Fascial Plane Blocks With Glucocorticoids or Liposomal Bupivacaine Versus Local Infiltration for Laparoscopic Non-donor Nephrectomy: A Propensity Score-Weighted Study.

Study objective The purpose of this study is to investigate the analgesic efficacy of ultrasound-guided fascial plane blocks (FPBs) versus local infiltration in patients undergoing laparoscopic non-donor nephrectomy. This study specifically compares the efficacy of FPBs with liposomal bupivacaine (LB) versus FPBs with dexamethasone sodium phosphate (DXP) and methylprednisolone acetate (MPA) versus surgical site local anesthetic infiltration without FPBs.  Design This is a retrospective cohort study conducted over a five-year period (January 2018-December 2022). Setting The study was conducted in a tertiary care, academic, multi-hospital healthcare system.  Participants Patients who underwent elective radical or partial laparoscopic non-donor nephrectomy were included in the study. Intervention Patients either received preoperative FPBs without intraoperative surgical site local anesthetic infiltration or received surgical site local anesthetic infiltration without FPBs (n = 141) at participating hospitals. Measurements The primary endpoint of this study was postoperative opioid use, measured as oral milligram morphine equivalents (MME). Secondary endpoints included postoperative pain scores, length of hospital stays, and significant adverse events within 30 days. The impact of medications utilized in FPBs was determined by univariate and multivariable analyses with covariates balancing propensity score weighting. Main results Patients undergoing non-donor laparoscopic radical or partial nephrectomy who received FPBs with bupivacaine or ropivacaine plus glucocorticoids DXP and MPA were more likely to be opioid-free 24-48 hours postoperatively compared to those who received FPBs with LB or surgical site local anesthetic infiltration without FPBs (40.5% vs. 30% vs. 13.9%, respectively; p = 0.017). Patients who received FPBs with glucocorticoids also reported the lowest pain scores at rest and with activity 0-12 hours postoperatively as compared to patients who received LB or local infiltration (p = 0.006 and p = 0.014, respectively). Additionally, patients who received FPBs with glucocorticoids received over 30% fewer opioids during the first 48 hours postoperatively compared to patients who received surgical site local anesthetic infiltration alone (30 MME vs. 44 MME, respectively). However, there was no significant difference in total opioid use during the first 48 hours postoperatively between patients who received FPBs with bupivacaine plus glucocorticoids and those who received FPBs with bupivacaine plus LB (mean ratio: 0.91, (95% CI: 0.05 ~ 15.97); p = 0.948). There was also no difference in the length of hospital stays or rate of adverse events between the groups. Conclusion Perioperative FPBs for non-donor laparoscopic nephrectomy using glucocorticoids as an adjuvant to long-acting local anesthetics may decrease postoperative opioid use and reduce pain scores as compared to FPBs with LB or surgical site local anesthetic infiltration. Bupivacaine or ropivacaine combined with DXP and MPA is a safe and effective alternative to LB for FPBs in laparoscopic nephrectomy.

The Efficacy of Thumb Spica Casting With or Without Corticosteroid Injection for De Quervain's Tenosynovitis.

Background and objective De Quervain's tenosynovitis is a highly prevalent wrist pathology primarily caused by chronic thumb overuse. Its management typically begins with conservative methods, progressing to corticosteroid injections or surgery if necessary. This study compares the efficacy of thumb spica casting plus corticosteroid injection versus casting alone for treating De Quervain's tenosynovitis. Materials and methods This quasi-experimental study was conducted at the Department of Orthopaedics, Khyber Teaching Hospital, Peshawar, and enrolled adults aged 18-50 who presented with De Quervain's tenosynovitis. Patients were assigned to receive either corticosteroid injection plus thumb spica cast (Group A) or thumb spica cast alone (Group B). The primary outcome assessed the treatment success rate, while the secondary outcome evaluated the treatment effectiveness using visual analog scale (VAS) scores and Quick Disabilities of Arm, Shoulder, and Hand (QuickDASH). Results Of the initial 65 patients enrolled, 61 completed the study. Group A demonstrated a significantly higher treatment success rate (83.9%, n=26) compared to Group B (40%, n=12) (p<0.001). Pain reduction, as measured by VAS, was markedly greater in Group A (8.4 ± 1.0 to 0.4 ± 0.5) than in Group B (9.0 ± 0.8 to 5.9 ± 1.3) (p<0.001). Similarly, functional improvement assessed by QuickDASH favored Group A (89.6 ± 8.2 to 8.9 ± 6.8) over Group B (84.3 ± 10.1 to 49.1 ± 12.3) (p<0.001). No serious adverse effects related to treatments were noted in either of the groups. Conclusions This study supports the superiority of thumb spica casting along with local corticosteroid injection over casting alone for treating De Quervain's tenosynovitis. The combined approach led to significantly better pain relief and functional outcomes, highlighting its effectiveness as a treatment option despite the positive outcomes observed with casting alone.

Effects of Intracerebroventricular Injection of the Steroidal and Non-Steroidal Anti-Inflammatory Drugs on the Seizures during the Estrous Cycle in Rat.

Because of the mutual relationship between neural inflammation and seizure, this study aimed to determine the effects of intracerebroventricular (ICV) injection of the steroidal and non-steroidal anti-inflammatory drugs on pentylenetetrazol (PTZ)-induced seizures during the estrous cycle in rats. A total of 105 adult female Wistar rats were selected and divided into seven groups, including the control (saline), ketorolac tris salt (7.5, 15, and 30 µg), and methylprednisolone acetate (0.15, 0.3, and 0.6 µg), each with four subgroups (proestrus, estrus, metestrus, and diestrus) and three replicates (n=5). After a week of acclimatization, the estrous phase determination and synchronization were performed. Acute epilepsy was inspired by the intraperitoneal injection of 80 mg/kg of PTZ 30 min after the ICV injection of ketorolac and methylprednisolone acetate. The initiation time of myoclonic seizures (ITMS), the initiation time of tonic-clonic seizures (ITTS), seizure duration (SD), and mortality rate (MR) were measured for 30 min. Data were shown as mean±SD and analyzed using One-way ANOVA followed by Tukey-Kramer multiple comparison post hoc test (P<0.05). According to the results, ketorolac (15 and 30 µg) and methylprednisolone acetate (0.3 and 0.6 µg) significantly increased the ITTS and ITMS but decreased SD during the estrous cycle, compared to the control (P<0.05). Moreover, MR and SD were significantly decreased by ketorolac (7.5, 15, and 30 µg) and methylprednisolone (0.3 and 0.6 µg), compared to the control during the estrous cycle (P<0.05). Therefore, it seems that both ketorolac and methylprednisolone possess dose-dependent anticonvulsant effects that may decrease neural inflammation.

Preliminary experience on systemic effects of perineural dexamethasone sodium phosphate and methylprednisolone acetate through adductor canal block in total knee arthroplasty: A single center retrospective study.

Background and Aims: Glucocorticoids are commonly utilised as adjuvants to enhance nerve block quality and prolong the analgesic duration. Its systemic effects, after a single-injection adductor canal block (ACB) followed by a continuous infusion, are unclear. The aim of the study was to assess the systemic effects of a single dose of dexamethasone sodium phosphate (DEX), or a combination of DEX and methylprednisolone acetate (MPA), on fasting blood glucose (FBG) and white blood cell count (WBC) when administered perineurally via ACB. Material and Methods: A single-center retrospective study on total knee arthroplasty (TKA) was performed and a total of 95 patients were included in the final analysis. Patients were divided into three groups based on adjuvants received in ACB: Control group (N = 41) and two treatment groups, DEX group (N = 33) and DEX/MPA group (N = 21). Our primary outcomes were the change of FBG from its preoperative baseline value on postoperative day (POD) 2. The secondary outcomes included change of FBG on POD 0 and POD 1, and change of WBC on POD 0, POD 1, and POD 2. Results: The FBG change from baseline in the DEX group was significantly higher than that in the control group (difference = 14.04, 95% CI: 1.3 to 26.77), P = 0.031) on POD 0. The WBC change from baseline in the DEX/MPA group was statistically significant higher than control on POD 0 (2.62 (1.52 to 3.37), P < 0.0001). No significant differences between DEX and DEX/MPA group were found on any given postoperative days for FBG and WBC. Conclusion: This study provided preliminary safety data on the use of a combination of glucocorticoids with hydrophilic (DEX) and lipophilic (MPA) properties as local anesthetic adjuvants in ACB, which induced similar levels of changes on FBG and WBC as those from both control and DEX alone group.

Transforaminal Injections of Platelet-Rich Plasma Compared with Steroid in Lumbar radiculopathy: A Prospective, Double-Blind Randomized Study.

Purpose: To evaluate and compare the clinical efficacy of transforaminal steroid and platelet-rich plasma (PRP) injections in patients with discogenic lumbar radiculopathy. Methods: 60 patients were randomized to be treated with single transforaminal injection of PRP (n = 29) or steroid (methylprednisolone acetate [n = 31]). Clinical assessment was done with Visual analogue scale (VAS), modified Oswestry low back pain disability index (MODI), and straight leg raise test (SLRT). Baseline assessment of outcomes was done followed by post-intervention evaluation at 1, 3, and 6 months. Both groups had similar baseline characteristics. Results: There was a significant statistical improvement of VAS and MODI in both groups at follow-up (P < 0.05). In PRP group, minimal clinically important change (> 2 cm difference of mean for VAS and > 10-point change in MODI) for both outcome scores was achieved at all follow-up intervals (1, 3, 6 months), while as in steroid group, it was seen only at 1 and 3 months for both VAS and MODI. On intergroup comparison, better results were seen in steroid group at 1 month (P < 0.001 for both VAS and MODI), and in PRP group at 6 months (P < 0.001 for both VAS and MODI) with non-significant difference at 3 months (P = 0.605 for MODI and P = 0.612 for VAS). More than 90% tested SLRT negative in PRP group and 62% in steroid group at 6 months. No serious complications were seen. Conclusion: Transforaminal injections of PRP and steroid improve short-term (up to 3 months) clinical outcome scores in discogenic lumbar radiculopathy, but clinically meaningful improvements sustaining for 6 months were provided by PRP only.

Systemic Effects of Perineural Glucocorticoids on Fasting Serum Glucose, Potassium, and White Blood Cell Count in Total Hip Arthroplasty.

Purpose: Glucocorticoids are commonly used as regional anesthesia adjuvants to improve blockade quality and duration. There are limited data in the literature regarding the potential systemic effects and safety of perineural glucocorticoids. This study examines the effects of perineural glucocorticoids on serum glucose, potassium, and white blood cell count (WBC) in the immediate postoperative period after primary total hip arthroplasty (THA). Patients and Methods: A retrospective cohort study was carried out at a tertiary academic medical center utilizing electronic health records of 210 patients who underwent THA, for which patients received either a periarticular local anesthetic injection alone (PAI, N=132) or additional peripheral nerve blocks (PNB, N=78) containing 10 mg dexamethasone and 80 mg methylprednisolone acetate (PAI+PNB). The primary outcome was change in serum glucose from a preoperative baseline on postoperative days (POD) 1, 2, and 3. Secondary outcomes included changes in WBC and serum potassium. Results: The change in serum glucose from baseline was found to be significantly higher in the PAI+PNB group compared to the PAI group on POD 1 (mean difference 19.87 mg/dL, 95% CI [12.42, 27.32]; P<0.001) and POD 2 (mean difference 17.5 mg/dL, 95% CI [9.66, 25.44], P<0.001). No significant difference was found on POD 3 (mean difference -8.18 mg/dL, 95% CI [-19.07, 2.70], P=0.14). Statistically significant but clinically insignificant differences were detected in serum potassium in the PAI+PNB group compared to the PAI group on POD1 (mean difference 0.16 mEq/L, 95% CI [0.02, 0.30], P=0.03) and WBC on POD 2 (mean difference 3.18 × 1000/mm3, 95% CI [2.14, 4.22], P<0.001). Conclusion: Patients who underwent THA and received PAI+PNB with glucocorticoid adjuvants demonstrated higher elevations in serum glucose for the first two PODs compared to patients who received PAI alone. These differences resolved by a third POD and are likely to be of no clinical significance.

Perineural Methylprednisolone Depot Formulation Decreases Opioid Consumption After Total Knee Arthroplasty.

Purpose: Opioid consumption after total knee arthroplasty (TKA) remains a challenge with single injection nerve blocks even with common local anesthetic adjuvants dexamethasone (DEX). This study aimed to investigate the effects of adding methylprednisolone acetate (MPA) to adductor canal blocks (ACB) and interspace between the popliteal artery and capsule of the posterior knee (iPACK) blocks on postoperative opioid consumption. Methods: A retrospective analysis was conducted on 100 consecutive TKA patients equally assigned into two groups, with one group receiving DEX through ACB and iPACK block and the other group receiving DEX and methylprednisolone acetate (DEX/MPA) through the same nerve blocks. The primary outcome was cumulative opioid consumption (oral milligram morphine equivalent, OME) during hospitalization for up to three days. Secondary outcomes included daily opioid consumption, highest rest and active pain scores, prosthetic knee joint active range of motion (AROM), laboratory studies including fasting serum glucose (FSG) and white blood cell count (WBC) on each postoperative day (POD), and length of hospital stay. Results: Cumulative opioid consumption was significantly lower in the DEX/MPA group vs DEX group (median difference (95% CI) = -45.3 (-80.5 to -10), P = 0.011). The highest rest and active pain scores were both significantly lower in the DEX/MPA group than in DEX group on POD 2 (least square mean difference (95% CI) = -1.3 (-2.3 to -0.4), P = 0.005 and -0.9 (-1.8 to -0.1), P = 0.031, respectively). Except on POD 1, FSG values were significantly lower in the DEX/MPA group (median difference (95% CI) = -22.5 (-36 to -8.9), P = 0.001). AROM, WBC, and length of stay were comparable between both groups. Conclusion: Compared to perineural DEX alone, the addition of MPA further decreases postoperative opioid consumption without clinically significant changes on FSG and WBC. Level of Evidence: III.

Comparison of the Efficacy of Systemic Versus Local Steroid Treatment in Idiopathic Granulomatous Mastitis: A Cohort Study.

INTRODUCTION: Steroid therapy is known to be effective against granulomatous mastitis. We aimed to compare the efficacy of local versus systemic steroid administration in patients with idiopathic granulomatous mastitis. MATERIALS AND METHODS: This prospective cohort study included 58 patients who had either local (n = 42) or systemic (n = 16) treatment due to granulomatous mastitis between 2015 and 2019. Recurrence rates were determined as per ultrasound and magnetic resonance imaging examinations and the rate of side effects was evaluated as per patient complaints and physical examinations at the end of a 2-year follow-up period. RESULTS: Median doses of 140 mg and 3810 mg were administered to the local and systemic group, respectively. Six (14.3%) patients in the local treatment group and 13 (81.3%) in the systemic treatment group had steroid-related side effects. The local treatment group had significantly fewer side effects than the systemic treatment group (P < 0.001). The recurrence rates were similar in both groups (P > 0.05). CONCLUSIONS: Local steroid injection was as effective as systemic steroid therapy. Compared to systemic therapy, local steroid administration can be considered as a new therapeutic protocol with a lower dose and side effect rate.

The effect of subcutaneous injection of methylprednisolone acetate and lidocaine for refractory postherpetic neuralgia: a prospective, observational study.

BACKGROUND: Postherpetic neuralgia (PHN) is the most common and bearable complication of herpes zoster (HZ). This pain may have negative impact on the patient's all aspects of daily life and health-related quality of life (HRQOL). Despite numerous advances in treatment, many patients remain resistant to the current therapy options. It is the first time subcutaneous injection of methylprednisolone acetate and lidocaine has been used to treat refractory PHN. We report the results of this treatment evaluating pain relief and HRQOL improvement in this disorder. METHODS: A total of 43 patients with refractory PHN was enrolled in the observational study. All patients received daily subcutaneous injection of methylprednisolone acetate and lidocaine for 10 consecutive days. The severity of pain was assessed by using Visual Analog Scale (VAS), and 36-Item Short Form Survey (SF-36) was applied to evaluate HRQOL. Assessment of the pain and HRQOL was carried out at baseline and posttreatment at 4 weeks as well as 6 and 12 months. RESULTS: At baseline, all patients experienced severe PHN with average VAS scores of 8.44 ± 0.85 (minimum 7; maximum 10). At 4 weeks, 6 months, and 12 months after treatment, the pain had significantly decreased (P < .001), and all subjects showed significant improvement in all eight domains of HRQOL. No major adverse events associated with the subcutaneous injection were observed. CONCLUSIONS: Our results indicate that subcutaneous injection of methylprednisolone acetate and lidocaine can be an effective and safe treatment for PHN.

Elastic intramedullary nailing combined with methylprednisolone acetate injection for treatment of unicameral bone cysts in children: a retrospective study.

PURPOSE: The aetiology of unicameral bone cysts (UBCs) is unclear. This study aims to evaluate the feasibility of elastic intramedullary nailing (EIN) combined with injections of methylprednisolone acetate (MPA) for the treatment of UBCs in children. METHODS: We retrospectively analyzed 53 children with UBCs in our hospital between January 2010 and April 2016. A total of 24 patients (Group A) were treated by EIN and MPA, whilst 29 patients (Group B) were treated by curettage, bone grafts and EIN fixation. The radiographs of the UBCs were evaluated following the Capanna criteria. All patients were followed-up on the third, sixth, 12th, 24th and 36th months. Fixation time, hospitalization time and complications were evaluated. RESULTS: In Group A, the mean number of MPA injections was 1.8 (1 to 3). Based on radiographic evaluation, eight patients were healed (Capanna grade I), 14 were healed with residual cysts (Capanna grade II), one showed recurrence (Capanna grade III) and one showed no response to the treatment (Capanna grade IV). In Group B, 11 patients were evaluated as Capanna grade I, 12 as Capanna grade II, three as Capanna grade III and three as Capanna grade IV. There was significant difference in the early postoperative function activity (p < 0.001), hospitalization time (p = 0.028), blood loss during surgery (p < 0.001) and surgery time (p < 0.001). CONCLUSION: The combination of EIN and MPA for the treatment of UBCs in children is feasible, has little operative trauma, short surgery time, short hospitalization time, less blood loss and a low risk of incision infection. LEVEL OF EVIDENCE: III.

Methylprednisolone acetate mitigates IL1ß induced changes in matrix metalloproteinase gene expression in skeletally immature ovine explant knee tissues.

OBJECTIVE AND DESIGN: This study aimed at evaluating the effect of methylprednisolone (MPA) on messenger ribonucleic acid (mRNA) expression levels in immature ovine knee joint tissue explants following interleukin (IL)1ß induction and to assess responsiveness of the explants. MATERIAL OR SUBJECTS: Explants were harvested from the articular cartilage, synovium, and infrapatellar fat pad (IPFP) from immature female sheep. TREATMENT: Methylprednisolone. METHODS: The samples were allocated into six groups: (1) control, (2) MPA (10-3 M), (3) MPA (10-4 M), (4) IL1ß, (5) IL1ß + 10-3 M MPA, or (6) IL1ß + 10-4 M MPA. mRNA expression levels for molecules relevant to inflammation, cartilage degradation/anabolism, activation of innate immunity, and adipose tissue/hormones were quantified. Fold changes with MPA treatment were compared via the comparative CT method. RESULTS: Methylprednisolone treatment significantly suppressed MMPs consistently across the cartilage (MMP1, MMP3, and MMP13), synovium (MMP1 and MMP3), and IPFP (MMP13) (all p < 0.05). Other genes that were less consistently suppressed include endogenous IL1ß (cartilage) and IL6 (IPFP) (all p < 0.05), and others not affected either by IL-1 exposure or subsequent MPA include TGFß1, TLR4, and adipose-related molecules. CONCLUSIONS: Methylprednisolone significantly mitigated IL1ß induced mRNA expression for MMPs in the immature cartilage, synovium, and IPFP, but the extent of the responsiveness was tissue-, location-, and gene-specific.

In vitro Effects of Methylprednisolone Acetate on Equine Deep Digital Flexor Tendon-Derived Cells.

Primary deep digital flexor tendon (DDFT) pathologies and those accompanying degenerative changes of navicular bone fibrocartilage are major causes of lameness associated with navicular disease. Intrasynovial corticosteroids are mainstay in the treatment due to the anti-inflammatory effects, but their effect on DDFT cell biosynthesis are unknown. The objective of this in-vitro study was to investigate the effects of methylprednisolone acetate (MPA) on cells isolated from the dorsal fibrocartilaginous region of forelimb DDFTs (DDFT-derived cells) of 5 horses (aged 11-17 years). Non-adherent aggregate cultures were established from third passage cells over a 72 to 96-h duration prior to treating with medium containing 0 (control), 0.05 and 0.5 mg/mL MPA for 24 h. Tendon and cartilage extracellular matrix (ECM) related gene expression, cell aggregate and culture medium GAG contents, culture medium collagen and MMP-3 and-13 concentrations were measured. After 24 h of treatment, only the higher MPA concentration (0.5 mg/mL) significantly down-regulated tendon ECM related genes; whereas, both MPA doses significantly down-regulated cartilage ECM related genes. MPA treatment did not affect the total GAG content of DDFT-derived cells or total GAG, soluble collagen and MMP-3 and-13 contents in culture medium compared to untreated controls. Future studies to determine the response of DDFT-derived cells with longer exposure times to corticosteroids and in the presence of inflammatory cytokines are necessary. These results are a first step in assessing the effects of intrasynovial medications on equine DDFT, for which currently no information exists.

Methylprednisolone acetate injection with casting versus casting alone for the treatment of De-Quervain's Tenosynovitis: a randomized controlled trial.

OBJECTIVE: To compare the success of treatment between thumb spica cast with "methylprednisolone acetate injection" versus thumb spica cast alone for the treatment of de Quervain's disease as functional outcomes, complications and patient compliance. METHODS: A single blinded randomized controlled trial using a probability sampling technique was conducted from January 2014 to h February 2017at the Orthopaedic Unit II, King Edward Medical University / Mayo Hospital, Lahore. A total of 134 patients of both genders, between 30-60 years of age presented with wrist pain and diagnosed de Quervain's disease, were included in the study. Patients were randomly divided into two group by the computer allocation method. Patients in Group-A received thumb spica cast with methylprednisolone acetate and xylocaine injection while patients in Group-B were treated with thumb spica cast alone. The outcome variable was frequency of successful treatment which was noted and compared among the groups. RESULTS: Amongst the total 134 patients, the age of the patients ranged from 30 to 60 years with a mean of 37.16±5.15 years. Most of the patients were aged between 30 40 years (78.8%) followed by 41-50 years (21.2%). There were 38 (28.4%) male and 96 (71.6%) female patients in the study group with a male to female ratio of 1:2.5. In group-A mean VAS and Quick DASH score before treatment and after the treatment was statistically significant (p-value <0.001). In group-B mean VAS and Quick DASH score before and after the treatment was also significant (p-value <0.001) ( Table-2). CONCLUSIONS: The effectiveness of treatment was significantly higher in patients treated with thumb spica cast with methylprednisolone acetate injection as compared to thumb spica cast alone.

A Breast Cancer Survivor's Self-Controlled Case Report: Methylprednisolone Acetate Provided a Week Longer Analgesia Than Dexamethasone Sodium Phosphate via Thoracic Paravertebral Blockade.

Proper perioperative pain control with opioid-sparing techniques that extend into post-discharge arena is desirable yet hard to accomplish in breast cancer patients. We here reported a case where we took advantage of long-acting local anesthetics in conjunction with glucocorticoids of different hydrophilic/lipophilic properties and achieved prolonged analgesia for days after single administration thoracic paravertebral blockade. Further exploration into the potential effects of long-acting glucocorticoids in breast cancer patients through peripheral nerve blockage is warranted.

Comparative assessment of hypothalamic-pituitary-adrenal axis suppression secondary to intrabursal injection of different glucocorticoids: a pilot study.

BACKGROUND: Hypothalamic-pituitary-adrenal axis (HPAA) suppression is the most common and dangerous, although often unrecognized and untreated, side effect of glucocorticoid administration. The risk and duration depend both on patient and treatment characteristics. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) currently represents the gold standard method to evaluate the metabolism of endogenous and exogenous steroids. OBJECTIVE: To assess prevalence, severity, and duration of HPAA suppression subsequent to the injection of two steroids with equivalent potency but different pharmacokinetics. SUBJECTS AND METHODS: Single-blind randomized case-control pilot study. Forty patients (22 F; age 48.7 ± 7.2 years) with shoulder calcific tendinopathy received an intrabursal injection of 40 mg of 6α-methylprednisolone acetate (MA) or triamcinolone acetonide (TA). Just before (T0) and after 1 (T1), 7 (T2), 15 (T3), 30 (T4) and 45 (T5) days, we assessed morning blood cortisol and ACTH by RIA, and 24-h urinary levels of MA, TA and free cortisol by HPLC-MS/MS. RESULTS: HPAA function was normal at baseline. At T1, all patients presented HPAA suppression reaching the lowest cortisol, ACTH and UFC levels, that were similar between groups. At T2, mean cortisol remained lower than at baseline (p < 0.0001) in the TA group. In both groups, mean cortisol and ACTH levels progressively normalized, suggesting HPA recovery, except for three patients in the MA and two in the TA group. UFC levels remained lower than normal (p < 0.0001) up to T5, despite the disappearance of exogenous GCs. No patient developed manifestations of hypocortisolism. CONCLUSIONS: A single 40-mg intrabursal injection of MA or TA is sufficient to suppresses HPAA up to 45 days. Although typically asymptomatic, patients should be instructed to recognize and report symptoms suggestive for hypocortisolism, to provide prompt diagnosis, and eventually, treatment, thus avoiding severe complications.

Safety of intrathecal route: focus to methylprednisolone acetate (Depo-Medrol) use.

PURPOSE: Complications of the intrathecal route may cause potential toxicity related to the medical device and properties of the administered drug and/or excipient. A description of clinical and histological effects of polyethylene glycol and miripirium after Depo-Medrol injection, and the adverse reactions of particulate methylprednisolone acetate was conducted. The safety of the intrathecal route with excipients, label and off-label drugs is discussed. METHODS: A bibliographic search in Medline, Google, and Cochrane database from 1940 to June 2016 was performed. The keywords included 'intrathecal methylprednisolone acetate', 'miripirium', 'myristyl-gamma-picolinium', 'side effects', 'intrathecal Depo-Medrol', 'polyethylene glycol', and 'intrathecal devices' used individually or in combination. RESULTS: Adverse reactions have been reported with this intrathecal administration route such as arachnoiditis, bladder dysfunction, headache, meningitis. Some pharmaceutical excipients have been associated with specific toxicity issues and with allergic and anaphylaxis reactions. Additives of methylprednisolone acetate formulations such as polyethylene glycol and miripirium chloride can be neurotoxic when injected intrathecally. Polyethylene glycol-an antimicrobial agent widely used in pharmaceutical drugs-has been associated with cardiovascular, hepatic, respiratory, and CNS toxicity. CONCLUSIONS: Intrathecal methylprednisolone acetate (Depo-Medrol) therapy seems not fully safe due to reported adverse events. The use of other forms of corticosteroid therapy free from excipients should be emphasized such as soluble methylprednisolone sodium succinate.

Providing hyper-branched dendrimer conjugated with ß-cyclodextrin based on magnetic nanoparticles for the separation of methylprednisolone acetate.

This study introduced a developed approach for dendritic ß-cyclodextrin (ß-CD) in order to obtain high sorption capacity. Synthetic strategy exploits the reactivity between acrylic acid and allyl glycidyl ether for high-yielding assembly via grafting on to the magnetic nanoparticles that are modified using 3-mercaptopropyltrimethoxysilane for various building branches and host-guest molecules of ß-CD. The methodology has been applied for the preparation of a series of ß-CD conjugated magnetic nanoparticles with dendrimers as a nano-sorbent for the extraction of methylprednisolone acetate. This study allowed us to probe (i) the effects of the dendric-cyclodextrin architecture on the affinity of sorption capacity, (ii) the drug influence between the cyclodextrin core and the polyester dendrimer, and (iii) the result of sorbent formation for using the anti-inflammatory drug as a target guest into the ring of ß-CD on biological extraction. It was found that the adsorption behavior could be fitted by the Langmuir adsorption isotherm model. The adsorption capacity of MPA is found to be 12.4 mg g-1 and indicated the homogeneous sites onto polymer grafted magnetite nano-sorbent surface. Our results confirm the high capability of this type of dendrimer-ß-CD for drug extraction in biological fluids and pharmaceutical samples. This nano-sorbent assists the magnetic solid phase extraction technique represented in the high extraction yield (up to 97%) for methylprednisolone acetate in biological human fluids and pharmaceutical samples. Moreover, the achieved polymeric nano-sorbent of the reaction combination was facilitated by a magnetic field and reusability was performed without any notable loss in the sorbent activity.

Posttraumatic Osteoarthritis Development and Progression in an Ovine Model of Partial Anterior Cruciate Ligament Transection and Effect of Repeated Intra-articular Methylprednisolone Acetate Injections on Early Disease.

BACKGROUND: Partial anterior cruciate ligament (p-ACL) ruptures are a common injury of athletes. However, few preclinical models have investigated the natural history and treatment of p-ACL injuries. PURPOSE: To (1) demonstrate whether a controlled p-ACL injury model (anteromedial band transection) develops progressive gross morphological and histological posttraumatic osteoarthritis (PTOA)-like changes at 20 and 40 weeks after the injury and (2) investigate the efficacy of repeated (0, 5, 10, and 15 weeks) intra-articular injections of methylprednisolone acetate (MPA; 80 mg/mL) in the mitigation of potential PTOA-like changes after p-ACL transection. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty-one 3- to 5-year-old female Suffolk-cross sheep were allocated to 4 groups: (1) nonoperative controls (n = 5), (2) 20 weeks after p-ACL transection (n = 5), (3) 40 weeks after p-ACL transection (n = 6), and (4) 20 weeks after p-ACL transection + MPA (n = 5). Gross morphological grading and histological analyses were conducted. mRNA expression levels for inflammatory, degradative, and structural molecules were assessed. RESULTS: p-ACL transection led to significantly more combined gross damage ( P = .008) and significant aggregate histological damage ( P = .009) at 40 weeks after p-ACL transection than the nonoperative controls, and damage was progressive over time. Macroscopically, MPA appeared to slightly mitigate gross damage at 20 weeks after p-ACL transection in some animals. However, microscopic analysis revealed that repeated MPA injections after p-ACL transection led to significant loss in proteoglycan content compared with the nonoperative controls and 20 weeks after p-ACL transection ( P = .008 and P = .008, respectively). CONCLUSION: p-ACL transection led to significant gross and histological damage by 40 weeks, which was progressive over time. Multiple repeated MPA injections were not appropriate to mitigate injury-related damage in a p-ACL transection ovine model as significant proteoglycan loss was observed in MPA-treated knees. CLINICAL RELEVANCE: A p-ACL injury leads to slow and progressive PTOA-like joint damage, and multiple repeated injections of glucocorticoids may be detrimental to the knee joint in the long term.

Effect of intrathecal glucocorticoids on the central glucocorticoid receptor in a rat nerve ligation model.

BACKGROUND AND AIMS: Despite widespread use, the efficacy of neuraxial glucocorticoids for neuropathic pain is subject to debate. Since most glucocorticoid actions are mediated through its receptor, we explored the effects of intrathecal methylprednisolone acetate (MPA) on total glucocorticoid receptor (tGR) levels and activation of the glucocorticoid receptor (phosphorylated state=pGR) within the spinal dorsal horn (SDH) and dorsal root ganglion (DRG) in a spinal nerve ligation (SNL) model in rats. METHODS: Rats received unilateral ligation of the L5/L6 spinal nerves and were treated with two intrathecal doses of either 400µg MPA or 0.9% saline with a 72-h interval. Plantar tactile thresholds were measured over time. Seven days after drug treatment, DRG and SDH were harvested to assess tGR and pGR levels using immunohistochemistry and qPCR. RESULTS: Allodynia, defined by lowered tactile withdrawal thresholds after SNL, was unaltered by intrathecal MPA. In saline controls, mRNA levels of tGR did not change after SNL in the DRGs or SDH. tGR and pGR protein levels in the SDH however, significantly increased on the ipsilateral side of SNL compared to the contralateral side and to naïve tissue. When treating rats with MPA, tGR mRNA levels were significantly reduced in the SDH compared to saline controls. tGR and pGR protein levels, however were not significantly lower compared to saline controls. CONCLUSIONS: In intrathecal MPA treated rats, tGR mRNA levels decreased after SNL. However this did not result in lower tGR and pGR protein levels compared to saline controls, and did not decrease ligation-induced mechanical hypersensitivity. IMPLICATIONS: Intrathecal MPA treatment after SNL did not result in lower tGR and pGR levels within the SDH and DRG compared to saline controls. In present study we did not differentiate between the various isoforms of the GR which might clarify this finding.

Dry Needling Versus Cortisone Injection in the Treatment of Greater Trochanteric Pain Syndrome: A Noninferiority Randomized Clinical Trial.

Study Design Prospective, randomized, partially blinded. Background Greater trochanteric pain syndrome (GTPS) is the current terminology for what was once called greater trochanteric or subgluteal bursitis. Cortisone (corticosteroid) injection into the lateral hip has traditionally been the accepted treatment for this condition; however, the effectiveness of injecting the bursa with steroids is increasingly being questioned. An equally effective treatment with fewer adverse side effects would be beneficial. Objective To investigate whether administration of dry needling (DN) is noninferior to cortisone injection in reducing lateral hip pain and improving function in patients with GTPS. Methods Forty-three participants (50 hips observed), all with GTPS, were randomly assigned to a group receiving cortisone injection or DN. Treatments were administered over 6 weeks, and clinical outcomes were collected at baseline and at 1, 3, and 6 weeks. The primary outcome measure was the numeric pain-rating scale (0-10). The secondary outcome measure was the Patient-Specific Functional Scale (0-10). Medication intake for pain was collected as a tertiary outcome. Results Baseline characteristics were similar between groups. A noninferiority test for a repeated-measures design for pain and averaged function scores at 6 weeks (with a noninferiority margin of 1.5 for both outcomes) indicated noninferiority of DN versus cortisone injection (both, P<.01). Medication usage (P = .74) was not different between groups at the same time point. No adverse side effects were reported. Conclusion Cortisone injections for GTPS did not provide greater pain relief or reduction in functional limitations than DN. Our data suggest that DN is a noninferior treatment alternative to cortisone injections in this patient population. Level of Evidence Therapy, level 1b. Registered December 2, 2015 at www.clinicaltrials.gov (NCT02639039). J Orthop Sports Phys Ther 2017;47(4):232-239. Epub 3 Mar 2017. doi:10.2519/jospt.2017.6994.