs. Various desensitization protocols have been proposed for each drug. The optimization of drug concentration, target dosage, administration interval, and route of administration is key to successful desensitization. In addition, the desensitization protocol should be individualized for each patient with consideration of the severity of the initial hypersensitivity response, the characteristics of the culprit drug, and the nature of the breakthrough reactions.

Resolution of the Council of Experts of May 20, 2023 "Issues of safety in the treatment of a rheumatological patient"

At the meeting of the Expert Council on May 20, the safety of treatment for patients with osteoarthritis (OA), the most common form of joint disease, was discussed. The first step in the treatment of OA should be the administration of symptomatic delayed-acting agents (SYSADOA) and nonsteroidal anti-inflammatory drugs (NSAIDs). However, given the current understanding of the pathogenesis of inflammation, as well as the fact that it is an active process involving multiple proinflammatory and pro-resolving mediators, it is reasonable to limit the cyclooxygenase-2 suppressive treatment and to include medications with multipurpose effects that contribute to the resolution of inflammation, in particular Zeel® T and Traumeel® S. Traumeel® S affects all stages of inflammation, mostly on the pro-resolving mediators synthesis, and Zeel® T affects chondrogenesis, inflammation, metabolic processes in cartilage tissue and prevents angiogenesis.It was found that it is advisable to use Traumeel® S when it is not possible to prescribe systemic NSAIDs for pain relief. The combination of the proven therapeutic efficacy of Zeel® T and Traumeel® S with a minimal number of adverse events and the absence of interactions with other drugs allows them to be used as an independent treatment regimen for OA.

Giant cell carcinoma of the lung with hypertrophic pulmonary osteoarthropathy as a paraneoplastic syndrome: a case report

BackgroundHypertrophic pulmonary osteoarthropathy is a rare syndrome characterized by a triad that includes periostitis, digital clubbing, and painful arthropathy of the large joints, especially large joints in the lower limbs with lung cancer. Herein we describe a case of a giant cell carcinoma of the lung with hypertrophic pulmonary osteoarthropathy as a paraneoplastic syndrome. The tumor was successfully resected, and complete remission of the syndrome was achieved after surgery.Case presentationA 48-year-old man with right fingers and bilateral ankle arthralgias was referred to our hospital. These arthropathies were painful and refractory to the oral administration of several non-steroidal anti-inflammatory drugs; thus, oxycodone hydrochloride hydrate was prescribed. Additionally, the fingers and toes had a clubbed appearance and the tubular bones were shown as double lines on radiographs of both arms and legs, indicating periosteal thickening. A 45-mm mass-like shadow was present on the right upper-to-middle lung field on the chest x-ray, which was confirmed to be a mass in the upper lobe of the right lung on the chest CT scan. An abnormal uptake was observed in the area of the mass on the FDG-PET scan; the standardized uptake value maximum was 11.8. The histologic diagnosis of a bronchoscopic biopsy was an undifferentiated carcinoma, and the clinical diagnosis was non-small cell lung cancer. The clinical stage was c-T2bN0M0 with paraneoplastic syndrome as a hypertrophic pulmonary osteoarthropathy. A right upper lobectomy with an S6 partial resection adjacent to the upper lobe of the right lung and an ND2a-2 lymph node dissection was performed. The postoperative course was uneventful. The pathologic diagnosis was a giant cell lung carcinoma, which was classified as p-T3 (52 mm in diameter) N0M0, stageIIB. A gradual decrease in arthritic pain was observed from the first operative day. No anodyne, including oxycodone, was required approximately 2 months after surgery. No tumor or paraneoplastic syndrome recurrence was observed 2 years postoperatively.ConclusionsHypertrophic pulmonary osteoarthritis may occur as a secondary manifestation of lung malignancies. Thus, the paraneoplastic syndrome should be considered in such cases.

Perioperative pain management protocols of veterinarians in the United States for horses undergoing routine orchiectomy (castration)

SummaryBackgroundAnalgesic protocols related to orchiectomy or castration of young horses vary widely depending on geographic location, educational background of the veterinarian, and other demographic factors. Specific practices of equine veterinarians in the United States (US) have not been reported.ObjectivesTo determine perioperative pain management practices of equine veterinarians in the United States as they relate to castration of healthy yearling colts.Study designCross‐sectional survey.MethodsAn internet‐based questionnaire included items related to analgesic drugs used in association with castration of healthy yearling colts. Demographic, educational, and experiential factors associated with routine recommendation of analgesic medications after castration were analysed with calculation of odds ratios (OR) with 95% confidence intervals (CI) and multivariable logistic regression.ResultsResponses from 146 equine veterinarians in the United States revealed that 112/146 (76.7%) administered a nonsteroidal anti‐inflammatory drug (NSAID) at the time of castration, and 107/143 respondents (73.3%) recommended administration of NSAIDs for a median of 3 days (IQR = 3–5) after surgery. Veterinarians who recommended NSAID analgesia after castration provided a higher pain severity score for horses at 24 h after a routine castration. Routine recommendation of post‐castration NSAID analgesia was associated with veterinarians who were employed in a multi‐veterinarian practice (OR = 2.7, 95% CI = 1.2–6.1) and completed their veterinary education in the year 2000 or more recently (OR = 2.6, 95% CI = 1.1–5.9).Main limitationsPossible distribution, self‐selection, and response biases as a result of convenience sampling methodology and possible recall bias of respondents.ConclusionsPerioperative pain management practices vary widely among US veterinarians but the majority of veterinarians, especially more recent graduates and those in multi‐veterinarian practices, recommend administration of an NSAID at the time of castration and for a median of 3 days after surgery.

Preemptive Analgesic Efficacy of Dexamethasone and Diclofenac in Mitigating Post-surgical Complications After Mandibular Third-Molar Surgery: A Systematic Review.

Mandibular third-molar extraction is a frequently executed minor oral surgical procedure, with a subsequent recovery period lasting several days. Typically, preemptive administration of non-steroid anti-inflammatory drugs (NSAIDs) and steroids has been employed, resulting in a notable decrease in postoperative complications like pain, facial swelling, trismus, and alveolar osteitis. This systematic review's primary goal was to investigate the efficacy of preemptive analgesia with dexamethasone and diclofenac in minimizing the post-surgical complications following the surgical extraction of the mandibular third molars. The systematic search was carried out to identify relevant literature in digital databases including PubMed®, Cochrane Library, Web of Science, and Scopus, from January 1990 to January 2022. The search used specific keywords. The randomized clinical trials assessing the efficacy of dexamethasone and diclofenac or dexamethasone alone compared to diclofenac or placebo as preemptive analgesics were consideredinclusion criteria for this systematic review. Case reports, literature reviews, letters to the editor, and non-English publications were not included. Two authors screened the titles and abstracts, and articles fulfilling the study criteria were included. After reading the full text and data collection, analysis was performed. The included article's bias was evaluated by the Risk of Bias 2 (RoB 2) tool. Adigital database search yielded a total of 207 articles. After excluding duplicates and articles written in languages other than English, 90 were removed. Based on the title and abstract, out of 177, 95 studies were excluded.After full-text reading of 22 articles, 17 were eliminated because they did not meet the inclusion and exclusion criteria. The remaining five studies were found eligible and included in the systematic review. Four studies were of low risk, while one study had some concerns. Two studies evaluated the combination of dexamethasone with diclofenac, while three evaluated dexamethasone alone. Total samples included samples of 436 third-molar surgeries in 420 patients. There was a substantial decrease in the mean pain score and swelling measurement when diclofenac alone was compared with coadministration of diclofenac and dexamethasone. Preemptive administration of dexamethasone and diclofenac has been shown to effectively reduce pain and facial swelling, with the exception of trismus, in third-molar surgeries when compared to diclofenac alone. As a result, it is recommended to administer these drugs prior to the commencement of third-molar extraction. However, further research is mandatory, specifically good quality randomized controlled trials involving large cohorts, in order to assess any significant variations and validate these findings.

Unusual Case of Biliary Peritonitis in a Dog Secondary to a Gastric Perforation

Biliary peritonitis is a pathological condition representing a medical emergency with a high risk of mortality. This condition is reported in both human and veterinary medicine following biliary tract rupture, extrahepatic biliary obstructions, gallbladder rupture, trauma, or duodenal perforation. In this report, the first-ever case of biliary peritonitis due to gastric perforation in a Bobtail purebred dog is described, which was probably induced by the administration of nonsteroidal anti-inflammatory drugs (NSAIDs). After an elective splenectomy and castration, the dog was referred to our hospital for medical management for inappetence, mental depression, and multiple episodes of gastric vomits with traces of blood. Clinical diagnostic tests showed the presence of biliary peritonitis. Due to worsening clinical conditions, the patient was subjected to euthanasia. Macroscopic examination showed a free brownish abdominal effusion and the presence of perforating ulcer of the stomach pylorus region.

Effect of Firocoxib and Flunixin Meglumine on Large Colon Mural Thickness of Healthy Horses

Nonsteroidal anti-inflammatory drug (NSAID) administration carries risks of gastrointestinal toxicity. Selective COX-2 inhibitors (“coxibs”) were designed to reduce risks of adverse effects but are still associated with gastrointestinal complications in humans. The effect of coxibs on colonic inflammation and integrity in horses is unknown. The study objective was to compare the effects of the coxib firocoxib and the nonselective NSAID flunixin meglumine on ultrasonographic indicators of colonic inflammation in healthy horses. Twelve healthy adult horses were administered flunixin meglumine (1.1 mg/kg IV q12h) and omeprazole (1 mg/kg PO q24h) for 5 days, allowed a 6-month washout period, then administered firocoxib (0.3 mg/kg PO once, then 0.1 mg/kg PO q24h for 4 days) and omeprazole. Transabdominal ultrasonographic examination and serum chemistry profiles were performed at the beginning and end of each treatment week. Colon wall thickness increased over time when horses received firocoxib (median post treatment 5.8 mm, interquartile range 2.8 mm; P < .001), but not flunixin (median 3 mm, interquartile range 1.2 mm; P = .7) and was significantly greater following firocoxib compared to flunixin (P = .003). Subjectively, colonic edema was noted more frequently following treatment with firocoxib (11/12 horses), compared to flunixin (1/12 horses). There were no clinically significant alterations in hematologic parameters after administration of either drug. The increase in colon wall thickness following treatment with the COX-2 selective NSAID firocoxib may suggest a risk of subclinical colitis in healthy horses. Monitoring colonic health when NSAIDs are used in a clinical setting is warranted.

Enhanced recovery protocol after cesarean delivery: impact on opioid use and pain perception

Opioids are routinely prescribed to patients postoperatively after cesarean delivery. With rates of cesarean deliveries increasing globally and the opioid epidemic continuing to have deleterious effects, finding methods to achieve effective pain control without opioids is of increasing importance. The ERAS (Enhanced Recovery After Surgery) protocol applied following cesarean delivery engages multimodal perioperative management techniques to encourage early recovery. In the obstetrical surgery setting, these interventions include increasing scheduled nonsteroidal anti-inflammatory drug administration and laxative use to improve postoperative gastrointestinal motility and pain scores. Postcesarean patients are also encouraged to use abdominal binders, incentive spirometry, and early movement as pain modulators. This quality improvement study aimed to measure whether the introduction of an ERAS protocol following cesarean delivery at a United States-based health network would improve outcomes such as the use of opioid medications for pain and pain control. This single-center retrospective cohort study compared patients who gave birth via cesarean delivery before (n=1425) and after (n=3478) the implementation of the postsurgical recovery protocol. Outcomes of interest included total postoperative opioid medications used, discharge opioid prescription, average pain score, pain scores by postoperative day, and highest pain score. Patients with a history of opioid use disorder, those who underwent a cesarean hysterectomy, and those who experienced a major surgical complication at delivery were excluded. Data were collected from the electronic medical record. Patients in the postimplementation period used significantly fewer opioid medications than those who gave birth before the protocol was introduced at the institution. The total median opioid use before implementation was 75 morphine milligram equivalents (interquartile range, 45-112.5) vs 30 (interquartile range, 15-52.5) after implementation (P<.001). The median discharge prescription was 225 (interquartile range, 150-225) before implementation vs 112.5 (interquartile range, 75-150) after implementation (P<.001). Pain scores were also significantly lower after implementation. The median highest pain score was 8 (interquartile range, 6-8) on a 10-point pain scale before implementation vs 7 (interquartile range, 6-8) after implementation (P<.001). The average pain score before implementation was 3.4 (interquartile range, 2.4-4.5) vs 2.9 (interquartile range, 1.9-3.9) after implementation (P<.001). Results of paired-sample analyses of 177 patients who gave birth by cesarean delivery in both time periods showed statistically significant outcomes similar to those of the larger cohort groups. Implementation of multimodal pain regimens following cesarean delivery, such as the ERAS protocol, which incorporate both pharmacologic (nonsteroidal anti-inflammatory drugs, laxatives) and nonpharmacologic methods (abdominal binders, deep breathing, movement) can be effective for pain control and may decrease postoperative opioid prescribing needs, thus mitigating the potential for opioid misuse and dependence.

An Open-Label Randomized Controlled Trial Comparing Effectiveness of Aggressive Hydration Versus High-dose Rectal Indomethacin in the Prevention of Postendoscopic Retrograde Cholangiopancreatographic Pancreatitis (AHRI-PEP).

Although rectal administration of nonsteroidal anti-inflammatory drugs is recommended as the standard pharmacologic modality to prevent postendoscopic retrograde cholangiopancreatography (ERCP) post-ERCP pancreatitis (PEP), vigorous periprocedural hydration (vHR) with lactated Ringer's solution (LR) is emerging as an effective prophylaxis modality for PEP. There has been no head-to-head comparison between these 2. This was a single-center, randomized, open-label, noninferiority, parallel-assigned, equal allocation, controlled clinical trial in a tertiary care hospital. Consecutive adults referred for ERCP, satisfying predefined inclusion criteria, underwent simple randomization and blinded allocation into 2 groups. Those allocated to vHR received intravenous LR at 3 mL/kg/h during procedure, 20 ml/kg bolus immediately afterward, and then at 3 mL/kg/h for another 8 hours. Those randomized to rectal Indomethacin received only per-rectal 100 mg suppository immediately post-ERCP. Assuming PEP of 9% in Indomethacin arm and noninferiority margin of 4%, we calculated sample size of 171 patients in each arm for 80% power and α-error 5%. Primary outcome was incidence of PEP, within 1 week, as defined by Cotton's criteria. All analysis were done by intention-to-treat. Between October, 2017 to February, 2018, 521 patients were assessed. In all, 352 were enrolled, 178 randomized to vHR, and 174 to per-rectal Indomethacin. Baseline details and ERCP outcomes were not different between 2 groups. PEP occurred in 6 (1.7%) overall, with 1 (0.6%) in hydration arm, and 5 (2.9%) in indomethacin arm; an absolute risk reduction of 2.3% (95% confidence interval: 0.9%-3.5%) and odds ratio of 0.19 (95% confidence interval: 0.02-1.65). Three patients developed severe PEP, all receiving indomethacin. vHR with LR is noninferior to postprocedure per-rectal Indomethacin for PEP prevention (ClinicalTrials.govID:NCT03629600).

Impact of postoperative NSAIDs administration on anastomotic leak after esophago-gastric surgery: systematic review and meta-analysis.

Anastomotic leak (AL) is a feared complication of esophago-gastric surgery. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat postoperative pain. Previous analyses conveyed heterogeneous data for colorectal surgery with a tendency toward high risk for AL after NSAIDs administration. In the setting of upper gastrointestinal (GI) surgery data are even more puzzled. The purpose of the present study was to assess whether an association exists between postoperative NSAIDs administration and AL after esophago-gastric surgery. PubMed, MEDLINE, Scopus, and Web of Science were searched up to November 2022. The included studies evaluated outcomes for NSAIDs vs. no NSAIDs administration after esophago-gastric surgery. The primary outcome was anastomotic leak (AL). Risk ratio (RR) and 95% confidence intervals (95% CI) were used to assess pooled effect size and relative inference. Six studies (43,784 patients) were included. The patient age ranged from 31 to 84years, 82.4% were males and preoperative BMI ranged from 15 to 31kg/m2. Esophagectomy was performed in 95% of patients. NSAIDs were administered in 18,075 (41.3%) patients. The cumulative incidence of AL was similar for NSAIDs vs. no NSAIDs (13.6% vs. 13.4%). The risk for postoperative AL was similar for NSAIDs vs. no NSAIDs administration (RR 1.49; 95% CI 0.81-2.75; p = 0.19). The cumulative incidence of postoperative gastrointestinal bleeding (0.36% vs. 0.39%), acute kidney injury (0.62% vs. 0.71%), and in-hospital mortality (2.39% vs. 2.66%) were comparable. NSAIDs administration for postoperative analgesia seems not associated with an increased risk for AL after esophago-gastric surgery.

An Overview and Management of Painful Menstrual Disorder (Dysmenorrhea): A Narrative Literature Review

Primary dysmenorrhea is menstrual pain associated with the release of prostaglandins in the ovulatory cycle, but not with the pelvic disease. Approximately 90% of all women experience dysmenorrhea, 15% of whom are unable to last 1 to 3 days because of the severity of the pain. This literature review aimed to describe an overview and management of dysmenorrhea. Primary dysmenorrhea usually begins with the onset of ovulation cycles, with the highest prevalence in adolescence. In contrast, secondary dysmenorrhea is associated with pelvic pathology (i.e., ovarian cysts, adenomyosis, endometriosis) that manifests in later reproductive years and can occur at any point in the menstrual cycle. Administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is the treatment of choice because these drugs reduce the activity of the cyclooxygenase (COX) enzyme and, thus, the production of prostaglandins. NSAIDs work in the majority of women with primary dysmenorrhea and are most effective when started at the first sign of bleeding or cramping.

Abstract 6333: Repurposing NSAIDs for chemo-immunotherapy: mechanisms beyond COX inhibition

Abstract It has been well-established that some nonsteroidal anti-inflammatory drugs (NSAIDs) have antitumor activities. The beneficial effects of these NSAIDs are mainly attributed to their ability to inhibit the production and activity of cyclooxygenases (COX1 and COX2) and prostaglandin (PGE2), which are known to promote tumor progression, angiogenesis, metastasis and immunosuppression. We recently reported that administration of indomethacin, a prototypical NSAID, can enhance the antitumor efficacy of adoptive T cell therapy in animal models. However, currently adoptive T cell therapy as a treatment option is only suitable for selected patients with certain types of cancer. Here, we set out to explore the utility of indomethacin in a chemo-immunotherapy setting that is readily applicable to a wide range of cancers. Cyclophosphamide (CTX) is a widely used antineoplastic chemotherapeutic agent with immunostimulatory activities when used at low-medium doses. We show that indomethacin had no impact on tumor growth but can significantly enhance the antitumor effect of CTX in multiple mouse tumor models. The beneficial effect of indomethacin was diminished in immunodeficient mice or CD8 T cell-depleted wild-type mice, indicating the requirement for the host immunity. Furthermore, the CTX and indomethacin regimen can sensitize tumors to anti-PD1 immunotherapy. scRNAseq analysis of tumor samples revealed the impact of indomethacin on the tumor microenvironment. Our data also indicate that the immunopotentiating effect of indomethacin can be independent of PGE2 inhibition, and involves the TRAIL-DR5 axis in promoting tumor regression. Other potential mechanisms, including modulation of chronic interferon signaling in tumor cells, have also been investigated. Altogether, our study sheds light on the multiple mechanisms underlying indomethacin’s beneficial effects, and highlights the potential of NSAID administration as a readily applicable and cost-effective approach to augment the efficacy of chemo-immunotherapy. Citation Format: Ogacheko D. Okoko, Md Y. Gazi, Xin Wang, Caitlin Brandle, Mercy Kehinde-Ige, Gary A. Piazza, Huidong Shi, Gang Zhou. Repurposing NSAIDs for chemo-immunotherapy: mechanisms beyond COX inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6333.

Analgesic Patterns and Opioid Administration in Children Hospitalized With Acute Pancreatitis.

Pain is the most common symptom of acute pancreatitis (AP), and opioids have been utilized as the cornerstone of treatment. Despite the adverse effects of opioids, data on effective analgesia in children with AP is lacking. We aimed to evaluate analgesia prescribing patterns in pediatric AP, identify factors associated with opioid administration, and test the associations between opioid administration and hospital length of stay (LOS). This is a retrospective cohort study of pediatric AP hospitalizations in a single institution from 2010 to 2020. Opioid administration was calculated for the first 48 hours of admission (morphine milligram equivalent; MME48). Data on multimodal analgesia [defined as the administration of acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs)] during hospitalization was captured. The sample included 224 patients, mean age 12.0 years (standard deviation = 4.9) and 58.9% female. Median LOS was 4 days (interquartile range 2-9). Most patients (71.4%) were prescribed opioids, 77.7% acetaminophen, 40.2% NSAIDs, and 37.5% multimodal analgesia. Opioid administration decreased over the study period; in contrast, there was an increase in multimodal analgesia administration. Opioid administration did not differ by sex, age, biliary versus non-biliary etiology, or race/ethnicity. In a multivariate regression model, lower albumin values ( P < 0.01) and younger age ( P < 0.05) were significant predictors of increased LOS, while MME48 was not associated with increased LOS. Opioids were commonly administered; only 37.5% of children were administered multimodal analgesia during their hospitalization for AP. Opioid administration was not associated with increased LOS. Prospective studies are needed to determine optimal pain management for pediatric AP.

New Biologic Therapies in the Management of Psoriatic Arthritis: An Overview

Psoriatic arthritis is an inflammatory musculoskeletal condition that represents a major cause of physical and psychological disability. This disorder represents a significant diagnostic and management challenge, given that it has different forms of clinical presentation, associated comorbidities, and high rates of therapeutic resistance. Early diagnosis is of crucial importance in impacting the prognosis of the disease. Typical treatment includes the administration of non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, and the use of biological medicines. Currently, multiple biological therapies have proven to be advantageous in managing psoriatic arthritis, but they have not been fully approved for use in routine clinical practice. Therefore, in this article, we aim to provide an overview of the role of new biological therapies for the management of psoriatic arthritis.

The early inhibition of the COX-2 pathway in viperid phospholipase A2-induced skeletal muscle myotoxicity accelerates the tissue regeneration

The administration of non-steroidal anti-inflammatory drugs in the treatment of injury and muscle regeneration is still contradictory in effectiveness, especially regarding the timing of their administration. This can interfere with the production of prostaglandins originating from inflammatory isoform cyclooxygenase-2 (COX-2), which is essential to modulate tissue regeneration. The phospholipases A2 (PLA2) from viperid venoms cause myotoxicity, therefore constituting a tool for the study of supportive therapies to improve skeletal muscle regeneration. This study investigated the effect of early administration of lumiracoxib (selective inhibitor of COX-2) on the degeneration and regeneration stages of skeletal muscle after injury induced by a myotoxic PLA2. After 30 min and 48 h of intramuscular injection of PLA2, mice received lumiracoxib orally and histological, functional, and transcriptional parameters of muscle were evaluated from 6 h to 21 days. Inhibition of COX-2 in the early periods of PLA2-induced muscle degeneration reduced leukocyte influx, edema, and tissue damage. After the second administration of lumiracoxib, in regenerative stage, muscle showed increase in number of basophilic fibers, reduction in fibrosis content and advanced recovery of functionality characterized by the presence of fast type II fibers. The expression of Pax7 and myogenin were increased, indicating a great capacity for storing satellite cells and advanced mature state of tissue. Our data reveals a distinct role of COX-2-derived products during muscle degeneration and regeneration, in which early administration of lumiracoxib was a therapeutic strategy to modulate the effects of prostaglandins, providing a breakthrough in muscle tissue regeneration induced by a myotoxic PLA2.

EFFECTIVENESS OF NSAIDS FOR PAIN MANAGEMENT IN PERIODONTAL SURGERY

Introduction: The perception of pain is subjective and many factors may affect its power and duration in various oral surgical procedures. An effective treatment suggests a certain volume of knowledge and skills of dental practitioners. A combination of non-pharmacological and pharmacological agents is often used to relieve the pain. There is evidence that non-steroidal anti-inflammatory drugs (NSAIDs) are effective in treating acute pain. Hypotheses suggest that NSAIDs have analgesic and anti-inflammatory effects by reducing the synthesis of arachidonic acid’s metabolites - prostaglandins (PGE2, PGI2), thromboxane (TxA2, TxB2) which are responsible for the occurrence of both - inflammation and pain. With the hyperalgesia initiated by PGE2 and bradykinin, we can explain the presence of postoperative pain because it reduces the pain threshold and increases susceptibility to available threshold inducements. Aim: To evaluate the effectiveness of postoperative NSAID administration in order to prevent the production of inflammatory components induced by the surgical treatment. Material and methods: The study included 15 patients who received surgical therapy. The selective COX-2 inhibitor of the new class Aulin® and the non-selective COX-2 inhibitor Ibuprofen® were taken from the patients as systemic administration postoperatively for a period of 3 days. The VRS-4 scale was used to assess the pain. Results: The assessment of the mean values for the degree of pain did not show statistically significant differences in the inhibition of pain for the two drugs in the three postsurgical days. Conclusion: In the absence of a significant difference between the two drugs - Aulin® and Ibuprofen®, we may confirm that according to our study they are both sufficiently effective in controlling postoperative pain in surgical periodontal procedures.

Prevention of post-ERCP pancreatitis: current strategies and novel perspectives.

Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced endoscopic procedure that might lead to severe adverse events. Post-ERCP pancreatitis (PEP) is the most common post-procedural complication, which is related to significant mortality and increasing healthcare costs. Up to now, the prevalent approach to prevent PEP consisted of employing pharmacological and technical expedients that have been shown to improve post-ERCP outcomes, such as the administration of rectal nonsteroidal anti-inflammatory drugs, aggressive intravenous hydration, and the placement of a pancreatic stent. However, it has been reported that PEP originates from a more complex interaction of procedural and patient-related factors. Appropriate ERCP training has a pivotal role in PEP prevention strategy, and it is not a chance that a low PEP rate is universally considered one of the most relevant indicators of proficiency in ERCP. Scant data on the acquisition of skills during the ERCP training are currently available, although some efforts have been recently done to shorten the learning curve by way of simulation-based training and demonstrate competency by meeting technical requirements as well as adopting skill evaluation scales. Besides, the identification of adequate indications for ERCP and accurate pre-procedural risk stratification of patients might help to reduce PEP occurrence regardless of the endoscopist's technical abilities, and generally preserve safety in ERCP. This review aims at delineating current preventive strategies and highlighting novel perspectives for a safer ERCP focusing on the prevention of PEP.

Phonophoresis through Nonsteroidal Anti-Inflammatory Drugs for Knee Osteoarthritis Treatment: Systematic Review and Meta-Analysis.

Knee osteoarthritis (OA) is the most common joint disease. The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) by phonophoresis is a therapeutic alternative to relieve pain in inflammatory pathologies. The main aim was to analyze the efficacy of the application of NSAIDs by phonophoresis in knee OA. A systematic review and meta-analysis of controlled clinical trials were performed between January and March 2021 in the following databases: Web of Science, Scopus, PubMed, Cinahl, SciELO, and PEDro. The PEDro scale was used to evaluate the level of evidence of the selected studies. The RevMan 5.4 statistical software was used to obtain the meta-analysis. Eight studies were included, of which five were included in the meta-analysis, involving 195 participants. The NSAIDs used through phonophoresis were ibuprofen, piroxicam, diclofenac sodium, diclofenac diethylammonium, ketoprofen, and methyl salicylate. The overall result for pain showed not-conclusive results, but a trend toward significance was found in favor of the phonophoresis group compared to the control group (standardized mean difference (SMD) = -0.92; 95% confidence interval: -1.87-0.02). Favorable results were obtained for physical function (SMD = -1.34; 95% CI: -2.00-0.68). Based on the selected studies, the application of NSAIDs by phonophoresis is effective in relieving the symptoms of knee OA. Future long-term studies are recommended.

Rectal administration of low-dose diclofenac does not reduce post-endoscopic retrograde cholangiopancreatography pancreatitis: a propensity score matching analysis.

Endoscopic retrograde cholangiopancreatography (ERCP) is a popular technique; however, post-ERCP pancreatitis (PEP) remains a major adverse event. The administration of rectal nonsteroidal anti-inflammatory drugs (NSAIDs) is reportedly effective in preventing PEP. However, the recommended dose varies and the efficacy of low-dose rectal NSAIDs remains unclear. Therefore, we decided to investigate the effectiveness of low-dose rectal diclofenac on PEP prevention, using propensity score matching. This single-center retrospective study included 401 patients who underwent ERCP between July 2015 and March 2020. After December 2016, we administered rectal diclofenac within 30min before the ERCP procedure as widely as possible. Patients were divided into those who did (diclofenac group) and did not (control group) receive rectal diclofenac. Patients weighing ≥ 50kg were administered a 50mg dose, while those weighing < 50kg were administered a 25mg dose. The incidence and severity of PEP in the two groups were assessed by propensity score matching analysis. Among 401 patients undergoing ERCP, 367 fulfilled the inclusion criteria. Overall, 187 patients received rectal diclofenac (diclofenac group) and 180 did not (control group). After propensity score matching, 105 pairs were selected for evaluation. Overall, seven (6.7%) patients in the diclofenac group and 10 (9.5%) in the control group developed PEP (P = 0.45). Moderate or severe PEP occurred in four (3.8%) patients in the diclofenac group and six (5.7%) in the control group (P = 0.52). The administration of low-dose rectal diclofenac could not reduce the incidence and severity of PEP.