Intake Of Non-steroidal Anti-inflammatory Drugs Research Articles

Early-Life Exposure to Antibiotics and Risk for Crohn's Disease: A Nationwide Danish Birth Cohort Study.

Early-life antibiotic use can alter the intestinal flora and modify the risk of developing Crohn disease (CD), but rigorous epidemiological evidence is limited, with inconsistent results. We identified all children born in Denmark from 1995 to 2009 and followed them from birth until death, emigration, a diagnosis of CD, or January 1, 2013. Using Cox regression, we assessed the association between antibiotic exposure in the first year of life and subsequent risk for CD, adjusting for sex, degree of urbanization, birth order, birth year, route of delivery, gestational age, smoking during pregnancy, intake of nonsteroidal anti-inflammatory drugs in the first year of life, and family history of CD. During a median 9.5 years (9.3 million total person-years), CD was diagnosed in 208 of 979,039 children. Antibiotic use in the first year of life was associated with a higher risk of CD (adjusted hazard ratio, 1.4; 95% confidence interval [CI], 1.1-1.8), with the highest risk with ≥6 courses of antibiotics (adjusted hazard ratio, 4.1; 95% CI, 2.0-8.5). A family history of CD did not modify these risk associations. The cumulative risk of CD at the 11th birthday for children exposed to antibiotics in their first year of life was 0.16‰ (95% CI, 0.11‰-0.22‰) compared to 0.11‰ (95% CI, 0.08‰-0.15‰) for children unexposed to antibiotics in their first year of life. Antibiotic use in the first year of life is associated with a modestly increased risk for CD, although the absolute risk is very low.

Short-term glucocorticoids reduce risk of chronic NSAID and analgesic use in early methotrexate-treated rheumatoid arthritis patients with favourable prognosis: subanalysis of the CareRA randomised controlled trial

ObjectiveTo explore non-steroidal anti-inflammatory drug (NSAID) and analgesic use in early rheumatoid arthritis (eRA) patients with a favourable risk profile initiating methotrexate (MTX) with or without glucocorticoid (GC) bridging.MethodsPatients with...

Link between postoperative ileus and anastomotic leakage: A structural equation modelling approach

IntroductionPostoperative ileus(POI) and anastomotic leakage(AL) are highly associated but the direction of this link is unknown. Indeed, it has traditionally been stated that AL leads to POI(secondary POI). The objective was to statistically determine the best model of link between POI and AL by comparing different Structural Equation Models(SEM). MethodsThis is a retrospective analysis of a prospective multicentric database from the Francophone Group for Enhanced Recovery after surgery(GRACE) including patients undergoing colorectal resection or Hartmann reversal between 2014 and 2017. The main outcome measure was the occurrence of postoperative ileus defined by the absence of Gastrointestinal (GI)-3 recovery in or after postoperative day 4 and the occurrence of AL. ResultsAmong the 2227 patients included, 223 patients experienced POI (10 %) and 72 patients experienced anastomotic leakage (3.2 %). In all the models, POI was significantly increased in case of male gender, older age, opioids consumption, right colectomy, chronic obstructive bronchopneumopathy disease and performance of a stoma, and reduced by Enhanced Recovery Programs (ERP) compliance ≥ 70 % and intake of Non-Steroidal Anti-Inflammatory Drugs. Open surgery was not significantly associated with POI in all the models. In contrast, the male gender was the only factor increasing AL in the model drawn with ERP risk factors for AL. In all the models, POI was highly associated with AL and statistical analyses advocate for POI leading to AL. ConclusionThe findings of the present large study suggest that the more statistically probable model is the one in which POI come first before AL.

Prescription pattern of non-steroidal anti-inflammatory drugs (NSAIDs) among community patients with musculoskeletal and co-morbid conditions: A crosssectional study from an Iraqi province

Purpose: To determine the pattern of prescription of non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) co-prescription with NSAIDs in a sample of patients suffering from musculoskeletal disorders with and without co-morbid cardiovascular (CV) disease conditions in Baghdad Province, Iraq.Methods: A descriptive, cross-sectional study was conducted using a structured questionnaire to assess the clinical characteristics of patients that used NSAIDs alone or with PPIs for the treatment of different musculoskeletal disorders with and without co-morbid cardiovascular (CV) disease conditions.Results: A total of 102 participants were enrolled in the study. More than half of the participants had comorbid disease conditions (53.9 %), particularly hypertension (47.1 %). Nearly a quarter of the participants with CV disease conditions used non-selective NSAIDs (25.5 %). The majority of NSAIDs intake were orally administered for more than one month (79.4 %). Physicians were the major source for patient education about the risk of NSAIDs-associated complications according to 59.6 % of the participants. The majority of participants reported non-adherence to the prescribed PPIs (86.5 %). There was a statistically significant difference between the participants that used NSAIDs alone, and those with PPI co-prescription within the age group of 31 - 60 years (p < 0.0001) and for a duration of more than one month for NSAIDs administration (p < 0.0001).Conclusion: There is improper use of NSAIDs, particularly the non-selective agents, among patients with co-morbid cardiovascular disease conditions, as well as poor medication adherence and improper co-prescription of PPIs. This requires periodic revision for long-term intake of NSAIDs, while applying more care to high-risk patients regarding co-prescription of NSAIDs with PPIs.
 Keywords: Cardiovascular, Co-morbidity, Gastrointestinal complications, NSAIDs, Proton-pump inhibitors

Evaluation of the efficacy and safety of bioactive concentrate from small sea fish in elderly patients with knee osteoarthritis

Objective: to evaluate the efficacy and safety of Alflutop (the bioactive concentrate from small sea fish) in patients aged 75 years and older with knee osteoarthritis (OA). Patients and methods. The investigation enrolled 38 patients aged 75 years and older with knee OA (according to the American College of Rheumatology (ACR) criteria, 1986), Kellgren–Lawrence grades II–III, ≥40 mm pain visual analogue scale (VAS), who required continuous non-steroidal anti-inflammatory drug (NSAID) use. All the patients received Alflutop in the standard regimen: a 1-ml intramuscular injection daily for 20 days. The dynamics of pain during movement was assessed using the VAS scale, the WOMAC, and the EQ-5D questionnaire. Comorbidity was determined according to the Charlson comorbidity index, polypharmacy, and the safety of therapy in all the patients. The investigation duration was 8 weeks.Results and discussion. On day 21 of Alflutop therapy, there was a statistically significant reduction in pain, stiffness, and functional insufficiency according to the WOMAC index (p< 0.001) and improvements in quality of life as shown by the EQ-5D questionnaire (p< 0.001); on day 56, the number of NSAID intake days decreased (p=0.005). The findings suggest that there is a high level of comorbidity in the majority (94.7%) of patients. The mean number of drugs taken was 5.0±1.5, which indicates the presence of polypharmacy. No serious or severe adverse events were recorded.Conclusion. The results of the investigation showed the statistically significant efficacy and safety of Alflutop in patients with knee OA in the elderly group.

Idiopathic Peptic Ulcer: a Separate Entity or Diagnostic Uncertainty?

Idiopathic peptic ulcer disease (IPUD) is an ulcer with no identifiable etiology. The major causes of peptic ulceration are Helicobacter pylori infection and ingestion of non-steroidal anti-inflammatory drugs. Is this a truly idiopathic disease or simply a misdiagnosis? The diagnosis of H. pylori infection can be missed if patients are taking antibiotics or proton pump inhibitors or when gastrointestinal bleeding occurs. A history of NSAID ingestion is often also overlooked. The proportion of IPUDs has increased over time. IPUDs occur more commonly in older patients and those with comorbidities. They run a more aggressive course, often presenting with bleeding and other ulcer complications and are more difficult to manage. IPUD is a distinct albeit a small group of ulcers. The diagnosis is made after careful exclusion of H. pylori infection, NSAID ingestion, and other obscure causes of peptic ulcers.

Effect of low salicylate diet on clinical and inflammatory markers in patients with aspirin exacerbated respiratory disease \u2013 a randomized crossover trial

BackgroundAspirin-exacerbated respiratory disease (AERD) is characterized by eosinophilic rhinosinusitis, nasal polyposis, and bronchial asthma, along with the onset of respiratory reactions after the ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid (ASA). In addition to the therapeutic routines and surgical options available, a low dietary intake of food salicylate has been suggested as adjunctive therapy for this condition.This study aimed to assess the influence of a short-term low salicylate diet on inflammatory markers in patients with AERD and whether that would result in symptomatic improvement.MethodsProspective study with randomization to either a high or low salicylate diet for 1 week, followed by cross-over to the other study arm. Participants were asked to record their dietary salicylate for each week of the study. Urinary creatinine, salicylate and leukotriene levels were measured at the time of recruitment, end of week one and end of week two and the SNOT-22 questionnaire was filled out at the same time points.ResultsA total of seven participants completed the study. There was no statistical difference in the urinary salicylate and leukotriene levels between the two diets; nevertheless, participants on low salicylate diet reported improved SNOT-22 symptoms scores (p = 0.04), mainly in the rhinologic, ear/facial, and sleep dysfunction symptom domains. In addition, these last two domains outcomes were more significant than the minimal clinically important difference.ConclusionsA short-term low salicylate diet may not result in biochemical outcomes changes but seems to provide significant symptomatic relief for patients with AERD.Trial registrationNCT01778465 (www.clinicaltrials.gov)Graphical abstract

Результаты применения малоинвазивной двухэтапной декомпрессии с костной аллопластикой при аваскулярном некрозе головки бедренной кости

Avascular necrosis of the femoral head is a complex medical and social problem. The rapid development of the disease, the complexity of diagnosis and the prevalence among young patients leads to impaired hip joint function and further disability. To improve the quality of life of patients, the Orthopedic Department of the Traumatology Center of Khabarovsk developed a method of minimally invasive two-stage decompression. Surgical treatment was performed in 30 cases in patients with ANFH of stages 0, 1, 2 (by ARCO). Evaluation of treatment results was carried out before operative treatment, after 6 and 12 months. 12 months after surgical treatment, positive dynamics was noted, namely, pain reduction, a walking distance increase, abandonment of crutches, opportunity to use public transport, ability to sit for a long time in one and the same position, to put on shoes, and the abandonment of constant intake of non-steroidal anti-inflammatory drugs. The assessment of hip joint function in 20% of cases showed an excellent result, in 26,6% of cases — a good result, in 40% — satisfactory, and in 13,3% (4 people) — unsatisfactory result, which proves the effectiveness of the proposed treatment method and the feasibility of its use.

Hemosuccus pancreaticus due to a small arterial pseudoaneurysm detected by CE-EUS and successfully treated with angiographic coiling (with video).

In hemosuccus pancreaticus,[1] potentially life-threatening bleeding into the pancreatic duct is usually caused by a large arterial pseudoaneurysm (average size of 52 mm) in chronic pancreatitis.[2] Bleeding from the papilla can be seen by endoscopy, and pseudoaneurysm can be detected by standard cross-sectional imaging. In this case report, a small pseudoaneurysm of the splenic artery with a fistula to the pancreatic duct could only be discovered by contrast-enhanced EUS (CE-EUS). A 54-year-old man with nonsteroidal anti-inflammatory drug intake and history of chronic alcohol pancreatitis was admitted for tarry stools. A cause for bleeding could not be identified by gastroscopy, ileocolonoscopy, abdominal ultrasound, and computed tomography [Figure 1]. However, the gastrointestinal bleeding continued. Small bowel video capsule endoscopy was performed and showed traces of blood in the duodenum. Repeated duodenoscopy presented a slight hemobilia from the papilla [Figure 2]. Therefore, hemosuccus pancreaticus was assumed, and CE-EUS indeed detected an arterial fistula to the pancreatic duct [Figure 3 and Video 1]. In the following, angiography showed a small pseudoaneurysm of the splenic artery [Figure 4], which was successfully treated by angiographic coiling [Figure 5] according to common guidelines.[3] Bleeding stopped after transfusion of summed up 9 units of blood. In some cases, EUS combined with Doppler ultrasound might be sufficient for the detection of the fistula[4] but failed in this patient. The useful application of CE-EUS in hemosuccus pancreaticus was previously shown in only one case report, in which the feeding vessel of a large pseudoaneurysm (42 mm) could not have been detected by angiography.[5] In conclusion, CE-EUS might be useful to detect hemosuccus pancreaticus due to small arterial pseudoaneurysms in patients with occult gastrointestinal bleeding.Figure 1: Computed tomography of the abdomen showing chronic pancreatitis with calcifications but cannot identify the source of gastrointestinal bleedingFigure 2: Slight hemobilia from the papilla is shown in repeated duodenoscopyFigure 3: Selected image from Video 1 showing the fistula from the arterial pseudoaneurysm to the pancreatic ductFigure 4: Selective angiography showing a small pseudoaneurysm (<20 mm) of the splenic artery. Fistula from the pseudoaneurysm to the pancreatic duct is not demonstratedFigure 5: Successfully treated pseudoaneurysm of the splenic artery by angiographic coiling. Direct application of the coils into the pseudoaneurysm had to be avoidedBRIEF DESCRIPTION CE-EUS was helpful to detect hemosuccus pancreaticus due to a small arterial pseudoaneurysm of the splenic artery in a patient with chronic pancreatitis and on-going occult gastrointestinal bleeding. Hemosuccus pancreaticus was successfully treated by angiographic coiling. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Unusual case of recurrent intestinal obstruction

Intestinal diaphragm disease is a very rare entity and is generally recurrent subacute intestinal obstruction. A 38-year-old male admitted to hospital with subacute intestinal obstruction. The patient had a history of long-term nonsteroidal anti-inflammatory drugs (NSAIDs) intake. On computed tomography scan, no pathology found except for dilated bowel loops. He underwent diagnostic laparoscopy which showed stricture along distal jejunum with proximal dilated gut loops with collapsed distal gut loops, found unusual thin intraluminal diaphragm with pinpoint 3 mm opening along with it there was one more diaphragm 2 cm distal to it with 2 mm pinpoint opening, resection of both the stricturous part was done, and end-to-end jejunojejunostomy was done. Here on, histopath grossly received a segment of the intestine in two pieces along with fibrofatty tissue. Cut-open specimen showed narrowing of the lumen and at one place is marked band-like constriction. Microscopic appearance shows ulcerations of lining epithelium. The submucosa shows fibrosis along with the proliferation of the muscle fiber, neural, and vascular elements giving impression consistent with the jejunal diaphragm. Here, we report an unusual case of intestinal diaphragm disease in relation to the use of NSAIDs. The aim is to sensitize the medical officers regarding the rational use of NSAIDs.

Capsule retention caused by cryptogenic multifocal ulcerous stenosing enteritis.

cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is a rare illness. Capsule retention (CR) has been reported in a few cases of CMUSE. we present four cases of CMUSE with CR. None of the patients showed any symptoms or signs of small bowel obstruction before capsule endoscopy (CE). All patients denied a history of non-steroidal anti-inflammatory drugs intake, radiotherapy treatment or abdominal surgery. CE disclosed circumferential stenosis with or without ulcers in the small bowel, some accompanied by mucosal edema, white spots and nodules. All patients underwent an elective surgery to remove the retained capsule and resect the lesions. CE plays a positive role in diagnosing CMUSE. CE findings are as important as CR to alert about the diagnosis of CMUSE.

Nonsteroidal anti-inflammatory drugs, muscle relaxants, and B-group vitamins in the treatment of lumbar ischialgia

Nonsteroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants are used orally or intramuscularly (IM) to treat lumbar ischialgia caused by musculoskeletal disorders or radiculopathy. A comparative study has been conducted to investigate the efficacy and safety of the NSAID meloxicam (Amelotex®) injected intramuscularly and into the trigger points in combination with tolperisone and B-group vitamins for lumbar ischialgia.Patients and methods. The investigation enrolled 62 patients aged 30–60 years with lumbar ischialgia, who were randomized into three equal groups. Group 1 patients were injected with meloxicam 1.5 ml (15 mg of its active ingredient) into the trigger points daily for 3 days, followed by one 15-mg tablet daily for 14 days; Group 2 received IM meloxicam 15 mg daily for 3 days, followed by one 15-mg tablet daily for 14 days; Group 3 had IM meloxicam 15 mg daily for 3 days, followed by one 15-mg tablet daily for 14 days in combination with tolperisone (Calmirex®) as tablets: 150 mg (Day 1 of therapy), 300 mg (Day 2), and 450 mg daily (Day 3 until the end of therapy). All the patients received IM Vitamin B complex (Compligam B®) 2 ml for 5 days. The treatment efficiency was evaluated using the pain visual analogue scale (VAS), the Oswestry disability questionnaire, and the McGill pain questionnaire, the range of motion, and the severity of neurodystrophic syndrome.Results and discussion. All the patient groups showed a rapid and substantial pain reduction on the VAS and a functional activity improvement according to the Oswestry scale, which made it possible to complete the treatment within an average of 9.6 days. Groups 3 and 1 exhibited a faster improvement and, as a result, a shorter therapy duration on 8.6±1.2 and 9.2±0.9 days than did Group 2 (8.6±1.2 days). On day 2 of treatment, there was a more considerable pain reduction on the VAS in Group 1 that received meloxicam injections into the trigger zones. The administration of meloxicam intramuscularly and into the trigger zones in combination with tolperisone and vitamin B complex was noted to be safe and well tolerated.Conclusion. The injection of Amelotex into the trigger zones is highly effective and safe in treating lumbar ischialgia. An NSAID (meloxicam) in combination with a muscle relaxant (tolperisone) speeds up recovery and shortens the duration of NSAID intake.

Chronological effects of non-steroidal anti-inflammatory drug therapy on oxidative stress and antioxidant status in patients with rheumatoid arthritis

Non-steroidal anti-inflammatory drugs (NSAIDs) are effective in reducing pain and inflammation in rheumatoid arthritis and other joint- and muscle-associated diseases. However, the extensive, long-term, and over the counter administration of NSAIDs may cause various side effects in the patients. In the present study, the chronological effect of NSAIDs on oxidative stress and antioxidant status in patients with rheumatoid arthritis was studied. The study included 100 female individuals categorized in four major groups: (1) control group consisting of age- and gender-matched healthy individuals, (2) NRA-NSAID individuals taking NSAIDs without any history of RA, (3) RA individuals with a history of RA but not taking NSAIDs, and (4) RA-NSAID individuals with chronic RA and taking NSAIDs for a long period. The sera of the participants were analyzed for the oxidative stress and antioxidant status. The RA-NSAID group showed the significantly highest oxidative stress, in terms of malondialdehyde content and lipid-reducing ability as determined in thiocyanate and hemoglobin-induced linoleic acid systems. However, the free radical scavenging ability of the RA-NSAID group, against 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, superoxide, and 2,2-azino-bis-tetrazolium sulfate radicals, was found to be lower than those of the other study groups. The regression analysis of the experimental data showed a significant positive relationship between duration of NSAID intake and malondialdehyde production, lipid-reducing ability, and metal chelating ability in the RA-NSAID patients. The free radical scavenging abilities of the RA-NSAID group were negatively correlated with the duration of NSAID intake. The prolonged use of NSAIDs significantly increased the oxidative stress and decrease the antioxidant potential of both the RA patients and NRA individuals. The study provides awareness to the public particularly the RA patients regarding the risk of oxidative stress-associated abnormalities caused by the frequent and prolonged use of NSAIDs for temporary relief from pain. Key Points • The study presents the effects of long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) on antioxidant status of patients with rheumatoid arthritis. • The continuous administration of NSAIDs has been found to significantly increase the oxidative stress of the patients with rheumatoid arthritis as well as the individuals with no signs of rheumatoid arthritis. • The prolonged NSAID therapy also decreased the antioxidant potential of the patients with rheumatoid arthritis as well as the individuals with no signs of rheumatoid arthritis. • The study would be a significant and valuable contribution to the literature for the awareness regarding the use of NSAIDs.

Risk factors of the gastric cancer – the short review

Introduction and purpose: Gastric cancer (GC) is one of the most frequent malignancies around the world. There were nearly 1 million new cases in 2018. Gastric malignancies have heterogeneous etiopathogenesis. Lifestyle, socioeconomic status, blood group A, medical condition, Helicobacter Pylori infection, family history, genetic polymorphism, diet, demographic characteristics, occupational exposure, ionizing radiation are considered as predisposing factors.Objective: The purpose of our study is to review a currently available data on PubMed about risk factors of gastric cancer to consider better understanding of gastric cancer etiology.A brief description of the state of knowledge: Current studies suggest that red meat, pickled vegetable or alcohol consumption, low socioeconomic status, cigarette smoking, blood group A and Helicobacter Pylori infection increase risk of GC. Decreased risk of gastric cancer is observed in case of white meat consumption, statin and non-steroidal anti-inflammatory drugs intake. It seems that family history and other genetic predispositions may have a crucial role in gastric cancer development.Conclusions: Variety of environmental, genetic and medical factors are considered with an increased risk of gastric cancer. The awareness of its existence facilitates pathogenesis of gastric malignancies and enables the implementation of proper diagnostic procedures, screening programs and prophylaxis.

Clinical Control of CSU with Antihistamines Allows for Tolerance of NSAID-Exacerbated Cutaneous Disease

Many patients with chronic spontaneous urticaria (CSU) experience exacerbations after the administration of nonsteroidal anti-inflammatory drugs (NSAIDs), with clinical implications for the selection of therapeutic options for pain management. Case reports suggest that antihistamines could prevent these reactions. To determine whether antihistamines can prevent NSAID-exacerbated reactions in patients with CSU. Data on 121 patients with CSU and a history of NSAID exacerbations were evaluated. Two types of challenge with NSAIDs were performed using the NSAIDs reported in the medical record (a diagnostic challenge test without the use of antihistamines and a challenge test using antihistamines). The order in which the tests were performed in each patient was dependent on the treating physician. Patients with a positive first diagnostic challenge underwent a second challenge using H1-antihistamines (anti-H1), patients with a negative first challenge using anti-H1 underwent a second diagnostic challenge without the use of anti-H1, and patients with a negative first diagnostic challenge or a positive first challenge using anti-H1 did not undergo a second challenge. In some patients, additional challenges were performed with an alternative NSAID before performing the diagnostic challenge test or the challenge test using anti-H1. In the diagnostic challenge test, 96 patients tested positive. Seventy-two (75%) of these patients tolerated the NSAIDs involved in the reaction when they used antihistamines. NSAID restrictions create many inconveniences for patients with CSU. Clinical control of CSU with the use of antihistamines can prevent further exacerbations due to NSAID intake in many patients to help them avoid unnecessary restrictions.

Idiosyncratic Drug-Induced Neutropenia and Agranulocytosis in Elderly Patients.

Agranulocytosis is a rare, but serious and life-threatening hematologic disorder in elderly patients. Idiosyncratic drug-induced agranulocytosis (IDIA) has been classically defined by a neutrophil count below 0.5 × 109/L. The annual incidence of IDIA in Europe is about 1.6–9.2 cases per million inhabitants. Increasing age and female sex have been considered as risk factors for the development of this condition. Besides, it is well known that older people take on average more drugs than younger people. This condition is most often associated with the intake of antibacterial agents, antiplatelets, antithyroids, antipsychotics, antiepileptics and nonsteroidal anti-inflammatory drugs (NSAIDs). Initially, agranulocytosis may present without symptoms, but may quickly progress to a severe infection and sepsis. The causative drug should be immediately stopped. In febrile patients, blood cultures and where indicated, site-specific cultures should be obtained and early treatment with empirical broad-spectrum antibiotics started. Even with adequate treatment, the mortality rate is higher in elderly patients reaching up to 20%. Hematopoietic growth factors have proven to be useful as they shorten the duration of neutropenia. However, data on neutropenia and agranulocytosis in the elderly meeting the criteria of evidence-based medicine are still poor in the literature. This review analyzes the results of our experience as well as other published studies of the universal literature.

Influence of Pain Killers on the Urinary Anabolic Steroid Profile.

Anabolic androgenic steroids (AAS) are prohibited as performance-enhancing drugs in sports. Among them, testosterone and its precursors are often referred to as "pseudoendogenous" AAS, that is, endogenous steroids that are prohibited when administered exogenously. To detect their misuse, among other methods, the World Anti-Doping Agency-accredited laboratories monitor the steroid profile (concentrations and concentration ratios of endogenous steroids, precursors and metabolites) in urine samples collected from athletes in and out of competition. Alterations in steroid profile markers are used as indicators for misuse of anabolic steroids in sports. Therefore, especially their metabolic pathways with possible interactions are crucial to elucidate. As steroid metabolism is very complex, and many enzymes are involved, certain non-prohibited drugs may influence steroid metabolite excretion. One important group of steroid-metabolizing enzymes is aldo-keto reductases (AKRs). An inhibition of them by non-steroidal anti-inflammatory drugs (NSAIDs), which are neither prohibited nor monitored, but frequently used drugs in sports, was demonstrated in vitro. Thus, this work aims to investigate the influence of NSAID intake on the urinary steroid profile. Kinetic and inhibitory studies were performed using 5α-dihydrotestosterone as substrate. The results obtained from in vitro experiments show that ibuprofen inhibits AKR1C2 and thus influences steroid biotransformation. For in vivo investigations, urine samples prior, during and postadministration of ibuprofen were analyzed using routine methods to monitor the steroid profile. Changes in markers of the steroid profile of volunteers were observed. The combination of in vitro and in vivo results suggests that monitoring of ibuprofen may be useful in doping control analysis. The presented work illustrates the importance to consider co-administration of (non-prohibited) drugs during antidoping analysis. Intake of multiple substances is likely leading to interfering effects. Divergent results in antidoping analysis may therefore be observed and misinterpretation of analytical data may occur. Similar considerations may be appropriate for other fields of forensic applications.

Idiopathic acute pancreatitis: a single-center investigation of clinical and biochemical features

Acute pancreatitis (AP) is termed as idiopathic (IAP) when the underlying conditions of pancreatic inflammation remain unknown. The aim of this study was to identify different clinical features in patients with IAP and AP of known aetiology. All patients hospitalized in our Gastroenterology Unit with an initial diagnosis of AP were recruited. AP was classified as of known aetiology or idiopathic according to clinical examination, serum biochemistry testing, and radiological imaging investigations, and clinical data in both patient groups were compared. A total of 127 patients (80 males, mean age: 57years) were eligible for the analysis, 92 of which (73%) with AP of known aetiology and 35 (27%) with IAP. The major causes of AP were biliary obstruction (65%) or alcohol abuse (25%). Previous cholecystectomy was more frequent in patients with AP of known aetiology than in patients with IAP (14% versus 0%); patients with IAP showed lower gamma-glutamyl transpeptidase levels, lower daily alcohol intake, and higher frequency of gastroenteritis than patients with AP of known aetiology (34.3% versus 15.2%). Previous intake of nonsteroidal anti-inflammatory drugs was more frequent in patients with IAP than in patients with AP of known aetiology (23% versus 0%). No further differences in clinical features were found between the two patient groups. IAP accounts for almost 20% of cases of AP. An association of AP with gastroenteritis or the use of NSAIDs should be considered if time-related with disease onset, especially in patients with no recurrent attacks.

RGS4 promotes allergen- and aspirin-associated airway hyperresponsiveness by inhibiting PGE2 biosynthesis

Allergens elicit host production of mediators acting on G-protein-coupled receptors to regulate airway tone. Among these is prostaglandin E2 (PGE2), which, in addition to its role as a bronchodilator, has anti-inflammatory actions. Some patients with asthma develop bronchospasm after the ingestion of aspirin and other nonsteroidal anti-inflammatory drugs, a disorder termed aspirin-exacerbated respiratory disease. This condition may result in part from abnormal dependence on the bronchoprotective actions of PGE2. We sought to understand the functions of regulator of G protein signaling 4 (RGS4), a cytoplasmic protein expressed in airway smooth muscle and bronchial epithelium that regulates the activity of G-protein-coupled receptors, in asthma. We examined RGS4 expression in human lung biopsies by immunohistochemistry. We assessed airways hyperresponsiveness (AHR) and lung inflammation in germline and airway smooth muscle-specific Rgs4-/- mice and in mice treated with an RGS4 antagonist after challenge with Aspergillus fumigatus. We examined the role of RGS4 in nonsteroidal anti-inflammatory drug-associated bronchoconstriction by challenging aspirin-exacerbated respiratory disease-like (ptges1-/-) mice with aspirin. RGS4 expression in respiratory epithelium is increased in subjects with severe asthma. Allergen-induced AHR was unexpectedly diminished in Rgs4-/- mice, a finding associated with increased airway PGE2 levels. RGS4 modulated allergen-induced PGE2 secretion in human bronchial epithelial cells and prostanoid-dependent bronchodilation. The RGS4 antagonist CCG203769 attenuated AHR induced by allergen or aspirin challenge of wild-type or ptges1-/- mice, respectively, in association with increased airway PGE2 levels. RGS4 may contribute to the development of AHR by reducing airway PGE2 biosynthesis in allergen- and aspirin-induced asthma.

Aspirin-exacerbated respiratory disease: longitudinal assessment of a large cohort and implications of diagnostic delay.

Aspirin-exacerbated respiratory disease (AERD) refers to the combination of asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and acute respiratory tract reactions to ingestion of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). There have been no in the literature investigating diagnostic delay in AERD. We aimed to investigate whether delay of diagnosis of AERD is associated with poorer clinical outcomes as well as to characterize the role of specialty evaluation in diagnosis. We conducted a retrospective observational study of 254 subjects with incident AERD diagnoses between 2009 and 2016 among Kaiser Permanente Northern California (KPNC) members. Descriptive and bivariate statistics were employed to analyze clinical characteristics and outcomes of AERD subjects with and without delay in diagnosis (defined as 1 year or greater from symptom onset to diagnosis). Of the 254 patients in the AERD cohort, 24.4% had a delayed diagnosis. Patients with allergies were significantly less likely to have a delay in diagnosis (p < 0.01). Patients with a delay in diagnosis were more likely to have 2 or more courses of systemic steroids (p = 0.04). Allergists, otolaryngologists, and primary care physicians diagnosed 56%, 36%, and 8% of patients, respectively. There was no association between provider specialty at time of diagnosis and delay in diagnosis (p = 0.22). A substantial proportion of AERD patients have a diagnostic delay. Patients with allergies have a lower risk for this delay. This study is the first to describe diagnostic delay in AERD patients.