The mechanosensitive ion channel ASIC2 mediates both proprioceptive sensing and spinal alignment.

By translating mechanical forces into molecular signals, proprioceptive neurons provide the CNS with information on muscle length and tension, which is necessary to control posture and movement. However, the identities of the molecular players that mediate proprioceptive sensing are largely unknown. Here, we confirm the expression of the mechanosensitive ion channel ASIC2 in proprioceptive sensory neurons. By combining in vivo proprioception-related functional tests with ex vivo electrophysiological analyses of muscle spindles, we showed that mice lacking Asic2 display impairments in muscle spindle responses to stretch and motor coordination tasks. Finally, analysis of skeletons of Asic2 loss-of-function mice revealed a specific effect on spinal alignment. Overall, we identify ASIC2 as a key component in proprioceptive sensing and a regulator of spine alignment.

Is Tension Band Wire Fixation Superior to Plate Fixation for Simple Displaced Olecranon Fractures? A Randomized Trial With Median Follow-up of 7.5 Years.

BACKGROUND: Surgeons disagree about the best surgical treatment for simple, displaced olecranon fractures. Although the tension band wiring technique and plate fixation are the most common surgical options for fixation, studies comparing both are limited. To date, there have been no randomized trials comparing patient-reported outcomes and complications at more than 5 years of follow-up. QUESTIONS/PURPOSES: (1) Does tension band wiring or plate fixation result in better ROM and patient-reported outcome scores for simple displaced olecranon fractures? (2) What is the risk of complications associated with each technique? METHODS: Between November 2012 and October 2017, 68 patients were treated for acute, displaced olecranon fracture in a hand and upper extremity surgery unit at a tertiary-care center. Patients 18 years or older with traumatic, nonpathologic, simple olecranon fractures who presented within 2 weeks of injury were considered potentially eligible. Based on that, 74% (50) of patients met the inclusion criteria; 16% (11) of patients declined to participate in the study, and another 10% (seven) were excluded because they did not meet the prespecified inclusion criteria. Patients were randomized on a 1:1 basis to either tension band wiring or plate fixation and were evaluated at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year after surgery. At the final follow-up interval, 16% (eight) were lost to follow-up: 4% (two) in the tension band wiring group and 12% (six) in the plate fixation group. The median follow-up time was 8 years (IQR 7 to 9 years). We evaluated complications at a minimum of 6 years after surgery. The primary outcome measure was the 1-year postoperative DASH score. Additional outcome measures included the patient-reported Oxford Elbow Score, ROM, and the proportion of patients in each group who reported hardware-related symptoms and had subsequent implant removal or postoperative infection. RESULTS: No differences were observed in the DASH score (tension band wiring 18 [range 3 to 65] versus plate fixation 24 [range 3 to 52], median difference -6 [95% CI -12.7 to 14.9]; p = 0.73), Oxford Elbow Score (tension band wiring 36 [range 10 to 48] versus plate fixation 39 [range 17 to 47], median difference -3; p = 0.53), or all ROM measurements (p > 0.05) between the groups at 1 year of follow-up. The odds of having surgery for symptomatic implant removal were lower for plate fixation than for tension band wiring (one of 19 versus eight of 23, OR 9.6 [95% CI 1.08 to 85.7]; p =0.02); the odds of infection, however, were higher in the plate group (three of 19 versus 0 of 23; p = 0.048). CONCLUSION: No differences were observed between the two techniques in terms of ROM or patient-reported outcomes. Surgeons should consider that although the risk of implant removal is higher in tension band wiring, patients older than 85 years undergoing plate fixation for simple olecranon fractures are at a greater risk of postoperative infection. LEVEL OF EVIDENCE: Level I, therapeutic study.

Frostbite of The Extremities - Recognition, Evaluation and Treatment.

OBJECTIVES: Frostbite refers to the freezing of body tissue which is caused by prolonged exposure to cold temperatures and results in tissue destruction. Tissue damage is due to both immediate cold-induced cell death and the more gradual development of localized inflammatory processes and tissue ischemia. A detailed treatment plan based on the current UpToDate literature is needed to decrease morbidity and mortality rates. METHODS: The United States National Library of Medicine (PubMed/Medline), EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews were systematically searched to identify publications relevant to this review. CONCLUSION: In this review, we present the current knowledge on the diagnosis and treatment of frostbite injuries. We then provide an extended and detailed treatment plan, from first aid in the field to treatment of short and long-term complications .

Neonatal Enthesis Healing Involves Noninflammatory Acellular Scar Formation through Extracellular Matrix Secretion by Resident Cells.

Wound healing typically recruits the immune and vascular systems to restore tissue structure and function. However, injuries to the enthesis, a hypocellular and avascular tissue, often result in fibrotic scar formation and loss of mechanical properties, severely affecting musculoskeletal function and life quality. This raises questions about the healing capabilities of the enthesis. Herein, this study established an injury model to the Achilles entheses of neonatal mice to study the effectiveness of early-age enthesis healing. Histology and immunohistochemistry analyses revealed an atypical process that did not involve inflammation or angiogenesis. Instead, healing was mediated by secretion of collagen types I and II by resident cells, which formed a permanent hypocellular and avascular scar. Transmission electron microscopy showed that the cellular response to injury, including endoplasmic reticulum stress, autophagy, and cell death, varied between the tendon and cartilage ends of the enthesis. Single-molecule in situ hybridization, immunostaining, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays verified these differences. Finally, gait analysis showed that these processes effectively restored function of the injured leg. These findings reveal a novel healing mechanism in neonatal entheses, whereby local extracellular matrix secretion by resident cells forms an acellular extracellular matrix deposit without inflammation, allowing gait restoration. These insights into the healing mechanism of a complex transitional tissue may lead to new therapeutic strategies for adult enthesis injuries.

Does Radial Head Resection Impair Hand and Wrist Function? A Long-Term Follow-Up.

OBJECTIVE: To evaluate the long-term outcome in patients after radial head resection surgery for isolated Mason type III radial head fractures. DESIGN: An observational retrospective case series. SETTING: A Hand and Upper-Extremity Surgery Unit in a tertiary care center. PATIENTS: Data were collected from files of patients who were operated between the years 1980 and 2020. Of 352 patients who underwent surgery for radial head fractures, 25 patients were eligible and were enrolled in the study. INTERVENTION: All participants underwent radial head resection surgery and a follow-up clinical and radiographic evaluation by 2 senior orthopaedic surgeons. OUTCOME MEASUREMENTS: Objective evaluation included active range of motion of the elbow and wrist joints, ulnohumeral angle, key pinch and grip measurements, and radiographic imaging of elbow and wrist joints. Subjective evaluation included visual analog scale measurements, disability of arm shoulder and hand questionnaire, Mayo wrist score, Michigan hand outcome, and Oxford elbow score. RESULTS: The mean follow-up was 18 years. Mean elbow range of motion and mean grip strength were lower in the operated hand, as compared to the contralateral hand. Mean proximal radial migration was 1.6 mm. Mean results of visual analog scale, disability of arm shoulder and hand, Mayo wrist score, Michigan hand outcome, and Oxford elbow score indicated good functional outcome and high patient satisfaction. CONCLUSIONS: In our study population, long-term functional outcomes after radial head resection were encouraging. Thus, this procedure may be considered as a surgical alternative when radial head reconstruction or replacement fails. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Piezo2 expressed in proprioceptive neurons is essential for skeletal integrity.

In humans, mutations in the PIEZO2 gene, which encodes for a mechanosensitive ion channel, were found to result in skeletal abnormalities including scoliosis and hip dysplasia. Here, we show in mice that loss of Piezo2 expression in the proprioceptive system recapitulates several human skeletal abnormalities. While loss of Piezo2 in chondrogenic or osteogenic lineages does not lead to human-like skeletal abnormalities, its loss in proprioceptive neurons leads to spine malalignment and hip dysplasia. To validate the non-autonomous role of proprioception in hip joint morphogenesis, we studied this process in mice mutant for proprioceptive system regulators Runx3 or Egr3. Loss of Runx3 in the peripheral nervous system, but not in skeletal lineages, leads to similar joint abnormalities, as does Egr3 loss of function. These findings expand the range of known regulatory roles of the proprioception system on the skeleton and provide a central component of the underlying molecular mechanism, namely Piezo2.

New functions for the proprioceptive system in skeletal biology.

Muscle spindles and Golgi tendon organs (GTOs) are two types of sensory receptors that respond to changes in length or tension of skeletal muscles. These mechanosensors have long been known to participate in both proprioception and stretch reflex. Here, we present recent findings implicating these organs in maintenance of spine alignment as well as in realignment of fractured bones. These discoveries have been made in several mouse lines lacking functional mechanosensors in part or completely. In both studies, the absence of functional spindles and GTOs produced a more severe phenotype than that of spindles alone. Interestingly, the spinal curve phenotype, which appeared during peripubertal development, bears resemblance to the human condition adolescent idiopathic scoliosis. This similarity may contribute to the study of the disease by offering both an animal model and a clue as to its aetiology. Moreover, it raises the possibility that impaired proprioceptive signalling may be involved in the aetiology of other conditions. Overall, these new findings expand considerably the scope of involvement of proprioception in musculoskeletal development and function.This article is part of the Theo Murphy meeting issue 'Mechanics of development'.

The Proprioceptive System Masterminds Spinal Alignment: Insight into the Mechanism of Scoliosis.

Maintaining posture requires tight regulation of the position and orientation of numerous spinal components. Yet, surprisingly little is known about this regulatory mechanism, whose failure may result in spinal deformity as in adolescent idiopathic scoliosis. Here, we use genetic mouse models to demonstrate the involvement of proprioception in regulating spine alignment. Null mutants for Runx3 transcription factor, which lack TrkC neurons connecting between proprioceptive mechanoreceptors and spinal cord, developed peripubertal scoliosis not preceded by vertebral dysplasia or muscle asymmetry. Deletion of Runx3 in the peripheral nervous system or specifically in peripheral sensory neurons, or of enhancer elements driving Runx3 expression in proprioceptive neurons, induced a similar phenotype. Egr3 knockout mice, lacking muscle spindles, but not Golgi tendon organs, displayed a less severe phenotype, suggesting that both receptor types may be required for this regulatory mechanism. These findings uncover a central role for the proprioceptive system in maintaining spinal alignment.

The Proprioceptive System Regulates Morphologic Restoration of Fractured Bones.

Successful fracture repair requires restoration of bone morphology and mechanical integrity. Recent evidence shows that fractured bones of neonatal mice undergo spontaneous realignment, dubbed "natural reduction." Here, we show that natural reduction is regulated by the proprioceptive system and improves with age. Comparison among mice of different ages revealed, surprisingly, that 3-month-old mice exhibited more rapid and effective natural reduction than newborns. Fractured bones of null mutants for transcription factor Runx3, lacking functional proprioceptors, failed to realign properly. Blocking Runx3 expression in the peripheral nervous system, but not in limb mesenchyme, recapitulated the null phenotype, as did inactivation of muscles flanking the fracture site. Egr3 knockout mice, which lack muscle spindles but not Golgi tendon organs, displayed a less severe phenotype, suggesting that both receptor types, as well as muscle contraction, are required for this regulatory mechanism. These findings uncover a physiological role for proprioception in non-autonomous regulation of skeletal integrity.

[Carpal tunnel syndrome in pregnancy].

Pregnancy related carpal tunnel syndrome (PRCTS) is the most frequent mononeuropathy during pregnancy. The reported incidence of PRCTS varies widely and ranges from 0.8% to 70% depending on the diagnostic method and the physician. The etiology for PRCTS is related to hormonal fluctuations, fluid accumulation, glucose level fluctuations, median nerve hypersensitivity etc. The diagnosis of PRCS is the same as carpal tunnel syndrome (CTS) in the gereral population and includes a thorough history, typical symptoms and physical examination. Electrodiagnostic studies such as EMG are valuable tools for the ratification of the diagnosis of CTS in the general population. But in light of the fact that the EMG examination is painful and can cause discomfort to the patient, its routine use during pregnancy is controversial and is not required for determining the diagnosis. Generally, the syndrome tends to pass after birth, on the other hand, according to the literature, it might not pass in lactating women until they stop breastfeeding and even afterwards. Treatment of PRCS is mostly conservative, and if there is lack of improvement local intracarpal injection of a steroid is indicated. Intracarpal injections have demonstrated a significant decrease in symptoms and low recurrence in comparison to the general population, and do not put the fetus or his mother at risk. A surgical intervention is rarely indicated during pregnancy.