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OBJECTIVE This study aimed to determine the feasibility of diffusion-weighted imaging for detecting endometrial fibrosis in patients with intrauterine injury. METHODS This prospective study included 34 patients with endometrial fibrosis and 34 healthy controls. All participants underwent T2-weighted and diffusion-weighted magnetic resonance imaging with b values of 0 and 1000 s/mm2 during the periovulatory phase with a dominant follicle. The endometrial apparent diffusion coefficient (ADC) and uterine anatomical parameters (endometrial thickness [EMT], length of the uterine cavity [LUC], and junctional zone thickness [JZT]) were measured and compared. Performance of the uterine endometrial ADC and anatomical parameters in diagnosing endometrial fibrosis was evaluated. RESULTS Patients with endometrial fibrosis showed a lower endometrial ADC, lower EMT, shorter LUC, and higher JZT than did healthy controls (all, P < 0.001). Endometrial ADC value and uterine anatomical parameters showed good performance in diagnosing endometrial fibrosis, with the areas under the receiver operating characteristic curves of 0.976, 0.870, 0.883, and 0.864, respectively. The area under the curve of ADC was significantly higher than those of EMT (z = 1.973, P = 0.0485), LUC (z = 2.059, P = 0.0395), and JZT (z = 2.484, P = 0.0130). Intraobserver and interobserver agreements of endometrial ADC value measurements were excellent for both patients (intraclass correlation coefficient = 0.987 and 0.983, respectively) and healthy women (intraclass correlation coefficient = 0.986 and 0.989, respectively). CONCLUSIONS Our preliminary results suggest that diffusion-weighted imaging has the potential to be a noninvasive imaging tool for the quantitative assessment of endometrial fibrosis.

Background: Radiation-induced muscle fibrosis is a long-term side effect of radiotherapy that significantly affect the quality of life and even reduces the survival of cancer patients. We have demonstrated that radiation induces satellite cell (SC) activation at the molecular level; however, cellular evidence in a rat model of radiation-induced muscle fibrosis was lacking. In this study, we evaluated SC activation in vivo and investigated whether radiation affects the proliferation and differentiation potential of SCs in vitro. Methods: For in vivo studies, Sprague-Dawley rats were randomly divided into six groups (n = 6 per group): a non-irradiated control group and 90 Gy-1 w, 90 Gy-2 w, 90 Gy-4 w, 90 Gy-12 w, and 90 Gy-24 w groups.Left groin area of the rats received a single dose of irradiation and rectus femoris tissues were collected in the indicated weeks. Fibrosis, apoptosis, and autophagy were evaluated by Masson’s trichrome staining, TUNEL staining, and electron microscopy, respectively. SC activation and central nuclear muscle fibers were evaluated by immunofluorescence staining and hematoxylin and eosin staining. IL-1β concentrations in serum and irradiated muscle tissue samples were determined by ELISA. For in vitro studies, SCs were isolated from rats with radiation-induced muscle fibrosis and their proliferation and differentiation were evaluated by immunofluorescence staining.Results: In vivo, fibrosis increased over time following irradiation. Apoptosis and autophagy levels, IL-1β concentrations in serum and irradiated skin tissues, and the numbers of SCs and central nuclear muscle fibers were increased in the irradiated groups when compared with control group. In vitro, cultured SCs from irradiated muscle were positive for proliferation marker Pax7, and differentiated SCs were positive for myogenic differentiation marker MyHC.Conclusion: This study provided cellular evidence of SC activation and proliferation in rats with radiation-induced muscle fibrosis. Radiation does not affect the proliferation and differentiation potential of SCs in vitro.

Duchenne muscular dystrophy (DMD), the most common muscular dystrophy, is a severe muscle disorder, causing muscle weakness, loss of independence, and premature death. Here, we establish the link between sphingolipids and muscular dystrophy. Transcripts of sphingolipid de novo biosynthesis pathway are up-regulated in skeletal muscle of patients with DMD and other muscular dystrophies, which is accompanied by accumulation of metabolites of the sphingolipid pathway in muscle and plasma. Pharmacological inhibition of sphingolipid synthesis by myriocin in the mdx mouse model of DMD ameliorated the loss in muscle function while reducing inflammation, improving Ca 2+ homeostasis, preventing fibrosis of the skeletal muscle, heart, and diaphragm, and restoring the balance between M1 and M2 macrophages. Myriocin alleviated the DMD phenotype more than glucocorticoids. Our study identifies inhibition of sphingolipid synthesis, targeting multiple pathogenetic pathways simultaneously, as a strong candidate for treatment of muscular dystrophies.

» Rotator cuff tear arthropathy (RCTA) describes a pattern of glenohumeral degenerative changes following chronic rotator cuff tears that is characterized by superior humeral head migration, erosion of the greater tuberosity of the humeral head, contouring of the coracoacromial arch to create a socket for the humeral head, and eventual glenohumeral arthritis. » Acute and chronic inflammatory changes following rotator cuff tears are thought to contribute to cartilage damage, muscle fibrosis, and fatty infiltration in the glenohumeral joint. » In vitro animal studies targeting various inflammatory modulators, including macrophages, insulin-like growth factor-I, and transforming growth factor-beta pathways, provide promising therapeutic targets to improve healing after rotator cuff tears. » The role of platelet-rich plasma in the treatment and prevention of RCTA has been investigated, with conflicting results.

Intrauterine adhesion (IUA) is an endometrial fibrosis disease caused by repeated operations of the uterus and is a common cause of female infertility. In recent years, treatment using mesenchymal stem cells (MSCs) has been proposed by many researchers and is now widely used in clinics because of the low immunogenicity of MSCs. It is believed that allogeneic MSCs can be used to treat IUA because MSCs express only low levels of MHC class I molecules and no MHC class II or co-stimulatory molecules. However, many scholars still believe that the use of allogeneic MSCs to treat IUA may lead to immune rejection. Compared with allogeneic MSCs, autologous MSCs are safer, more ethical, and can better adapt to the body. Here, we review recently published articles on the immunomodulation of allogeneic and autologous MSCs in IUA therapy, with the aim of proving that the use of autologous MSCs can reduce the possibility of immune rejection in the treatment of IUAs.

Recently, few noninvasive methods have been reported to evaluate endometrial fibrosis. Our study was to investigate the feasibility of intravoxel incoherent motion (IVIM) MR imaging in the detection of endometrial fibrosis in patients with intrauterine injury. 30 patients with hysteroscopy-confirmed endometrial fibrosis and 28 healthy women were enrolled to undergo MR examination including the IVIM sequence. Endometrial thickness (ET); apparent diffusion coefficient (ADC); and IVIM parameters, including pure diffusion coefficient (D), pseudodiffusion coefficient (D*) and vascular fraction (f) were evaluated. A multivariable model combing ADC, D, and f values using binary logistic regression analysis was built to diagnose endometrial fibrosis. Endometrial fibrosis patients demonstrated lower endometrial ADC, D, f values and ET (all p D, f values and ET performed well in diagnosing endometrial fibrosis with AUC of 0.979, 0.965, 0.920, 0.901 and 0.833, respectively. The multivariable model revealed a better diagnostic accuracy than D, f and ET (all p D, and f (all p > 0.05); between ET and D (p > 0.05); and between ET and f (p > 0.05). The reproducibility of ADC, D, f and D* values in patients with endometrial fibrosis and healthy women were good to excellent (ICC: 0.614–0.951). IVIM parameters exhibit promising potential to serve as imaging biomarkers in the noninvasive assessment of endometrial fibrosis.

International audience; Among rare diseases caused by mutations in LMNA gene, Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B are characterized by muscle weakness and wasting, joint contractures, cardiomyopathy with conduction system disorders. Circulating biomarkers for these pathologies have not been identified. Here, we analyzed the secretome of a cohort of patients affected by these muscular laminopathies in the attempt to identify a common signature. Multiplex cytokine assay showed that transforming growth factor beta 2 (TGF β2) and interleukin 17 serum levels are consistently elevated in the vast majority of examined patients, while interleukin 6 and basic fibroblast growth factor are altered in subgroups of patients. Levels of TGF β2 are also increased in fibroblast and myoblast cultures established from patient biopsies as well as in serum from mice bearing the H222P Lmna mutation causing Emery-Dreifuss Muscular Dystrophy in humans. Both patient serum and fibroblast conditioned media activated a TGF β2-dependent fibrogenic program in normal human myoblasts and tenocytes and inhibited myoblast differentiation. Consistent with these results, a TGF β2 neutralizing antibody avoided fibrogenic marker activation and myogenesis impairment. Cell intrinsic TGF β2-dependent mechanisms were also determined in laminopathic cells, where TGF β2 activated AKT/mTOR phosphorylation. These data show that TGF β2 contributes to the pathogenesis of Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B and can be considered a potential biomarker of those diseases. Further, the evidence of TGF β2 pathogenetic effects in tenocytes provides the first mechanistic insight into occurrence of joint contractures in muscular laminopathies.

Skeletal muscle fibrosis occurs with aging and has been suggested to impair muscle performance, thereby decreasing quality of life. Recently, muscle stiffness, a surrogate measure of muscle fibrosis, was noninvasively quantified as the shear modulus using ultrasound shear wave elastography (SWE) in humans. We aimed to investigate thigh muscle stiffness in females and males, respectively, across a broad range of ages by using SWE. Eighty-six community-dwelling Japanese people who were aged 30 to 79 years and did not regularly exercise participated in this study. The vastus lateralis (VL) shear modulus was measured at three different knee joint angles: full extension, 90° of flexion, and full flexion. There were no significant main effects of sex or age on the VL shear modulus in full extension or 90° of flexion of the knee. However, the VL shear modulus in knee full flexion was significantly smaller in females than in males and increased with age from 47.9 years. The results suggest that the accelerated increase in VL stiffness that occurs after an individual passes their late 40s may be an important therapeutic target for developing effective treatments and programs that preserve and improve quality of life.

Item does not contain fulltext The healing of skeletal muscle injuries after major trauma or surgical reconstruction is often complicated by the development of fibrosis leading to impaired function. Research in the field of muscle regeneration is mainly focused on the restoration of muscle mass while far less attention is paid to the prevention of fibrosis. In this review, we take as an example the reconstruction of the muscles in the soft palate of cleft palate patients. After surgical closure of the soft palate, muscle function during speech is often impaired by a shortage of muscle tissue as well as the development of fibrosis. We will give a short overview of the most common approaches to generate muscle mass and then focus on strategies to prevent fibrosis. These include anti-fibrotic strategies that have been developed for muscle and other organs by the delivery of small molecules, decorin and miRNAs. Anti-fibrotic compounds should be delivered in aligned constructs in order to obtain the organized architecture of muscle tissue. The available techniques for the preparation of aligned muscle constructs will be discussed. The combination of approaches to generate muscle mass with anti-fibrotic components in an aligned muscle construct may greatly improve the functional outcome of regenerative therapies for muscle injuries.

The goal of this paper was to evaluate the possibility of bi-component T1ρ and T2 relaxation mapping of human skeletal muscle at 3 T in clinically feasible scan times. T1ρ- and T2-weighted images of calf muscle were acquired using a modified 3D-SPGR sequence on a standard 3 T clinical MRI scanner. The mono- and biexponential models were fitted pixel-wise to the series of T1ρ and T2 weighted images. The biexponential decay of T1ρ and T2 relaxations was detected in ~30% and ~40% of the pixels across all volunteers, respectively. Monoexponential and bi-exponential short and long T1ρ relaxation times were estimated to be 26.9 ms, 4.6 ms (fraction 22%) and 33.2 ms (fraction: 78%), respectively. Similarly, the mono- and bi-exponential short and long T2 relaxation times were 24.7 ms, 4.2 ms (fraction 15%) and 30.4 ms (fraction 85%) respectively. The experiments had good repeatability with RMSCV 60%. This approach could potentially be used in exercise intervention studies or in studies of inflammatory myopathies or muscle fibrosis, permitting greater sensitivity and specificity via measurement of different water compartments and their fractions.

Background: There are many published surgical techniques for the correction of crow's feet deformity, but subsequent contour irregularities and early recurrence are often reported. Objective: The authors present a radiofrequency (RF) technique to treat crow's feet that can prevent complications while simultaneously maintaining long-term results. Methods: From April 2010 to February 2012, a total of 52 consecutive patients (3 men and 49 women) underwent surgical correction of crow's feet with an RF current. Following elevation of the skin flap in the temporal area, the lateral portion of the orbicularis oculi muscle was partially elevated and splayed. Then the RF current was applied to the elevated muscle flap until the target temperature of 60°C to 80°C was reached. Clinical outcomes were observed through photographs with patients in a natural smiling position. Results: Mean (SD) patient age was 52.7 (2.2) years (range, 31–73 years). Patients were followed postoperatively during a mean period of 23 months (range, 15–36 months). There were no recurrences of crow's feet during the follow-up period. No major complications were noted. Conclusions: The main advantage of this surgical technique is preserving continuity of the orbicularis oculi muscle while selectively decreasing muscle tone. Hence, this technique may prevent any contour irregularities. The RF current causes irreversible muscle fibrosis, which in turn provides long-lasting results. While the early results of this series show promising long-term efficacy and a good safety profile, the small number of patients and short-term follow-up period warrant further study. Level of Evidence: 4 ![Graphic][1] [1]: /embed/inline-graphic-1.gif

Muscle fibrosis, the disruption, of functional parenchyma by stromal elements, is an often overlooked sequela of traumatic muscle injury, ageing, and congenital disease. The remarkable regenerative capacity of skeletal muscle is dependent on the interaction of myogenic progenitors and the same stromal connective tissue elements responsible for fibrosis generation and propagation. The coordination of effective therapeutic strategies to mitigate muscle fibrosis following injury requires a clear understanding of the prominent cellular progenitors, extracellular constituents, and signaling mechanisms involved in muscle healing. Recent studies have begun to elucidate the critical cellular processes that delineate physiologic regeneration and dysregulated healing resulting in muscle fibrosis. This review presents the salience of these novel findings in the context of the current treatment paradigms for muscle fibrosis.

The aim of this study was to estimate the rate of intrauterine adhesions and subsequent pregnancy outcome in patients with residual trophoblastic tissue treated with hysteroscopic resection versus ultrasound-guided dilation and evacuation (DE).Cohort study from 2 centers (Canadian Task Force classification II-2).Two surgical teams at the University of Duesseldorf Medical Center and the PAN Clinic in Cologne, Germany.Women with residual trophoblastic tissue after first- or second-trimester miscarriage or term delivery.Two techniques were used for the removal of residual trophoblastic tissue: ultrasound-guided evacuation with a curette (DE) and hysteroscopic resection of trophoblastic tissue (HR).We evaluated 95 patients who underwent secondary intervention for residual trophoblastic disease. A total of 42 patients underwent dilation of the cervix and ultrasound-guided curettage. In a second series of 53 patients, a resectoscope fitted with a 4-mm cutting loop was used for the removal of residual trophoblastic tissue used without application of current. Three months after the intervention, second-look office hysteroscopy was performed. Differences between both treatment groups were statistically significant. After HR, mild intrauterine adhesions were found in 2 patients (4.2%). After DE, 12 patients (30.8%) presented with intrauterine adhesions (mild intrauterine adhesions: n = 7 [17.9%]; single dense adhesions: n = 3 [7.7%]; and extensive endometrial fibrosis n = 1 [2.6%]). Eighty-two patients wanted to become pregnant. Conception rate of all patients examined was 68.8% (HR) and 59.9% (DE) (p.05). In patients younger than 35 years of age who underwent HR, the pregnancy rate was significantly (p.05) increased compared with patients who underwent DE (78.1% vs 66.6%). In addition, patients from the HR group demonstrated a significantly (p.05) shorter time to conception (11.5 month vs 14.5 month).The results of this study indicate that selective HR of residual trophoblastic tissue significantly reduces the incidence of intrauterine adhesions and increases pregnancy rates.

Background: Lower leg compartment syndrome can lead to severe sequelae affecting patient autonomy. Ischemic muscle fibrosis and retraction result in foot and ankle deformities ranging from claw toes to complex multiplanar dislocations with soft tissue impairment requiring amputation. Although these deformities have been reported in relation to compartment syndrome, they have rarely been discussed specifically in the light of a long term follow up. Materials and Methods: Between 1981 and 2006, 151 patients were treated in our hospital for compartment syndrome of the lower limb. Ten of them later required further surgery to treat sequelae on the foot and ankle and were followed up prospectively. Personal data and surgical events were recorded, as well as potential risk factors for sequelae and functional outcome. The data was analyzed and compared to that available in previous literature. We analyzed and describe the different surgical procedures available for the management of this condition including arthroscopic ankle arthrodesis which could be a less invasive and efficient technique in mild equinus deformities. Results: All ten patients were diagnosed late for compartment syndrome. The anterior and lateral compartments were most often involved but rarely accounted for late sequelae. The deep posterior compartment seems to be the key element in generating after effects. Functional results were good in eight patients. Two required amputation after failed secondary surgery. Conclusion: The late, post-compartment syndrome affecting the foot and ankle can be treated efficiently provided surgery is performed acurately, taking into account the multiplanar deformity. However, the best treatment for this condition remains prevention. Level of Evidence: IV, Retrospective Case Series

A 24-year-old female with 5 year history of heroin abuse experienced painless stiffness of elbow joints and weakness of shoulder and upper limb muscles. She was injecting herself 4-6 times daily alternatively in the upper extremities, sparing the lower limbs. Electromyography (EMG) showed myopathic changes in clinically affected and unaffected muscles. Magnetic resonance imaging (MRI) revealed muscle fibrosis in directly injected muscles, whereas in subcutaneous fat and within muscles of anterior and posterior compartments of both thighs, not directly injected, there were signal changes supportive of oedema and inflammation. EMG and MRI were congruent in showing abnormalities in muscles not directly injected, suggesting long distant effects of heroin or adulterants with a mechanism either toxic or immunologically mediated.

Since 1997, focused shock waves therapy (FSWT) has been reported to be useful in the treatment of muscle hypertonia and dystonia. More recently, also radial shock wave therapy (RSWT) has been successfully used to treat muscle hypertonia. The studies where FSWT and RSWT have been used to treat muscle hypertonia and dystonia are reviewed in this paper. The more consistent and long lasting results were obtained in the lower limb muscles of patients affected by cerebral palsy with both FSWT and RSWT and in the distal upper limb muscles of adult stroke patients using FSWT. The most probable mechanism of action is a direct effect of shock waves on muscle fibrosis and other nonreflex components of muscle hypertonia. However, we believe that up to now the biological effects of shock waves on muscle hypertonia and dystonia cannot be clearly separated from a placebo effect.

Supplemental Digital Content is available in the text, Unilateral fibrous contracture of the sternocleidomastoid (SCM) muscle is the major pathophysiology in infants with congenital muscular torticollis (CMT). Physical examination is not always sufficient to detect minimal muscle fibrosis in involved SCM muscles. A prospective study for SCM muscle fibrosis in CMT infants by quantifying echotexture and muscle thickness during the course of treatment is highlighted in the study. Convenience samples of 21 female and 29 male infants with CMT, who were 1 to 12 months old, underwent physiotherapy for at least 3 months and were followed for 4.7 ± 0.4 months. All infants had at least 2 clinical assessments and ultrasonographic examinations for bilateral SCM muscles during follow-up. The K value, derived from the difference in echo intensities between the involved and uninvolved SCM muscles on longitudinal sonograms, was used to represent the severity of muscle fibrosis. Bilateral SCM muscle thickness and ratio of involved to uninvolved muscle thickness (Ratio I/U) were obtained simultaneously. Clinical outcome was also recorded. No subjects underwent surgical intervention during follow-up. The K value decreased from 6.85 ± 0.58 to 1.30 ± 0.36 at the end of follow-up (P

Contains fulltext : 181501.pdf (Publisher’s version ) (Open Access) BACKGROUND: Muscle fibrosis characterizes degenerated muscles in muscular dystrophies and in late onset myopathies. Fibrotic muscles often exhibit thickening of the extracellular matrix (ECM). The molecular regulation of this process is not fully understood. In oculopharyngeal muscular dystrophy (OPMD), an expansion of an alanine tract at the N-terminus of poly(A)-binding protein nuclear 1 (PABPN1) causes muscle symptoms. OPMD patient muscle degeneration initiates after midlife, while at an earlier age carriers of alanine expansion mutant PABPN1 (expPABPN1) are clinically pre-symptomatic. OPMD is characterized by fibrosis in skeletal muscles but the causative molecular mechanisms are not fully understood. METHODS: We studied the molecular processes that are involved in OPMD pathology using cross-species mRNA expression profiles in muscles from patients and model systems. We identified significant dysregulation of the ECM functional group, among which the procollagen C-endopeptidase enhancer 1 gene (PCOLCE) was consistently down-regulated across species. We investigated PCOLCE subcellular localization in OPMD muscle samples and OPMD model systems to investigate any functional relevance of PCOLCE down-regulation in this disease. RESULTS: We found that muscle degeneration in OPMD is associated with PCOLCE down-regulation. In addition to its known presence at the ECM, we also found PCOLCE within the nucleus of muscle cells. PCOLCE sub-cellular localization changes during myoblast cell fusion and is disrupted in cells expressing mutant expPABPN1. Our results show that PCOLCE binds to soluble PABPN1 and co-localizes with aggregated PABPN1 with a preference for the mutant protein. In muscle biopsies from OPMD patients we find that extracellular PCOLCE is depleted with its concomitant enrichment within the nuclear compartment. CONCLUSIONS: PCOLCE regulates collagen processing at the ECM. Depletion of extracellular PCOLCE is associated with the expression of expPABPN1 in OPMD patient muscles. PCOLCE is also localized within the nucleus where it binds to PABPN1, suggesting that PCOLCE shuttles between the ECM and the nucleus. PCOLCE preferentially binds to expPABPN1. Nuclear-localized PCOLCE is enriched in muscle cells expressing expPABPN1. We suggest that nuclear entrapment of PCOLCE and its extracellular depletion represents a novel molecular mechanism in late-onset muscle fibrosis.

Strabismus after retinal detachment surgery is temporary in most cases. Long-term diplopia, however, is seen in 5% to 25% of patients. In most cases the cause is restrictive strabismus due to adhesions, muscle fibrosis, or scarring involving the buckling material. Deviations due to direct muscle injury and "sensory" deviations due to poor vision also occur. Nonsurgical treatments include prisms and botulinum toxin injections. Surgical intervention using adjustable sutures is successful in most cases.

We report a case of extensive subcutaneous and muscle fibrosis in a 26-year-old Indian woman caused by repeated intramuscular pentazocine injections over five years to highlight the extent and sequelae of this avoidable condition.

We report on a girl with progressive multiple pterygium syndrome in association with gluteal muscle fibrosis and nemalin-myopathy. This girl has been followed for 12 years. Clinical findings, natural history, and the presence of nemalin myopathy suggest the possibility of a distinct form of multiple pterygium syndrome in this patient.

Three patients had iatrogenic muscle fibrosis, without weakness or sensory loss. Deltoid muscle fibrosis produced the unique clinical sign of gradual, involuntary, and irreducible arm levitation. The third patient had both levitated arms and levitated legs, a result of injections in the rectus femoris muscles. Repeated intramuscular injections apparently resulted in muscle fibrosis and intramuscular nerve-twig damage. Pentazocine (Talwin) is a particularly offending agent. One patient showed an unusual tissue reaction to foreign material, which may have played a role in her muscle fibrosis. Nevertheless, dramatic recovery of muscle function followed surgical sectioning of the fibrous deltoid bands. (JAMA234:621-624, 1975)

• A progressive bilateral sciatic neuropathy appeared in a 52-year-old man as an unusual complication of pentazocine-induced muscle fibrosis. Surgical neurolysis showed that the sciatic nerves were firmly compressed by large fibrous bands involving the entire gluteal musculature.