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This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

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Historically, patients undergoing surgery for adolescent idiopathic scoliosis (AIS) have been nursed postoperatively in a critical care (CC) setting because of the challenges posed by prone positioning, extensive exposures, prolonged operating times, significant blood loss, major intraoperative fluid shifts, cardiopulmonary complications, and difficulty in postoperative pain management. The primary aim of this paper was to determine whether a scoring system, which uses Cobb angle, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and number of levels to be fused, is a valid method of predicting the need for postoperative critical care in AIS patients who are to undergo scoliosis correction with posterior spinal fusion (PSF).

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Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells.

Duchenne muscular dystrophy (DMD) is a prevalent childhood neuromuscular disease characterized by progressive skeletal and cardiac muscle degeneration due to dystrophin protein deficiency. Despite ongoing drug development efforts, no cure exists, with limited success in preclinical studies. To expedite DMD drug development, we introduce an innovative organ-on-a-chip (OOC) platform. This microfluidic device sustains up to six 3D patient-derived skeletal muscle tissues, enabling real-time evaluation of anti-DMD treatments. Our in vitro model recreates myotube integrity loss, a hallmark of DMD, by encapsulating myogenic precursors in a fibrin-composite matrix using a PDMS casting mold. Continuous contractile regimes mimic sarcolemmal instability, monitored through tissue contractibility and Creatine Kinase (CK) levels—an established marker of muscle damage. We further enhance our platform with a nanoplasmonic CK biosensor, enabling rapid, label-free, and real-time sarcolemmal damage assessment. Combining these elements, our work demonstrates the potential of OOCs in accelerating drug development for DMD and similar neuromuscular disorders

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This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

Prior to the introduction of steroid management in Duchenne Muscular Dystrophy (DMD), the prevalence of scoliosis approached 100%, concomitant with progressive decreases in pulmonary function. As such, early scoliosis correction (at 20-25°) was advocated, prior to substantial pulmonary function decline. With improved pulmonary function and delayed curve progression with steroid treatment, the role of early surgery has been questioned. The purpose of this study was to compare the post-operative outcomes of early versus late scoliosis correction in DMD. We hypothesize that performing later surgery with larger curves would not lead to worse post-operative complications. Retrospective cohort study. Patients with DMD who underwent posterior scoliosis correction, had pre-operative pulmonary function testing, and at least 1-year post-operative follow-up, were included; divided into 2 Groups by pre-operative curve angle – 1: ≤45°, 2: >45°. Primary outcome was post-operative complications by Clavien-Dindo (CD) grading. Secondary outcomes included: age at surgery, forced vital capacity (FVC), steroid utilization, fractional shortening (FS) by echocardiogram, surgery duration, blood transfusion requirements, ICU length of stay (LOS), days intubated post-operatively, hospital LOS, infection, curve correction. Two-tailed t-test and chi-square testing were used for analysis of patient factors and CD complication grade, respectively. 31 patients met the inclusion criteria, with a mean total follow-up of 8.3±3.2 years. Steroid treatment (prednisone, deflazacort) was utilized for 21 (67.7%) patients, for a mean duration of 8.2±4.0 years. Groups were comparable for steroid use, FVC, echo FS, and age at surgery (p>0.05). Primary curve angle was 31.7±10.4° and 58.3±11.1° for Groups 1 and 2, respectively (p 0.05). Surgery duration, ICU LOS, days intubated, hospital LOS, were also not different between Groups. For the entire cohort, however, the overall complication rate was higher for patients with steroid treatment [61.9% vs 10%, respectively (p=0.008)], the majority being CDII. Neither FVC nor echo FS were different between Groups at final follow-up (p=0.6; p=0.4, respectively). Post-operative complication rates were not different for early and late scoliosis correction in DMD. In general, however, patients undergoing steroid treatment were at higher risk of blood transfusion and deep infection. Delaying scoliosis correction in DMD while PF is favourable is reasonable, but patients with prior steroid treatment should be counseled regarding the higher risk of complications

Scoliosis correction surgery is one of the longest and most complex procedures of all orthopedic surgery. The complication rate is therefore not negligible and is particularly high when the surgery is performed in patients with neuromuscular or connective tissue disease or complex genetic syndromes. In fact, these patients have various comorbidities and organ deficits (respiratory capacity, swallowing / nutrition, heart function, etc.), which can compromise the outcome of the surgery. In these cases, an accurate assessment and preparation for surgery is essential, also making use of external consultants. To make this phase simpler, more effective and homogeneous, a multidisciplinary path of peri-operative optimization is being developed in our Institute, which also includes the possibility of post-operative hospitalization for rehabilitation and recovery. The goal is to improve the basic functional status as much as possible, in order to ensure faster functional recovery and minimize the incidence of peri-operative complications, to be assessed by clinical audit. The path model and the preliminary results on the first patients managed according to the new modality are presented here. The multidisciplinary path involves the execution of the following assessments / interventions: • Pediatric visit with particular attention to the state of the upper airways and the evaluation of chronic or frequent inflammatory states • Cardiological Consultation with Echocardiogram. • Respiratory Function Tests, Blood Gas Analysis and Pneumological Consultation to evaluate indications for preoperative respiratory physiotherapy cycles, Non-Invasive Ventilation (NIV) cycles, Cough Machine. Possible Polysomnography. • Nutrition consultancy to assess the need for nutritional preparation in order to improve muscle trophism. • Consultation of the speech therapist in cases of dysphagia for liquids and / or solids. • Electroencephalogram and Neurological Consultation in epileptic patients. • Physiological consultation in patients already being treated with a cough machine and / or NIV. • Availability of postoperative hospitalization in the rehabilitation center (with skills in respiratory and neurological rehabilitation) for the most complex cases. When all the appropriate assessments have been completed, the anesthetist in charge at our Institute examines the clinical documentation and establishes whether the path can be considered complete and whether the patient is ready for surgery. At the end of the surgery, the patient is admitted to the Post-operative Intensive Care Unit of the Institute. If necessary, a new program of postoperative rehabilitation (respiratory, neuromotor, etc.) is programmed in a specialist reference center. To date, two patients have been referred to the preoperative optimization path: one with Ullrich Congenital Muscular Dystrophy, and one with 6q25 Microdeletion Syndrome. In the first case, the surgery was performed successfully, and the patient was discharged at home. In the second case, after completing the optimization process, the surgery was postponed due to the finding of urethral malformation with the impossibility of bladder catheterization, which made it necessary to proceed with urological surgery first. The preliminary case series presented here is still very limited and does not allow evaluations on the impact of the program on the clinical practice and the complication rate. However, these first experiences made it possible to demonstrate the feasibility of this complex multidisciplinary path in which a network of specialists takes part

Introduction. Hip dysplasia is the most common congenital deformity of the musculoskeletal system. This is a pathology that brings the hip joint from subluxation to dislocation. Frequency of hip dysplasia − 16 children per 1000 newborns. Materials and Methods. Diagnostic methods of research are X-ray inspection which is necessarily carried out at internal rotation (rotation) of an extremity as lateral rotation of a hip on the radiograph always increases an angle of a valgus deviation of a neck. Surgical treatment is performed in the subclavian area of the femur. An external fixation device is applied and a corrective corticotomy is performed, and valgus deformity and anteversion are eliminated. The duration of treatment is 2.5–3 months. Results. Frequency of hip dysplasia − 16 children per 1000 newborns. We perform about 30 operations a year, including 60% girls and 40% boys. In addition, valgus deformity can be traced -. - in cerebral palsy. - after polio. - at progressing muscular dystrophies. - tumor in the area of the epiphyseal cartilage. At insufficient stability in a hip joint at insufficiently expressed roof of an acetabulum of rotational deformation of a neck of a hip, for prevention of a coxarthrosis and normalization of a ratio of articular ends operation detorsion-varying subvertebral corticotomy of a femur is shown. Conclusions. The operation is minimally invasive, with accesses of 5–6 mm, anatomical and topographical features are taken into account, which will eliminate damage to tissues, nerve trunks and the circulatory system

The development of spinal deformity in children with underlying neurodisability can affect their ability to function and impact on their quality of life, as well as compromise provision of nursing care. Patients with neuromuscular spinal deformity are among the most challenging due to the number and complexity of medical comorbidities that increase the risk for severe intraoperative or postoperative complications. A multidisciplinary approach is mandatory at every stage to ensure that all nonoperative measures have been applied, and that the treatment goals have been clearly defined and agreed with the family. This will involve input from multiple specialities, including allied healthcare professionals, such as physiotherapists and wheelchair services. Surgery should be considered when there is significant impact on the patients’ quality of life, which is usually due to poor sitting balance, back or costo-pelvic pain, respiratory complications, or problems with self-care and feeding. Meticulous preoperative assessment is required, along with careful consideration of the nature of the deformity and the problems that it is causing. Surgery can achieve good curve correction and results in high levels of satisfaction from the patients and their caregivers. Modern modular posterior instrumentation systems allow an effective deformity correction. However, the risks of surgery remain high, and involvement of the family at all stages of decision-making is required in order to balance the risks and anticipated gains of the procedure, and to select those patients who can mostly benefit from spinal correction.

Aims

The health-related quality of life (HRQoL) of paediatric patients with orthopaedic conditions and spinal deformity is important, but existing generic tools have their shortcomings. We aim to evaluate the use of Paediatric Quality of Life Inventory (PedsQL) 4.0 generic core scales in the paediatric population with specific comparisons between those with spinal and limb pathologies, and to explore the feasibility of using PedsQL for studying scoliosis patients’ HRQoL.

The ability to edit DNA at the nucleotide level using clustered regularly interspaced short palindromic repeats (CRISPR) systems is a relatively new investigative tool that is revolutionizing the analysis of many aspects of human health and disease, including orthopaedic disease. CRISPR, adapted for mammalian cell genome editing from a bacterial defence system, has been shown to be a flexible, programmable, scalable, and easy-to-use gene editing tool. Recent improvements increase the functionality of CRISPR through the engineering of specific elements of CRISPR systems, the discovery of new, naturally occurring CRISPR molecules, and modifications that take CRISPR beyond gene editing to the regulation of gene transcription and the manipulation of RNA. Here, the basics of CRISPR genome editing will be reviewed, including a description of how it has transformed some aspects of molecular musculoskeletal research, and will conclude by speculating what the future holds for the use of CRISPR-related treatments and therapies in clinical orthopaedic practice.

Cite this article: Bone Joint Res 2020;9(7):351–359.

Aims

Severe spinal deformity in growing patients often requires surgical management. We describe the incidence of spinal deformity surgery in a National Health Service.

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It is uncertain whether instrumented spinal fixation in nonambulatory children with neuromuscular scoliosis should finish at L5 or be extended to the pelvis. Pelvic fixation has been shown to be associated with up to 30% complication rates, but is regarded by some as the standard for correction of deformity in these conditions. The incidence of failure when comparing the most caudal level of instrumentation, either L5 or the pelvis, using all-pedicle screw instrumentation has not previously been reported. In this retrospective study, we compared nonambulatory patients undergoing surgery at two centres: one that routinely instrumented to L5 and the other to the pelvis.

Introduction. The exact mechanisms leading to tendinopathies and tendon ruptures remain poorly understood while their occurrence is clearly associated with exercise. Overloading is thought to be a major factor contributing to the development of tendon pathologies. However, as animal studies have shown, heavy loading alone won't cause tendinopathies. It has been speculated, that malfunctioning adaptation or healing processes might be involved, triggering tendon tissue degeneration. By analysing the expression of the entirety of degrading enzymes (degradome) in pathological and non-pathological, strained and non-strained tendon tissue, the aim of this study was to identify common or opposite patterns in gene regulation. This approach may generate new targets for future studies. Materials and Methods. RNA was extracted from different tendon tissues: normal (n=7), tendinopathic (n=4) and ruptured (n=4) Achilles tendon; normal (n=4) and tendinopathic (n=4) posterior tibialis tendon; normal hamstrings tendon with or without subjection to static strain (n=4). The RNA was reverse transcribed, then pooled per group The expression of 538 protease genes was analysed using Taqman low-density array quantitative RT-PCR. To be considered relevant, changes had to be at least 4fold and measurable at a level below 36 Cts. Results. In general, there was little common regulation when exercised was compared with pathological tissue. The expression of PAMR1 and TNFαIP3 was upregulated with exercise (169-fold and 78-fold), Achilles tendinopathy (9724-fold and 7-fold) and Achilles tendon rupture (1809-fold and 10-fold), while DDI1, PSMB11 and PSH2 which were down-regulated with exercise were upregulated with Achilles pathology. Discussion. The newly found targets may deliver insights into the initiation and progression of tendon pathologies: PAMR1, a regeneration associated muscle protease which has been shown to be downregulated in Duchenne muscular dystrophy and upregulated in regenerating muscle fibers, might also be involved in tendon regeneration; TNFαIP3, which negatively regulates the NF-κB/pro-inflammatory pathway, could have anti-inflammatory function in tendon regeneration. PSMB11 and PSH2 are for the first time shown to be expressed in tendon and regulated in tendon pathology. Using this approach we were able to generate new targets and to add information on function, regulation and expression sites of recently identified proteins

Boys affected by Duchenne Muscular Dystrophy (DMD) often develop significant scoliosis in the second decade of life and require scoliosis surgery. Our aim was to establish whether cardiac MRI (CMR) improves the preoperative risk assessment in DMD patients and evaluate the current risk of surgery. Case records were retrospectively reviewed for 62 consecutive DMD boys who underwent pre-surgical evaluation at a single tertiary neuromuscular centre between 2008–2013. 62 DMD patients aged 7–18 years underwent pre-operative assessment for a total of 70 procedures (45 spinal, 19 foot, 6 gastrostomy). Echocardiography data were available for 68 procedures. Echo revealed a median left ventricular (LV) shortening fraction (SF) of 29% (range: 7–44). 34% of boys (23/68) had abnormal SF <25%, 48% (31/65) showed dyskinesia and 22% (14/64) had LV dilatation. CMR was routinely performed on 35 patients. Of those who underwent CMR, median left ventricular ejection fraction (LVEF) was 52% (range: 27–67%), 71% of boys (25/35) had dyskinesia. Echocardiography shortening fraction (SF) correlated significantly with CMR LVEF (r. s. = 0.67; p<0.001). Increasing severity of dyskinesia on CMR correlated with reduced CMR LVEF (r. s. = −0.64; p<0.001) and reduced echo SF (r. s. = −0.47; p = 0.004). Although functional echocardiography and CMR data tended to correlate in 35 DMD boys who underwent both imaging modalities nine (26%) had discrepant results. Seven (20%) had evidence of dysfunction on CMR (LVEF < 55%) not detected on echocardiography (SF ≥ 27%); in two cases echocardiogram measured worse function than CMR. Based on multi-disciplinary risk assessment, surgery was considered too high risk in 23 out of 67 (34%) cases. In 21 cases (91%) this was due to underlying cardiomyopathy. The highest risk among older boys assessed for spinal surgery; 21 out of 43 (49%). Of 19 boys undergoing spinal surgery, six (32%) experienced complications: two wound infections; three patients required readmission to intensive care; one patient died in the post-operative period with acute heart failure

We report the incidence of and risk factors for complications after scoliosis surgery in patients with Duchenne muscular dystrophy (DMD) and compare them with those of other neuromuscular conditions.

We identified 110 (64 males, 46 females) consecutive patients with a neuromuscular disorder who underwent correction of the scoliosis at a mean age of 14 years (7 to 19) and had a minimum two-year follow-up. We recorded demographic and peri-operative data, including complications and re-operations.

There were 60 patients with cerebral palsy (54.5%) and 26 with DMD (23.6%). The overall complication rate was 22% (24 patients), the most common of which were deep wound infection (9, 8.1%), gastrointestinal complications (5, 4.5%) and hepatotoxicity (4, 3.6%). The complication rate was higher in patients with DMD (10/26, 38.5%) than in those with other neuromuscular conditions (14/84, 16.7% (p = 0.019). All hepatotoxicity occurred in patients with DMD (p = 0.003), who also had an increased rate of deep wound infection (19% vs 5%) (p = 0.033). In the DMD group, no peri-operative factors were significantly associated with the rate of overall complications or deep wound infection. Increased intra-operative blood loss was associated with hepatotoxicity (p = 0.036).

In our series, correction of a neuromuscular scoliosis had an acceptable rate of complications: patients with DMD had an increased overall rate compared with those with other neuromuscular conditions. These included deep wound infection and hepatotoxicity. Hepatotoxicity was unique to DMD patients, and we recommend peri-operative vigilance after correction of a scoliosis in this group.

Cite this article: Bone Joint J 2014; 96-B:943–9.

Aim:. Our aim was to report the rate and risk factors for post-operative complications in Duchenne Muscular Dystrophy (DMD) patients undergoing spinal arthrodesis for scoliosis, with a comparison to neuromuscular scoliosis of other aetiology. Methods:. From a prospective single surgeon spinal deformity database, we identified all patients with neuromuscular disorders who underwent surgical correction for progressive scoliosis. We recorded demographic and peri-operative data, including complications and subsequent procedures. The rate and risk factors for complications was determined, with a sub-analysis of the DMD group to determine any peri-operative factors predictive of overall complication rates. Results:. There were 98 patients, 59 (60%) were male with mean age at surgery 14 yrs (7–19 yrs). Forty-eight patients had cerebral palsy (n=48, 49%) and 26 DMD (27%). The overall complication rate was 18.4% (n=18), with deep wound infection (DWI; n=9, 9.2%) and acute liver injury (ALI; n=4, 4.0%) most frequent. The complication rate was significantly higher in DMD patients (35%) compared to other neuromuscular disorders (13%; p=0.013). All ALIs occurred in DMD patients (p=0.004), with an increased DWI rate (19% vs 6%; p=0.053). On subanalysis, no peri-operative factors correlated with overall complication rate or DWI rate. Increased intraoperative blood loss was the only factor associated with ALI (p=0.036). Discussion:. Scoliosis correction has an acceptable complication rate in patients with neuromuscular diagnoses. DMD patients have an increased complication rate when compared to other neuromuscular disorders. ALI in our series was unique to DMD patients and we would recommend peri-operative vigilance for hepatotoxicity in these patients. Conflict Of Interest Statement: No conflict of interest

The ability of mesenchymal stem cells (MSCs) to differentiate in vitro into chondrocytes, osteocytes and myocytes holds great promise for tissue engineering. Skeletal defects are emerging as key targets for treatment using MSCs due to the high responsiveness of bone to interventions in animal models. Interest in MSCs has further expanded in recognition of their ability to release growth factors and to adjust immune responses.

Despite their increasing application in clinical trials, the origin and role of MSCs in the development, repair and regeneration of organs have remained unclear. Until recently, MSCs could only be isolated in a process that requires culture in a laboratory; these cells were being used for tissue engineering without understanding their native location and function. MSCs isolated in this indirect way have been used in clinical trials and remain the reference standard cellular substrate for musculoskeletal engineering. The therapeutic use of autologous MSCs is currently limited by the need for ex vivo expansion and by heterogeneity within MSC preparations. The recent discovery that the walls of blood vessels harbour native precursors of MSCs has led to their prospective identification and isolation. MSCs may therefore now be purified from dispensable tissues such as lipo-aspirate and returned for clinical use in sufficient quantity, negating the requirement for ex vivo expansion and a second surgical procedure.

In this annotation we provide an update on the recent developments in the understanding of the identity of MSCs within tissues and outline how this may affect their use in orthopaedic surgery in the future.

Cite this article: Bone Joint J 2014;96-B:291–8.