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Musculoskeletal regeneration: a zebrafish perspective

Musculoskeletal injuries are common in humans. The cascade of cellular and molecular events following such injuries results either in healing with functional recovery or scar formation. While fibrotic scar tissue serves to bridge between injured planes, it undermines functional integrity. Hence, faithful regeneration is the most desired outcome; however, the potential to regenerate is limited in humans. In contrast, various non-mammalian vertebrates have fascinating capabilities of regenerating even an entire appendage following amputation. Among them, zebrafish is an important and accessible laboratory model organism, sharing striking similarities with mammalian embryonic musculoskeletal development. Moreover, clinically relevant muscle and skeletal injury zebrafish models recapitulate mammalian regeneration. Upon muscle injury, quiescent stem cells - known as satellite cells - become activated, proliferate, differentiate and fuse to form new myofibres, while bone fracture results in a phased response involving hematoma formation, inflammation, fibrocartilaginous callus formation, bony callus formation and remodelling. These models are well suited to testing gene- or pharmaco-therapy for the benefit of conditions like muscle tears and fractures. Insights from further studies on whole body part regeneration, a hallmark of the zebrafish model, have the potential to complement regenerative strategies to achieve faster and desired healing following injuries without any scar formation and, in the longer run, drive progress towards the realisation of large-scale regeneration in mammals. Here, we provide an overview of the basic mechanisms of musculoskeletal regeneration, highlight the key features of zebrafish as a regenerative model and outline the relevant studies that have contributed to the advancement of this field.AKKP is supported by a Nanyang Technological University (Lee Kong Chian School of Medicine) Research Scholarship. PWI is supported by the Toh Kian Chui Foundation

Multiple Clay Shoveler’s Fractures of the Thoracic Spine

Typically, a clay shoveler’s fracture is a stress-type avulsion fracture involving the spinous processes of the lower cervical or upper thoracic vertebrae. Even though C7 and T1 are the most commonly involved spinal levels, these avulsion fractures can occur at any lower cervical or upper thoracic level, either as solitary or multiple fractures. This fracture used to be common in workers who shovel heavy loads of clay for long periods, hence its name. It does not cause any structural, functional, or neurological impairments and is therefore considered a stable fracture. Management is mostly conservative, involving rest, analgesics, and activity modification for a period of 4–6 weeks. Here, we present a 35-year-old male who sustained a motor vehicle accident. Except for midline tenderness in the back, there were no other positive findings. Plain radiographs showed a T11 vertebral compression fracture and absent or deviated spinous process shadows for most of the upper thoracic vertebrae. Computed tomography (CT) imaging clearly revealed multiple spinous process fractures extending from T2 to T8 levels. Considering the stability of these fractures, the patient was managed conservatively with rest, bracing, and analgesics. The recovery was quick, and he was back to his full functional status by six weeks

Healthcare virtualization amid COVID-19 pandemic : an emerging new normal

The COVID-19 pandemic has impacted us at various levels. Currently, we cannot predict how long this pandemic is going to last nor if there will be a second wave. Hence, it is necessary that we stay diligent on the safe distancing policy that is in practice in most institutions. In line with this policy, hospitals need to restrict patient numbers both in the outpatient clinics and inpatient wards. For this reason, hospitals are now encouraging virtual healthcare wherever possible, shedding the earlier hesitation to adopt the same [1,2].Published versio

A rare case of extensive cervico-thoracic ossification of the posterior longitudinal ligament causing myelopathy

Ossification of the posterior longitudinal ligament (OPLL) most commonly occurs in the cervical spine, usually involving two to three segments; however, the disease has the potential to occur anywhere in the spine. We encountered a fifty-one year old male with progressive unsteadiness and bilateral lower limb weakness for a period of six months which eventually became worse resulting in inability to walk without assistance. Neurological examination revealed normal upper limb function; however, the lower limbs demonstrated motor dysfunction. Signs of myelopathy were elicited and the patient was subjected to detailed radiological evaluation. CT and MRI scans revealed an extensive cervico-thoracic continuous OPLL from C3 to T3 causing significant cord compression. In view of the deteriorating neurological status, extensive C3-T3 laminectomy with instrumented posterolateral fusion was done and the patient recovered without any immediate or delayed C5 palsy. This case highlights a rare occurrence or extensive OPLL involving eight segments at the cervico-thoracic region. This report also discusses surgical strategies for managing such extensive presentations and our technique to prevent C5 palsy

Fibrodysplasia ossificans progressiva : current concepts from bench to bedside

Heterotopic ossification (HO) is a disorder characterised by the formation of ectopic bone in soft tissue. Acquired HO typically occurs in response to trauma and is relatively common, yet its aetiology remains poorly understood. Genetic forms, by contrast, are very rare, but provide insights into the mechanisms of HO pathobiology. Fibrodysplasia ossificans progressiva (FOP) is the most debilitating form of HO. All patients reported to date carry heterozygous gain-of-function mutations in the gene encoding activin A receptor type I (ACVR1). These mutations cause dysregulated bone morphogenetic protein (BMP) signalling, leading to HO at extraskeletal sites including, but not limited to, muscles, ligaments, tendons and fascia. Ever since the identification of the causative gene, developing a cure for FOP has been a focus of investigation, and studies have decoded the pathophysiology at the molecular and cellular levels, and explored novel management strategies. Based on the established role of BMP signalling throughout HO in FOP, therapeutic modalities that target multiple levels of the signalling cascade have been designed, and some drugs have entered clinical trials, holding out hope of a cure. A potential role of other signalling pathways that could influence the dysregulated BMP signalling and present alternative therapeutic targets remains a matter of debate. Here, we review the recent FOP literature, including pathophysiology, clinical aspects, animal models and current management strategies. We also consider how this research can inform our understanding of other types of HO and highlight some of the remaining knowledge gaps.Nanyang Technological UniversityPublished versionA.-K.K.-P. is supported by a Nanyang Technological University (Lee Kong Chian School of Medicine) Research Scholarship. P.W.I. is supported by the Toh Kian Chui Foundation.

Is spinal surgery safe for elderly patients aged 80 and above? Predictors of mortality and morbidity in an Asian population

Objective: We aimed to determine the 2-year mortality and morbidity rates following spine surgery in elderly patients (age ≥80 years) and to study the associated risk factors. Methods: The records of patients ≥80 years of age who underwent spine surgery during the years 2003–2015 at Tan Tock Seng Hospital, Singapore were retrospectively reviewed. Information was collected on their demographic characteristics, comorbidities, diagnosis, general and neurological status, type of surgery, and outcomes. The mortality and morbidity rates over a 2-year period were analyzed. Bivariate analyses were carried out to identify factors associated with mortality. Results: We selected 47 patients (mean age, 83.3 years; range, 80–91 years) who were followed up for a mean duration of 27.7 months. The mortality rates at 30 days, 6 months, 1 year, and 2 years following surgery were 2.1%, 8.5%, 10.6%, and 12.8%, respectively. The factors significantly associated with mortality included multiple comorbidities, nondegenerative aetiology, and vertebral fractures. The overall morbidity rate was 48.9%, and 17% of this cohort had major complications. Conclusion: Surgeons should strategize management protocols with due consideration of the mortality and morbidity rates, and be wary of operating on patients with multiple comorbidities, nondegenerative conditions, and vertebral fractures.Published versio

Delayed extensive lumbar sub-dural effusion following discectomy - Clinical imaging and case report

Incidental durotomy during lumbar spine surgery is a commonly reported complication. Those presenting with cerebrospinal fluid (CSF) leak are usually recognized and repaired intraoperatively. In some circumstances, it may either be unrecognised or occur as a delayed complication. Such delayed occurrences cannot be predicted and its management remain a challenge to the surgeon, especially when it presents as a subdural effusion. We report a 55-year-old man who underwent mini open lumbar discectomy through left side for a prolapsed L4-L5 disc. Recurrent worsening radicular symptoms along with a palpable cystic swelling at the previous surgical site became eminent, three months after surgery. MRI revealed distinctive anterior translation of all rootlets with subdural fluid collection posterior to it, within a normally placed dura, extending from L1 to L5 levels. A concomitant pseudomeningocele with a fistulous tract was also evident. Draining of pseudomeningocele with widening of previous laminotomies revealed a dural defect of less than 0.5 cms that prompted the CSF leak. Subdural effusion was drained following which the defect was repaired with inlay polyester urethane dural substitute patch and augmented with fibrin sealant. Symptoms regressed and follow up was uneventful. Occurrence of sub-dural effusion in lumbar spine is inevitably uncommon. We advise to suspect this condition in patients with recurrent symptoms following satisfactory lumbar decompression surgeries. Recognising this condition, followed by appropriate drainage of subdural effusion and direct repair of the dural defect is highly recommended for a better prognosis

“Less is More” for Low Grade Lumbar Spondylolytic Spondylolisthesis

We analysed if in-situ posterior stabilization and posterolateral fusion without decompression is appropriate for low grade lumbar spondylolytic spondylolisthesis (LLSS). Patients in whom posterior stabilization and interbody fusion with decompression was performed were Group 1 [n = 27; Age = 48.7±13] and those in whom in-situ posterior stabilization and posterolateral fusion without decompression was performed were Group 2 [n = 37; Age = 46.3±16.4]. All preoperative parameters, intra-operative blood loss, duration of surgery and period of hospitalization were similar between the groups. Statistical comparison of outcomes at 2-years follow-up demonstrated no significant difference in back pain score [p = 0.61], sciatic pain score [p = 0.23] and functional assessment [p = 0.71]. Even though we do much less on performing in-situ posterior stabilization and posterolateral fusion without decompression, it offers similar results as that of posterior stabilization and interbody fusion with decompression in selective LLSS patients.