Anti-inflammatory Regimens Research Articles

CSF and blood signatures support classification of limbic encephalitis subtypes

Autoimmune limbic encephalitis (ALE) represents a heterogeneous disease associated with antibodies targeting extracellular (ALEextra) epitopes, intracellular (ALEintra) epitopes, anti-glutamic acid decarboxylase65 ALE (ALEGAD65), and ALE without detectable antibodies (ALEabneg). Combining analysis of cellular parameters, investigated by flow cytometry, and soluble parameters in the blood and cerebrospinal fluid (CSF) from a large cohort of 148 ALE patients (33 ALEextra, 12 ALEintra, 28 ALE-GAD65, 37 ALEabneg) in comparison to paradigmatic examples for neuro-inflammatory (51 relapsing remitting MS patients (RRMS)), and neuro-degenerative (34 Alzheimer’s disease patients (AD)) diseases revealed discrete immune signatures in ALE subgroups. Identification of ALE-subtype specific markers facilitated classification of rare ALE-associated tumors, which may prompt further diagnostic efforts in clinical practice. While ALEintra exhibited features of neuro-inflammation, ALEextra displayed features of neuro-inflammation as well as neuro-degeneration. Moreover, ALEGAD65 and ALEabneg lacked hallmarks of inflammation. This may explain the low efficacy of anti-inflammatory treatment regimens in ALEGAD65 and presumably also ALEabneg.

An Approach to Controlling Inflammation and Coagulation in Pig-to-Baboon Cardiac Xenotransplantation.

Inflammatory responses and coagulation disorders are a relevant challenge for successful cardiac xenotransplantation on its way to the clinic. To cope with this, an effective and clinically practicable anti-inflammatory and anti-coagulatory regimen is needed. The inflammatory and coagulatory response can be reduced by genetic engineering of the organ-source pigs. Furthermore, there are several therapeutic strategies to prevent or reduce inflammatory responses and coagulation disorders following xenotransplantation. However, it is still unclear, which combination of drugs should be used in the clinical setting. To elucidate this, we present data from pig-to-baboon orthotopic cardiac xenotransplantation experiments using a combination of several anti-inflammatory drugs. Genetically modified piglets (GGTA1-KO, hCD46/hTBM transgenic) were used for orthotopic cardiac xenotransplantation into captive-bred baboons (n = 14). All animals received an anti-inflammatory drug therapy including a C1 esterase inhibitor, an IL-6 receptor antagonist, a TNF-α inhibitor, and an IL-1 receptor antagonist. As an additive medication, acetylsalicylic acid and unfractionated heparin were administered. The immunosuppressive regimen was based on CD40/CD40L co-stimulation blockade. During the experiments, leukocyte counts, levels of C-reactive protein (CRP) as well as systemic cytokine and chemokine levels and coagulation parameters were assessed at multiple timepoints. Four animals were excluded from further data analyses due to porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) infections (n = 2) or technical failures (n = 2). Leukocyte counts showed a relevant perioperative decrease, CRP levels an increase. In the postoperative period, leukocyte counts remained consistently within normal ranges, CRP levels showed three further peaks after about 35, 50, and 80 postoperative days. Analyses of cytokines and chemokines revealed different patterns. Some cytokines, like IL-8, increased about 2-fold in the perioperative period, but then decreased to levels comparable to the preoperative values or even lower. Other cytokines, such as IL-12/IL-23, decreased in the perioperative period and stayed at these levels. Besides perioperative decreases, there were no relevant alterations observed in coagulation parameters. In summary, all parameters showed an unremarkable course with regard to inflammatory responses and coagulation disorders following cardiac xenotransplantation and thus showed the effectiveness of our approach. Our preclinical experience with the anti-inflammatory drug therapy proved that controlling of inflammation and coagulation disorders in xenotransplantation is possible and well-practicable under the condition that transmission of pathogens, especially of PCMV/PRV to the recipient is prevented because PCMV/PRV also induces inflammation and coagulation disorders. Our anti-inflammatory regimen should also be applicable and effective in the clinical setting of cardiac xenotransplantation.

Evaluation of Dry Eye Treatment with Sodium Hyaluronate- and Dexpanthenol-Containing Eye Drops on Ocular Surface Improvement after Cataract Surgery.

To clinically evaluate how dry eye symptoms in preoperatively diagnosed dry eye patients change with the use of sodium hyaluronate- and dexpanthenol-containing eye drops (HYLO CARE (HC), URSAPHARM Arzneimittel GmbH, Saarbruecken, Germany) after cataract surgery. The aim of the study was not to compare different eye drops but to implement standard treatment in patients with dry eye undergoing cataract surgery. The impact of treatment was evaluated using Symptom Assessment Tools for Dry Eye. In this prospective, single-center, open-label clinical trial, 49 patients undergoing cataract surgery were included who showed signs and symptoms of dry eye disease assessed by the Symptom Assessment in Dry Eye (Visual Analogue Scale (VAS)) questionnaire, Ocular Surface Disease Index (OSDI), and fluorescein tear break-up Time (TBUT). Patients were instructed to apply HC three to four times a day for 5 weeks in the operated eye in addition to the standard postoperative topical anti-inflammatory regimen. The primary endpoint was the change in TBUT. Secondary endpoints were the assessment of the subjective symptoms (VAS), corrected distance visual acuity (CDVA), and slit-lamp examination including the corneal staining score, Schirmer test, and intraocular pressure. At 5 weeks after operation, the mean TBUT increased from 6.42 ± 1.57 s (s) to 7.81 ± 1.83 s in the per-protocol (PP) population (p > 0.001) and from 6.33 ± 1.64 s to 7.71 ± 2.05 s in the intention-to-treat (ITT) population (p < 0.001). There was a statistically significant decrease in all scores (p < 0.05) from the VAS questionnaire except for the tearing score (p = 0.062) at 5 weeks after operation. The mean total corneal staining score also decreased statistically significantly from 8.85 ± 2.49 before operation to 5.61 ± 3.37 at 5 weeks after operation on a 15-point scale. Controlled standardized dry eye treatment (with HC) improved tear film stability, ocular surface defects, and subjective symptoms of dry eye disease in patients 5 weeks after undergoing cataract surgery. Both the patient and physician assessments indicated high efficacy, tolerability, and a reliable safety profile, as indicated by the low number of at least possibly related adverse events (AE), suggesting its beneficial role in the postoperative management of the ocular surface (OS) in patients with dry eye symptoms prior to and after cataract surgery.

Effects of intracameral dexamethasone injection versus topical steroids post phacoemulsification operation

Introduction Cataract surgery is one of the most commonly performed surgeries worldwide, with nearly 20 million cases annually. Ophthalmologists usually use a prophylactic perioperative regimen consisting of topical corticosteroids and nonsteroidal anti-inflammatory drugs to reduce the risk of inflammation. However, patient compliance and other problems concerning administration with elderly patients self-administering medication drops can vary widely and a wide proportion of them fail to comply with a long-term regimen. Aim Evaluation of intracameral dexamethasone injection efficacy and safety versus topical anti-inflammatory eyedrop regimens for postphacoemulsification inflammation for better postoperative management of cataract patients. Methodology A prospective randomized clinical trial. Participants were divided into two groups in group A, dexamethasone sodium-phosphate (0.4 mg/0.1 mL) was injected intracamerally at the end of phacoemulsification surgeries without topical steroids postoperatively. Group B: took the routine postoperative anti-inflammatory steroidal and nonsteroidal eye drop regimen. Results Included the corneal thickness that showed no discernible change between postoperative numbers in both groups. Nevertheless, there was a statistically significant increase in CCT postoperatively in both groups. The intraocular pressure decreased significantly after 1 month of phacoemulsification operation in both groups simultaneously. Postoperative cell density and hexagonality were significantly lower in both groups compared with preoperative values. There was also no significant difference between both groups regarding the anterior chamber cells’ index. Moreover, the Dexamethasone-injected group showed better compliance on the postoperative visits regarding their prescriptions taken after the operation compared with the Prednisone acetate eye drops group. Conclusions Better results regarding the severity of the endothelial damage with the use of a single intraoperative injection post phacoemulsification compared with the group who did not get injected but took postoperative prednisone acetate eye drops. The obligatory single intraoperative injection of dexamethasone has handled the poor compliance of some patients’ post phacoemulsification.

The Wiser Strategy of Using Beta-Agonists in Asthma: Mechanisms and Rationales.

Concerns regarding the safety of beta-2 agonists have led to revisions of the major asthma guidelines to better address these issues. Although these updates allow for a combination of previous and current strategies, they may confuse clinical practitioners. Beta-2 agonists are vital for alleviating asthma symptoms by relaxing smooth muscles; however, they also pose significant risks by inducing pro-inflammatory mediators both in vitro and in vivo. In addition to the risks of overuse and symptom masking, the use of beta-agonists alone at therapeutic doses can worsen airway inflammation and enhance virus-induced inflammation during asthma exacerbation. Inhaled corticosteroids (ICS) can effectively prevent these adverse effects. With new insights into the mechanisms of these adverse events, reserving short-acting beta-agonists for acute symptom relief during exacerbations and only for those who are already on ICS or oral steroids represents a careful approach to using beta-agonists with least adverse effects in patients with asthma. However, a major drawback of this approach is the potential non-compliance with ICS, leading to beta-agonist use without the necessary counteraction by ICS. An optimal strategy, both during and outside exacerbations, would integrate beta-agonists into an anti-inflammatory regimen that includes ICS, ideally combined with the same inhaler to ensure their concurrent use where finances allow. This would maintain the beneficial effects of beta-agonists, such as bronchodilation, while preventing the adverse effects from the induction of inflammatory mediators. This method is aligned with diverse clinical settings, maximizes the safe use of beta-agonists, and supports a comprehensive guideline-compliant management strategy.

Can we predict lung sequelae in post-COVID-19 patients?

Amaç: COVID-19 pnömonisi ile hastaneye yatırılan hastalar, uzun süreli standart tedavi veya antienflamatuar rejim uygulansa bile enfeksiyon sonrası akciğer fibrozisine ilerleyebilir. Hangi hasta grubunun ilerleyici akciğer hastalığına sahip olacağını tahmin etmek zordur. Bu çalışma enfeksiyonun başlangıcından itibaren daha sonra akciğer fibrozisini öngörebilecek olası biyobelirteçleri tanımlamayı amaçlamaktadır.&#x0D; Gereç ve Yöntemler: Ocak-Aralık 2020 tarihleri arasında COVID-19 pnömonisi nedeniyle yatan ve PCR pozitif olan hastalar çalışmaya alındı. COVID-19 sonrası semptomlar ve akciğer sekel oluşumu açısından hastalar 12 ay boyunca takip edildi.&#x0D; Bulgular: Çalışmaya ortanca yaşı 62 (R: 17-93) olan toplam 64 hasta dahil edildi ve %42.2 kadındı (n=27). 35 hastada (%54.7) COVID sonrası semptomlar mevcuttu, 8 hasta (%12.5) kaybedildi ve 22’si (%34.4) yeniden hastaneye yatırıldı. Hastaların %76.6'sının klinik seyri iyiydi ancak hastaların %54.7'sinde enfeksiyon sonrası sekel gelişti. Pnömoni skoru, kan oksijen satürasyon düzeyi, CRP ve başvuru sırasındaki troponin düzeyleri sekel gelişimi ile anlamlı olarak ilişkiliydi (p

Remission of organ failure in patients with predicted severe acute pancreatitis treated by somatostation, octreotide and cyclooxygenase-2 inhibitors

Background/Objectives: Persistent organ failure (OF) in severe acute pancreatitis (SAP) is caused by activation of cytokine cascades, resulting in inflammatory injury. Anti-inflammation may be helpful in OF remission in early SAP. To assess the efficacy of anti-inflammatory regimens for OF prevention and remission in patients with predicted SAP and display clinical doctors' acceptance of these strategies, we conducted this retrospective study in the real world. MethodsClinical data of patients with predicted SAP from 2010 to 2017 were retrospectively reviewed. Cases were divided into conventional support (C), C+ somatostatin/octreotide (C + S/O), and C + S/O + Cyclooxygenase-2-inhibitors (C + S/O + COX-2-I). The occurrence of SAP, OF, changes of proportion for three strategies, length of hospital stay, meperidine injection, and cytokine levels were compared. The constituent ratios of the three schemes over eight years were evaluated. ResultsA total of 580 cases (C = 124, C + S/O = 290, C + S/O + COX-2-I = 166) were included. The occurrences of SAP in the C + S/O (28.3 %) and C + S/O + COX-2-I (18.1 %) groups were significantly lower than that in C group (60.5 %, P < 0.001), mainly by reducing persistent respiratory failure (P < 0.001) and renal failure (P = 0.002). C + S/O and C + S/O + COX-2-I regimens significantly decreased new onset OF and enhanced OF amelioration within 48 h when compared with C treatment (P < 0.001) in patients with OF score <2 and ≥ 2 on admission, respectively. C + S/O and C + S/O + COX-2-I as compared with C group significantly decrease OF occurrences in a multivariate logistic regression analysis (P < 0.05). ConclusionsSomatostatin or its analogs and cyclooxygenase-2 inhibitors are promising for OF prevention and remission in patients with predicted SAP. The acceptance of combined strategies in the real world has increased, and the occurrence of SAP has decreased annually.

Efficacy of the Fluocinolone Acetonide (Yutiq) Intravitreal Implant as Monotherapy for Uveitis

ABSTRACT Purpose To evaluate the efficacy of the fluocinolone acetonide intravitreal implant (Yutiq) as monotherapy for uveitis. Design Retrospective cohort study. Participants Patients at a single academic health-care institution. Methods Medical record review of patients with non-infectious uveitis actively suppressed on an alternative anti-inflammatory regimen who received a fluocinolone acetonide implant. The primary outcome was continued control of inflammation based on clinical examination, optical coherence tomography, and fluorescein angiography. Results Thirteen patients (19 eyes) received an implant. Median follow-up was 6 months. Uveitis control was achieved in 14 eyes (74%), though three (21%) required a topical steroid after insertion. The remaining five eyes (26%) required additional intraocular treatments. Conclusion The fluocinolone acetonide implant may not suffice as monotherapy for all patients with uveitis, but it may be effective as an adjunctive treatment. We propose a clinical workflow for the selection and treatment of patients who may benefit from it.

Co-treatment of Naringenin and Ketoprofen-RGD Suppresses Cell Proliferation via Calmodulin/PDE/cAMP/PKA Axis Pathway in Leukemia and Ovarian Cancer Cells.

Naringenin (Nar) has anti-inflammatory and anticarcinogenic properties. Arginine-glycine- aspartate (RGD) is a tripeptidic sequence used as an integrin ligand and targeting system for delivering chemotherapeutic agents to cancer cells. In this study, the inhibitory effects of Nar and ketoprofen-RGD on leukemia and ovarian cancer cells (K562 and SKOV3) were explored for the first time, focusing on their proliferation activity and their anti-inflammatory capacity. Analyses were conducted on the calmodulin (CaM)-dependent phosphodiesterase 1 (PDE1) activation by ketoprofen-RGD, Nar, and their combination. These drugs' effects on protein kinase A (PKA) activation, intracellular cyclic adenosine monophosphate (cAMP) level, and PDE1 inhibition were identified. Later, it was also evaluated if ketoprofen-RGD alone or in combination with Nar had anti-inflammatory effects. Nar improved the antagonizing consequences of ketoprofen-RGD on the CaM protein, which hinders PDE1, improving PKA activity and cAMP levels. A mixture of ketoprofen-RGD and Nar and ketoprofen-RGD alone diminished K562 and SKOV3 cell viability through the cAMP/PKA pathway by inhibiting PDE1 and CaM. These two compounds showed anti-inflammatory effects on both cell lines. This study indicated for the first time that combining ketoprofen-RGD and Nar can be a promising anti-inflammatory therapeutic regimen for treating leukemia and ovarian cancer.

Approach to dysmenorrhoea in primary care.

Approach to dysmenorrhoea in primary care.

Early Inflammation Control After Trabeculectomy by Steroid and Non-steroidal Eye Drops: A Randomized Controlled Trial.

To compare the effect of three different anti-inflammatory regimens consisting of preservative-free dexamethasone (DEX), diclofenac (DICLO) eye drops, and their combination (DEX+DICLO) following trabeculectomy on early postoperative inflammation. A prospective randomized controlled trial. Sixty-nine patients undergoing trabeculectomy were randomized to receive either postoperative treatment with topical DEX (n=23), topical DICLO (n=23), or a combination of topical DEX and topical DICLO (n=23) after trabeculectomy. The primary outcome was the anterior chamber flare measurement in the first 3months postoperatively. Secondary outcomes included intraocular pressure, central corneal thickness, conjunctival injection, and number of cells in the anterior chamber from baseline to 3months postoperatively. Anterior chamber flare reached a maximum 1 day after trabeculectomy with an increase of 55% (95% CI 37-73%) for DEX, 64% (95% CI 47-82%) for DICLO, and 57% (95% CI 39-75%) for DEX+DICLO and returned to near pre-operative values 6weeks after surgery. There were no significant differences in anterior chamber flare [effect size for DICLO: 0.16 (95% CI - 4.3 to 4.6), effect size for DEX+DICLO: 0.09 (95% CI - 4.1 to 4.3)], intraocular pressure, central corneal thickness, conjunctival injection, or number of cells in the anterior chamber between DEX, DICLO, or DEX+DICLO groups. We found that topical diclofenac was not statistically different from topical dexamethasone in controlling early postoperative inflammation after trabeculectomy, while combining diclofenac and dexamethasone offered no added anti-inflammatory control compared to dexamethasone alone. www. gov (NCT04054830).

Steroid Response after Trabeculectomy-A Randomized Controlled Trial Comparing Dexamethasone to Diclofenac Eye Drops.

This prospective randomized controlled trial aimed to compare changes in intraocular pressure in three different anti-inflammatory regimens following trabeculectomy. Sixty-nine patients were randomized to receive either postoperative prophylaxis with topical preservative-free dexamethasone (DEX), diclofenac (DICLO), or their combination (DEX+DICLO). Our main outcome measure was an intraocular pressure (IOP) change of a minimum 4 mmHg following the withdrawal of anti-inflammatory prophylaxis 9 weeks after trabeculectomy. We found that the IOP decreased ≥ 4 mmHg in 18.6% of eyes after cessation of the topical steroid DEX (n = 3/22) and DEX+DICLO (n = 5/21), whereas a decrease in IOP was not observed in the DICLO group. In conclusion, IOP decreased in nearly 1/5 of patients after cessation of topical steroidal anti-inflammatory prophylaxis after trabeculectomy. This points toward a steroid-induced increase in IOP even after trabeculectomy. Thus, increased postoperative IOP may be related to steroid use, and the success or failure of a trabeculectomy cannot be fully evaluated before anti-inflammatory prophylaxis with steroids is stopped or changed to non-steroidal eye drops.

Hot topics on fecal microbiota transplantation for the treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic intestinal mucosal inflammatory disease with complex etiology. Traditional anti-inflammatory treatment regimens have yielded unsatisfactory results. As research continues to deepen, it has been found that the gut microbiota of patients with IBD is generally altered. The presence of microorganisms in the human gastrointestinal tract is inextricably linked to the regulation of health and disease. Disruption of the microbiotic balance of microbiota in the gastrointestinal tract is called dysbiosis, which leads to disease. Therefore, in recent years, the exploration of therapeutic methods to restore the homeostasis of the gut microbiota has attracted attention. Moreover, the use of the well-established fecal microbiota transplantation (FMT) regimen for the treatment of Clostridioides difficile infection has attracted the interest of IBD researchers. Therefore, there are an increasing number of clinical studies regarding FMT for IBD treatment. However, a series of questions regarding FMT in the treatment of IBD warrants further investigation and discussion. By reviewing published studies, this review explored hot topics such as the efficacy, safety, and administration protocol flow of FMT in the treatment of IBD. Different administration protocols have generally shown reassuring results with significant efficacy and safety. However, the FMT treatment regimen needs to be further optimized. We believe that in the future, individual customized or standard FMT implementation will further enhance the relevance of FMT in the treatment of IBD.

Abstract 14984: Transient Constrictive Pericarditis: Pericardiectomy to the Rescue

Case Presentation: A 47 years old male presented with progressive dyspnea, bilateral leg and abdominal swelling, weight gain, and intermittent low-grade fever. He had a history of hypertension and chronic lymphocytic pericarditis complicated by an episode of constrictive pericarditis. Exam showed jugular venous pressure of 10 cmH2O, pericardial knock, and abdominal distention. Inflammatory markers were elevated (CRP 87.3 mg/dL, ESR 29 mm/hr). Echo showed abnormal increase in septal longitudinal motion and Doppler interrogation of the hepatic veins showed diastolic flow reversal at the end of expiration. Cardiac MRI showed pericardial thickening and circumferential delayed pericardial enhancement. Patient was diagnosed with transient constrictive pericarditis (TCP) and was treated with ibuprofen, colchicine, and prednisone and had improvement in his symptoms and inflammatory markers. However, he experienced another recurrence 6 months later and underwent pericardiectomy. Pathology showed organized fibrosis overlying the parietal fibrosa layer, mild neovascularization and perivascular chronic inflammation, confirming the diagnosis of TCP. After pericardiectomy, patient had significant symptomatic improvement and returned to his baseline activity level. Postoperative echo showed normalization of annulus longitudinal motion and cardiac MRI showed near resolution of pericardial delayed enhancement. He was successfully tapered off of his anti-inflammatory regimen. Discussion: TCP is a sub-type of constrictive pericarditis characterized by pathological findings of pericardial edema, acute or subacute inflammation, and fibrin deposition, as opposed to the fixed pericardial fibrosis and calcification seen in constrictive pericarditis. Constriction may resolve spontaneously, and anti-inflammatory therapy is the mainstay of treatment but in refractory cases like these, pericardiectomy comes to the rescue.

Abstract 15317: An Unusual Case of Recurrent Chest Pain: Lymphocytic Myocarditis

Case Presentation: A 42-year-old male with a past medical history of recurrent myopericarditis treated with a combination of NSAIDs, colchicine, and steroids presented for left-sided chest pain. The pain first recurred when he attempted a prednisone taper and he was started on Anakinra. Upon presentation, physical examination and laboratory findings were within normal limits. Echocardiography and electrocardiogram were within normal limits. Cardiac magnetic resonance imaging (CMR) showed transmural enhancement of the basal-mid inferolateral segments and patchy mid-myocardial enhancement in the basal-mid anterolateral segments. Nuclear medicine PET showed FDG uptake in the basal anteroseptal, anterolateral, inferolateral, inferior, and apical segments suggestive of active inflammation. Initially, the diagnosis was thought to be recurrent myopericarditis of unknown etiology. Subsequent right heart catheterization with endomyocardial biopsy (EMB) showed mononuclear infiltrates in the interstitium associated with myocyte infiltration and focal moderate interstitial fibrosis. Due to his clinical, imaging, and pathologic findings, he was diagnosed with lymphocytic myocarditis. His anti-inflammatory therapy regimen was reinstated, and he was started on Mycophenolate Mofetil. On follow-up, the patient had significant symptomatic improvement. Discussion: Lymphocytic myocarditis is a pattern of myocardial inflammation that is typically associated with autoimmune and idiopathic causes. Myocarditis frequently manifests with signs and symptoms of heart failure, including chest pain, dyspnea, and arrhythmias. Diagnosis of myocarditis is often supported by CMR and FDG-PET findings, however, EMB is the gold standard for the diagnosis of myocarditis. Treatment is generally supportive, though immunomodulatory therapies have gained increased popularity due to benefits in treating symptoms and preventing complications of heart failure.

Changes in Perioperative Antimicrobial and Anti-Inflammatory Drugs Regimens for Colic Surgery in Horses: A Single Center Report.

Simple SummaryThe administration of postoperative anti-inflammatory and antimicrobial drugs after colic surgery is based on an empirical approach, and for this reason, in recent years, it has been questioned. Recent guidelines recommend that antimicrobials should be administered for the shortest effective period possible. The use of non-steroidal anti-inflammatory drugs is also discussed given the side effects especially on the gastrointestinal tract. Consequently, the antimicrobial and anti-inflammatory drugs administration in horses has changed in our practice over the years to modulate therapies according to the postoperative complications that eventually arise. The description of these changes and the reasons behind them can help define an appropriate stewardship. Over the years, the administration of postoperative antibiotics has been limited, and treatments have been started only in case of complications that justified their use. As for anti-inflammatories, there was a variation of dosages of flunixin meglumine and the addition of new types of anti-inflammatories, both non-steroidal anti-inflammatory drugs and corticosteroids. These changes in prophylaxis protocols were not associated with an increase in postoperative complications.Reducing postoperative incisional infection is the main reason to administer postoperative antimicrobials (AMD) after emergency laparotomy in horses, while reducing inflammation and providing analgesia are the reasons to administer anti-inflammatory drugs (AID). The basis for postoperative AMD and AID administration is empirical and only recently has been questioned. Empirical approaches can be changed, and these changes, along with the description of their outcomes, can help produce appropriate stewardship. The aim of this study is to report the changes in AMD and AID regimens in horses undergoing emergency laparotomy at a referral teaching hospital between 2017 and 2021. Signalment, pathology, surgery, prophylactic AMD and AID administration were obtained from the medical records. Difference in AMD and AID regimens throughout the study period were also reported. In 234 postoperative records considered, ninety-two horses received prophylactic AMD, while 142 received pre-operative antimicrobials only. There was a progressive change in regimens throughout the years, increasing the number of AID molecules used. AMD and AID administration in horses has changed in our practice over the years to modulate therapies according to the postoperative complications that eventually arise. In this study, horses not receiving postoperative routine AMD treatment did not show an increased incidence of complications.

The aortic expression pattern of mechanosensitive stem cell genes is spatially deranged by western-type diet but can be regulated with colchicine-based anti-inflammatory treatment

Abstract Background Inflammatory dysregulation of mechanosensitive stem cell genes may be central to atherogenesis. Purpose In the present animal model, we utilized colchicine-based regimens to curtail the development of thoracic and abdominal aortic atheromatosis. We also explored the effect of anti-inflammatory therapy on atheroprotective (Klotho, HOXA5, NOTCH1, OCT4) and proatherogenic (HIF1a, SOX2, BMP4, NANOG) genes. Methods Twenty-eight New Zealand White rabbits were divided to four groups. The control group (n=6) was fed standard chow, group A (n=6) was fed chow enriched with 1% w/w cholesterol, group B (n=8) was fed the same cholesterol-enriched diet plus 2 mg/kg body weight/day colchicine and 250 mg/kg body weight/day fenofibrate, while group C (n=8) was fed the same diet plus 2 mg/kg body weight/day colchicine and 15 mg/kg body weight/day N-acetylcysteine (NAC). After seven weeks, all animals were euthanized, and their aortas were resected. Atherosclerotic plaque area was estimated via morphometric analysis. Gene expression was quantified with qRT-PCR. Results Group A developed significantly more extensive thoracic and abdominal aortic atherosclerosis compared to groups B (p&amp;lt;0.001) and C (p&amp;lt;0.001). Combining colchicine with NAC instead of fibrate resulted in stronger atheroprotection both in the thoracic (MD: 6.6, 95% CI: 0.9–12.3) and the abdominal aorta (MD: 11.1, 95% CI: 6.0–16.3). In group A thoracic aortas, Klotho was downregulated compared to controls (MD: 8.79, 95% CI: 1.82–15.76). Both colchicine regimens upregulated Klotho back to baseline levels (p&amp;lt;0.001). Colchicine/fenofibrate also significantly upregulated thoracic NOTCH1 compared to controls (MD: −4.29, 95% CI: −8.09 to −0.48). Colchicine/NAC significantly reduced thoracic NANOG expression compared to hyperlipidemic diet alone (MD: 4.33, 95% CI: 0.37–8.29). In the abdominal aorta, cholesterol-enriched diet alone resulted in significant downregulation of HOXA5 (MD: 1.39, 95% CI: 0.03–2.74) which was reversed with colchicine/NAC back to baseline levels (MD: 0.16, 95% CI: −1.19 to 1.51). On the other hand, colchicine/fenofibrate downregulated HIF1a compared to baseline (MD: 3.64, 0.83–6.44). No statistically significant differences were noted in terms of BMP4, SOX2, and OCT4 expression in thoracic and abdominal aortic specimens. Conclusions The aortic expression pattern of mechanosensitive stem cell genes is spatially influenced by western-type diet and can be modified using anti-inflammatory regimens. In our experiment, hyperlipidemic diet drove thoracic and abdominal aortic atheromatosis by downregulating Klotho and HOXA5, respectively. Both colchicine regimens curtailed thoracic atheromatosis via upregulating Klotho. In the thoracic aorta, combining colchicine with fenofibrate also increased NOTCH1, while the addition of NAC reduced NANOG. In the abdominal aorta, combining colchicine with fenofibrate reduced HIF1a, whereas the addition of NAC upregulated HOXA5. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This research was funded by the Hellenic Surgical Society and the Hellenic Atherosclerosis Society.

Asthma-related hospitalizations after implementing SABA-free asthma management with a maintenance and anti-inflammatory reliever regimen

ABSTRACT Overreliance on short-acting β2-agonists (SABA) has been a common feature of asthma management globally for at least 30 years. However, given the evidence against the long-term use of SABA, including potentially increased risk of exacerbations, emergency room visits, overall healthcare resource utilization, and mortality, the latest Global Initiative for Asthma report no longer recommends SABA only therapy. Since 2014, we implemented an ICS-containing reliever strategy at our asthma center at the G Baigorria Hospital in Argentina; we only administered budesonide/formoterol via a single inhaler device across the spectrum of asthma severity and completely eliminated the use of SABA therapy. In this article, we compare hospitalization data from our center, previously reported in the EAGLE study (when inhaled corticosteroids plus as-needed SABA was administered) for the years 1999 and 2004 with data from 2017 to 2018 (when budesonide/formoterol in a single inhaler device was administered as maintenance and/or anti-inflammatory reliever therapy [MART/AIR] without any SABA) from our center, to assess the impact of two distinct asthma management strategies on asthma-related hospitalizations. MART/AIR regimens in our SABA-free center reduced asthma hospitalizations from 9 (1999 and 2004) to 1 (2017 and 2018) (Fisher’s exact test, p = 0.031; odds ratio = 0.11; 95% confidence interval [CI] = 0.013–0.98); the hospitalization rate was reduced by 92% (1.47% in 1999 and 2004 to 0.12% in 2017 and 2018). Our data provide preliminary real-world evidence that MART/AIR with budesonide/formoterol simultaneously with SABA elimination across asthma severities is an effective asthma management strategy for reducing asthma-related hospitalizations.

Comparison of postcataract surgery anti-inflammatory regimens on the incidence of cystoid macular edema, iritis, pain, and photophobia.

To compare postcataract surgery anti-inflammatory regimens of intracanalicular dexamethasone insert and topical bromfenac on the incidence of cystoid macular edema (CME), iritis, pain, and photophobia. Eyes of York Cataract & Laser Center, York, Pennsylvania. Retrospective chart review. Case records of 647 consecutive patients (1001 eyes) who underwent cataract surgery and received dexamethasone intracanalicular insert 0.4 mg (Group 1; 482 eyes) or topical nonsteroidal anti-inflammatory drug (NSAID) (bromfenac 0.075% 2 times a day) for 4 weeks postoperatively (Group 2; 519 eyes) were included. Both groups received intracameral moxifloxacin and phenylephrine/ketorolac. Patients with prior CME, vitreomacular traction, combined cataract/glaucoma surgery, and medication protocols different from those examined in this study were excluded. Compared with the dexamethasone insert group, the topical NSAID group had a significantly lower incidence of CME (0.4% [2/519] vs 3.9% [19/482], P < .001) and photophobia (1.9% [10/519] vs 4.8% [23/482], P = .012). The incidence of breakthrough iritis (3.5% [18/519] vs 5.6% [27/482], P = .104) and pain also trended lower (4.0% [21/519] vs 5.4% [26/482], P = .314) in the topical NSAID group. Topical NSAIDs were found to be more effective in controlling CME, pain, iritis, and photophobia after cataract surgery compared with the intracanalicular dexamethasone insert in the presence of intracameral phenylephrine/ketorolac.

Rationale and design of the CORE (COrticosteroids REvised) study: protocol

IntroductionCorticosteroids are an important pillar in many anti-inflammatory and immunosuppressive treatment regimens and are available in natural and synthetic forms, which are considered equipotent if clinical bioequivalence data are used....