The Relative Efficacy of Available Proteasome Inhibitors in Preventing Muscle Contractures Following Neonatal Brachial Plexus Injury.

BACKGROUND: Contractures following neonatal brachial plexus injury (NBPI) are associated with growth deficits in denervated muscles. This impairment is mediated by an increase in muscle protein degradation, as contractures can be prevented in an NBPI mouse model with bortezomib (BTZ), a proteasome inhibitor (PI). However, BTZ treatment causes substantial toxicity (0% to 80% mortality). The current study tested the hypothesis that newer-generation PIs can prevent contractures with less severe toxicity than BTZ. METHODS: Unilateral brachial plexus injuries were surgically created in postnatal (5-day-old) mice. Following NBPI, mice were treated with either saline solution or various doses of 1 of 3 different PIs: ixazomib (IXZ), carfilzomib (CFZ), or marizomib (MRZ). Four weeks post-NBPI, mice were assessed for bilateral passive range of motion at the shoulder and elbow joints, with blinding to the treatment group, through an established digital photography technique to determine contracture severity. Drug toxicity was assessed with survival curves. RESULTS: All PIs prevented contractures at both the elbow and shoulder (p < 0.05 versus saline solution controls), with the exception of IXZ, which did not prevent shoulder contractures. However, their efficacies and toxicity profiles differed. At lower doses, CFZ was limited by toxicity (30% to 40% mortality), whereas MRZ was limited by efficacy. At higher doses, CFZ was limited by loss of efficacy, MRZ was limited by toxicity (50% to 60% mortality), and IXZ was limited by toxicity (80% to 100% mortality) and loss of efficacy. Comparisons of the data on these drugs as well as data on BTZ generated in prior studies revealed BTZ to be optimal for preventing contractures, although it, too, was limited by toxicity. CONCLUSIONS: All of the tested second-generation PIs were able to reduce NBPI-induced contractures, offering further proof of concept for a regulatory role of the proteasome in contracture formation. However, the narrow dose ranges of efficacy for all PIs highlight the necessity of precise proteasome regulation for preventing contractures. Finally, the substantial toxicity stemming from proteasome inhibition underscores the importance of identifying muscle-targeted strategies to suppress protein degradation and prevent contractures safely. CLINICAL RELEVANCE: Although PIs offer unique opportunities to establish critical mechanistic insights into contracture pathophysiology, their clinical use is contraindicated in patients with NPBI at this time.

Burn Injury Complications Impacting Rehabilitation.

Successful post-burn rehabilitation requires an understanding of a wide range of complications to maximize functional recovery. This article reviews a range of potential challenges including burn scar contracture, amputation, peripheral nerve injury, heterotopic ossification, dysphagia, altered skin physiology, pain, and pruritis. The overall focus is to serve as a guide for post-injury therapy and rehabilitation spanning the phases of care and considering evidence-based approaches, prevention, and treatment with an ultimate goal of aiding in the functional recovery and long-term quality of life for burn survivors.

Vitamin C as a Potential Prophylactic Measure Against Frozen Shoulder in an In Vivo Shoulder Contracture Animal Model.

BACKGROUND: Frozen shoulder is a common, painful, and movement-restricting condition. Although primary frozen shoulder is idiopathic, secondary frozen shoulder can occur after trauma or surgery. Prophylactic and therapeutic options are often unsatisfactory. Vitamin C (ascorbic acid) is a potent physiological antioxidant and likely inhibits the activation of nuclear factor κB, which plays a decisive role in inflammatory reactions. HYPOTHESIS: Because of its anti-inflammatory effects, vitamin C may be valuable in the prevention of secondary frozen shoulder. STUDY DESIGN: Controlled laboratory study. METHODS: An in vivo shoulder contracture model was conducted by fixation of the right proximal limb of Sprague-Dawley rats. A treatment group (n = 8) receiving vitamin C orally was compared with a control group (n = 9) without vitamin C. The primary outcome was capsular thickness at the shoulder joint measured on magnetic resonance imaging (MRI) examination. Further histological examination was performed but was not statistically analyzed because of variability of the cutting plane through the glenoid. RESULTS: Vitamin C treatment resulted in less thickening of the axillary fold of the operated shoulder at 2 of the 3 locations measured on MRI compared with untreated controls (insertion to the glenoid, P = .074; insertion to the humerus, P = .006; middle of the axillary recess, P = .008). The observed structural changes in histological examination corroborated the significant changes obtained from the MRI measurements. CONCLUSION: Prophylactic vitamin C seemed to reduce the thickening of the axillary recess in secondary frozen shoulder in this preclinical study. CLINICAL RELEVANCE: Vitamin C may be helpful as a noninvasive therapeutic measure to prevent secondary frozen shoulder (eg, within the context of surgery in the shoulder region or immobilization) or to treat primary frozen shoulder at an early stage. Further studies are required to evaluate the effect of this treatment in humans and the necessary dosage in humans.

Frequency, facilitators, and barriers for range of motion to prevent shoulder contracture in brachial plexus birth injury: A pilot study.

PURPOSE: This pilot study investigated the efficacy of passive range of motion (PROM) during the first year of life to prevent development of shoulder contractures in children with brachial plexus birth injury (BPBI) and identified facilitators and barriers to caregiver adherence with daily PROM. METHODS: Five caregivers of children with upper trunk BPBI participated in retrospective interviews about the frequency with which they performed PROM during their child's first year of life including facilitators and barriers to daily adherence. Medical records were reviewed for documentation of caregiver-reported adherence and documented evidence of shoulder contracture by age one. RESULTS: Three of the five children had documented shoulder contractures; all three had delayed initiation or inconsistent PROM in the first year of life. Two without shoulder contractures received consistent PROM throughout the first year of life. Making PROM part of the daily routine was a facilitator to adherence while family contextual factors were barriers. CONCLUSION: Absence of shoulder contracture may be related to consistent PROM throughout the first year of life; decreased frequency of PROM after the first month of life did not increase the risk of shoulder contracture. Consideration of family routines and context may facilitate adherence with PROM.

Effects of millimeter-wave for preventing joint stiffness in the immobilized knee rat model.

AIM: To explore the effects and mechanism of millimeter-wave treatment on the development of joint stiffness in the immobilized knee rat model. METHODS: Twenty-four Sprague-Dawley (SD) rats were randomly divided into the control group (O, n = 8), the surgical control group (OC, n = 8), and the millimeter-wave treatment group (MO, n = 8). After immobilized knee modeling, the knee mobility and quadriceps diameter was measured at the 6th week. Hematoxylin and eosin and Masson staining were performed to detect the pathology and fibrous lesions of the knee joint. Furthermore, the expression of TGF-ß1 and Collagen I was quantified by immunohistochemical assay in the knee capsule, and Western blotting was performed to quantify the protein expression of NF-κB and MuRF1 in skeletal muscle. RESULTS: Compared with the O group, knee mobility, and quadriceps diameter was decreased (P < 0.01), and articular capsule fibrosis and quadriceps atrophy occurred in all rats with fixed knee joints. Compared with the OC group, millimeter-wave treatment significantly increased articular mobility and the quadriceps diameter; and improved the fibrotic lesions of the joint capsule and quadriceps atrophy. Moreover, levels of TGF-ß1, Collagen I, and MuRF1 were upregulated (P < 0.01) by knee immobilization, and collagen fiber content in the articular capsule was also increased (P < 0.01). However, millimeter-wave treatment reversed it. The most noteworthy result was that NF-κB expression was not significantly different in all groups. CONCLUSION: Millimeter-wave treatment reversed joint contracture and quadriceps atrophy caused by joint fixation, inhibited TGF-ß1 and Collagen I protein expression of the joint capsule and reduced MuRF1 expression of the quadriceps muscle, thereby inhibiting the development of joint stiffness.

Difference in the Occurrence of Capsular Contracture According to Tissue Characteristics in an Irradiated Rat Model.

BACKGROUND: This study was performed to evaluate the hypothesis that capsule formation varies according to the radiation dose in muscle tissues; chest wall tissues, including the ribs; and acellular dermal matrices (ADM) that are in contact with the silicone implant. METHODS: In this study, 20 Sprague-Dawley rats underwent submuscular plane implant reconstruction using ADM. They were divided into four groups: an unradiated control group ( n = 5), nonfractionated radiation at a dose of 10 Gy ( n = 5), nonfractionated radiation at a dose of 20 Gy ( n = 5), and fractionated radiation at a dose of 35 Gy ( n = 5). Three months after surgery, hardness was measured, and histologic and immunochemical analyses of the capsule tissues of the ADM, muscle tissues, and chest wall tissues were analyzed. RESULTS: As the radiation dose increased, the silicone implant became harder, but no significant difference in capsule thickness according to the radiation dose was observed. Based on the tissue in contact with the silicone implant, ADM had a thinner capsule thickness than the muscle tissues, as well as less inflammation and less neovascularization compared with the other tissues. CONCLUSIONS: This study describes a new rat model of clinically relevant implant-based breast reconstruction using a submuscular plane and ADM with irradiation. The ADM in contact with the silicone implant, even after irradiation, was protected from radiation compared with the other tissues. CLINICAL RELEVANCE STATEMENT: These research results could support the use of ADM in implant-based breast reconstruction for prevention of the capsular contracture, even after radiation.

Stem Cell-Enriched Hybrid Breast Reconstruction Reduces Risk for Capsular Contracture in a Hybrid Breast Model.

BACKGROUND: Hybrid breast reconstruction (HBR) combines silicone implants with fat grafting to improve implant coverage, treating local tissue deficiencies and leading to a more natural breast appearance. Recent data also indicated less capsular contracture after HBR. The authors developed a novel technique and animal model of cell-assisted (CA) HBR to illuminate its effects on capsular contracture. METHODS: Animals received silicone implants in a dorsal submuscular pocket. Although animals of the HBR group received fat grafting around the implant without stem cell enrichment, rats of the CA-HBR1 and the CA-HBR2 groups received stem cell-enriched fat grafting with 2 × 10 6 and 4 × 10 6 adipose-derived stem cells immediately after implant insertion. On day 60, animals underwent sonography and elastography imaging and were euthanized, and outcome analysis was performed by means of histology, immunohistochemistry, chemical collagen quantification, and gene expression analysis. RESULTS: With this novel technique, long-term survival of adipose-derived stem cells within the implant pocket was demonstrated after 60 days after implant insertion. CA-HBR led to significantly reduced thickness and collagen density of capsular contractures. In addition, CA-HBR resulted in reduced fibrotic responses with less occurrence of collagen type I and transforming growth factor-ß in capsule tissue. Moreover, the addition of stem cells suppressed fibrotic and inflammatory responses on a genetic level with significant underexpression of collagen type I and transforming growth factor-ß1. CONCLUSIONS: With this new technique and animal model, the authors observed a preventive effect on capsular contracture substantiating the basis of clinical outcomes of HBR. The authors propose that the addition of stem cells to HBR might booster its beneficial results. CLINICAL RELEVANCE STATEMENT: Stem cell-enriched fat grafting around silicone implants may reduce the risk for capsular contracture after silicone breast implantation. While fat grafting alone already shows beneficial effects, the addition of stem cells to the fat graft can potentiate this effect.

Factors associated with joint contractures in adults: a systematic review with narrative synthesis.

PURPOSE: The primary objective of the review was to collate the available evidence on factors associated with joint contractures in adults. METHODS: A systematic literature search was conducted on MEDLINE, CINAHL, AMED, and EMBASE. Studies that involved participants aged ≥18 and assessed joint contracture as a primary or secondary outcome were included. Two independent reviewers screened studies against the eligibility criteria, performed data extraction, and assessed the quality of evidence. A narrative synthesis by domain and sub-domain was undertaken. The protocol was registered on PROSPERO: CRD42019145079. RESULTS: Forty-seven studies were included in the review. Identified factors were broadly classified into three major domains: sociodemographic factors, physical factors, and proxies for bed confinement. Sociodemographic factors were not associated with joint contractures. Functional ability, pain, muscle weakness, physical mobility, and bed confinement provided the most consistent evidence of association with joint contractures. The evidence regarding the relationship between spasticity and joint contractures remains unclear. Other factors might be important, but there was insufficient evidence to make inferences. CONCLUSIONS: The review identified and collated evidence on factors associated with joint contractures, which can be utilised to develop effective prevention and management strategies. Implications for rehabilitationClinical interventions based on the timely identification of risks related to joint contractures in vulnerable adults have the potential to prevent or ameliorate their development or progression.Quality and consistency of care for vulnerable adults would be enhanced by developing effective joint contracture prevention and rehabilitation strategies based on the evidence presented in this review.As many vulnerable adults are located in the community or non-acute care settings, strategies should target these loci of care.Structured risk assessments that can support non-physiotherapy staff working in these loci of care to identify risks related to joint contractures would provide an important resource for risk management.

Extracorporeal shockwave therapy in an immobilized knee model in rats prevents progression of joint contracture.

Joint immobilization, which ensures rest and accelerates tissue recovery in musculoskeletal disorders, often causes joint contracture, for which there is still no effective prevention. To address this, we investigated the effects of extracorporeal shockwave therapy (ESWT) in preventing joint contracture, in a unilaterally immobilized knee rat model. Under general anesthesia, ESWT (0.25 mJ/mm2 , 3000 shot, 4 Hz, 3 days/week) was administered from 1 day after immobilization up to 2, 4, and 6 weeks. The immobilized control group received general anesthesia without ESWT. We evaluated joint angle, tissue elasticity, and gene and protein expression related to fibrosis, inflammation, and angiogenesis in the joint capsule. Relative to the control, the ESWT group had greater joint angle at 4 and 6 weeks, and lower posterior-capsule elasticity at 6 weeks. In the ESWT group, at 6 weeks, gene expression of collagen type I (col1α1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) was significantly downregulated, whereas interleukin-6 (IL-6) and hypoxia-inducible factor-1α (HIF-1α) gene expression was upregulated, relative to that in the control. Compared with that in the control, at 4 and 6 weeks, the ratio of CTGF+ cells was significantly lower in the ESWT group; at 4 weeks, the ESWT group had significantly fewer CD68+ cells in the adhesion area, and at 6 weeks, significantly more blood vessels. Statement of Clinical Significance: In a rat model, ESWT counteracted fibrosis, suppressed macrophage infiltration, and promoted neovascularization, reducing elasticity, and increasing joint range-ofmotion. ESWT offers a potential new strategy to prevent progression in joint contracture.

Muscle contractile exercise through a belt electrode device prevents myofiber atrophy, muscle contracture, and muscular pain in immobilized rat gastrocnemius muscle.

PURPOSE: Immobilization of skeletal muscles causes muscle atrophy, muscle contracture, and muscle pain, the mechanisms of which are related to macrophage accumulation. However, muscle contractile exercise through a belt electrode device may mitigate macrophage accumulation. We hypothesized that such exercise would be effective in preventing myofiber atrophy, muscle contracture, and muscular pain. This study tested this hypothesis in immobilized rat gastrocnemius muscle. MATERIALS AND METHODS: A total of 32 rats were divided into the following control and experimental groups: immobilization (immobilized treatment only), low-frequency (LF; immobilized treatment and muscle contractile exercise with a 2 s (do) /6 s (rest) duty cycle), and high-frequency (HF; immobilized treatment and muscle contractile exercise with a 2 s (do)/2 s (rest) duty cycle). Electrical stimulation was performed at 50 Hz and 4.7 mA, and muscle contractile exercise was applied to the lower limb muscles for 15 or 20 min/session (once daily) for 2 weeks (6 times/week). After the behavioral tests, the bilateral gastrocnemius muscles were collected for analysis. RESULTS: The number of macrophages, the Atrogin-1 and MuRF-1 mRNA expression, and the hydroxyproline content in the HF group were lower than those in the immobilization and LF groups. The cross-sectional area (CSA) of type IIb myofibers in the superficial region, the PGC-1α mRNA expression, and the range of motion of dorsiflexion in the HF group were significantly higher than those in the immobilization and LF groups. The pressure pain thresholds in the LF and HF groups were significantly higher than that in the immobilization group, and the nerve growth factor (NGF) content in the LF and HF groups was significantly lower than that in the immobilization group. CONCLUSION: Muscle contractile exercise through the belt electrode device may be effective in preventing immobilization-induced myofiber atrophy, muscle contracture, and muscular pain in the immobilized rat gastrocnemius muscle.

Pharmacological Approaches for the Prevention of Breast Implant Capsular Contracture.

Capsular contracture is a common complication associated with breast implants following reconstructive or aesthetic surgery in which a tight or constricting scar tissue capsule forms around the implant, often distorting the breast shape and resulting in chronic pain. Capsulectomy (involving full removal of the capsule surrounding the implant) and capsulotomy (where the capsule is released and/or partly removed to create more space for the implant) are the most common surgical procedures used to treat capsular contracture. Various structural modifications of the implant device (including use of textured implants, submuscular placement of the implant, and the use of polyurethane-coated implants) and surgical strategies (including pre-operative skin washing and irrigation of the implant pocket with antibiotics) have been and/or are currently used to help reduce the incidence of capsular contracture. In this article, we review the pharmacological approaches-both commonly practiced in the clinic and experimental-reported in the scientific and clinical literature aimed at either preventing or treating capsular contracture, including (i) pre- and post-operative intravenous administration of drug substances, (ii) systemic (usually oral) administration of drugs before and after surgery, (iii) modification of the implant surface with grafted drug substances, (iv) irrigation of the implant or peri-implant tissue with drugs prior to implantation, and (v) incorporation of drugs into the implant shell or filler prior to surgery followed by drug release in situ after implantation.

Low-level laser therapy attenuates arthrogenic contracture induced by anterior cruciate ligament reconstruction surgery in rats.

Therapeutic approaches to treat joint contracture after anterior cruciate ligament (ACL) reconstruction have not been established. Arthrofibrosis accompanied by joint inflammation following ACL reconstruction is a major cause of arthrogenic contracture. In this study, we examined whether anti-inflammatory treatment using low-level laser therapy (LLLT) can prevent ACL reconstruction-induced arthrogenic contracture. Rats underwent ACL transection and reconstruction surgery in their right knees. Unoperated left knees were used as controls. After surgery, rats were reared with or without daily LLLT (wavelength: 830 nm; power output: 150 mW; power density: 5 W/cm2; for 120 s/day). We assessed the passive extension range of motion (ROM) after myotomy at one and two weeks post-surgery; the reduction in ROM represents the severity of arthrogenic contracture. ROM was markedly decreased by ACL reconstruction at both time points; however, LLLT partially attenuated the decrease in ROM. One week after ACL reconstruction, the gene expression of the proinflammatory cytokine interleukin-1beta in the joint capsule was significantly upregulated, and this upregulation was significantly attenuated by LLLT. Fibrotic changes in the joint capsule, including upregulation of collagen type I and III genes, shortening of the synovium, and thickening were caused by ACL reconstruction and seen at both time points. LLLT attenuated these fibrotic changes as well. Our results indicate that LLLT after ACL reconstruction could attenuate the formation of arthrogenic contracture through inhibition of inflammation and fibrosis in the joint capsule. Thus, LLLT may become a novel therapeutic approach for ACL reconstruction-induced joint contracture.

The collagenase of the bacterium Clostridium histolyticum does not favor metastasis of breast cancer.

BACKGROUND: Breast cancer is the most common malignancy among women worldwide. As survival rates increase, breast reconstruction and quality of life gain importance. Of all women undergoing breast reconstruction, approximately, 70% opt for silicone implants and 50% of those develop capsular contracture, the most prevalent long-term complication. The collagenase of the bacterium Clostridium histolyticum (CCH) showed promising results in the therapy of capsule contracture; however, its influence on residual cancer cells is unknown. The aim of this study was to investigate whether CCH-treatment negatively impacts breast cancer cells in vitro and in vivo. METHODS: MDA-MB-231 and MCF-7 cells were used in this study. In vitro, we tested the influence of CCH on proliferation, wound healing, migration and cell cycle by MTT-assay, scratch-assay, transwell-migration-assay, and flow cytometry. In vivo, solid tumors were induced in immune-deficient mice. CCH was injected into the tumors and tumor growth and metastasis formation was monitored by caliper measurement, in vivo bioluminescence imaging and histology. Gene expression analysis was performed by microarray including 27,190 genes. RESULTS: CCH-incubation led to a dose-dependent reduction in proliferation for both cell lines, while wound healing was reduced only in MDA-MB-231 cells. No morphological alterations were monitored in cell cycle or apoptosis. In vivo, bioluminescence imaging and histology did not show any evidence of metastasis. Although CCH led to changes in gene expression of breast cancer cells, no relevant alterations in metastasis-related genes were monitored. CONCLUSION: CCH has no impact on tumor growth or metastasis formation in vitro and in vivo. This paves the way for first clinical trials.

The formation mechanism of the bilayer capsular contracture after an augmentation mammoplasty with a rough-surface prosthesis and its prevention and treatment.

BACKGROUND: The present study aimed to explore the formation mechanism of the bilayer capsular contracture after augmentation mammoplasty with a rough-surface prosthesis and its prevention and treatment. METHODS: The nursing process, clinical signs, intraoperative findings, and pathological data after an augmentation mammoplasty with rough-surface prosthesis were observed and collected, the formation mechanism of the bilayer capsular contracture was analyzed, and the prevention and treatment were also discussed. RESULTS: A total of 18 patients were included into the present study, among which 15 patients underwent capsule relaxation plus secondary augmentation mammoplasty and three patients encountered a single-layer capsular contracture after the operation; the recurrence rate was 16%. All patients were followed up for 1-13 years without a presentation of recurrence. CONCLUSIONS: The formation of the bilayer capsular contracture after augmentation mammoplasty is correlated with the formation of the inner capsule, inadequate separation of cavities, foreign body reaction, and an improper massage of the breasts, and the effective preventive measures include removing new cavities, resecting the capsular contracture capsule, stopping bleeding, replanting a rough-surface or smooth prosthesis, and correcting breast massaging.

Tranexamic acid combined with compression dressing reduces blood loss in gluteal muscle contracture surgery.

BACKGROUND: Blood loss and incision-related complications caused by the surgical procedure to release gluteal muscle contracture (GMC) put negative effects on the surgical outcomes. Current procedures to prevent blood loss and complications are not satisfactory. The current study aimed to determine whether tranexamic acid (TXA) in combination with pressure dressing reduce the amount of blood loss, the rate of incision-related complications, and the rate of readmission for patients undergoing surgeries to release GMC. METHODS: 49 GMC patients were finally included in the study and were randomly divided into two groups: study group and control group. Patients in both groups received minimally invasive surgery to release GMC except that in the study group, patients were administered a dosage of 20 mg/kg of intravenous TXA preoperatively, and 2 subsequent dosages of TXA at 10 mg/kg at two time points: 3 and 6 h after the first dose. Gauze soaked with TXA was used to pack the wound for 10 min before the incision closure. Then the wound was pressure-wrapped with a hip-spica bandage for 24 h after the surgery in the study group. RESULTS: The level of UBL in the study group was significantly lower compared to that in the control group. Similar results were also found for UMHD and UMAD. The incision-related postoperative complications were greatly decreased in the study group compared to those of the control group as well. So was the 30-day readmission rate. All patients in both groups reached "excellent" or "good" level with respect to the postoperative function evaluation. CONCLUSIONS: Intravenous and topical application of TXA combined with 24 h pressure hip-spica bandage reduces perioperative blood loss, rate of incision-related complications, and the rate of readmission for GMC patients undergoing minimally invasive surgical releasing procedure. Trial Registration Chinese Clinical and Trial Registry ChiCTR2000039216, registration date 2020/10/22, retrospectively registered.

Platelet-rich plasma as a potential prophylactic measure against frozen shoulder in an in vivo shoulder contracture model.

INTRODUCTION: Frozen shoulder (adhesive capsulitis) is a common painful and functionally-limiting disease affecting around 2% of the population. So far, therapeutic options are limited and often unsatisfactory. Platelet-rich plasma (PRP) has been used as a treatment option in other orthopedic diseases since it contains growth factors that stimulate tissue repair. So far, the effect of PRP on frozen shoulder lacks evidence. We hypothesized that PRP may be valuable in the prophylaxis and treatment of secondary frozen shoulder due to capsular remodeling. MATERIALS AND METHODS: An experimental study of an in vivo frozen shoulder model was conducted. Twenty Sprague-Dawley rats underwent surgery in which the body of the scapula was connected to the humerus with a high-strength suture. Two groups of 8 weeks survival time were allocated; a treatment group with one intraoperative injection of PRP into the glenohumeral joint (n = 10) and a control group without PRP (n = 10). The primary outcome was the structural change in the posterior synovial membrane of the posterior and inferior part of the glenohumeral joint using a semi-quantitative grading from 0 (lowest) to 3 (highest). RESULTS: The posterior synovial membrane structural changes were significantly lower in the PRP group (median = 1 [interquartile range (IQR) = 0-1]) compared to controls (median = 2 [IQR = 1-3]) (p = 0.028). There were no differences for the remaining synovial membrane changes and fibrous capsule responses between groups. CONCLUSIONS: In this in vivo shoulder contracture model, PRP injections seem to reduce the histological severity grade of some parts (i.e., posterior synovial membrane changes) of the secondary frozen shoulder without causing any side effects. It may be considered to investigate this effect further in future studies as a potential prophylaxis of secondary frozen shoulder (e.g., in operated or immobilized shoulders) or as a treatment option for patients with frozen shoulder in the early stage.

Mechanomodulation of Burn Scarring Via Pressure Therapy.

Significance: The physical and psychological sequalae of burn injuries account for 10 million disability-adjusted life years lost annually. Hypertrophic scarring (HSc) after burn injury results in reduced mobility, contracture, pain, itching, and aesthetic changes for burn survivors. Despite the prevalence of scarring and the number of scar therapies available, none are highly effective at preventing HSc after burn injury. Recent Advances: Recent studies modulating the mechanical environment surrounding incisional and excisional wounds have shown off-loading of tension to be a powerful strategy to prevent scar formation. Preclinical studies applying force perpendicular to the surface of the skin or using a combination of pressure both circumferentially and perpendicularly have shown substantial reductions in scar thickness and contraction after burn injury. Critical Issues: Though pressure therapy is highly effective in preclinical studies, outcomes in clinical studies have been variable and may be a result of differing therapy protocols and garment material fatigue. A recent adult clinical study reported a significant reduction in pressure after 1 month of use and significant reduction between 1 and 2 months of use, resulting in below therapeutic doses of pressure applied after only 1 month of use. Future Directions: To enhance efficacy of pressure garments, new low-fatigue materials must be developed for use in standard garments or garments must be redesigned to allow for adjustment to compensate for the loss of pressure with time. Additionally, measurements of applied pressure should be performed routinely during clinic visits to ensure that therapeutic doses of pressure are being delivered.

Preventive effect and possible mechanisms of ultrashort wave diathermy on myogenic contracture in a rabbit model.

The purpose of this study was to determine the preventive effect of ultrashort wave diathermy on immobilization-induced myogenic contracture and to explore its underlying mechanisms. Forty-two rabbits were randomly assigned into control (Group C), immobilization (Group I, which was further divided into one week, Group I-1; two weeks, Group I-2; and four weeks, Group I-4, subgroups by the length of immobilization) and ultrashort wave prevention (Group U, which was further divided into one week, Group U-1; two weeks, Group U-2; and four weeks, Group U-4, by time of treatment) groups. Intervention effects were assessed by evaluating rectus femoris cross-sectional area (CSA), knee range of motion, and the protein levels for myogenic differentiation (MyoD) and muscle atrophy F-box (MAFbx-1) in the rectus femoris. Compared with those of Group C, in Groups I and U, total contracture, myogenic contracture, MyoD and MAFbx-1 levels were significantly elevated, and CSA was significantly smaller (p < 0.05). Compared with those of Group I at each time point, MyoD levels were significantly elevated, MAFbx-1 levels were significantly lower, CSA was significantly larger, and myogenic contracture was significantly alleviated in Group U (p < 0.05). In the early stages of contracture, ultrashort wave diathermy reduces muscle atrophy and delays the process of myogenic contracture during joint immobilization; the mechanism of this may be explained as increased expression of MyoD triggered by suppression of the MAFbx-1-mediated ubiquitin-proteasome pathway.

Interleukin-1 receptor antagonist inhibits arthrofibrosis in a post-traumatic knee immobilization model.

BACKGROUND: Therapies for arthrofibrosis after knee surgery are needed to prevent loss of joint function. Interleukin-1 receptor antagonists (IL-1RA) have shown promise in treating established arthrofibrosis in pilot clinical studies. The objective of this study was to evaluate the ability of intra-articular injection of IL-1RA to prevent knee joint contracture in a post-traumatic knee immobilization model. METHODS: 20 male Sprague Dawley rats were block randomized into two groups: control and IL-1RA. Rats underwent intra-articular surgical trauma of the right knee with placement of an immobilization suture, securing the knees in 150° flexion. On post-operative days 1 and 8, each group received a 0.1 ml intra-articular injection of either saline (control) or anakinra (IL-1RA:single dosage; 2.63 mg/kg). Rats were euthanized fourteen days after surgery and the immobilization femorotibial angles were measured on the operative limbs with the suture and musculature intact. Subsequently, musculature was removed and femorotibial angles were measured in the operative and non-operative limbs with a defined extension moment applied with the posterior capsule intact or cut. A contracture angle was calculated as the angular difference between the operative and non-operative limb. RESULTS: The immobilization knee flexion angle did not differ (P = 0.761) between groups (control: 152 ± 9; IL-1RA: 150 ± 11). The joint contracture angles (smaller angle = improved outcome) were reduced by 12 degrees on average in the IL-1RA group compared to the control for both the capsule intact (P = 0.024) and cut (P = 0.019) states. CONCLUSIONS: Intra-articular IL-1RA injection was found to diminish knee extension deficits associated with arthrofibrosis in a post-traumatic joint immobilization model.

Effect of metformin treatment and its time of administration on joint capsular fibrosis induced by mouse knee immobilization.

Joint contracture leads to major patient discomfort. Metformin, one of the most extensively used oral drugs against type 2 diabetes has recently been found to suppress tissue fibrosis as well. However, its role in suppressing tissue fibrosis in joint contractures remains unknown. In this study, we examined the role of metformin treatment in suppressing joint capsular fibrosis and the most effective time of its administration. Joint capsular fibrosis was induced by immobilizing the knee joints of mice using splints and tapes. Metformin was administered intraperitoneally every alternate day after immobilization. Histological and immunohistochemical changes and expression of fibrosis-related genes were evaluated. Metformin treatment significantly suppressed fibrosis in joint capsules based on histological and immunohistochemical evaluation. Joint capsular tissue from metformin-treated mice also showed decreased expression of fibrosis-related genes. Early, but not late, metformin administration showed the same effect on fibrosis suppression in joint capsule as the whole treatment period. The expression of fibrosis-related genes was most suppressed in mice administered with metformin early. These studies demonstrated that metformin treatment can suppress joint capsular fibrosis and the most effective time to administer it is early after joint immobilization; a delay of more than 2 weeks of administration is less effective.