Knee Extensor Mechanism Tendinopathy: Evaluation, Treatment, and Prevention.

ABSTRACT: Knee extensor mechanism tendinopathy, including patellar and quadriceps tendinopathy, is common among athletes and those involved in jumping sports. It is largely a clinical diagnosis that presents as anterior knee pain and stiffness with associated tenderness over the affected tendon. Imaging modalities, including ultrasound and/or magnetic resonance imaging, may be helpful with the diagnosis of difficult cases or in the planning of interventional procedures. Focused and structured rehabilitation using eccentric or heavy slow resistance exercise in conjunction with load management is important for recovery. Adjuvant therapies (e.g., injections or surgery) may be necessary in recalcitrant cases or those with insufficient response to rehabilitation efforts. Prevention strategies focus on improving biomechanics, landing mechanism and lower-extremity balance, flexibility, and strength.

Clinical Radiofrequency Ablation Outcomes of Combined Sensory Nerve Branch and Dorsal Entry Root Zone Complex Lesions for Sacroiliac Joint Complex Pain.

BACKGROUND: Chronic lower back pain (LBP) with or without leg pain (LP) is the most commonly reported anatomical site of pain among Canadian adults with chronic pain. A common cause for LBP and LP arises from dysfunction of the sacroiliac joint (SIJ) complex. When conventional medical management or rehabilitative efforts for SIJ-related LBP and LP fail to provide analgesia, pulsed radiofrequency (PRF) and/or radiofrequency ablation (RFA) of the dorsal entry root zone complex lesions (DREZC) and/or their more peripheral branches can also be a suitable means for treatment. Both PRF and RFA are interventional techniques that utilize heat to attenuate or ablate transmission of painful signals, respectively. The purpose of this chart review is to explore the clinical outcomes of patients experiencing SIJ-related pain who have undergone procedures with combined sensory nerve branch RFA and DREZC PRF lesions targeting the SIJ complex. METHODS: Following institutional review board approval, a retrospective chart review was performed from June 2018 to February 2021 for patients with LBP and/or LP refractory to physical rehabilitative efforts and medical management that underwent combined PRF and RF treatments for a diagnosis of SIJ complex pain. RF and PRF procedures were anatomically guided with the addition of sensory stimulation to ensure appropriate needle placement. Charts were reviewed for percentage of analgesia at final follow-up, duration of effect, degree of analgesia, patients' functional improvements, and changes in medication use patterns. RESULTS: Data was reviewed from 180 patients with LBP or LP who underwent combined PRF and RF treatments for a diagnosis of SIJ complex pain. The group consisted of 69 men and 111 women with a mean age of 59 years. All patients had lesions to their dorsal roots and/or branches (lumbar medial and sacral lateral), as determined using their pain profile as well as sensory stimulation. In the sample of 180 patients a total of 276 SIJs were treated over the period of data collection. Overall, 85.0% (n = 234) of procedures were considered successful with more than 50% analgesic relief at final follow-up. Of 234 successful outcomes, 110 reported ongoing analgesia (mean = 80.3% pain relief, SD ± 18.0) on the last date of follow up (mean = 53.2 days, SD ± 41.8) prior to being lost to follow-up. For patients not lost to follow-up, the mean amount of analgesia was reported to be 83.9% with an average duration of 86.3 days. Among all treatments, 6.9% (n = 19) provided no analgesic effect. Among the successful procedure outcomes, 54.4% (n = 150) reported increased activity/mobility, 24.3% (n = 67) reported improved sleep, 49.3% (n = 136) reported improved mood, and 11.6% (n = 32) reported decreased medication usage. Nine patients reported complications following the procedure. Complications included transient soreness, bruising, tenderness, myofascial pain, and two mild vagal responses without lasting sequelae. CONCLUSION: This review suggests that combined sensory nerve branch RFA and DREZC PRF lesions targeting the SIJ complex is a suitable intervention to treat SIJ-related LBP and/or LP refractory to physical rehabilitative efforts and medical management. Approximately 85% of these cases were successfully treated with the majority of patients report lasting analgesic effects with minimal complications, supporting the use of sensory stimulation-guided combined RF and PRF lesions for treatment of refractory SIJ complex pain.

The aging athlete.

Aging athletes, those 60 years and older, are a growing population of mature, active individuals who value sports and exercise participation throughout their lifespan. Although recommendations for younger and masters athletes have been extrapolated to this population, there remains a paucity of specific guidelines, treatment algorithms, and considerations for aging athletes. The benefits of living an active lifestyle must be weighed against the risks for unique cardiovascular, metabolic, and musculoskeletal injuries requiring diagnostic and therapeutic interventions. In this article, we review the unique cardiovascular and muscular physiology of aging athletes and how it influences the risk of specific medical conditions. We also discuss general prevention and treatment strategies. Finally, we identify areas of future research priorities and emerging treatments.

Early functional mobilization for non-operative treatment of simple elbow dislocations: a systematic review.

Purpose: This systematic review aims to elucidate a non-operative rehabilitation program that optimizes recovery based on published approaches and outcomes. Methods: Searches of four databases from inception to 1 January 2020 were performed to identify clinical studies addressing the non-operative management of simple elbow dislocations. Results: Of 2435 studies that were eligible for title screen, 15 studies satisfied inclusion criteria. Three randomized control studies demonstrated that early mobilization expedited the return of range of motion, function and return to work or activities, however, resulted in increased pain within the six-week rehabilitation period compared to Plaster of Paris casting for 21 days. Patients returned to work sooner after early mobilization (10 vs. 18 days; p = 0.02) compared to Plaster of Paris casting. In all studies, early mobilization resulted in similar re-dislocation rates of 1.3% (3/237) versus 2.2% (12/549) in those with Plaster of Paris casting as well as lower incidence of heterotopic ossification (36% vs. 54%). No significant differences between rehabilitation protocols were determined; however, the large majority of recent papers utilized rehabilitation protocols. Conclusion: Early mobilization of simple elbow dislocations results in early return of Range-of-Motion, function and return to work with no increase in complication rates; however, increased pain during the rehabilitation period.

Clinical evaluation and management of calcific tendinopathy: an evidence-based review.

Calcific tendinopathy (CT) is an important musculoskeletal condition most commonly seen in the shoulder girdle, accounting for 10-42% of all shoulder pain. Despite the high prevalence within the shoulder region, CT has been demonstrated in many tendons throughout the axial and appendicular skeleton. Unlike degenerative tendinopathies, CT appears to be a self-limiting condition that affects otherwise-healthy tendon with deposition of calcium hydroxyapatite crystals between healthy tenocytes. In patients with functionally limiting symptoms or pain, the clinical course may be accelerated through a multitude of treatments including physical therapy and pain management, extracorporeal shock wave therapy, ultrasound-guided percutaneous lavage (UGPL), and operative debridement. Currently, the most efficacious and frequently utilized treatment for shoulder CT is UGPL due to its ability to effectively reduce calcium burden and pain while limiting soft-tissue damage. However, more evidence regarding the treatment and course of CT is needed before determining the most appropriate treatment at all potential sites of CT.

Pulsed Radiofrequency in Interventional Pain Management: Cellular and Molecular Mechanisms of Action - An Update and Review.

BACKGROUND: Pulsed radiofrequency (PRF) treatment uses low energy, short pulsations to modulate tissue characteristics. PRF treatment has been effective as an interventional pain management technique to treat a variety of chronic neuropathic pain (neuralgia) disorders, but a comprehensive review of its biological mechanism has not been updated in a decade. OBJECTIVES: In this literature review, we performed a literature search in PubMed to identify publications describing the mechanisms of action of pulsed radiofrequency for pain indications. STUDY DESIGN: Narrative literature review. METHODS: A systematic search was performed through PubMed from database inception to December 31, 2019, to identify all articles addressing the cellular or molecular mechanisms of action of PRF on neuropathic pain. The search terms "pulsed radiofrequency" and "pulsed radiofrequency mechanisms" were used. Cellular and molecular mechanisms of PRF interventions were subdivided into 3 broad categories: nociceptive signalling, immune activity, and synaptic function. A total of 20 publications were identified for inclusion in this updated review. RESULTS: It was found that pulsed radiofrequency impacts many different biological pathways involved in the modulation of chronic neuropathic pain (neuralgia). With regards to nociceptive signalling, PRF treatment modulates ion channels (Na/K ATPase, HCN, P2X3), CGRP, neurotransmitters (aspartate, citrulline, M-ENK, glutamate), postsynaptic receptors (AMPA-R, GABA-B), and synaptic function (KCC2). PRF treatment also modulates immune activity, including microglial markers (CD3, CD56, Iba1), inflammatory cytokines (IL-6, IL-17, IRF8, IFN-g, TNFa), and intracellular proteins implicated in immune mediated neuropathic pain (BDNF, b-catenin, JNK, p38, ERK1/2). LIMITATIONS: This review is primarily limited by the diverse data sets that needed to be collated and correlated, as no study was comprehensive in addressing all markers, cytokines, pathways, neurotransmitters, ion channels, proteins, genes, and gene expression changes, along with their clinical outcomes concurrently. As such, the interplay of these individual pathways and mechanisms and their isolated effects on efficacy of PRF cannot be concluded. Rather, the large majority of findings can be seen as associations instead of definitive causal relationships to clinical outcomes. CONCLUSIONS: Herein describes a clinically relevant collated update describing the cellular and molecular mechanisms of action of PRF for pain management.

Knee Ablation Approaches.

Genicular nerve radiofrequency ablation has quickly become one of the most promising interventions for chronic knee pain secondary to osteoarthritis, with consistent improvements in pain and function. Although there are multiple techniques using slightly variable lesion locations, cannulas, lesion types, and imaging modalities, the clinical effectiveness targeting the anterior branches of the superior medial, superolateral, and inferior medial has reproducibly demonstrated clinically and statistically significant improvements up to 24 months after the procedure with minimal adverse events. This article summarizes the current knowledge of the sensory innervation of the knee joint, the principles of radiofrequency ablation, and the current literature on clinical outcomes.

Management and Complications in Nonoperative Fractures of the Tibial Spine: A Systematic Review.

Effective options exist for acute nonoperative management of anterior tibial spine fractures, yet there exists a paucity of literature describing long-term outcomes for these patients. This systematic review thus aims to consolidate management strategies and complications for patients with nonoperative anterior tibial spine fractures. In accordance with PRISMA guidelines, 5 databases (CINAHL, MEDLINE, EMBASE, Cochrane, and Pubmed) were searched and screened in duplicate. Quality assessment was performed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. Of 485 studies identified in the initial search, a total of 18 studies involving 369 patients were eligible for this review. These were stratified into 173 type I, 124 type II, and 72 type III injuries as described by Meyers and McKeever. All patients were treated with knee immobilization in either full extension or slight flexion, with possible closed reduction and/or aspiration of hemarthrosis. Complications at final follow-up comprised 33.9% of patients with persistent stiffness, 19.4% persistent instability, 11.1% mechanical symptoms, 6.37 delayed anterior cruciate ligament reconstruction, 4.9% delayed operative intervention for other complications, and 1.9% extension impingement. Given the lack of comparative studies in this review, definitive conclusions for nonoperative management are difficult to establish on the basis of the current body of literature alone. A modestly higher rate of arthrofibrosis and persistent laxity are seen in higher-grade injuries, however, only a minority of studies stratified complications by Meyers and McKeever classification in this review. A better understanding of variables in treatment decision making require further prospective study focused on the collection of functional and patient-reported outcome measures, whereas also further delineating complications by injury severity.

Acute Fifth Metatarsal Tuberosity Fractures: A Systematic Review of Nonoperative Treatment.

OBJECTIVE: Acute metatarsal fractures are a common lower extremity injury. Although surgery may be recommended in specific cases, most are treated nonoperatively. Treatment protocols vary significantly among practitioners, with no consensus on the most efficacious approach. This systematic review aims to identify the effect of treatment protocols on union rate and functional outcome after an acute fifth metatarsal tuberosity fracture. LITERATURE SURVEY: Multiple databases, including CINAHL, EMBASE, MEDLINE, and the Cochrane CEntral Register of Controlled Trials (CENTRAL) were searched from database inception to March 4, 2018 to identify clinical studies addressing nonoperative management of metatarsal fractures reporting nonunion, pain, and/or length of recovery. METHODOLOGY: Two reviewers independently completed title, abstract, and full-text screening. Data abstraction was completed in duplicate. Outcome measures and complications were descriptively analyzed. SYNTHESIS: A total of 1941 studies were eligible for screening. Seven studies (four randomized controlled trials and three prospective cohort studies) satisfied inclusion criteria. This resulted in a total of 388 patient with acute fifth metatarsal tuberosity fractures in 12 different treatment arms, with the most common treatment including plaster casting (7). The mean age was 42 years (27 to 56 years), and the overall nonunion rate was low (1.1%). Four unique functional scores were reported across all studies, and all showed good to excellent short-term results. The overall qualities of studies were moderate, with particular limitations in randomization and concealment allocation. CONCLUSION: Most acute fifth metatarsal tuberosity fractures heal well, with good-to-excellent functional outcomes with nonoperative treatment, regardless of technique. We recommend a conservative rehabilitation framework, including 2 to 3 weeks of immobilization in a walking cast, followed by gradual increase in activity and strengthening until clinical union is achieved.

Effectiveness of Platelet-Rich Plasma Injections for Nonsurgical Management of Carpal Tunnel Syndrome: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To systematically review and evaluate the efficacy and complication profile of platelet-rich plasma (PRP) injection into the carpal tunnel for management of carpal tunnel syndrome (CTS). DATA SOURCES: PubMed, MEDLINE, SCOPUS, EMBASE, Google Scholar, Cochrane Central Register of Controlled Trials, and Web of Sciences (from inception to January 1, 2019). STUDY SELECTION: Controlled trials addressing PRP for CTS. DATA EXTRACTION: Two reviewers independently screened the titles, abstracts, and full texts, extracting data from eligible studies. The outcomes of interest were the visual analog score (VAS) for pain and the Boston Carpal Tunnel Questionnaire (BCTQ), including the subscales of the symptom severity scale (SSS) and the Functional Status Scale (FSS). Other reported outcome measures and complications were analyzed descriptively. DATA SYNTHESIS: Four randomized controlled studies satisfied the inclusion criteria and analyzed a total of 191 cases with a final follow-up of either 3 or 6 months. Control groups included splinting in 2 studies, corticosteroid injection in 1 study, and saline injection in 1 study. There was a statistically and clinically significant improvement in the BCTQ (standardized mean difference=-2.06; 95% confidence interval [CI], -3.41 to -0.70; P=.003) between groups. Subgroup analysis showed significant improvement in SSS (standardized mean difference=-1.95; 95% CI, -3.65 to -0.25; P=.02) but not for FSS (standardized mean difference=-2.19; 95% CI, -4.77 to 0.40; P=.10). There was a similar improvement in VAS and nerve conduction studies in those receiving PRP compared to controls. Complication rate in the included studies was low with 4 of 97 participants receiving PRP injections experiencing transient pruritis, burning, or tingling. CONCLUSIONS: PRP represents a promising therapy for patients with mild to moderate CTS; however, included studies were limited as follow-up was short, the studies included patients that were heterogeneous, and the number of included studies was low. Further investigation is necessary to determine the true efficacy and effect of PRP and to better delineate the long-term results in patients with CTS.

Effectiveness of Dextrose Prolotherapy for Rotator Cuff Tendinopathy: A Systematic Review.

OBJECTIVE: To systematically review and evaluate the efficacy and complication profile of prolotherapy using hyperosmolar dextrose solution injection for rotator cuff tendinopathy. LITERATURE SURVEY: MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (from inception to 1 July, 2019). METHODOLOGY: A comprehensive search was completed to identify randomized controlled trials addressing prolotherapy using hyperosmolar dextrose solution for rotator cuff tendinopathy. Two reviewers independently screened the titles, abstracts, and full texts, and then extracted data from eligible studies. All reported outcome measures and complications were analyzed descriptively. SYNTHESIS: Five studies satisfied inclusion criteria. Included studies analyzed a total of 272 participants with a final follow-up ranging from 6 weeks to 12 months. Prolotherapy differed greatly among studies. Two studies used a multisite enthesis injection protocol while the other three used ultrasound-guided protocols. Two of the studies used an intrasubstance supraspinatus injection and three used a supraspinatus enthesis injection. Control groups consisted of nonoperative rehabilitation including physical therapy and medical management in three studies, supraspinatus saline enthesis injection in one study, and corticosteroid injection in one study. There was statistically significant improvement in pain intensity with multisite injection protocols compared to physical therapy and medical management in both studies. Ultrasound-guided supraspinatus injection trials did not find any statistically significant difference in pain intensity, range of motion, strength, function, or ultrasound characteristics compared to controls of enthesis saline injection or corticosteroid. The complication rate was low, with only 6/272 participants experiencing adverse events consisting of transient increase in pain for 1 to 2 days postintervention. CONCLUSIONS: Prolotherapy with hyperosmolar dextrose solution is a potentially effective adjuvant intervention to physical therapy for patients with rotator cuff tendinopathy ranging from tendinosis to partial-thickness and small full-thickness tears. Further studies are necessary to determine effects in subpopulations as well as optimal technique including dextrose concentration, volume, and location.

Arthroscopic Superior Capsular Reconstruction for Massive, Irreparable Rotator Cuff Tears: A Systematic Review of Modern Literature.

PURPOSE: To systematically review and evaluate the efficacy and complication profile of superior capsular reconstruction (SCR) as a technique to address massive, irreparable rotator cuff tears (MIRCTs). METHODS: Searches of the Cochrane Database of Systematic Reviews, Embase, MEDLINE, PubMed, and conference abstracts of 4 major conferences identified clinical studies addressing SCR for MIRCTs. Two reviewers independently screened the titles, abstracts, and full texts, extracting data from eligible studies. Reported outcome measures and complications were descriptively analyzed. RESULTS: A total of 10 studies, 7 full texts and 3 conference abstracts, satisfied the inclusion criteria. The included studies examined a total of 350 shoulders with a mean patient age of 60.6 years and mean follow-up period of 20.6 months postoperatively. Only 4 studies had a minimum of 24-month follow-up data. Statistically significant improvements in pain and function were noted in all studies reporting results, with mean improvement ranging from 29.4 to 68.5 and from 2.5 to 5.9 points across the American Shoulder and Elbow Surgeons score and visual analog scale score, respectively. Mean improvement in range of motion ranged from 21.7° to 64.0° in elevation and from 9.0° to 15.0° in external rotation. Statistically significant improvements in the postoperative acromiohumeral distance were noted in 4 of 5 reporting studies, with a mean increase ranging from 2.2 to 5.0 mm. The combined clinical and radiographic failure and/or retear rate ranged from 3.4% to 36.1%. Complications for all studies included deep infection (0%-2%), symptomatic suture anchor loosening (0%-4%), and severe shoulder contracture (0%-2%). CONCLUSIONS: Arthroscopic SCR represents an accepted surgical option for patients with MIRCTs, with short-term improvements shown in pain, range of motion, and function. Although early results are promising, further studies are necessary to determine the long-term success of this technique and to better delineate the clinical indications, survivorship, and risk factors for failure in this population. LEVEL OF EVIDENCE: Level IV, systematic review of Level III and IV studies.

Healing, Pain and Function after Midshaft Clavicular Fractures: A Systematic Review of Treatment with Immobilization and Rehabilitation.

OBJECTIVE: To systematically evaluate the scientific literature examining the efficacy of nonoperative management for midshaft clavicular fractures, specifically looking at the effect of immobilization and/or functional rehabilitation. TYPE: Systematic review. LITERATURE SURVEY: MEDLINE (PubMed), EMBASE, CINAHL databases were searched. METHODOLOGY: Inclusion criteria included adult patients enrolled in a controlled study evaluating bony healing, pain and/or function-related improvements after a strict nonoperative treatment plan for management of midshaft clavicle fractures. SYNTHESIS: A total of 10 articles were included in the study. Only four studies contained level I evidence; four studies were prospective case series without a control, and one was a retrospective case series without a control. Half of studies used a strict immobilization period, and most utilized a period of functional rehabilitation. There were no direct comparisons between rehabilitation protocols. Studies without a strict immobilization period had a nonunion rate of 5% to 24% and residual pain in 35% to 83% of patients compared to studies with a strict immobilization period with a nonunion rate of 3% to 29% and residual pain in 14% to 49% of patients. Studies including functional rehabilitation protocol reported functional as measured by the Constant Shoulder Score of 87.8 to 96, out of a maximum of 100 representing no functional limitations, and nonunion rates of 12% to 25% compared to 81 to 85 and 3% to 29% in those without a rehabilitation protocol. CONCLUSIONS: No studies directly examine the effect of immobilization and functional rehabilitation on clinical outcomes for midshaft clavicular fractures. Future studies are needed to better elucidate the most effective treatment. LEVEL OF EVIDENCE: I.

Hydrodilatation With Corticosteroid for the Treatment of Adhesive Capsulitis: A Systematic Review.

BACKGROUND: Current evidence suggests that corticosteroid injection alone expedites the recovery of pain-free range of motion (ROM) in patients with adhesive capsulitis compared to physiotherapy or placebo. However, it remains unclear whether the addition of hydrodilatation with corticosteroid provides improvement in pain-free ROM as well as pain relief. OBJECTIVE: A review of the literature was conducted to determine whether the combined intervention of hydrodilatation and corticosteroid injection expedites restoration of pain-free ROM compared to a control treatment of corticosteroid injection in patients with adhesive capsulitis. METHODS: EMBASE, MEDLINE, and CINAHL were searched from database inception to January 2017. Relevant studies were determined as randomized controlled trials written in English, comparing the outcomes of hydrodilatation and corticosteroid injection to a control group treated with corticosteroid injection alone in patients with adhesive capsulitis. Two independent reviewers assessed manuscripts for study inclusion and extracted data. RESULTS: A total of 2276 studies were identified through the search, of which 6 randomized controlled studies (involving 410 shoulders) met criteria for inclusion in this review. Mean age ranged from 51-61 years, with mean symptom duration of 4-9 months. Studies varied significantly regarding the volume of injectate, anatomical injection approach, symptom duration, and the method of glenohumeral capsule distension (capsular rupture versus preservation). Two studies demonstrated clinically and statistically significant improvement in the combination group at 3-month follow-up, and one study demonstrated clinically significant improvement only in ROM and/or pain/functional scales, compared to 3 studies demonstrating no benefit when compared to corticosteroid injection alone. CONCLUSION: Combining hydrodilatation with corticosteroid injection potentially expedites recovery of pain-free ROM. The greatest benefit is experienced within the first 3 months of intervention. Differences in hydrodilatation techniques, inclusion of capsular preservation, anatomical approach, and length of symptoms may explain the variability in efficacy demonstrated. Further trials using larger sample sizes, better anatomical approaches, image guidance, and hydrodilatation techniques are required to determine the true nature of benefits of hydrodilatation with corticosteroid injection. LEVEL OF EVIDENCE: II.

Adhesive capsulitis of the hip: a review addressing diagnosis, treatment and outcomes.

Adhesive capsulitis (AC) of the hip (i.e. 'Frozen Hip'), in part due to its difficulty in diagnosis, is an often overlooked and underappreciated entity of hip morbidity. This review aimed to elucidate a diagnostic approach and the surgical treatment options (with associated outcomes) of employing hip arthroscopy in the setting of AC. Electronic databases (EMBASE, MEDLINE and PubMed) were searched for available sources for all relevant clinical studies addressing the surgical management of AC. Additionally, reference lists of studies were hand-searched to find all relevant articles. Articles were systematically screened in duplicate, with agreement and descriptive statistics presented. Ten studies satisfied inclusion criteria. A total of 40 patients (mean age of 47.1 ± 14.8 years) were included. Diagnosis of AC of the hip commonly encompassed a combination of: decreased joint capacity; hip pain exacerbated by weight bearing or activity; and progressive decrease in global range of motion. Diagnostic arthroscopy was utilized in nine patients, and successful diagnosis of AC was achieved in all nine patients. Common treatments included pressure dilation (11 cases) and manipulation under anesthesia (11 cases). AC continues to be a difficult clinical entity to diagnose. Similarities are seen between hip AC and shoulder AC as diagnosis is often a result of ruling out all other possible conditions, and treatment options and outcomes resemble those of the shoulder counterpart. With successful outcomes harping on timely diagnosis and effective treatment, the use of hip arthroscopy may be of benefit to achieving this.

Palmitate differentially regulates the polarization of differentiating and differentiated macrophages.

The tissue accumulation of M1 macrophages in patients with metabolic diseases such as obesity and type 2 diabetes mellitus has been well-documented. Interestingly, it is an accumulation of M2 macrophages that is observed in the adipose, liver and lung tissues, as well as in the circulation, of patients who have had major traumas such as a burn injury or sepsis; however, the trigger for the M2 polarization observed in these patients has not yet been identified. In the current study, we explored the effects of chronic palmitate and high glucose treatment on macrophage differentiation and function in murine bone-marrow-derived macrophages. We found that chronic treatment with palmitate decreased phagocytosis and HLA-DR expression in addition to inhibiting the production of pro-inflammatory cytokines. Chronic palmitate treatment of bone marrows also led to M2 polarization, which correlated with the activation of the peroxisome proliferator-activated receptor-γ signalling pathway. Furthermore, we found that chronic palmitate treatment increased the expression of multiple endoplasmic reticulum (ER) stress markers, including binding immunoglobulin protein. Preconditioning with the universal ER stress inhibitor 4-phenylbutyrate attenuated ER stress signalling and neutralized the effect of palmitate, inducing a pro-inflammatory phenotype. We confirmed these results in differentiating human macrophages, showing an anti-inflammatory response to chronic palmitate exposure. Though alone it did not promote M2 polarization, hyperglycaemia exacerbated the effects of palmitate. These findings suggest that the dominant accumulation of M2 in adipose tissue and liver in patients with critical illness may be a result of hyperlipidaemia and hyperglycaemia, both components of the hypermetabolism observed in critically ill patients.

Prolonged Endoplasmic Reticulum-Stressed Hepatocytes Drive an Alternative Macrophage Polarization.

Relatively little is known about the effects of hepatocytes on hepatic macrophages, particularly under the situation of endoplasmic reticulum (ER) stress. We examined the effects of hepatocytes conditioned media (CM) from HepG2 treated with ER stress inducers, tunicamycin or thapsigargin, on the secretion of cytokines, expression of ER stress markers, and polarization of phorbol myristate acetate-activated THP-1 cells (pTHP-1). We found that CM decreased the production of the proinflammatory cytokines including tumor necrosis factor α, interleukin 6 (IL-6), and IL-1ß as well as other cytokines and chemokines from pTHP-1 cells. These effects are mediated by the inhibition of TLR4 expression and nuclear factor κB signaling pathway. In addition, hepatocytes CM increased the expression of binding immunoglobulin protein and the transcription factor C/EBP homologous protein (CHOP) in pTHP-1 cells. Preconditioning with ER stress inhibitor, small molecular chaperone 4-phenylbutyrate before addition of ER stressors, attenuated the ER stress in macrophages, the property of hepatocytes CM to alter tumor necrosis factor α production and nuclear factor κB expression by macrophages. Remarkably, treatment of macrophage with these CM leads to an alternative activation of macrophages mediated by peroxisome proliferator-activated receptor γ signaling pathway, which might be resulted from the secretion of IL-10 and IL-4 as well as releasing apoptotic bodies from hepatocytes under ER stress. Our results highlight a mechanism of ER stress transmission from hepatocytes to macrophage that drives an alternative activation of macrophages, which depends on the exposure of hepatocytes to severe and prolonged ER stress.

Efficacy of Hip Arthroscopy for the Management of Septic Arthritis: A Systematic Review.

PURPOSE: This systematic review assessed the role of hip arthroscopic irrigation and debridement for eradication of infection in native joints to ascertain outcomes and complications associated with this surgical approach. METHODS: The Medline, Embase, and PubMed databases were searched on July 20, 2014, for English-language studies that addressed arthroscopic treatment of native septic hip arthritis. The studies were systematically screened and data abstracted in duplicate, with qualitative findings presented. RESULTS: There were 11 eligible studies (1 case-control study, 8 case series, and 2 case reports) reporting on 65 patients (65 hips) treated by arthroscopic irrigation and debridement for septic hip arthritis. The mean length of patient follow-up was 19.1 months (range, 6 to 84 months). The indications for surgery were as follows: pyrexia, anterior groin or hip pain with limited hip range of motion and an inability to bear weight, associated leukocytosis, an elevated erythrocyte sedimentation rate or C-reactive protein level, and/or hip imaging or aspiration results consistent with infection. Specific contraindications for surgery reported across studies included tuberculous of fungal infection, coexistence of osteomyelitis, immunocompromised individuals, and pre-existing surgery on the affected hip. The initial rate of infection eradication was 100%. All studies reported significant improvements in patient pain and function. Improvements were also observed in range of motion, as well as across both the Bennett radiographic and clinical assessments and Harris Hip Score. No complications, major or minor, were reported, and only 1 of 65 hips (1.5%) required revision arthroscopy for recurrence because of a methicillin-resistant Staphylococcus aureus infection. CONCLUSIONS: Arthroscopic native hip irrigation and debridement for septic arthritis appear to comprise a safe and effective treatment option for selected patients (e.g., no deformity, no bacterial infections, and not immunocompromised). Timely diagnosis and intervention, however, remain the most critical prognostic factors for successful outcomes. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV and V studies.

Femoroacetabular impingement in skeletally immature patients: a systematic review examining indications, outcomes, and complications of open and arthroscopic treatment.

PURPOSE: Improvements in physical examination and radiographic appreciation of symptomatic femoroacetabular impingement (FAI) has increased the focus on early diagnosis and treatment in an adolescent population. This systematic review aimed to establish specific indications, outcomes, and complications of surgical management of adolescent FAI. METHODS: The Medline, Embase, and PubMed online databases were searched from inception until April 21, 2014, for English-language studies that addressed open and/or arthroscopic treatment of FAI in patients aged 10 to 19 years inclusively. The studies were systematically screened and data abstracted in duplicate, with qualitative findings presented. RESULTS: There were 6 eligible case series (4 with arthroscopic and 2 with open technique) and 2 conference abstracts examining 388 patients in total (435 hips), 81% of which were treated with hip arthroscopy. Overall, patients were followed up for a mean of 23.4 months postoperatively (range, 3 to 75 months). The main indication for surgery was a confirmed diagnosis of FAI with persistent pain and impaired function refractory to nonoperative interventions (activity modification, intra-articular injections, and so on). Specific contraindications included Tönnis grade 2, 3, or 4 chondral changes and acetabular dysplasia. All studies reported significant improvements in patient pain, function (e.g., no patients were "abnormally" or "severely abnormally" impaired), and satisfaction rates (84% to 100% with arthroscopic technique v 79% with open technique). Improvements also were observed in range of motion and alpha angle correction, as well as across a variety of patient-reported functional scores, with all but 7 of 388 patients (1.8%) returning to activity/sport. No major complications were reported, with only 13 of 354 hips (3.7%) treated by arthroscopy requiring revision arthroscopy for lysis of adhesions and 1 of 81 open surgical dislocation hips (1%) having asymptomatic heterotopic ossification not requiring additional management. No cases of avascular necrosis, physeal arrest or growth disturbance, or iatrogenic deformity were reported. CONCLUSIONS: Both arthroscopic and open surgical dislocation approaches for the treatment of adolescent FAI appear to be safe and effective options for patients with persistent pain and limited function after an appropriate trial of nonoperative therapy. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.

IDH1 regulates phospholipid metabolism in developing astrocytes.

Isocitrate dehydrogenase 1 (IDH1) is an evolutionarily conserved enzyme that catalyzes the interconversion of isocitrate to α-ketoglutarate with the concomitant reduction of NADP(+) to NADPH. IDH1 has previously been shown to participate in lipid biosynthesis in various tissues such as the liver and adipose tissue. We examined the potential role of IDH1 in phospholipid metabolism in the brain. Here we show that IDH1 is highly expressed in the brain and astrocytes during embryonic development and the postnatal period and subsequently declines in adulthood. Silencing of IDH1 expression using siRNA in astrocytes isolated from E18.5 mouse cortices led to increased incorporation of [(3)H]-palmitate into the phosphatidylcholines (PCs) and decreased the incorporation of [(3)H]-palmitate into sphingomyelin and the phosphatidylethanolamines (PEs). In pulse-chase experiments, knock-down of IDH1 expression impaired the turnover of PCs and decreased the synthesis of PEs. The decrease in [(3)H]-palmitate incorporation into PEs when IDH1 was knocked-down in astrocytes was not due to impairments within the CDP-ethanolamine pathway or in the rate of decarboxylation of phosphatidylserine (PS). In conclusion, our results reveal a role for IDH1 in the synthesis/turnover of phospholipids in developing astrocytes and highlight the lipid alterations resulting from the loss of wild-type IDH1 activity.