Effect of short-term hindlimb immobilization on skeletal muscle atrophy and the transcriptome in a low compared with high responder to endurance training model

Skeletal muscle atrophy is a physiological response to disuse, aging, and disease. We compared changes in muscle mass and the transcriptome profile after short-term immobilization in a divergent model of high and low responders to endurance training to identify biological processes associated with the early atrophy response. Female rats selectively bred for high response to endurance training (HRT) and low response to endurance training (LRT; n = 6/group; generation 19) underwent 3 day hindlimb cast immobilization to compare atrophy of plantaris and soleus muscles with line-matched controls (n = 6/group). RNA sequencing was utilized to identify Gene Ontology Biological Processes with differential gene set enrichment. Aerobic training performed prior to the intervention showed HRT improved running distance (+60.6 ± 29.6%), while LRT were unchanged (-0.3 ± 13.3%). Soleus atrophy was greater in LRT vs. HRT (-9.0 ±8.8 vs. 6.2 ±8.2%; P<0.05) and there was a similar trend in plantaris (-16.4 ±5.6% vs. -8.5 ±7.4%; P = 0.064). A total of 140 and 118 biological processes were differentially enriched in plantaris and soleus muscles, respectively. Soleus muscle exhibited divergent LRT and HRT responses in processes including autophagy and immune response. In plantaris, processes associated with protein ubiquitination, as well as the atrogenes (Trim63 and Fbxo32), were more positively enriched in LRT. Overall, LRT demonstrate exacerbated atrophy compared to HRT, associated with differential gene enrichments of biological processes. This indicates that genetic factors that result in divergent adaptations to endurance exercise, may also regulate biological processes associated with short-term muscle unloading.

Conservative treatment of scaphoid fracture: Protocol for a systematic review

The scaphoid is the most commonly fractured carpal bone. Fractures affecting this bone affect young and active patients between 15 and 40 years of age. Stable scaphoid fractures are treated conservatively by plaster cast immobilization or other type of orthosis for an average period of four to 12 weeks. Failure to treat scaphoid fractures may result in avascular necrosis, nonunion, and early secondary osteoarthritis, which may result in significant economic and social impact due to the affected population, formed by young people of productive age. The management of this type of fracture varies significantly between different Institutions and orthopedic surgeons. This article describes a protocol for a systematic review that aims to evaluate the effects (benefits and harms) of conservative interventions in the treatment of scaphoid fractures in adults.

A Randomized Trial Assessing the Muscle Strength and Range of Motion in Elderly Patients Following Distal Radius Fractures Treated With 4- and 6-Week Cast Immobilization

Background: There is no consensus among orthopedic surgeons as to the required period of cast immobilization in distal radius fractures in elderly patients. The purpose of this study was to assess muscle strength and range of motion symmetry in elderly patients after distal radius fractures with different periods of cast immobilization. Methods: This study evaluated 50 patients (33 women and 17 men), aged over 65 years, after cast immobilization treatment for distal radius fracture. The mean age at the beginning of treatment was 71 years. The mean duration of follow-up was 1 year and 3 months. The first subgroup (n = 24) comprised the patients whose fractures had been immobilized in a cast for 6 weeks, another subgroup (n = 26) comprised the patients with 4-week cast immobilization. We assessed: 1) muscle strength, 2) range of motion. Results: The mean grip strength in the treated limb was 71% and 81% of that in the healthy limb in the groups with 4-week and 6-week cast immobilization, respectively (p = 0.0432). The study groups showed no differences in the mean grip strength in the treated limbs or the mean grip strength in the healthy limbs. The mean treated limb flexion was 62° and 75° in the 4-week and 6-week immobilization groups, respectively (p = 0.025). The evaluated groups showed no differences in terms of any other range of motion parameters. The grip strength and range of motion values were significantly lower in the treated limb than in the healthy limb in both evaluated groups. Only the values of wrist radial deviation in the 6-week cast immobilization group showed no differences between the treated and healthy limbs. Conclusion: Higher values of injured limb muscle strength and greater mean range of wrist flexion were achieved in the 6-week subgroup. Neither of the evaluated groups achieved a symmetry of muscle strength or range of motion after treatment. Full limb function did not return in any of the elderly distal radius fracture patients irrespective of cast immobilization duration.

Immediate mobilization of distal radius fractures stabilized by volar locking plate results in a better short-term outcome than a five week immobilization: A prospective randomized trial

Objective: To evaluate the impact of immediate (first day after surgery) mobilization compared to standard five weeks cast immobilization on the functional outcome after volar locking plate fixation of distal radius fractures. Design: Prospective randomized parallel group comparative trial. Setting: Trauma Hospital, Austria. Participants: Patients with isolated unstable distal radius fractures, stabilized with volar angular stable locking plate. Interventions: The immediate mobilization group received a removable forearm splint for one week and active supervised group physiotherapy and home exercises for the shoulder, elbow, wrist, and fingers from the first postoperative day. The cast immobilization group received a non-removable cast for five weeks. In the first five weeks supervised group physiotherapy and home exercises were performed for shoulder, elbow, and fingers. Thereafter additional supervised and home exercises for the wrist were started. Main measures: At regular intervals of six and nine weeks, three and six months, and one year post surgery range of motion, grip strength, and x-rays were evaluated. Additionally, the shortened disabilities of the arm, shoulder and hand ( QuickDASH) score, Patient-rated Wrist Evaluation, Mayo Wrist score, and pain according to the Visual Analog Scale score were analyzed. Results: One hundred and sixteen patients were prospectively randomized into two study groups. At the one-year follow-up, patients in the immediate mobilization group showed a significantly higher range of motion in extension/flexion (mean difference 10.2°, 99% confidence interval 0.6–19.8), grip strength (mean difference 5.1 kg, 99% confidence interval −0.5 to 10.7), and Mayo Wrist score (mean difference 7.9 points, 99% confidence interval 2.3–13.5) than the cast immobilization group. Range of motion in supination/pronation (mean difference 13.4°, 99% confidence interval 1.5–25.3) and in radial/ulnar deviation (mean difference 6.3°, 99% confidence interval 0.9–11.7) differed significantly up to nine weeks favoring the immediate mobilization group. The Patient-rated Wrist Evaluation revealed significantly better scores after three months (mean difference 9.3 points, 99% confidence interval 0.5–18.1) and QuickDASH after six months (mean difference 7.3 points, 99% confidence interval 0.3–14.3) in the immediate mobilization group. All other subsequent follow-up examinations indicated no significant differences in respect of pain, range of motion, and patient-reported outcome measurements between the study groups. There were no significant differences in respect of radiological loss of reduction and complications between the groups. Conclusions: Immediate mobilization in combination with supervised physiotherapy of the wrist after volar locking plate fixation of unstable distal radius fractures results in a significantly improved range of motion and grip strength after one year compared to cast immobilization. No increased risk for loss of reduction and other complications was observed.

Surgery versus non-operative treatment for ER-stress unstable Weber-B unimalleolar fractures: a study protocol for a prospective randomized non-inferiority (Super-Fin) trial

Roughly two-thirds of ankle fractures are unimalleolar injuries, the Weber B-type fibula fracture being by far the most common type. Depending on the trauma and the accompanying soft-tissue injury, these fractures are either stable or unstable. Current clinical practice guidelines recommend surgical treatment for unstable Weber B-type fibula fractures. An ongoing randomized, parallel group, non-inferiority trial comparing surgery and non-operative treatment for unstable Weber B-type ankle fractures with allocation ratio 1:1. The rationale for non-inferiority design is as follows: By being able to prove non-inferiority of non-operative treatment, we would be able to avoid complications related to surgery. However, the primary concern related to non-operative treatment is increased risks of ankle mortise incongruency, leading to secondary surgery, early post-traumatic osteoarthritis and poor function. After providing informed consent, 126 patients aged 16 years or older with an unimalleolar Weber B-type unstable fibula fracture were randomly assigned to surgery (open reduction and internal fixation) or non-operative treatment (6-week cast immobilization). We have completed the patient enrolment and are currently in the final stages of the 2-year follow-up. The primary, non-inferiority outcome is the Olerud-Molander Ankle Score (OMAS) at 2 years (primary time point). The predefined non-inferiority margin is set at 8 OMAS points. Secondary outcomes include the Foot and Ankle Score, a 100 mm Visual Analogue Scale for function and pain, the RAND-36-Item Health Survey for health-related quality-of-life, the range-of-motion of the injured ankle, malunion (ankle joint incongruity) and fracture union. Treatment-related complications and harms; symptomatic non-unions, loss of congruity of the ankle joint, reoperations and wound infections will also be recorded. We hypothesize that non-operative treatment yields non-inferior functional outcome to surgery, the current standard treatment, with no increased risk of harms.

Cast OFF-2: 1 week of plaster cast immobilization for non-reduced distal radius fractures—a study protocol for an implementation study

Background The distal radius fracture (DRF) is a common fracture, with the majority of these fractures being stable. Of all diagnosed fractures, 17% is a DRF, of which a large part is extra-articular and one-third is non-displaced. There is a large variation in treatment advisements for non-reduced DRF. Four to 5 weeks of immobilization is often the usual practice. Existing evidence shows that 1 week of immobilization is safe and does not lead to an increase in secondary displacement. Additionally, shorter immobilization periods may lead to less outpatient clinic visits and less home care for elderly people and may lead to earlier return to work and other social activities. Therefore, shorter immobilization periods for non-reduced distal radius fractures may also prove to be cost-effective. In this study, we aim to successfully implement 1 week of plaster cast immobilization for non-reduced distal radius fractures in twelve medical centers and to evaluate the functional outcome and cost-effectiveness. Methods This study will be performed using a multicenter randomized stepped wedge design in 12 centers. We aim to include in the study 440 patients with an isolated non-reduced DRF between the age of 18 and 85 years old. The patients in the intervention group will be treated with plaster cast immobilization for 1 week. Acceptability of the study protocol, patient-reported outcomes, quality of life, complications, pain catastrophizing score, pain and patient satisfaction, and cost-effectiveness will be measured. The total follow-up will be 12 months. Discussion The strength of this study is the combination of implementing 1 week of plaster cast immobilization for non-reduced DRF and the evaluation of functional outcome, acceptability of the study protocol, and cost-effectiveness in actual practice. Trial registration Netherlands Trial Register NL9278. Registered on 17 February 2021

Acute scaphoid fractures: making decisions for treating a troublesome bone

Seven aspects of the management of acute scaphoid fractures are open to debate: Diagnosis of true fractures among suspected fractures, assessment of fracture displacement, cast immobilization strategies, the role of surgical fixation, proximal pole fractures, assessment of union, and the underlying objective of treatment. We reviewed current evidence, and our varied interpretations of it, to highlight areas of uncertainty where more evidence might be helpful.

Open reduction of an old and unreduced posterior elbow dislocation

The old unreduced elbow dislocation is not very frequent, but when it is found, it is a challenge for every surgeon. We present a case of 65 years old man who came to the hospital with a dislocated elbow. After the first attempt to reduce, the elbow was mobilized in sling for 2 weeks, but during a small effort, the joint dislocated again. Another two orthopedic reduction were tried, followed by cast immobilization, but the elbow dislocated again. The patient presented in our service after two months from the injury with stiff joint in a vicious position. On imagistic examinations (Rx, CT, MRI), it was found comminuted fracture of coronoid process, posterior dislocation of olecranon and both collateral ligaments were torn. An open reduction was performed during which the joint surface was cleaned up, the anterior capsule was reattached to the coronoid process with an anchor, and then, collateral ligament was restored with the help of autograft, a gracilis muscle (bone fixed with two anchors). Postoperatively, the patient slowly began to mobilize the elbow with splint protection. After a year, the patient returned for follow-up; the function was completely restored and he had no pain.

Short-term physical inactivity induces diacylglycerol accumulation and insulin resistance in muscle via lipin1 activation

Physical inactivity impairs muscle insulin sensitivity. However, its mechanism is unclear. To model physical inactivity, we applied 24-h hind-limb cast immobilization (HCI) to mice with normal or high fat diet (HFD), and evaluated intramyocellular lipids and the insulin signaling pathway in the soleus muscle. While 2-wk HFD alone did not alter intramyocellular diacylglycerol (IMDG) accumulation, HCI alone increased it by 1.9-fold and HCI after HFD further increased it by 3.3-fold. Parallel to this, we found increased PKCε activity, reduced insulin-induced 2-deoxy-glucose (2-DOG) uptake, and reduced phosphorylation of IRβ and Akt, key molecules for insulin signaling pathway. Lipin1, which converts phosphatidic acid to diacylglycerol, showed increase of its activity by HCI, and dominant-negative lipin1 expression in muscle prevented HCI-induced IMDG accumulation and impaired insulin-induced 2-DOG uptake. Further, 24-h leg cast immobilization in human increased lipin1 expression. Thus, even short-term immobilization increases IMDG and impairs insulin sensitivity in muscle via enhanced lipin1 activity.

Redisplacement of paediatric distal radius fractures: what is the problem?

Purpose Distal radius fractures represent one of the most common fractures in children. Our purpose is to analyze risk factors for redisplacement in children with distal radius fractures treated by means of closed reduction and plaster cast immobilization. Methods Retrospective study, including children under the age of 17 years, who underwent closed manipulation and cast immobilization for a distal third radius fracture, between 2012 and 2015. Preoperative radiographs were reviewed for initial translation, angulation and shortening, distance of the fracture from the physis, degree of fracture obliquity and the presence of an ulna fracture. Postoperative radiographs were analyzed for translation, angulation and shortening, as well as the quality of closed reduction. Cast index, gap index and three-point index, were measured on the postoperative radiographs. Redisplacement and re-intervention during follow-up were registered. Results A total of 26 patients were included in this study. Comparison between post-reduction and immediate post-cast removal radiographs did not show any statistically significant difference between translation or shortening. Coronal (p = 0.002) and sagittal (p = 0.002) angulation showed a statistically significant difference, but both median values remained below cut-off values for redisplacement. Redisplacement was observed in four patients. Only one patient underwent remanipulation. All four had full remodelling and proper radiological alignment at final follow-up. Quality of reduction was found to be a statistically significant risk factor for redisplacement (p = 0.013). Conclusion Closed reduction and cast immobilization under general anaesthesia yields good results in the treatment of distal forearm fractures in paediatric patients. Quality of reduction was the only risk factor that we found to be predictive of redisplacement. Level of Evidence: Level III – Retrospective comparative study