Administration Of Anti-inflammatory Drugs Research Articles

Fulminant Heterotopic Ossification of the Lower Extremity After Gunshot Injury and Blunt Trauma: A Case Report.

Traumatic heterotopic ossification (HO) of the lower extremity is relatively rare but is of major importance in clinical practice. They are defined as posttraumatic abnormal formations of bone within soft tissue outside of the skeletal system. This article describes the clinical case of a 31-year-old male patient who suffered 2 traumatic events within 12 months-a gunshot wound in the lumbar spine/gluteal region followed by a severe traumatic brain injury with intracranial hemorrhage in a traffic accident as a pedestrian. Clinically, the patient was bedridden because of complete stiffening of the lumbar spine, both hip joints, and the left knee joint. After preoperative diagnosis, 3 surgical ablations of the HO were performed on both the hip joints and the left knee joint. In addition, physiotherapeutic exercise, postoperative nonsteroidal anti-inflammatory drug administration (25 mg of indomethazine for 6 weeks, 3 times a day), and perioperative radiation with 7 Gy for each operation were advised. After 4 years of follow-up, the patient showed significant improvement. In HO treatment, prophylactic local radiotherapy (pre- and postoperative radiation with a local single dose of 7 Gy) and postoperative administration of nonsteroidal anti-inflammatory drugs are often recommended. For therapeutic purposes, surgical resection is still indicated for pronounced cases.

Exploring Microemulsion Systems for the Incorporation of Glucocorticoids into Bacterial Cellulose: A Novel Approach for Anti-Inflammatory Wound Dressings.

The effective pharmacological treatment of inflamed wounds such as pyoderma gangraenosum remains challenging, as the systemic application of suitable drugs such as glucocorticoids is compromised by severe side effects and the inherent difficulties of wounds as drug targets. Furthermore, conventional semi-solid formulations are not suitable for direct application to open wounds. Thus, the treatment of inflamed wounds could considerably benefit from the development of active wound dressings for the topical administration of anti-inflammatory drugs. Although bacterial cellulose appears to be an ideal candidate for this purpose due to its known suitability for advanced wound care and as a drug delivery system, the incorporation of poorly water-soluble compounds into the hydrophilic material still poses a problem. The use of microemulsions could solve that open issue. The present study therefore explores their use as a novel approach to incorporate poorly water-soluble glucocorticoids into bacterial cellulose. Five microemulsion formulations were loaded with hydrocortisone or dexamethasone and characterized in detail, demonstrating their regular microstructure, biocompatibility and shelf-life stability. Bacterial cellulose was successfully loaded with the formulations as confirmed by transmission electron microscopy and surprisingly showed homogenous incorporation, even of w/o type microemulsions. High and controllable drug permeation through Strat-M® membranes was observed, and the anti-inflammatory activity for permeated glucocorticoids was confirmed in vitro. This study presents a novel approach for the development of anti-inflammatory wound dressings using bacterial cellulose in combination with microemulsions.

Comparing Metabolic Preconditioning and Diabetes As Risk Factors in Knee Arthroplasty Complications.

Advanced osteoarthritis of the knee joint severely affects the patient's mobility, compounded by pre-existing comorbidities such as metabolic preconditioning (such as obesity, dyslipidemia, hyperuricemia, and insulin resistance syndrome) and both type I and type II diabetes. The success of total knee arthroplasty is influenced by knowledge and management of risk factors. The present study aims to evaluate differences in the evolution of risk factors such as obesity, injuries, and sedentary lifestyle, distinguishing those with metabolic preconditions and diabetes. The objectives of our study include (1) investigating the prevalence of obesity among patients, highlighting their proportion in the five categories of body weight; (2) analyzing statistically significant differences between research groups in terms of weight status and physical activity; (3) evaluating postoperative evolution based on the administration of nonsteroidal anti-inflammatory drugs (NSAIDs) and without NSAIDs (N-NSAIDs), with an emphasis on overweight patients and those with diabetes; and (4) examining changes in metabolic preconditioning and the incidence of postoperative injury depending on the administration of anti-inflammatory drugs. A cohort involving 730 patients diagnosed with gonarthrosis was divided into two groupsaccording to the administration of anti-inflammatory drugs in the first seven postoperative days:N-NSAIDs group (394 patients, 55.3%)and respectively NSAIDs group (319 patients, 44.7%). Theprospective, observational study was conducted in terms ofrisk factors and complications that occurred upon treatment administration in relation to each type of intervention andimplant used. The outcomes were assessed in terms of the influence on quality of life, the data beingcollected and interpreted for the entire cohort, and for each study year individually. The results indicate that almost 69% of them were overweight, while only 31% had a normal weight. Significant differences in weight status were observed between research groups, highlighting the association between obesity and metabolic preconditions or diabetes. Physical activity was absent in a significant proportion, having a notable impact on postoperative evolution, especially in the group without metabolic precondition. Administration of anti-inflammatory drugs influenced postoperative outcomes, with significant differences in overweight and diabetic patients. The findings suggest the need to manage body weight, promote physical activity, and personalize postoperative treatments, given the complex interactions between obesity, metabolic preconditions, and the administration of NSAIDs.

Candidate Kidney Protective Strategies for Patients Undergoing Major Abdominal Surgery: A Secondary Analysis of the RELIEF Trial Cohort.

Acute kidney injury (AKI) is common after major abdominal surgery. Selection of candidate kidney protective strategies for testing in large trials should be based on robust preliminary evidence. A secondary analysis of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial was conducted in adult patients undergoing major abdominal surgery and randomly assigned to a restrictive or liberal perioperative fluid regimen. The primary outcome was maximum AKI stage before hospital discharge. Two multivariable ordinal regression models were developed to test the primary hypothesis that modifiable risk factors associated with increased maximum stage of postoperative AKI could be identified. Each model used a separate approach to variable selection to assess the sensitivity of the findings to modeling approach. For model 1, variable selection was informed by investigator opinion; for model 2, the Least Absolute Shrinkage and Selection Operator (LASSO) technique was used to develop a data-driven model from available variables. Of 2,444 patients analyzed, stage 1, 2, and 3 AKI occurred in 223 (9.1%), 59 (2.4%), and 36 (1.5%) patients, respectively. In multivariable modeling by model 1, administration of a nonsteroidal anti-inflammatory drug or cyclooxygenase-2 inhibitor, intraoperatively only (odds ratio, 1.77 [99% CI, 1.11 to 2.82]), and preoperative day-of-surgery administration of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker compared to no regular use (odds ratio, 1.84 [99% CI, 1.15 to 2.94]) were associated with increased odds for greater maximum stage AKI. These results were unchanged in model 2, with the additional finding of an inverse association between nadir hemoglobin concentration on postoperative day 1 and greater maximum stage AKI. Avoiding intraoperative nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors is a potential strategy to mitigate the risk for postoperative AKI. The findings strengthen the rationale for a clinical trial comprehensively testing the risk-benefit ratio of these drugs in the perioperative period.

Quantitative sensory testing, psychological factors, and quality of life as predictors of current and future pain in patients with knee osteoarthritis.

Substantial interindividual variability characterizes osteoarthritis (OA) pain. Previous findings identify quantitative sensory testing (QST), psychological factors, and health-related quality of life as contributors to OA pain and predictors of treatment outcomes. This exploratory study aimed to explain baseline OA pain intensity and predict OA pain after administration of a nonsteroidal anti-inflammatory drug in combination with paracetamol for 3 weeks. The Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score was used to estimate OA pain presentation. One hundred one patients were assessed at baseline and follow-up using QST (pressure pain thresholds and temporal summation of pain [TSP]), symptoms of depression and anxiety, pain catastrophizing scales (PCSs), and health-related quality of life. Linear regression with backward selection identified that PCS significantly explained 34.2% of the variability in baseline KOOS pain, with nonsignificant contributions from TSP. Pain catastrophizing score and TSP predicted 29.3% of follow-up KOOS pain, with nonsignificant contributions from symptoms of anxiety. When assessed separately, PCS was the strongest predictor (32.2% of baseline and 24.1% of follow-up pain), but QST, symptoms of anxiety and depression, PCS, and quality of life also explained some variability in baseline and follow-up knee OA pain. Further analyses revealed that only TSP and PCS were not mediated by any other included variables, highlighting their role as unique contributors to OA pain presentation. This study emphasizes the importance of embracing a multimodal approach to OA pain and highlights PCS and TSP as major contributors to the baseline OA pain experience and the OA pain experience after OA treatment.

Prognostic Factors for Severe-to-Fatal Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Multicenter Prospective Cohort Study.

The prognostic factors associated with severe-to-fatal post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remain unclear despite the extensive number of studies on PEP. In total, 3739 ERCP patients with biliary disease with an intact papilla and indicated for ERCP were prospectively enrolled at 36 centers from April 2017 to March 2018. Those with acute pancreatitis diagnosed before ERCP, altered gastrointestinal anatomy, and an American Society of Anesthesiologists (ASA) physical status > 4 were excluded. Univariate and multivariate logistic regression analyses were performed on patient-related factors, operator-related factors, procedure-related factors, and preventive measures to identify potential prognostic factors for severe-to-fatal PEP. Multivariate analyses revealed pancreatic guidewire-assisted biliary cannulation (OR 13.59, 95% CI 4.21-43.83, p < 0.001), post-ERCP non-steroidal anti-inflammatory drug (NSAID) administration (OR 11.54, 95% CI 3.83-34.81, p < 0.001), and previous pancreatitis (OR 6.94, 95% CI 1.45-33.33, p = 0.015) as significant risk factors for severe-to-fatal PEP. Preventive measures included endoscopic biliary sphincterotomy (EST; OR 0.29, 95% CI, 0.11-0.79, p = 0.015) and prophylactic pancreatic stents (PPSs; OR 0.11, 95% CI, 0.01-0.87, p = 0.036). In biliary ERCP, pancreatic guidewire-assisted biliary cannulation, NSAID administration after ERCP, and previous pancreatitis were risk factors for severe-to-fatal PEP, whereas EST and PPS were significant preventive measures for severe-to-fatal PEP.

A192 'GLYCOCAGED' DRUGS: PHARMACOKINETICS AND TRANSLATIONAL POTENTIAL FOR PEOPLE WITH IBD

Abstract Background Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gastrointestinal tract. Despite the alarming global increase in IBD burden with 1 in 121 Canadians affected, no cure exists. Systemic administration of anti-inflammatory drugs like corticosteroids is a front-line therapy for inducing remission. However, these drugs are limited in their application by deleterious off-target side effects. To target the drug to sites of inflammation and reduce systemic uptake, we developed a microbiome-cleavable, glycoconjugate drug delivery system, termed GlycoCage. We have demonstrated that GlycoCaged dexamethasone (Dex, a potent steroid), is effective at reducing inflammation at 10-fold lower doses than its uncaged counterpart in the SHIP-deficient (SHIP-/-) mouse model of CD-like intestinal inflammation. We hypothesize that GlycoCaged technology can expand the therapeutic window of IBD drugs by lowering effective doses and eliminating side effects. Aims: 1) Quantify Dex in systemic circulation. 2) Assess status of inflammation outside of the gut in SHIP-/- mice treated with caged Dex. 3) Measure decaging activity in people with IBD. Methods To compare systemic distribution of Dex to caged Dex, we orally gavaged SHIP+/+ and SHIP-/- mice with 3 mg/kg of Dex or the molar equivalent of caged Dex and collected serum for LC-MS/MS analysis at multiple timepoints post oral gavage. In addition to CD-like ileitis, SHIP-/- mice spontaneously develop enlarged mesenteric lymph nodes (MLNs) and inflamed lungs. After daily treatment of Dex or caged Dex for 2 weeks, MLNs and lungs were collected and analyzed for size and histopathology. We also obtained stool samples from healthy control participants and people with IBD to investigate the prevalence of prodrug-cleaving activity by direct enzymatic activity assay using fluorogenic resorufin as a prodrug proxy. Data from people with IBD were stratified to fecal calprotectin. Results Unlike free dexamethasone, caged dexamethasone did not enter systemic circulation or impact inflammation outside of the gut in SHIP-/- mice. All people have decaging activity that is not affected by IBD or the individual’s disease activity. Conclusions Our results highlight a novel glycoconjugated prodrug strategy to improve and broaden treatment options for people with IBD. In the future, we will evaluate GlycoCaged Dex in a mouse model of colitis and test the efficacy of other GlycoCaged drugs. Funding Agencies CCCGlycoNet

Ultrasound-guided erector spinae plane block for perioperative analgesia in patients undergoing laparoscopic nephrectomies surgery: a randomized controlled trial

BackgroundLaparoscopic nephrectomy is a commonly utilized surgical approach for the management of renal cancer. Despite its widespread acceptance, postoperative pain management remains a significant challenge for many patients undergoing this procedure. Traditional pain management techniques, including opioid and nonsteroidal anti-inflammatory drug administration, may not provide adequate pain relief and may result in adverse effects. In recent years, erector spinae plane block (ESPB) has emerged as a promising regional anesthesia technique due to its simplicity, safety, and potential efficacy in reducing postoperative pain. ESPB has demonstrated effectiveness in reducing postoperative pain in various surgical procedures. However, the efficacy of ESPB in laparoscopic nephrectomy for renal cancer has not been extensively studied. As such, further investigation is necessary to determine the potential benefits of ESPB in this context. The addition of adjuvants such as dexmedetomidine and dexamethasone to nerve blocks has been shown to improve both the duration and quality of the block. Multiple studies have demonstrated the safety and efficacy of these adjuvants in reducing postoperative pain and opioid consumption and improving patient satisfaction. The use of dexmedetomidine and dexamethasone as adjuvants for nerve blocks represents a promising approach for enhancing regional anesthesia and analgesia. In light of these findings, we have incorporated dexmedetomidine and dexamethasone into our nerve block protocol.MethodsThis study is a randomized controlled trial conducted at a single center, with 50 participants being randomized in a 1:1 ratio to either the ESPB group or the control group. The trial aims to investigate the efficacy of ESPB in patients diagnosed with kidney cancer who are scheduled for laparoscopic nephrectomy. The primary outcome measure is the total consumption of intraoperative sufentanil. Secondary outcomes include the VAS score at rest and during coughing at 1 h, 6 h, 12 h, 24 h, and 48 h after surgery; total intraoperative remifentanil consumption; the number of times rescue analgesia is required; and the incidence of nausea and vomiting in the first 24 h after surgery. This study is registered for a duration of 1 year and is being conducted in China.DiscussionThe objective of our study is to evaluate the potential benefits of erector spinae plane block (ESPB) in patients undergoing laparoscopic nephrectomy, with a focus on the impact of dexmedetomidine and dexamethasone as adjuvants on the quality and duration of the block, as well as postoperative pain and opioid consumption. By investigating the effects of these adjuvants in the context of ESPB, we hope to contribute to the growing body of literature on the use of adjuvants in nerve blocks and provide further insight into the potential benefits of this approach for improving patient outcomes following laparoscopic nephrectomy. This trial was approved by the Ethics Committee of the Second Affiliated Hospital of Army Medical University.Trial registrationChina Clinical Trial Register ChiCTR2300068578. Registered on 20 February 2023.

Diagnosis and treatment of Anaplasma centrale in a domestic cat at Animal Hospital of Hasanuddin University Makassar

Anaplasmosis is a disease caused by obligate gram-negative intracellular bacteria. Anaplasma in cats is generally infected by Anaplasma phagocytophilum, however there are very limited reports of Anaplasma bovis such as Anaplasma marginale and Anaplasma centrale being reported to infect cats. This is the first report of anaplasmosis caused by Anaplasma centrale in cats. The owner brought a one-year-old female domestic cat to the Animal Hospital of Hasanuddin University in Makassar with the condition of not wanting to eat, weak, lethargic, dehydrated, and not defaecating. Diagnosis is carried out through anamnesis, physical examination, clinical examination, and laboratory examination, in the form of haematology and blood smear tests. The results of the examination revealed flea infestation, a blood test identified Anaplasma centrale with characteristics such as the presence of morulae in the middle part of the erythrocytes, and routine blood work showed anaemia which was seen in the MCV parameters increasing and the MCHC values decreased. Treatment consists of administration of antibiotics, anti-inflammatory drugs, and supportive therapy. The cat showed good results, with symptoms starting to disappear and the animal appeared active.

Age and treatment on the day of embryo transfer in recipient mares affect likelihood of pregnancy.

This retrospective evaluation of data from a large commercial embryo transfer facility aimed to determine the extent to which age and treatment on the day of embryo transfer in recipient mares influence the likelihood of pregnancy. Embryo recovery was carried out on days 8-10 post-ovulation using transcervical uterine flushing. Recipient mares grouped according to their age were treated once on the day of embryo transfer (Day 3-8 post ovulation) and were assigned randomly to 1 of 3 groups: Mares in Group A (n=101) received antispasmodic, antimicrobial, and anti-inflammatory drugs. Mares in Group B (n=100) received gentamicin and flunixin meglumine. Group C (control) (n=103) did not receive any treatment. Detomidine (0.008 mg/kg bwt i.v.) was administered to all recipients before transfer of the embryo. The influence of treatment and recipient´s age was calculated using binary logistic regression. Day 16 post-transfer pregnancy rates were highest in Group A (74/101, 73.3a%), when compared to Group B (60/100, 60%), and Group C (57/103, 55.3b%) (a vs b, p<0.05). Pregnancy loss rates at D45 were not different between groups, A (8/74, 10.8%), B (5/60, 8.3%), and C (6/57, 10.5%), respectively (p>0.05). Pregnancy losses were increased in recipient mares 17-22 years (33.3a%) compared to younger recipient mares (2-6 years 7b%, 7-11 years 10%, 12-16 years 8b%) (a:b p<0.05). The regression model showed that the predicted probability for pregnancy after embryo transfer decreased as the age of the recipient mare increased for treated recipients in Group A (p=0.012), there was no effect of treatment and recipient´s age in Group B, and a decreased likelihood of pregnancy in recipients of advanced age (≥12 years of age) in untreated recipients (group C). Likelihood of pregnancy increased following single administration of antispasmodic, antimicrobial, and anti-inflammatory drugs at the time of embryo transfer in recipients 2-12 years of age. Likelihood of pregnancy in recipients decreased in recipients≥12 years of age. These results, obtained under the conditions of a large commercial embryo transfer program, offer an opportunity to improve pregnancy rates in recipient mares≤12 years of age.

Gastric ulcer in horses

Equine gastric ulcer comprises a complex of diseases associated with ulceration of the esophageal, gastric or duodenal mucosa. Ulceration occurs on nonglandular (squamous) and glandular gastric mucosa, with an average prevalence of 5% in pasture horses, 93% in racehorses and between 25% and 57% in foals. The incriminated causes are diet and incorrect feeding, stress and the administration of anti-inflammatory drugs (NSAIDs). Medication for gastric ulcers includes proton pump inhibitors, histamine (H2) receptor antagonists, prostaglandin analogs, and sucralfate.

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.

A survey on Flemish veterinary practitioners’ experience with stem cell therapy to treat equine tendon injuries

Horses in all equestrian disciplines are suffering from tendon injuries followed by several months of rehabilitation. Additionally, the scar tissue formed after injury is of inferior quality, resulting in high re-injury rates. Conventional treatments include rest, controlled exercise and anti-inflammatory drugs administration. In order to improve tissue regeneration and prevent reinjury, biological treatments, such as mesenchymal stem cells (MSCs) are gaining popularity. In this survey, the use of MSCs as treatment for tendon injuries by Flemish equine veterinary practitioners was evaluated. Although the respondents were in general unsatisfied with conventional therapy, it remains the preferred treatment. Approximately half of the survey population (47%) have already used MSCs therapy to treat tendon injuries. The other participants reported the high costs and complexity as major limitations. According to the respondents, the availability of strong scientific evidence of the mechanisms of action, accompanied by clear practical guidelines, could help to increase the practical application of MSC therapy.

Percentage of Th1 and Th17 cells and serum level of IL-17 and IFN-γ cytokines in COVID-19-associated mucormycosis.

The considerable number of the 2019 coronavirus disease (COVID-19) patients who developed mucormycosis infections in West and Central Asia urged a need to investigate the underlying causes of this fatal complication. It was hypothesized that an immunocompromised state secondary to the excessive administration of anti-inflammatory drugs was responsible for the outburst of mucormycosis in COVID-19 patients. Therefore, we aimed to study the implication of two major subsets of adaptive immunity T helper (Th)-1 and Th17 cells in disease development. Thirty patients with COVID-19-associated mucormycosis, 38 with COVID-19 without any sign or symptom of mucormycosis, and 26 healthy individuals were included. The percentage of Th1 and Th17 cells in peripheral blood, as well as the serum levels of interleukin (IL)-17 and interferon-gamma (IFN-γ), were evaluated using flow cytometry and ELISA techniques, respectively. Th17 cell percentage in patients with COVID-19-associated mucormycosis was significantly lower than in COVID-19 patients (P-value: <0.001) and healthy subjects (P-value: 0.01). In addition, the serum level of IL-17 in COVID-19 patients was significantly higher than that of healthy individuals (P-value: 0.01). However, neither the frequency of Th1 cells nor the serum level of IFN-γ was different between the study groups. Given the critical role of Th17 cells in the defense against mucosal fungal infections, these findings suggest that low numbers of Th17 and insufficient levels of IL-17 might be a predisposing factor for the development of mucormycosis during or after COVID-19 infection.

Molecular Mechanisms and Mediators of Hepatotoxicity Resulting from an Excess of Lipids and Non-Alcoholic Fatty Liver Disease

The paper reviews some of the mechanisms implicated in hepatotoxicity, which is induced by an excess of lipids. The paper spans a wide variety of topics: from the molecular mechanisms of excess lipids, to the therapy of hyperlipidemia, to the hepatotoxicity of lipid-lowering drugs. NAFLD is currently the leading cause of chronic liver disease in Western countries; the molecular mechanisms leading to NAFLD are only partially understood and there are no effective therapeutic interventions. The prevalence of liver disease is constantly increasing in industrialized countries due to a number of lifestyle variables, including excessive caloric intake, unbalanced diet, lack of physical activity, and abuse of hepatotoxic medicines. Considering the important functions of cell death and inflammation in the etiology of the majority, if not all, liver diseases, one efficient therapeutic treatment may include the administration of hepatoprotective and anti-inflammatory drugs, either alone or in combination. Clinical trials are currently being conducted in cohorts of patients with different liver diseases in order to explore this theory.

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.

Efficacy and Safety of Early Anti-inflammatory Drug Therapy for Secondary Injury in Traumatic Brain Injury.

Brain injury following head trauma occurs in 2 stages, namely an early stage attributable to mechanical damage and a delayed stage resulting primarily from neuroinflammation. In this study, we examined early proinflammatory cytokine upregulation in an animal model of traumatic brain injury (TBI) and examined the effects of early anti-inflammatory therapy on neuroinflammation, neuropathology, and systemic inflammatory activity. Seven-week-old C57BL/6 mice (20 g-25g) were subjected to sham treatment or closed skull impact from a 30-g round weight dropped 15cm onto the cortical midpoint. Model mice were then randomly assigned to receive intraperitoneal phosphate-buffered saline (control), 20mg/kg cyclosporine A, 2mg/kg dexamethasone, or 5mg/kg cholecalciferol 1hour post-TBI. Body weight, brain weight, cytokine expression in the brain and draining lymph nodes (DLNs), and histopathological changes were measured at multiple times post-TBI. Body weight did not significantly differ among the groups, whereas the brain-to-body weight ratio was significantly lower in the control group 7days post-TBI. The peak expression of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in the brain and DLNs 6hours post-TBI was significantly lower in the dexamethasone and cyclosporine A groups. Conversely, peak IL-10 expression in the brain and DLNs was elevated in the cholecalciferol group. Control mice exhibited earlier and more severe neuroinflammatory damage than those in the experimental groups. The administration of anti-inflammatory drugs or vitamin D analogs in the early period following TBI might help to reduce secondary injury from neuroinflammation.

SCGN deficiency is a risk factor for autism spectrum disorder

Autism spectrum disorder (ASD) affects 1–2% of all children and poses a great social and economic challenge for the globe. As a highly heterogeneous neurodevelopmental disorder, the development of its treatment is extremely challenging. Multiple pathways have been linked to the pathogenesis of ASD, including signaling involved in synaptic function, oxytocinergic activities, immune homeostasis, chromatin modifications, and mitochondrial functions. Here, we identify secretagogin (SCGN), a regulator of synaptic transmission, as a new risk gene for ASD. Two heterozygous loss-of-function mutations in SCGN are presented in ASD probands. Deletion of Scgn in zebrafish or mice leads to autism-like behaviors and impairs brain development. Mechanistically, Scgn deficiency disrupts the oxytocin signaling and abnormally activates inflammation in both animal models. Both ASD probands carrying Scgn mutations also show reduced oxytocin levels. Importantly, we demonstrate that the administration of oxytocin and anti-inflammatory drugs can attenuate ASD-associated defects caused by SCGN deficiency. Altogether, we identify a convergence between a potential autism genetic risk factor SCGN, and the pathological deregulation in oxytocinergic signaling and immune responses, providing potential treatment for ASD patients suffering from SCGN deficiency. Our study also indicates that it is critical to identify and stratify ASD patient populations based on their disease mechanisms, which could greatly enhance therapeutic success.

The Effect of Short-term Methylprednisolone on Clinical Outcome and Lung CT Scan in Severe COVID-19: In-hospital and Six Weeks Later Follow-up

Background: The severe coronavirus disease 2019 (COVID-19) induces widespread inflammatory responses that are attempted to be managed by the administration of anti-inflammatory drugs, along with antiviral drugs and respiratory support. This clinical trial study investigated the effect of short-term and low-dose methylprednisolone on the clinical outcome and radiological improvement of admitted patients with severe COVID-19. Methods: In this randomized clinical trial, two strains of patients with severe pneumonia of COVID-19 were evaluated before and after the use of corticosteroids. Inclusion criteria were age over 18 years, definitive case of COVID-19 based on positive reverse transcription polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), and arterial oxygen saturation (SaO2 )&lt;93%; furthermore, at least 7 days and 5 days should be passed since the onset of symptoms and antiviral treatment, respectively. Exclusion criteria were similar to contraindications to the administration of methylprednisolone for short-term injections and pregnancy. Patients received intravenous methylprednisolone succinate (1-1.75 mg/kg/day) for 5 days in addition to treatment based on the World Health Organization (WHO) approved protocol for COVID-19. Finally, demographic characteristics, dyspnea, peripheral oxygen saturation (SpO2), number of lymphocytes, and computed tomography (CT) scan of the patient’s chest before and after taking corticosteroids were evaluated. Results: The average oxygen saturation of patients increased significantly after taking methylprednisolone succinate (P&lt;0.001). Moreover, dyspnea and pulmonary insufficiency in CT scans improved significantly (P&lt;0.001), and among hematological parameters, only lymphocytes increased significantly (P=0.01). Furthermore, methylprednisolone succinate use had no effect on mortality and length of hospitalization. Conclusion: Methylprednisolone succinate use during the treatment period of COVID-19 improves clinical conditions, CT scan findings, and hematological parameters affected by inflammation, but it does not affect the mortality and length of hospitalization of patients.