Biomechanic, proteomic and miRNA transcriptional changes in the trabecular meshwork of primates injected with intravitreal triamcinolone.

Although biomechanical changes of the trabecular meshwork (TM) are important to the pathogenesis of glucocorticoids-induced ocular hypertension (GC-OHT), there is a knowledge gap in the underlying molecular mechanisms of the development of it. In this study, we performed intravitreal triamcinolone injection (IVTA) in one eye of 3 rhesus macaques. Following IVTA, we assessed TM stiffness using atomic force microscopy and investigated changes in proteomic and miRNA expression profiles. One of 3 macaques developed GC-OHT with a difference in intraocular pressure of 4.2 mmHg and a stiffer TM with a mean increase in elastic moduli of 0.60 kPa versus the non-injected control eye. In the IVTA-treated eyes, proteins associated with extracellular matrix remodeling, cytoskeletal rearrangement, and mitochondrial oxidoreductation were significantly upregulated. The significantly upregulated miR-29b and downregulated miR-335-5p post-IVTA supported the role of oxidative stress and mitophagy in the GC-mediated biomechanical changes in TM, respectively. The significant upregulation of miR-15/16 cluster post-IVTA may indicate a resultant TM cell apoptosis contributing to the increase in outflow resistance. Despite the small sample size, these results expand our knowledge of GC-mediated responses in the TM and furthermore, may help explain steroid responsiveness in clinical settings.

Efficacy of Intra-articular Triamcinolone and Hyaluronic Acid in a Frozen Shoulder Rat Model.

BACKGROUND: Intra-articular corticosteroid or hyaluronic acid (HA) is commonly prescribed for frozen shoulder. However, few studies have investigated histological and molecular changes after injection. PURPOSE: To compare the effectiveness of intra-articular injections of triamcinolone and HA in a frozen shoulder rat model and verify a greater effect of triamcinolone in passive shoulder abduction compared with HA. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty male Sprague-Dawley rats were randomly allocated into 4 groups (n = 5 in each): control group, which did not receive cast immobilization or injection, and 3 experimental groups, which received 3 weeks of unilateral shoulder immobilization followed by intra-articular injections (normal saline, triamcinolone, or HA) at the immobilized shoulder. Passive shoulder abduction angle, histological and immunohistochemical staining, and Western blotting results were assessed 2 weeks after injection. The intensity and extent of staining were converted to semiquantitative scores for further analysis. RESULTS: Shoulder abduction angles before sacrifice were 153.0°± 2.7° (control group), 107.0°± 5.7° (saline group), 139.0°± 9.6° (triamcinoline group), and 110.0°± 10.6° (HA group), showing significant differences between control and saline groups, control and HA groups, saline and triamcinoline groups, and triamcinoline and HA groups (P < .001) but not between control and triamcinoline groups (P = .053). Histologic evaluation revealed an increase in synovial folds and thickening of the capsular membrane in the saline and HA groups; this change was not evident in the triamcinolone group. A comparison of semiquantitative scores revealed greater expression levels of proteins involved in fibrosis and angiogenesis in the saline and HA groups compared with the control and triamcinolone groups. In Western blotting, the expression of inflammatory cytokines and the receptor for advanced glycation end products was significantly lower in the triamcinolone and HA groups than in the saline group. CONCLUSION: Triamcinolone injection was more effective than normal saline or HA injection in improving range of motion and reversing fibrotic and angiogenic features of frozen shoulder. Both triamcinolone and HA injections elicited anti-inflammatory effects. CLINICAL RELEVANCE: The antifibrotic and antiangiogenic properties of triamcinolone and the anti-inflammatory properties of both triamcinolone and HA should be considered when performing injections in clinical settings.

In Vitro Effects of Triamcinolone and Methylprednisolone on the Viability and Mechanics of Native Articular Cartilage.

BACKGROUND: The chondrotoxic effects of methylprednisolone acetate (MP) and triamcinolone acetonide (TA) have been well described. However, the mechanical effects of these commonly used steroids on native cartilage are largely unknown. PURPOSE: To investigate the in vitro effects of a single 1-hour MP or TA exposure on the viability, mechanics, and biochemical content of native articular cartilage explants. STUDY DESIGN: Controlled laboratory study. METHODS: Articular cartilage explants (n = 6 per group) were harvested from the femoral condyles of bovine stifles. Explants were exposed to chondrogenic medium containing a clinical dose of MP or TA for 1 hour, followed by fresh medium wash and exchange. Explants in the control group underwent the same treatment with chondrogenic medium alone. At 24 hours after treatment, samples were assessed for viability (live/dead), mechanical properties (creep indentation and Instron tensile testing), biochemical (collagen and glycosaminoglycan) content, and pyridinoline crosslinking via mass spectrometry. RESULTS: Mean cell viability was significantly decreased in native explants exposed to MP (35.5%) compared with the control (49.8%; P < .001) and TA (45.7%; P = .01) specimens. Significant decreases were seen in the mechanical properties of steroid-treated native explants when compared with controls, with decreases in aggregate modulus (646.3 vs 312.8 kPa [MP] and 257.0 kPa [TA]; P < .001), shear modulus (370.1 vs 191.2 kPa [MP] and 157.4 kPa [TA]; P < .001), and ultimate tensile strength (9.650 vs 5.648 MPa [MP; P = .021] and 6.065 MPa [TA; P = .0403]). No significant differences in collagen and glycosaminoglycan content were found in the steroid-treated groups. Pyridinoline crosslinking was significantly decreased in explants exposed to TA compared with controls (P = .027). CONCLUSION: Exposure of MP to articular cartilage explants was chondrotoxic, and exposure of articular cartilage explants to MP or TA resulted in significant decreases in mechanical properties of articular cartilage explants compared with controls. Clinicians should be judicious regarding use of intra-articular steroids, particularly in patients with intact healthy articular cartilage.

The effect of bevacizumab, 5-fluorouracil, and triamcinolone on the healing modulation of surgical wounds in rats.

In this study, we aimed to analyze the effect of 5-fluorouracil, triamcinolone, and bevacizumab on scar modulation in an experimental rat model of surgical lesions. Rats (Rattus norvegicus albinus) were divided into four groups: bevacizumab, 5-fluorouracil + triamcinolone, bevacizumab + 5-fluorouracil + triamcinolone, and control (received no medication) groups. A linear, dorsal incision was created and sutured for the first intention wound healing, mimicking the surgical incision of upper blepharoplasty. Treatments were initiated on day 7, and the rats were euthanized on day 14. Only in the 5-fluorouracil + triamcinolone group was there a difference in the number of infiltrated monocytes. There was 56%, 86%, and 85% decrease in the number of neovessels in the bevacizumab, 5-fluorouracil + triamcinolone, and bevacizumab + 5-fluorouracil + triamcinolone groups, respectively, compared with the control. Picrosirius red staining showed higher collagen density and more organized collagen in the treatment groups than in the control group. Scar modulation was observed in all groups, but the 5-fluorouracil + triamcinolone group presented the best results. To our knowledge, this is the first study to evaluate the influence of three medications in combination on healing. When used together, these medications can prevent the development of unsightly scars, and are therefore promising alternatives to corticosteroids.

The Comparative Effects of Rhus Coriaria and Triamcinolone in Patients with Recurrent Aphthous Stomatitis: A Single-Blinded Randomized Controlled Clinical Trial.

Background: Recurrent aphthous stomatitis (RAS) is a common oral lesion with unknown etiology. Several treatment strategies are introduced for the treatment of RAS. In this regard, the therapeutic effects of Rhus coriaria, as one of the potential treatments, have recently caught attention. Since the clinical efficacy of Rhus coriaria has not been examined adequately. This study aims at evaluating the therapeutic effects of Rhus coriaria among patients with RAS. Method: s. Twenty-two patients with RAS were divided into two groups (n = 11). The experimental group received three pills of Rhus coriaria daily for 6 days, while the control group received triamcinolone (oral paste) three times a day for 6 days. The pain and size of the lesion were measured on the 1st, 2nd, 3rd, 4th, 5th, and 6th days. The data were analyzed by SPSS 16. In this regard, Student's t-test and Sidak pairwise tests were used for assessment of inter and intragroup comparisons of the pain and the size of the lesion, respectively. Results: Intergroup comparisons indicate that there is no difference between the experimental and the control group (p > 0.05). Whereas, the intragroup analysis of the pain revealed significant changes (p < 0.05) in most of the time points for both groups. Besides, the intragroup analysis of the lesion size, showed significant changes in all the time points in the experimental group (p < 0.05). The results in the control group exhibited the same pattern, except on 1-5, 1-6, 2-6, and 3-6 intervals in the control group. Conclusions: The application of Rhus coriaria could significantly reduce lesion size and pain in patients with RAS. Accordingly, Rhus coriaria can be an effective medication for RAS treatment.

In vitro effect of triamcinolone and platelet-rich plasma on cytokine levels of elbow lateral epicondylitis-derived cells.

BACKGROUND: The pathogenesis and treatment of lateral elbow epicondylitis (LEE) are still controversial. The purpose of the current study was to evaluate the production of inflammatory cytokines by LEE-derived cells and to compare the anti-inflammatory effect of triamcinolone acetonide with platelet-rich plasma (PRP) on cytokines production in primary culture of these cells. METHODS: Third passage cells from primary cultures of LEE were assessed for the production of the cytokines IL-1ß, IL-6, IL-8, IL-10 and TNF-α by immune-enzymatic assay (ELISA), after the treatment with 1, 10 and 100 µM triamcinolone compared to no treated controls at the time points 6, 12, 18, 24, 48, 72 and 96 h, and to PRP at 48, 72 and 96 h. RESULTS: The cytokines IL-6 and IL-8 were produced in high concentrations by LEE cells. One, 10 and 100 µM triamcinolone induced significant decrease in the production of IL-6 and IL-8 at 48, 72 and 96 h, adding the time point 12 h for IL-8. Compared to controls, PRP caused a significant increase in the production of IL-6 and IL-8 and there was a significant increase in IL-10 production with the use of 100 µM triamcinolone at 48 h. The production of IL1-ß and TNF-α was very low and did not change when the cultures were treated with triamcinolone or PRP. CONCLUSION: LEE-derived cells produce IL-6 and IL-8, confirming the inflammatory nature of this condition. While triamcinolone inhibited the production of IL-6 and IL-8 by LEE cells, PRP induced an increase in these cytokines compared with controls.

Aldosterone and dexamethasone activate African lungfish mineralocorticoid receptor: Increased activation after removal of the amino-terminal domain.

Aldosterone, the main physiological mineralocorticoid in humans and other terrestrial vertebrates, first appears in lungfish, which are lobe-finned fish that are forerunners of terrestrial vertebrates. Aldosterone activation of the MR regulates internal homeostasis of water, sodium and potassium, which was critical in the conquest of land by vertebrates. We studied transcriptional activation of the slender African lungfish MR by aldosterone, other corticosteroids and progesterone and find that aldosterone, 11-deoxycorticosterone, 11-deoxycortisol and progesterone have half-maximal responses (EC50 s) below 1 nM and are potential physiological mineralocorticoids. In contrast, EC50 s for corticosterone and cortisol were 23 nM and 66 nM, respectively. Unexpectedly, truncated lungfish MR, consisting of the DNA-binding, hinge and steroid-binding domains, had a stronger response to corticosteroids and progesterone than full-length lungfish MR, indicating that the N-terminal domain represses steroid activation of lungfish MR, unlike human MR in which the N-terminal domain contains an activation function. BLAST searches of GenBank did not retrieve a GR ortholog, leading us to test dexamethasone and triamcinolone for activation of lungfish MR. At 10 nM, both synthetic glucocorticoids are about 4-fold stronger than 10 nM aldosterone in activating full-length lungfish MR, leading us to propose that lungfish MR also functions as a GR.

Anthocyanin complex niosome gel accelerates oral wound healing: In vitro and clinical studies.

An anthocyanin complex (AC), composed of extracts of purple waxy corn and blue butterfly pea petals, and AC niosomes, bilayered vesicles of non-ionic surfactants, were compared in in vitro and clinical studies. Cultured fibroblasts subjected to a scratch wound were monitored for cell viability, cell migration, nuclear morphology and protein expression. Scratched cells showed accelerated wound healing activity, returning to normal 24 h after treatment with AC niosomes (0.002 mg/mL). Western blots and immunocytochemistry indicated upregulation of type I, III and IV collagens, fibronectin and laminins in AC niosome-treated scratched cells. A randomized block placebo-controlled double-blind clinical trial in 60 volunteers (18-60 years old) with oral wounds indicated that AC niosome gel accelerated wound closure, reduced pain due to the oral wounds and improved participants' quality of life more than AC gel, triamcinolone gel and placebo gel. These data are consistent with enhanced delivery of AC to fibroblasts by use of niosomes. AC niosomes activated fibroblasts within wounded regions and accelerated wound healing, indicating that AC niosomes have therapeutic potential.

Efficacy of Absorbable Steroid-Impregnated Nasal Packing in Functional Endoscopic Sinus Surgery for Chronic Rhinosinusitis: A Systematic Review.

OBJECTIVE: To evaluate the efficacy of absorbable steroid-impregnated nasal packing on postoperative outcomes following functional endoscopic sinus surgery (FESS) for chronic rhinosinusitis (CRS). METHODS: A systematic review of the literature was conducted as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twelve databases (including Journals@Ovid, Embase®, Medline®, EBM Reviews and Joanna Briggs Institute EBP Database) were searched using relevant keywords and expanded with corresponding MeSH/Emtree terms. Results were narrowed to English articles assessing the efficacy of absorbable packing impregnated with steroids post-production placed at time of surgery under general anesthetic, with hollow-lumen devices and devices inserted in-office excluded. RESULTS: Eight studies met criteria and were included in this review. Five evaluated the efficacy of the intervention in only CRS with nasal polyposis (CRSwNP) patients, two included all subtypes of CRS, and one included only CRS without nasal polyposis (CRSsNP). Of the eight studies, four studied the efficacy of Nasopore®, three studied bioabsorbable gels, and one studied bioabsorbable calcium alginate. Four studies applied triamcinolone as the operative steroid, with the other studies utilizing betamethasone, budesonide, mometasone, and dexamethasone. Seven studies demonstrated statistically significant improvements in endoscopic outcomes using validated scoring scales, albeit at differing timepoints. The one study which included only CRSsNP patients failed to find a significant difference. CONCLUSION: Steroid-impregnated nasal packing appears to have positive effects on postoperative endoscopic outcomes in CRSwNP patients undergoing FESS. Additional research is needed to evaluate the efficacy of these interventions in more recently defined subtypes of CRS, and whether these interventions differ in their efficacy in eosinophilic and non-eosinophilic CRS. Laryngoscope, 131:1704-1714, 2021.

Effect of canakinumab on clinical and biochemical parameters in acute gouty arthritis: a meta-analysis.

BACKGROUND: Targeted anti-IL-1ß therapy may be a valuable option for the management of gouty arthritis. The present meta-analysis has evaluated the effect of canakinumab, an anti-IL-1ß monoclonal antibody in gouty arthritis. METHODS: A standard meta-analysis protocol was developed and after performing a comprehensive literature search in MEDLINE, Cochrane, and International Clinical Trial Registry Platform (ICTRP), reviewers assessed eligibility and extracted data from three relevant articles. A random-effects model was used to estimate the pooled effect size as the mean difference in Visual Analouge Scale (VAS) score, serum hsCRP, serum Amyloid A, and risk ratio for global assessment between the groups. Quality assessment was done using the risk of bias assessment tool and summary of findings was prepared using standard Cochrane methodology with GradePro GDT. RESULTS: Treatment with canakinumab showed a mean reduction of VAS score by 14.59 mm [95% CI - 19.42 to - 9.77], serum hsCRP by 15.36 mg/L [95% CI 1.62-29.11], serum Amyloid A by 67.18 mg/L [95% CI 17.06-117.31], and improvement in patient global assessment (RR = 1.478; 95% CI 1.29-1.67) and physician global assessment (RR = 1.44; 95% CI 1.28-1.61). The probability that future studies may have a mean difference in VAS score less than zero has been calculated to be 27.3% using a cumulative distribution function (CDF) calculator. CONCLUSION: This meta-analysis shows the beneficial effect of canakinumab over triamcinolone by reducing VAS score, serum hsCRP, serum amyloid A, and improvement in global assessments in acute gouty arthritis.

Long-term outcomes and recurrence-free interval after the treatment of keloids with a standardized protocol.

BACKGROUND: Recurrence rates of keloids have generally been reported at one time point. However, the longer the duration after treatment, the greater the likelihood that such lesions will recur. In this study, we analysed the time to recurrence during long-term follow-up. MATERIAL AND METHODS: We retrospectively reviewed recurrence-free interval in 52 patients with keloid (age 8-79 years) who had been treated between June 2006 and January 2011 using a standardised protocol developed by our group. RESULTS: Mean duration of follow-up was 37.5 (range, 7-120) months in patients with keloid. Kaplan-Meier survival curves revealed a statistically significant difference in recurrence-free interval between ear keloids and keloids excluding ear keloids. Recurrence rate for keloids was high in the first 2 years after treatment. CONCLUSIONS: Kaplan-Meier analysis was useful for understanding the tendency of recurrence of keloids after treatment using a standardised protocol.

Triamcinolone-Gold Nanoparticles Repolarize Synoviocytes and Macrophages in an Inflamed Synovium.

Understanding the crosstalk between synoviocytes and macrophages is very important for the development of strategies to regulate inflammatory responses in an inflamed synovium. Simultaneous regulation of the pro- and anti-inflammatory responses of synoviocytes and macrophages (repolarization) is critical for the treatment of arthritis. Thus, the immune regulatory functions of an ideal nanodrug should not only decrease the pro-inflammatory response but also effectively increase the anti-inflammatory response. In this study, crosstalk between synoviocytes and macrophages was found to be significantly involved in the activation and deactivation of inflammatory responses in the synovium. Interestingly, a developed triamcinolone-gold nanoparticle (Triam-AuNP) complex both decreased the pro-inflammatory responses and increased the anti-inflammatory responses of fibroblast-like synoviocytes (FLSs) and macrophages via repolarization of macrophages from the M1 to the M2 phenotype. In contrast, triamcinolone alone only decreased the pro-inflammatory responses of FLSs and macrophages without upregulating their anti-inflammatory responses. In vitro (human), ex vivo (human), and in vivo (mouse) analyses clearly indicated that Triam-AuNPs effectively regulated the expression of both pro- and anti-inflammatory cytokines in FLSs and effectively repolarized activity of macrophages in the inflamed synovium. Furthermore, Triam-AuNPs significantly promoted cartilage regeneration, whereas triamcinolone alone did not induce either FLS anti-inflammatory activity or macrophage repolarization.

Elastic net of polyurethane strands for sustained delivery of triamcinolone around silicone implants of various sizes.

We propose an elastic net made of a biocompatible polymer to wrap silicone implants of various sizes, which also allows for the sustained release of an anti-inflammatory drug, triamcinolone, to prevent fibrosis. For this, we first prepared a strand composed of a mixture of polyurethane and triamcinolone via electrospinning, which was then assembled to prepare the elastic drug-delivery net (DDN). The DDN was prepared to just fit for wrapping the small silicone implant sample herein, but was also able to wrap a sample 7 times as large at 72% strain due to the elastic property of polyurethane. The DDN exhibited sustained drug release for 4 weeks, the profile of which was not very different between the intact and strained DDNs. When implanted in a subcutaneous pocket in living rats, the DDN-wrapped silicone implant samples showed an obvious antifibrotic effect due to the sustained release of triamcinolone. Importantly, this effect was similar for the small and large silicone samples, both wrapped with the same DDN. Therefore, we conclude that this drug-loaded net made of an elastic, biocompatible polymer has high potential for sustained drug delivery around silicone implants manufactured in various sizes.

Chitosan coated liposomes (CCL) containing triamcinolone acetonide for sustained delivery: A potential topical treatment for posterior segment diseases.

Drug delivery to the posterior eye is limited by epithelial and mucosal barriers limiting the topical administration of drugs leading to invasive modes of repeated long-term painful administration of drugs. Several constructs of liposomes have been prepared to counter this challenge yet are often limited by size and surface charge resulting in poor encapsulation efficiency, low retention time, and poor permeability. In the present study, chitosan coated liposomes (CCL) were prepared to address these challenges. Conventional liposomes encapsulating Triamcinolone Acetonide (TA) were compared with their chitosan coated counterpart for drug loading and release studies. CCL showed a higher encapsulation efficiency (74%), and a highly positive surface charge (+41.1Mv), increased retention time and sustained release. Choroidal neovascularization (CNV) rat models were generated to assess the efficiency of CCLs as nanocarriers in drug delivery. Significant amount of TA was found to be present and retaining in the eye after fifteen days of treatment with CCL, as shown by HPLC analysis. The results showed successful penetration of the construct via corneal mucosal barrier and its accumulation in vitreous body. The analysis shows that this chitosan based liposomal construct can be employed as a potential topical delivery system for treating posterior segment diseases.

Addition of dexmedetomidine and neostigmine to 1.5 % lidocaine and triamcinolone for epidural block to reduce the duration of analgesia in patients suffering from chronic low back pain.

Lower back pain is one of the leading causes of disability in the world. The aim of this study was to evaluate the effect of supplementation of dexmedetomidine and neostigmine with lidocaine 1.5% and triamcinolone for epidural block in increasing the duration of analgesia among patients suffering from chronic low back pain. In this double-blind, randomized clinical trial, 33 patients with chronic low back pain were included in three groups of 11 patients for epidural blockage. Triamcinolone (40 mg/ml) was added to lidocaine 1.5% solution (2 cc/segment) for all three groups. In group N, neostigmine was used at a dose of 1 mg (mg), followed by group D (dexmedetomidine 35 µg [0.5 µg/kg]), and grou [ND (neostigmine 0.5 mg, and 35 µg dexmedetomidine, all of which were added to the triamcinolone and lidocaine solution in each group. Medications were injected into the epidural space using an interlaminar approach. Subsequently, scores of pain and duration of analgesia were recorded in questionnaires and analysed using SPSS version 23. One month after the injections, pain scores recorded in the N group were 7.6±1.4, followed by 5.88±1.2 in group D and 5.42 ±1.1 in group ND. Therefore, the pain scores were significantly higher in the neostigmine group than the other two groups (p = 0.02), but no significant difference was found between the two groups that received dexmedetomidine and a combination of dexmedetomidine + neostigmine. Three months after the injections, there was a significant difference in pain scores between the two groups (P = 0.01). Both neostigmine and dexmedetomidine were capable of reducing the pain of patients with chronic low back pain after epidural block. However, neostigmine's impact is lower compared to dexmedetomidine. The combination of the two drugs also reduced the pain scores of the patients after the intervention.

Normal and keloid fibroblasts are differentially influenced by IFN-γ and triamcinolone as well as by their combination.

Impaired wound healing as well as imbalanced cell proliferation and extracellular matrix synthesis and degeneration can cause aberrant scarring. The most severe impacts of such scarring on patients' lives are stigmatization and physical restriction. Although, a broad variety of combinatorial approaches with, e.g., glucocorticoids, chemotherapeutics, and immunomodulators are used, there is still a high recurrence rate of keloids. The aim of this study was to investigate which influence interferon γ (IFN-γ, 1.000-10.000 IU/mL) and/or triamcinolone acetonide (TA, 1 µg/mL) have on proliferation, cell viability, collagen type I synthesis, and cytokine secretion in healthy and keloid fibroblasts. It was shown that mono-treatment with IFN-γ or TA for 2 days induced a severe reduction of the proliferative potential in both cell species. The combinatory treatment (IFN-γ plus TA) of keloid fibroblasts enhanced the anti-proliferative effect of the mono-treatments, whereas no additional anti-proliferative effect was observed in normal fibroblasts. Furthermore, we observed that the combinatory treatment regimen reduced the expression of α-smooth muscle actin (α-SMA), an actin isotype contributing to cell-generated mechanical tension, in keloid fibroblasts. In normal fibroblasts, α-SMA was reduced by the mono-treatment with IFN-γ as well as by the combinatory treatment. The analysis of collagen-type I synthesis revealed that TA did not reduce collagen type I synthesis in normal fibroblasts but in keloid fibroblasts. IFN-γ reduced in both cell species the collagen type I synthesis. The combination of TA and IFN-γ intensified the previously observed collagen type I synthesis reduction in keloid fibroblasts. The herein presented data suggest the combinatory application of IFN-γ and TA as a promising therapy concept for keloids.

Exogenous steroid-induced hypoadrenalism in a person living with HIV caused by a drug-drug interaction between cobicistat and intrabursal triamcinolone.

We report a diagnosis of exogenous steroid-induced hypoadrenalism in a person living with HIV caused by a drug-drug interaction (DDI) between intrabursal triamcinolone and the pharmacokinetic booster cobicistat. A 53-year-old woman living with HIV, managed with dolutegravir and cobicistat-boosted darunavir, presented to the orthopaedic clinic with worsening hip pain. She was diagnosed with greater trochanteric pain syndrome (GTPS) of the hip and was treated with intrabursal injection of bupivacaine and triamcinolone. Seven days following this injection, she presented with Cushingoid features, an undetectable cortisol and was diagnosed with exogenous steroid-induced hypoadrenalism. Cobicistat is a cytochrome P450 3A inhibitor and in this case inhibited clearance of intrabursal triamcinolone, leading to exogenous glucocorticoid excess and adrenal suppression. This is the first report to describe this predictable DDI with cobicistat following intrabursal glucocorticoid injection. This case highlights the complexities in managing non-HIV-related chronic morbidities in people living with HIV.

Healing modulation in glaucoma surgery after application of subconjunctival triamcinolone acetate alone or combined with mitomycin C: an experimetal study. / Modulação da cicatrização na cirurgia do glaucoma após aplicação de acetato de triancinolona subconjuntival isolado ou em associação à mitomicina C: estudo experimental.

OBJECTIVE: to study the efficacy and safety of the use of subconjunctival triamcinolone acetate alone or in combination with mitomycin C as a modulator of trabeculectomy healing in rabbits. METHODS: we submitted thirty male, albino, New Zealand rabbits to bilateral trabeculectomy. We divided the animals into four experimental groups with 15 eyes per group: control, mitomycin C, triamcinolone acetate and triamcinolone acetate + mitomycin C. We performed aplanation tonometry and clinical analysis of the bleb through the Moorfields Graduation System in the postoperative period. For the evaluation of healing, we carried out the quantitative analysis of the inflammatory infiltrate (polymorphonuclear) through Hematoxylin & Eosin staining, and vascular proliferation, through immunohistochemistry. RESULTS: we observed a significant decrease in postoperative intraocular pressure in all groups compared with the preoperative pressure (p<0.001). However, there was no difference between groups (p=0.186). The triamcinolone + mitomycin C acetate group presented better indices as for the maximum bleb height and vascularization of the bleb central area (p=0.001); in addition, there was a lower inflammatory response (p=0.001) and lower vascular proliferation (p=0.001) in the intermediate phase of the study compared with the monotherapies. CONCLUSION: the combination of mitomycin C and triamcinolone acetate resulted in a synergistic action between these agents, with broader and more diffuse blebs, less inflammatory infiltrate and less vascular proliferation in the intermediate stages of follow-up in this animal model.

OBJETIVO: estudar a eficácia e segurança do uso de acetato de triancinolona subconjuntival isolado ou em associação à mitomicina C como modulador da cicatrização de trabeculectomias em coelhos. MÉTODOS: trinta coelhos machos, albinos, raça Nova Zelândia foram submetidos à trabeculectomia bilateralmente. Os animais foram divididos em quatro grupos experimentais com 15 olhos por grupo: controle, mitomicina C, acetato de triancinolona e acetato de triancinolona + mitomicina C. Tonometria de aplanação e análise clínica da bolha através do Sistema de Graduação de Moorfields foram obtidas no pós-operatório. Para a avaliação da cicatrização, procedeu-se à análise quantitativa do infiltrado inflamatório (polimorfonucleares) através da coloração Hematoxilina & Eosina e da proliferação vascular por imuno-histoquímica. RESULTADOS: foi observada em todos os grupos diminuição significativa da pressão intraocular pós-operatória em relação à pré-operatória (p<0,001). Contudo, não houve diferença entre os grupos (p=0,186). O grupo acetato de triancinolona + mitomicina C apresentou melhores índices na altura máxima da bolha e na vascularização da área central da bolha (p=0,001); além disso, houve menor resposta inflamatória (p=0,001) e menor proliferação vascular (p=0,001) na fase intermediária do estudo em relação às monoterapias. CONCLUSÃO: a associação da mitomicina C ao acetato de triancinolona resultou numa ação sinérgica entre esses agentes, com bolhas mais amplas e difusas e menor infiltrado inflamatório e menor proliferação vascular em estágio intermediário do acompanhamento neste modelo animal.

Sialendoscopy enhances salivary gland function in Sjögren's syndrome: a 6-month follow-up, randomised and controlled, single blind study.

OBJECTIVES: To assess the effect of sialendoscopy of the major salivary glands on salivary flow and xerostomia in patients with Sjögren's syndrome (SS). METHODS: Forty-nine patients with SS were randomly assigned to a control group (n=15) and two intervention groups: irrigation of the major glands with saline (n=16) or with saline followed by triamcinolone acetonide (TA) in saline (n=18). Unstimulated whole saliva flow (UWS), chewing-stimulated whole saliva flow (SWS), citric acid-stimulated parotid flow (SPF), Clinical Oral Dryness Score (CODS), Xerostomia Inventory (XI) score and the European League Against Rheumatism (EULAR) SS Patient-Reported Index (ESSPRI) were obtained 1 week (T0) before, and 1 (T1), 8 (T8), 16 (T16) and 24 (T24) weeks after sialendoscopy. RESULTS: Median baseline UWS, SWS and SPF scores were 0.14, 0.46 and 0.22 mL/min, respectively. After intervention, significant increases in UWS and SWS were observed in the saline group (at T8 (P=0.013) and T24 (P=0.004)) and the saline/TA group (at T24 (P=0.03) and T=16 (P=0.035)). SPF was increased significantly in the saline/TA group at T24 (P=0.03). XI scores declined after sialendoscopy in both intervention groups. Compared with the control group, CODS, XI and ESSPRI improved in the intervention groups. UWS, SWS and SPF were higher in the intervention groups compared with the control group, but these differences were not significant except for SPF in the saline/TA group at T24 (P=0.005). CONCLUSIONS: Irrigation of the major salivary glands in patients with SS enhances salivary flow and reduces xerostomia up to 6 months after sialendoscopy.

Relationship of Radiographic Osteoarthritis Severity with Treatment Outcomes after Imaging-Guided Knee Injections: A Prospective Outcomes Study.

INTRODUCTION: To be able to predict which patients are more likely to have a positive treatment outcome, the purpose of this study is 1: To compare outcomes after intra-articular corticosteroid knee injections with the Kellgren and Lawrence (KL) 5 and 3 grading systems for knee osteoarthritis, the Osteoarthritis Research Society International (OARSI) grading system and actual joint space measurements; and 2: To compare the reliability of these grading systems. MATERIALS AND METHODS: Knee radiographs of 117 patients who received intra-articular corticosteroid injections were independently evaluated by two radiologists blinded to the outcome. Evaluation included the KL5, KL3, OARSI systems and actual joint space widths. The numerical rating scale for pain was collected at baseline and along with the Patient's Global Impression of Change on day 1, in week 1 and in month 1. The number of 'improved' patients was compared between the OA grades using the Chi-square test. Logistic regression determined which findings were predictive for improvement. Agreement was assessed using Kappa statistics and the intraclass correlation coefficient (ICC). RESULTS: Patients with OARSI grade 2 reported the highest rates of 'improvement' at all time points, which was significant on day 1 (p = 0.004). No relationship with improvement was found with KL5, KL3 or actual joint space measurements. Patients with OARSI grade 2 were 8 times more likely to report improvement on day 1 (p = 0.024). Reliability was best for joint space measurements (ICC = 0.812 - 0.882), followed by the OARSI. CONCLUSION: The OARSI for joint space narrowing grade 2 (34 - 66 % narrowing) was linked with a better outcome on day 1 with trends in week 1 and month 1. The reliability of the OARSI was better than the KL5 or KL3 systems. KEY POINTS: · OARSI grading of OA had better reliability than KL3 or KL5.. · OARSI grade 2 was related to a better treatment outcome.. · Neither KL grades nor joint space measurements were related to improvement.. CITATION FORMAT: · Miletic I, Agten C, Sutter R et al. Relationship of Radiographic Osteoarthritis Severity with Treatment Outcomes after Imaging-Guided Knee Injections: A Prospective Outcomes Study. Fortschr Röntgenstr 2018; 190: 134 - 143.