Search

Key points: Regular exercise improves muscle functional capacity and clinical state of patients with idiopathic inflammatory myopathy (IIM).In our study, we used an in vitro model of human primary muscle cell cultures, derived from IIM patients before and after a 6‐month intensive supervised training intervention to assess the impact of disease and exercise on lipid metabolism dynamics.We provide evidence that muscle cells from IIM patients display altered dynamics of lipid metabolism and impaired adaptive response to saturated fatty acid load compared to healthy controls.A 6‐month intensive supervised exercise training intervention in patients with IIM mitigated disease effects in their cultured muscle cells, improving or normalizing their capacity to handle lipids.These findings highlight the putative role of intrinsic metabolic defects of skeletal muscle in the pathogenesis of IIM and the positive impact of exercise, maintained in vitro by yet unknown epigenetic mechanisms. Exercise improves skeletal muscle function, clinical state and quality of life in patients with idiopathic inflammatory myopathy (IIM). Our aim was to identify disease‐related metabolic perturbations and the impact of exercise in skeletal muscle cells of IIM patients. Patients underwent a 6‐month intensive supervised training intervention. Muscle function, anthropometric and metabolic parameters were examined and muscle cell cultures were established (m. vastus lateralis; Bergström needle biopsy) before and after training from patients and sedentary age/sex/body mass index‐matched controls. [14C]Palmitate was used to determine fat oxidation and lipid synthesis (thin layer chromatography). Cells were exposed to a chronic (3 days) and acute (3 h) metabolic challenge (the saturated fatty acid palmitate, 100 μm). Reduced oxidative (intermediate metabolites, −49%, P = 0.034) and non‐oxidative (diglycerides, −38%, P = 0.013) lipid metabolism was identified in palmitate‐treated muscle cells from IIM patients compared to controls. Three days of palmitate exposure elicited distinct regulation of oxidative phosphorylation (OxPHOS) complex IV and complex V/ATP synthase (P = 0.012/0.005) and adipose triglyceride lipase in patients compared to controls (P = 0.045) (immunoblotting). Importantly, 6 months of training in IIM patients improved lipid metabolism (CO2, P = 0.010; intermediate metabolites, P = 0.041) and activation of AMP kinase (P = 0.007), and nearly normalized palmitate‐induced changes in OxPHOS proteins in myotubes from IIM patients, in parallel with improvements of patients' clinical state. Myotubes from IIM patients displayed altered dynamics of lipid metabolism and impaired response to metabolic challenge with saturated fatty acid. Our observations suggest that metabolic defects intrinsic to skeletal muscle could represent non‐immune pathomechanisms, which can contribute to muscle weakness in IIM. A 6‐month training intervention mitigated disease effects in muscle cells in vitro, indicating the existence of epigenetic regulatory mechanisms. Key points: Regular exercise improves muscle functional capacity and clinical state of patients with idiopathic inflammatory myopathy (IIM).In our study, we used an in vitro model of human primary muscle cell cultures, derived from IIM patients before and after a 6‐month intensive supervised training intervention to assess the impact of disease and exercise on lipid metabolism dynamics.We provide evidence that muscle cells from IIM patients display altered dynamics of lipid metabolism and impaired adaptive response to saturated fatty acid load compared to healthy controls.A 6‐month intensive supervised exercise training intervention in patients with IIM mitigated disease effects in their cultured muscle cells, improving or normalizing their capacity to handle lipids.These findings highlight the putative role of intrinsic metabolic defects of skeletal muscle in the pathogenesis of IIM and the positive impact of exercise, maintained in vitro by yet unknown epigenetic mechanisms. [ABSTRACT FROM AUTHOR]

Imaging modalities have been widely used in diagnostics of idiopathic inflammatory myopathies and their importance continues to grow. MRI of the thigh muscles became the most often used imaging method. This modality provide detalied imaging of soft tissues and ongoing pathological processes, it can be helpful in guiding muscle biopsy and improving its diagnostic yield. The most frequently assessed morphological aspects are muslce oedema (areas of increased vascular permeability), muscle atrophy and fatty replacement following long-lasting muscle inflammation or denervation. There is still no universally accepted and validated scoring protocol for the evaluation and grading of muscle MRI pathology in patients with IIM. [ABSTRACT FROM AUTHOR]

Uterine fibroids are the most common tumors of the uterus in premenopausal women. Despite being asymptomatic in the majority of cases, uterine fibroids may cause abnormal vaginal bleeding, pain, dyspareunia, pregnancy losses and infertility. The treatment options include pharmacological, surgical and radiological treatment as well as myolysis or focused ultrasound treatment. The therapeutic modality selection should be strictly individualized based on the reproductive plans of the patient, desire to preserve the uterus and the presence and severity of the symptoms. The ideal treatment should thus be minimally invasive, safe, fertility-sparing, with long term effect and with a low risk of recurrence. [ABSTRACT FROM AUTHOR]

Michal Mara, Kristyna KubinovaDepartment of Obstetrics and Gynecology, General Faculty Hospital and First Medical Faculty of Charles University, Prague, Czech RepublicAbstract: Uterine artery embolization (UAE) is a minimally invasive procedure with large symptomatic potential in treatment of women with uterine leiomyomas. Due to specificities of this method and possible complications the appropriate indication is crucial. Patient' symptoms, age, plans for pregnancy, and surgical and reproductive history play a major role in decision-making regarding appropriate subjects for UAE. Close cooperation between the gynecologist and the interventional radiologist is necessary. UAE is usually offered as an alternative to surgical treatment. In patients with no fertility plans, it is a less invasive option than abdominal hysterectomy, with a comparable effect on fibroid-related symptoms and quality of life. The need for reintervention is markedly greater in patients after UAE (up to 35% within 5 years) than after hysterectomy. Women with large symptomatic fibroids wishing to retain the uterus and ineligible for minimally invasive (laparoscopic or vaginal) hysterectomy are good candidates for UAE. However, studies comparing UAE with minimally invasive hysterectomy are lacking. Use of UAE in younger women desiring pregnancy is more controversial, mainly because of the significant risk of miscarriage (as high as 64% in some studies) as well as the increased risk of other complications of pregnancy, such as preterm delivery, abnormal placentation, and post-partum hemorrhage. The risk of infertility or subfertility following UAE is unknown. Even poor candidates for myomectomy should be carefully selected for UAE after counseling about all possible adverse effects on fertility. Good prospective studies focused on fertility comparing UAE with no treatment or with myomectomy are needed but would be ethically questionable. This review summarizes the current knowledge regarding the benefits and potential risks of UAE from the point of view of the gynecologist, who should be responsible for proper indication of this treatment.Keywords: benefits, hysterectomy, myomectomy, risks, uterine artery embolization, uterine fibroid

Objectives: The aim of this cross-sectional study was to explore the circulating and skeletal muscle expression of clusterin (CLU) in inflammatory myopathies (IIM) and its potential implication in pathogenetic mechanisms of the disease., Methods: A total of 85 IIM patients and 86 healthy controls (HC) were recruited. In addition, 20 IIM patients and 21 HC underwent a muscle biopsy. Circulating CLU was measured by ELISA. Serum cytokine profile of patients and HC was assessed by Cytokine 27-plex Assay. Immunohistochemical localisation of CLU was assessed in 10 IIM and 4 control muscle tissue specimens. The expression of CLU and myositis related cytokines in muscle was determined by qPCR., Results: Serum levels of CLU were significantly increased in IIM patients compared to controls (86.2 (71.6-99.0) vs. 59.6 (52.6-68.4) μg/mL, p<0.0001) and positively correlated with myositis disease activity assessment (MYOACT) (r=0.337, p=0.008), myositis intention-to-treat activity index (MITAX) (r=0.357, p=0.004) and global disease assessment evaluated by physician (r=0.309, p=0.015). Moreover, serum CLU correlated with cytokines and chemokines involved in IIM and their combined effect on disease activity was revealed by multivariate redundancy analysis. In muscle tissue, CLU mRNA was increased in IIM patients compared to controls (p=0.032) and CLU accumulated in the cytoplasm of regenerating myofibres., Conclusions: We suggest that the up-regulation of clusterin in circulation and skeletal muscle of IIM patients may be an inflammation and atrophy induced response of the organism intended to limit the environment, favouring further muscle damage.

Background: The structural and functional changes of the skeletal muscles in idiopathic inflammatory myopathies (IIM) caused by inflammation and immune changes can be severely disabling. The objective of this study was to assess the effect of a 24-week program combining a supervised training of activities of daily living (ADL), resistance, and stability with home exercise for improving muscle function, compared to a daily home-based exercise representing the regular outpatient care., Methods: Fifty-seven patients with IIM were consecutively and non-selectively enrolled in an intervention (IG, n = 30) or control (CG, n = 27) group. Both groups were provided a standard-of-care pharmacological treatment and follow-up. Only the IG underwent the supervised intervention twice a week for 1 h per session. At baseline, 12, 24, and 48 weeks, all patients were assessed by an assessor blinded to the intervention for primary outcomes: muscle strength (Manual Muscle Testing of eight muscle groups [MMT-8]) and endurance (Functional Index-2 [FI-2]), and secondary outcomes: stability and body composition. Secondary outcomes also included questionnaires evaluating disability (Health Assessment Questionnaire [HAQ]), quality of life (Short Form 36 [SF-36]), depression (Beck's Depression Inventory-II [BDI-II]), and fatigue (Fatigue Impact Scale [FIS]), and analysis of the systemic and local inflammatory response and perceived exertion to assess the safety of the intervention., Results: Twenty-seven patients in the IG and 23 in the CG completed the entire program and follow-up. At week 24, compared to deterioration in the CG, we found a significant improvement in the IG in muscle strength (mean % improvement compared to baseline by 26%), endurance (135%), disability (39%), depression (26%), stability (11%), and basal metabolism (2%) and a stabilization of fitness for physical exercise. The improvement was clinically meaningful (a 24-week change by >20%) in most outcomes in a substantial proportion of patients. Although the improvement was still present at 48 weeks, the effect was not sustained during follow-up. No significant increase in the systemic or local expression of inflammatory markers was found throughout the intervention., Conclusions: This 24-week supervised intervention focused on ADL training proved to be safe and effective. It not only prevented the progressive deterioration, but also resulted in a significant improvement in muscle strength, endurance, stability, and disability, which was clinically meaningful in a substantial proportion of patients., Trial Registration: ISRCTN35925199 (retrospectively registered on 22 May 2020).

Objectives: The aim of this study was to investigate the systemic and skeletal muscle levels of atrophy-associated myokines in patients with idiopathic inflammatory myopathies (IIM) and their association with clinical characteristics of myositis., Methods: A total of 94 IIM patients and 162 healthy controls were recruited. Of those, 20 IIM patients and 28 healthy controls underwent a muscle biopsy. Circulating concentrations of myostatin, follistatin, activin A and TGF-β1 were assessed by ELISA. The expression of myokines and associated genes involved in the myostatin signalling pathway in muscle tissue was determined by real-time PCR., Results: We report decreased levels of circulating myostatin (median 1817 vs 2659 pg/ml; P = 0.003) and increased follistatin (1319 vs 1055 pg/ml; P = 0.028) in IIM compared with healthy controls. Activin A levels were also higher in IIM (414 vs 309 pg/ml; P = 0.0005) compared with controls. Myostatin was negatively correlated to muscle disease activity assessed by physician on visual analogue scale (MDA) (r = -0.289, P = 0.015) and positively to manual muscle testing of eight muscles (r = 0.366, P = 0.002). On the other hand, follistatin correlated positively with MDA (r = 0.235, P = 0.047). Gene expression analysis showed higher follistatin (P = 0.003) and myostatin inhibitor follistatin-like 3 protein (FSTL3) (P = 0.008) and lower expression of activin receptor type 1B (ALK4) (P = 0.034), signal transducer SMAD3 (P = 0.023) and atrophy marker atrogin-1 (P = 0.0009) in IIM muscle tissue compared with controls., Conclusion: This study shows lower myostatin and higher follistatin levels in circulation and attenuated expression of myostatin pathway signalling components in skeletal muscle of patients with myositis, a newly emerging pattern of the activin A-myostatin-follistatin system in muscle wasting diseases., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To describe imaging modalities for diagnosing and monitoring of patients with idiopathic inflammatory myopathies., Methods: A detailed literature search summarising recent data documenting the contribution of different imaging techniques to current management of idiopathic inflammatory myopathies was performed., Results: An overview of methods most frequently used for evaluation of inflammatory myopathies and the description of their role in the diagnostic and monitoring process is presented., Conclusions: MRI is currently the most useful method capable of demonstrating both inflammatory and post-inflammatory changes in the muscles and surrounding soft tissue. Several studies have documented potential usefulness of other imaging techniques, such as ultrasonography, positron emission tomography, scintigraphy, and dual-energy x-ray absorptiometry.

Purpose of Review: MRI is a promising imaging method commonly used to assess muscle involvement in patients with idiopathic inflammatory myopathies (IIM). MRI enables evaluation of both activity and damage and is therefore an ideal noninvasive diagnostic and monitoring tool. Despite its widespread use, there is no universally accepted method for scoring and reporting of MRI findings. The aim of this review is to provide an overview of systems used in the evaluation of MR images in patients with IIM., Recent Findings: A number of semi-quantitative and quantitative methods have been used to evaluate and record the severity of myopathy on MRI. These scoring systems differ in the number and type of parameters assessed and in their complexity; furthermore, they were evaluated in different patient populations, all of which make comparisons between them difficult., Summary: There is a need to create a standardized and validated protocol for evaluation of pathological changes in muscle MRI in IIM. The most appropriate number and distribution of muscle groups as well as evaluated pathological features need to be determined. Based on this literature search, the future scoring system should include assessment of muscle oedema, fatty infiltration, muscle atrophy and possibly the presence of fascial and subcutaneous inflammation. Whether the quantitative methods provide more reliable information regarding disease activity remains unclear.

Objective: To report up-to date knowledge on laparoscopic, uterine sparing treatment of uterine fibroids., Study Design: Review., Setting: Uterine Fibroids Center, Department of Obstetrics and Gynecology, Charles University, Prague., Methods: Analysis of our clinical experience and available literature resources., Results: The management of uterine fibroids depends on the symptoms, location, and size of fibroids and on the reproductive plans of the patient. The surgical treatment has changed from laparotomy to minimally invasive surgery. In general, laparoscopic myomectomy (LM) is considered the best option in symptomatic patients with pregnancy plans. The laparoscopic approach is associated with lower postoperative morbidity as well as lower incidence of massive postoperative adhesion formation compared to laparotomy. The limitation of laparoscopic myomectomy is the size and the number of fibroids but also the location and the accessibility for the laparoscopic suturing. Laparoscopic uterine artery occlusion (LUAO) represents one of the alternatives to LM in patients with multiple small myomas or in patients with fibroids in unfavorable location. LUAO may be advantageously used prior to LM in order to reduce peroperative blood loss or to prevent the persisting fibroids from growing. However there is no universal treatment of uterine fibroids in fertile patients and in each single patient the indication and surgical method should be thoroughly considered. .

Uterine fibroids are the most common pelvic tumors in women of reproductive age. The cause of development of uterine fibroids is still unknown, however recent cytogenetic and genetic studies led to advancement in understanding of etiology of these tumors. In accordance with the latest findings up to 40% of uterine fibroids bear some chromosomal abnormalities. The most common are aberration of chromosomes 6, 7, 12 and 14. Uterine fibroids have been linked to mutations of fumarate hydratase (FH) gene. Germline mutations in FH gene cause autosomal dominant syndromes MCUL1 (multiple cutaneous and uterine leiomyomata) and HLRCC (hereditary leiomyomatosis and renal cell cancer), characterized by multiple uterine and cutaneous leiomyomata and renal cancer. This paper reviews recent findings in the role of genetic in etiology of uterine fibroids.

Objective: To compare principle, advantages, disadvantages, and risks of conservative (i.e. uterus saving) methods of treatment of uterine fibroids, which are focused on elimination or reduction of their perfusion. To contribute to better understanding of this dynamic topic between gynecologists, especially in the field of appropriate indication criteria., Design: Review article., Setting: Department of Obstetrics and Gynecology, Charles University and General Faculty Hospital, Prague., Methods: Analysis of literature and our clinical experience., Conclusions: Within the last decade the spectrum of treatment of uterine fibroids has broaden with methods causing ischemia of fibroids. These include the minimally invasive surgical therapy (laparoscopic occlusion of uterine arteries /LUAO/ and Doppler assisted laparoscopic myolysis) and radiological catheterization treatment (uterine artery embolization, UAE). Compared to foreign countries where UEA is mainly used in perimenopausal women, we focus on the group of patients with further fertility plans. It is necessary to stress that in spite of the number of affirmative experiences with the new techniques of uterine fibroid treatment in both the indication groups (women with or without further fertility plans) these methods still remain an alternative to standard surgical treatment, because both myomectomy and hysterectomy can be performed by minimally invasive techniques in the majority of women. This review is also focused on the specific risks of the particular methods as well as on their mechanism of action which may dramatically differ despite of some analogies.

Objective: To find the consequences of laparoscopically assisted vaginal hysterectomy (LAVH) and total laparoscopic hysterectomy (TLH) for sexual functions in preoperatively asymptomatic women., Design: Prospective study., Setting: Department of Obstetrics and Gynecology, 1st Faculty of Medicine, Charles University and General Teaching Hospital in Prague., Material and Methods: In 100 women without subjective complaints hysterectomy was performed for benign uterine pathology. In all the women the uterus weighted less than 250 g, there were no salpingooophorectomies and no perioperative complications. Women were alternativelly assigned for LAVH (n = 50) or TLH (n = 50). Clinical documentation and questionnaires about sexual functions were evaluated in 87 women (in 40 women after LAVH and in 47 after TLH) 18 months after surgery or later., Results: According to our findings the type of surgery did not influence the frequency of sexual activity after surgery, there was no change in sexual manners using during coitus as well as no change in preferred way how to reach the sexual arousal (clitoridally, vaginally or combined). The type of surgery did not influence frequency, quality and duration of orgasm. From all the evaluated parameters there were only two significantly different: the presence of postoperative sexual activity (positive answer in all women from LAVH group and only in 85% women from TLH group, F test, p = 0.009) and the frequency of sexual satisfaction (in terms of both increase and also decrease in TLH group chi2 8,376, p = 0.015)., Conclusion: The type of laparoscopic hysterectomy (LAVH or TLH) does not significantly affect the sexual functions (frequency of sexual satisfaction, type of sexual arousability, intensity and duration of orgasm) in preoperatively asymptomatic women.

Uterine artery embolization (UAE) represents radiological treatment of uterine fibroids. It is highly effective and safe mainly in premenopausal patients with symptomatic fibroids and represents an alternative to hysterectomy in a group of women not suitable for minimally invasive surgical treatment (LAVH) and women desiring uterus sparing therapy. The future of UAE lies in optimal selection of patients based on volume-shrinkage prediction and fertility outcome. The second group is represented by methods based on direct fibroid tissue destruction using specific energy under MRI or UZ guidance. The common aim of these two groups is the volume shrinkage as well as the symptomatic relief. The second group is represented by radiofrequency ablation, focused ultrasound surgery, interstitial laser ablation and cryotherapy. Based on their non-surgical, percutaneous approach these can be classified as minimally-invasive methods. The second group of methods is suitable only for patients with the absence of any desire for child bearing due to the absence of their long-term outcome data.

Symphysis pubis rupture is rare but life-threatening complication of vaginal delivery. Prompt diagnosis and therapy of this complication is crucial. We present a case report of a patient with a symphysis pubis rupture followed by severe intraabdominal bleeding. The therapy of symphysis pubis rupture is usually conservative according to the available sources. In the case of our patient osteosynthesis was performed with an excellent result.

The aim of this study was to assess whether uterine artery Doppler velocimetry [pulsatility index (PI) and resistance index (RI)] and thickness of the endometrium (TE) are able to predict 3-year clinical outcome after endometrial ablation (EA) for dysfunctional uterine bleeding (DUB). This was a prospective, observational study of 29 women of whom 22 were amenorrhoeic (A) and 7 eumenorrhoeic (E) at the end of the first postoperative year. The PI, RI and TE were measured prior to and 1, 6 and 12 months after EA. Statistical analyses were performed using BMDP statistical software, discriminant analysis, ANOVA and T test. Using the calculated classification function (CF) with the three parameters PI, RI and TE measured 12 months after FEAT, we were able to accurately (100%) specify which of the women will have A or E in 3 years. The predictive value of PI, RI and TE has been confirmed clinically in a minimum 3-year follow-up of outcome (ranging from 36 to 72 months [mean 55]). All A and E women have stayed in the same group (A or E) during the minimum of 3 years. In conclusion we found that PI, RI and TE measured prior to EA cannot predict the outcome, however these measurements performed 1 year after FEAT can predict the duration of A or E in the 3-year follow up.