Nonsteroidal anti-inflammatory drugs before endoscopic ultrasound guided tissue acquisition to reduce the incidence of post procedural pancreatitis

Endoscopic ultrasound(EUS)with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and auto-immune pancreatitis or to analyze cyst fluid.The most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis,which is likely induced by the same pathophysiological mechanisms as after en-doscopic retrograde cholangiopancreatography(ERCP).According to the current European Society of Gastrointestinal Endoscopy guideline,nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate.A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition(TA)is harm-less in healthy adults.Since it is associated with low costs and,most important,may prevent a dreadsome complication,we strongly recommend the adminis-tration of 100 mg diclofenac rectally prior to EUS-TA.We will explain this recom-mendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.

Role of nonsteroidal anti-inflammatory drugs in the prevention of post-ERCP pancreatitis:a meta-analysis

BACKGROUND: The role of prophylactic nonsteroidal anti-inflammatory drugs (NSAIDs) for reduction of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) is debated. We performed a meta-analysis of all published randomized controlled trials to evaluate the efficacy of NSAIDs in the prevention of post-ERCP pancreatitis. DATA SOURCES: Searches were conducted in the databases PubMed, EMBASE and the Cochrane Library. Six randomized clinical trials that fulfilled the inclusion criteria and addressed the clinical questions of this analysis were further assessed. Data were extracted by two independent observers according to predetermined criteria. RESULTS: The risk of pancreatitis was lower in the NSAID group than in the placebo, group (OR: 0.46, 95% CI: 0.32 to 0.65, P < 0.0001). Two hours after ERCP, prophylactic administration of NSAIDs was associated with a lower serum amylase level (WMD: -91.09,95% CI: -149.78 to -32.40, P=0.002), but there was no difference in mean 24-hour serum amylase values (WMD: -379.00, 95% CI: -805.75 to 47.76, P=0.08). No deaths or NSAID-related complications were noted. CONCLUSIONS: Prophylactic administration of NSAIDs can reduce the incidence of post-ERCP pancreatitis; this administration in patients undergoing ERCP is recommended. Further randomized controlled trials are required before its introduction into routine care.

Effectiveness of nonsteroidal anti-inflammatory drugs in prevention of post-ERCP pancreatitis:A meta-analysis

AIM: To investigate the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). METHODS: Two independent reviewers searched Pub Med (1966 to October 2013), Embase (1984 to October 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 4, 2013) for relevant randomized controlled trials (RCTs) studying the effectiveness of prophylactic NSAID administration in the prevention of PEP. Using the Cochrane Collaboration Handbook, meta-analyses were conducted to evaluate the overall effect of NSAIDs in preventing the incidences of PEP and moderate to severe pancreatitis. RESULTS: Eight RCTs were identified from the literature search and included 1883 patients that underwent ERCP, with 971 patients in the NSAID group and 912 patients in the placebo group. Sixty-nine out of 971 (7.11%) patients developed PEP in the NSAID group in comparison to 143 out of 912 (15.68%) patients in the placebo group. The pooled RR of PEP incidence with prophylactic NSAID administration was 0.43 (95%CI: 0.33-0.56), which demonstrates that NSAID administration after ERCP significantly reduced the incidence of PEP when compared to the placebo group (P < 0.0001). Subgroup analysis was performed and revealed that the presence (NSAID group) or absence (placebo group) of NSAIDs had no significant effect on the development of moderate to severe pancreatitis (RR = 0.79, 95%CI: 0.52-1.18). Moreover, the administration of NSAIDs as a rectal suppository (RR = 0.35, 95%CI: 0.26-0.48; P < 0.0001) was more effective than oral administration (RR = 0.97, 95%CI: 0.53-1.80) or through infusion (RR = 0.43, 95%CI: 0.12-1.54). CONCLUSION: NSAIDs effectively reduce the incidence of PEP but not of moderate to severe pancreatitis. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use: Old question new insights

Previous reports clearly demonstrated that Helicobacter pylori(H.pylori)infection,nonsteroidal anti-inflammatory drugs(NSAID)or low dose aspirin(ASA)use significantly and independently increased the risk for the development of peptic ulcer disease.Today,the presence of H.pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications.Whether NSAID intake in the presence of H.pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate.Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years.In addition,the interaction between H.pylori infection and low-dose ASA remains even more controversial.In real clinical practice,we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors.These huge variety of possible combinations greatly hinder the decision making process of physicians.

Inflammatory myofibroblastic tumor successfully treated with chemotherapy and nonsteroidals:A case report

Inflammatory myofibroblastic tumor(IMT) occurring at retroperitoneal sites has rarely been reported.We report the case of a previously well 14-year-old girl with no history of abdominal disease whose past medical history and family tumor history were unremarkable.She complained of intermittent abdominal pain for one month.An abdominal mass was found on physical examination and abdominal contrast-enhanced computed tomography(CT) showed a hypodense soft mass,the size and location of which suggested a well delineated retroperitoneal tumor surrounding the superior mesenteric vessels measuring 3.3 cm × 4.5 cm × 4.5 cm with enlarged lymph nodes.The patient underwent an exploratory laparotomy followed by biopsy and was subsequently diagnosed with retroperitoneal IMT.She was successfully treated with postoperative chemotherapy and oral diclofenac sodium.Following completion of therapy the mass was no longer palpable and no longer visible on CT scanning.The use of methotrexate and cisplatin for aggressive myofibroblastic tumors is also reviewed.

Characteristics and clinical outcome of nonsteroidal anti-inflammatory drug-induced acute hepato-nephrotoxicity among Chinese patients

AIM: To determine the clinicopathological characteristics of nonsteroidal anti-inflammatory drug (NSAID)-induced acute hepato-nephrotoxicity among Chinese patients.

Split-dose or hybrid nonsteroidal anti-inflammatory drugs and Nacetylcysteine therapy for prevention of post-retrograde cholangiopancreatography pancreatitis

BACKGROUND Despite significant technical and training improvements, the incidence of postendoscopic retrograde cholangiopancreatography(ERCP) pancreatitis(PEP) has not significantly dropped. Although many studies have evaluated the efficacy of various agents, e.g. nonsteroidal anti-inflammatory drugs, octreotide,antioxidants, administered via various dosages, routes(oral, intrarectal or parenteral), and schedules(before or after the procedure), the results have been conflicting.AIM To evaluate efficacy of three pharmacologic prophylactic methods for prevention of PEP.METHODS In this prospective, single-center randomized trial, patients who underwent firsttime ERCP for choledocholithiasis were randomly assigned to three groups. The first group received 600 mg N-acetylcysteine 15 min prior to ERCP, and perrectum administration of 50 mg indomethacin both prior to and after completion of the ERCP. The second group was administered only the 50 mg indomethacin per-rectum both prior to and after the ERCP. The third group was administeredper-rectum 100 mg indomethacin only after the ERCP, representing the control group given the guideline-recommended regimen. The primary end-point was PEP prevention.RESULTS Among the total 211 patients evaluated during the study, 186 fulfilled the inclusion criteria and completed the protocol. The percentages of patients who developed PEP in each of the three groups were not significantly different(χ2 =2.793, P = 0.247). Among the acute PEP cases, for all groups, 14 patients developed mild pancreatitis(77.77%) and 4 moderate. No severe cases of PEP occurred, and in all PEP cases the resolution was favorable. No adverse events related to the medications(digestive hemorrhage, rectal irritation, or allergies)occurred.CONCLUSION The efficacies of split-dose indomethacin and combined administration(Nacetylcysteine with indomethacin) for preventing PEP were similar to that of the standard regimen.

Inhibitory effect of fluvastatin on ileal ulcer formation in rats induced by nonsteroidal antiinflammatory drug

AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs)cause gastrointestinal damage as one of their side effects in humans and experimental animals. Lipid peroxidation plays an important role in NSAID-induced ulceration. The aim of this study was to investigate the inhibitory effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)reductase inhibitors on the ulceration in small intestines of rats.METHODS: The effects of three HMG-CoA reductase inhibitors, fluvastatin, pravastatin and atorvastatin on ileal ulcer formation in 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl) thiophene (BFMeT)-treated rats were examined. Antioxidative activity of the inhibitors was measured by a redox-linked colorimetric method.RESULTS: Fluvastatin, which was reported to have antioxidative activity, repressed the ileal ulcer formation in rats treated with BFMeT an NSAIDs. However, the other HMG-CoA reductase inhibitors (pravastatin and atorvastatin)did not repress the ileal ulcer formation. Among these HMG-CoA reductase inhibitors, fluvastatin showed a significantly stronger reducing power than the others(pravastatin, atorvastatin).CONCLUSION: Fluvastatin having the antioxidaitive activity suppresses ulcer formation in rats induced by NSAIDs.

Gastric body diaphragm-like stricture as a rare complication of nonsteroidal anti-inflammatory drugs

Increased risk due to nonsteroidal anti-inflammatory drugs (NSAIDs) therapy has been observed in patients. Although diaphragm-like stricture in the small bowel and colon induced by NSAIDs therapy has been rarely reported, gastric body diaphragm-like stricture has not been reported. We describe the first case of gastric body diaphragm-like stricture due to NSAIDs in a 44-year-old male patient who was successfully treated by an endoscopic approach to avoid complicated surgery. This case highlights new insight into the disadvantages of NSAIDs and provides new data for future clinical studies.

Endoscopic and histopathological evaluation of acute gastric injury in high-dose acetaminophen and nonsteroidal anti-inflammatory drug ingestion with suicidal intent

AIM： To evaluate endoscopic and histopathologic aspects of acute gastric injury due to ingestion of high-dose acetaminophen and nonsteroidal antiinflammatory drugs （NSAIDs） with respect to some risk factors and patient characteristics. METHODS： The study group consists of 50 patients admitted to emergency department with high dose analgesic ingestion （group Ⅰ ） with suicidal intent. Thirty patients with or without mild complaints of dyspepsia （group Ⅱ） were selected as the control group. The study group was stratified according to the use of type and number of analgesics. Endoscopic findings were evaluated according to the Lanza score （LS）, expressing the severity of the gastroduodenal damage and biopsies according to a scoring system based on histopathologic findings of acute erosive gastritis. RESULTS： Gastroduodenal damage was significantly more severe in group Ⅰ compared to group Ⅱ （P 〈 0.01）. The LS was similar in both groups Ⅰ a and Ⅰb. However LS was significantly higher in patients who had ingested multiple NSAIDs （group Ⅰ c） compared to other patients （P 〈 0.01）. The LS was correlated to age （P 〈 0.01） and total amount of drug ingested （P 〈 0.05） in group Ⅰ ; but it was not correlated with Helicobacter pylori （H pylori） infection or duration of exposure （P 〉 0.05）. The biopsy score （BS） was higher in group Ⅰ than group Ⅱ （P 〈 0.01）, and higher in group Ⅰb than group Ⅰa （P 〈 0.05）. CONCLUSION： The histopathologic damage was more severe among NSAID ingesting patients compared to those ingesting only acetaminophen and there is no significant difference in the endoscopic findings between the groups. There is no significant difference in the LS between the groups. This lack of significance is remarkable in terms of the gastric effects of highdose acetaminophen.

Synthesis and Characterization of Naproxen-Salicylate Derivatives as Potential Dual-Targeted Inhibitors of Dihydrofolate Reductase

Dihydrofolate reductase (DHFR) is an enzyme that catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF). Chemotherapy drugs such as methotrexate help to slow the progression of cancer by limiting the ability of dividing cells to make nucleotides by competitively inhibiting DHFR. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been previously reported to exhibit competitive inhibition of DHFR, in addition to their primary action on cyclooxygenase enzymes. This interaction interferes with the enzymatic reduction of dihydrofolate to tetrahydrofolate, thereby impeding the folate metabolism pathway essential for nucleotide synthesis and cell proliferation. This activity stems from their structural resemblance to the p-aminobenzoyl-l-glutamate (pABG) moiety of folate, a substrate of DHFR. It has been established that NSAIDs containing a salicylate group (which has structural similarities to pABG), such as diflunisal, exhibit stronger DHFR-binding activity. In this study, we synthesized salicylate derivatives of naproxen with the aim of exploring their potential as inhibitors of DHFR. The interactions between these derivatives and human DHFR were characterized using a combination of biochemical, biophysical, and structural methods. Through polyacrylamide gel electrophoresis (PAGE) analysis, enzymatic assays, and quantitative ELISA, we investigated the binding affinity and inhibitory potency of the synthesized salicylate derivatives towards DHFR. The findings of this study suggest the potential of salicylate derivatives of naproxen as promising candidates for the inhibition of DHFR, thereby offering novel therapeutic opportunities for modulating the inflammatory process through multiple pathways. Further optimization of these derivatives could lead to the development of more efficacious dual-targeted analogs with enhanced therapeutic benefits.

Efficacy of Nonsteroidal Anti-inflammatory Drugs for Treatment of Uncomplicated Lower Urinary Tract Infections in Women:A Meta-analysis

Urinary tract infections(UTIs)are among the most frequent causes for antibiotic prescription and;therefore,alternative treatment options for UTIs can potentially reduce antibiotic usage and development of resistance.To evaluate the efficacy of nonsteroidal antiinflammatory drugs(NSAIDS)for the treatment of uncomplicated lower UTIs in women,this study implemented a meta-analytic approach to evaluate the results of available randomized clinical studies from online databases.A total of four trials involving 1144 patients with uncomplicated lower UTIs were included in the final evaluation.Results showed that symptom resolution at Day 3-4 in the NSAIDs group was significantly lower than that in the antibiotics group[pooled odds ratio(OR)=0.41,95%confidence interval(CI):0.23-0.74,P<0.05].However,there was no significant difference between the NSAIDs and antibiotics groups in symptom resolution at Day 7(pooled OR=0.43,95%CI:0.17-1.06,P=0.07),secondary antibiotic treatment rate at Day 28-30(pooled OR=1.15,95%CI:0.16-7.98,P=0.89)and adverse events rate(pooled OR=1.09,95%CI:0.61-1.96,P=0.77).Therefore,this metaanalysis suggests that,although inferior to antibiotics in fast symptom resolution,symptomatic treatment with NSAIDs can be considered as an alternative treatment option for uncomplicated lower UTIs in women.However,given the low number of randomized controlled trials that met inclusion criteria in this meta-analysis,efficacy of NSAIDs for treatment of uncomplicated lower UTIs should be further evaluated in more comprehensive clinical studies.

Clinical profile of medication-related emergencies among patients presenting to the emergency department:An observational study

Objective:To determine the clinical profile of patients presenting with medication-related emergencies to the Emergency Department of our institute.Methods:This was an observational study conducted between November 2018 and September 2020 at Bangalore Baptist Hospital,Karnataka.A total of 138 subjects who satisfied the inclusion criteria were included in the study.The severity of adverse drug reactions(ADR)is assessed based on the Hurwitz severity assessment scale of ADR.Glasgow coma scale at the time of presentation and source of medication were noted.The type of drug overdose,requirement of advanced airway and vasopressors,and the outcome were also assessed.Results:Among medication-related emergencies(n=138)in our study,ADR contributed to 70.3%(n=97)of the study population,and drug overdose accounted for 29.7%(n=41).One-third of the ADR occurred in patients aged above 60 years.Most patients were hemodynamically stable and did not require vasopressors,or advanced airway in both groups.Most patients had Glasgow coma scale ranging from 13-15 in both groups.Nonsteroidal anti-inflammatory drugs were the most used medicine(17/41,41.5%)and most medications were over the counter drugs(25/41,61.0%)in the drug overdose group;meanwhile in the ADR group,anti-diabetic medication was the most used medicine(34/97,35.1%)and most medications were prescribed in the ADR group(93/97,95.9%).Conclusions:Our study shows that ADR is the most common type of medication-related emergency.

外用非甾体抗炎药治疗肌肉骨骼系统疼痛的中国专家共识

【为了推动和规范中国外用非甾体抗炎药（nonsteroidal anti-inflammatory drugs,NSAIDs）用于运动损伤所致的轻、中度疼痛的治疗,中华医学会运动医疗分会于2014年10月在北京成立了外用NSAIDs疼痛治疗中国专家委员会,同时召开了外用NSAIDs药物临床应用专家咨询会。

镇痛剂肾病合并ANCA相关性血管炎2例

非甾体抗炎药（nonsteroidal antiinflammatory drugs,NSAIDs）可造成各种类型的肾损害,包括由于前列腺素合成障碍导致的急性肾功能衰竭、高钾血症和水钠潴留,细胞免疫介导的急性间质性肾炎、肾病综合征以及慢性间质性肾炎和肾乳头坏死。镇痛剂肾病（analgesic nephropathy,AN）指长期大量应用NSAIDs及其复方制剂造成的慢性肾小管间质性肾病和肾乳头坏死[1]。

非甾体抗炎药与肾脏毒性

非甾体抗炎药(nonsteroidal anti-in flammatory drugs,NSAIDs)原称解热镇痛药,是一大类不同质的化合物,包括水杨酸类的阿司匹林和氟苯水杨酸,多环酸类的吲哚美辛、苏灵大、萘普生、布洛芬、苯氧布洛芬。

Microvessel density is a prognostic marker of human gastric cancer

AIM: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine the possible role of COX-2 and VEGF in gastric cancer angiogenesis.METHODS: Forty-seven formalin-fixed paraffin-embedded tissue samples of gastric cancer were evaluated for COX-2, VEGF by immunohitochemical staining. To assess tumor angiogenesis, MVD was determined by immunohitochemical staining of endothelial protein factor Ⅷ-related antigen. The relationship among COX-2 and VEGF expression, MVD, and clinicopathologic parameters was analyzed. RESULTS: Among the 67 samples, high MVD was significantly associated with lymph node metastasis and poor survival. Multivariate survival analysis showed that MVD value and lymph node metastasis were independent prognostic factors. The expression rate of COX-2 and VEGF was significantly higher than that of the adjacent tissues. COX-2 and VEGF expression in gastric cancer was significantly correlated with tumor differentiation and depth of invasion, but not with survival. The mean MVD value of COX-2 or VEGF positive tumors was higher than that of COX-2 or VEGF negative tumors. A significant correlation was found between the expressions of COX-2and VEGF. CONCLUSION: MVD may be one of the important prognostic factors for gastric cancer patients. COX-2 and VEGF may play an important role in tumor progression by stimulating angiogenesis. VEGF might play a main role in the COX-2 angiogenic pathway. The inhibition of angiogenesis or COX-2, VEGF activity may have an important therapeutic benefit in the control of gastric cancer.

Efficacy of intramuscular diclofenac and fluid replacement in prevention of post-ERCP pancreatitis

AIM： TO assess the efficacy of intramuscular diclofenac and fluid replacement for prevention of post-endoscopic retrograde cholangiopancreatography （ERCP） pancreatitis.METHODS： A prospective, placebo-controlled study was conducted in 80 patients who underwent ERCP. Patients were randomized to receive parenteral diclofenac at a loading dose of 75 mg followed by the infusion of 5-10 mL/kg per hour isotonic saline over 4 h after the procedure, or the infusion of 500 mL isotonic saline as placebo. Patients were evaluated clinically, and serum amylase levels were measured 4, 8 and 24 h after the procedure.RESULTS： The two groups were matched for age, sex, underlying disease, ERCP findings, and type of treatment. The overall incidence of pancreatitis was 7.5% in the diclofenac group and 17.5% in the placebo group （12.5% in total）. There were no significant differences in the incidence of pancreatitis and other variables between the two groups. In the subgroup analysis, the frequency of pancreatitis in the patients without sphincter of Oddi dysfunction （SOD） was significantly lower in the diclofenac group than in the control group （ρ = 0.047）.CONCLUSION： Intramuscular diclofenac and fluid replacement lowered the rate of pancreatitis in patients without SOD.

Is rectal indomethacin effective in preventing of post-endoscopic retrograde cholangiopancreatography pancreatitis?

AIM: To investigate the effectiveness of rectally administered indomethacin in the prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and hyperamylasaemia in a multicentre study.

What are the effects of proton pump inhibitors on the small intestine?

Generally, proton-pump inhibitors(PPIs) have great benefit for patients with acid related disease with less frequently occurring side effects. According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury.Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth(SIBO) compared to patients who lack the aforementioned conditions.Furthermore, there is insufficient evidence that these conditions induce Clostridium difficile infection. At this time, PPI-induced dysbiosis is considered a type of SIBO. It now seems likely that intestinal bacterial flora influence many diseases, such as inflammatory bowel disease, diabetes mellitus, obesity, nonalcoholic fatty liver disease, and autoimmune diseases.When attempting to control intestinal bacterial flora with probiotics, prebiotics, and fecal microbiota transplantation, etc., the influence of acid suppression therapy, especially PPIs, should not be overlooked.