Predictors of Mortality Amongst Tocilizumab Administered COVID-19 Asian Indians: A Predictive Study From a Tertiary Care Centre.

Introduction Hyper-cytokinemia is a dreaded complication of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection and an important predictor of mortality in coronavirus disease 2019 (COVID-19). The current evidence at best is still ambiguous for use of tocilizumab in cytokine storm in COVID-19. Moreover, the factors that are associated with beneficial response from tocilizumab are unknown in COVID-19. We aimed to study the clinical outcomes especially mortality vis-à-vis clinical and laboratory characteristics of patients administered tocilizumab and identify predictors of mortality benefits amongst deceased vs recovered COVID-19 patients. Methods The present study is a retrospective observation of the demographic, clinical, and biological data of all the consecutive patients treated with tocilizumab for COVID-19 pneumonia at the COVID tertiary care centre from July 2020 to October 2020 at Ahmedabad, India. We compared the deceased group with those who recovered/discharged and evaluated patient-level demographics, clinical attributes, and laboratory investigations available to identify subgroups in whom tocilizumab reduced mortality. Results Of the 112 patients included, the mean (SD) age was 56.84 ± 13.56 years and 80 (71.4%) were male. There were 97 (86.6%) patients in the survivors and 15 (13.39%) in the deceased group. Deceased were older than the recovered group (mean: 66.14, SD: 14.41 vs mean: 55.36, SD: 12.98; p=0.04). Hypertension (33.03%) was the commonest comorbidity observed. Mortality was significantly higher in patients with cancer and type-2 diabetes (p=0.05 and p=0.01, respectively). Level of D-dimer and lactate dehydrogenase (LDH) showed trends towards significance as a predictor of mortality (p=0.07 and p=0.08, respectively) not reaching significance. D-dimer level > 5,000 nanograms per millilitre (ng/mL) was the significant predictor of subsequent deaths (p<0.0001). Fourteen patients reported adverse events of tocilizumab. Patients who developed in-hospital complications (such as septic or vasodilatory shock and/or sepsis, acute kidney injury, multiorgan dysfunction) had significantly higher mortality (p<0.0001, p=0.009, and p=0.03, respectively). Conclusion Tocilizumab might be more beneficial in younger patients without sepsis/ septic shock, acute kidney injury, multiorgan dysfunction, and who were non-ventilated. The predictors of mortality amongst Asian Indians treated with tocilizumab were older patients, the presence of type-2 diabetes, cancer, in-hospital complication (such as acute kidney injury, sepsis/septic shock, multiorgan dysfunction), higher D-dimer > 5,000 ng/mL. A larger study with pre-defined inclusion cut-offs of these variables may aid in defining patient's characteristics of Asian Indians who may benefit from tocilizumab in COVID-19.

Preoperative and Postoperative, Three-dimensional Gait Analysis in Surgically Treated Patients With High-grade Spondylolisthesis.

BACKGROUND: High-grade spondylolisthesis (HGS) (Myerding grade III-V) in adolescents can lead to a marked alteration of gait pattern and maybe the presenting symptom in these patients. This characteristic gait pattern in patients with HGS has been referred to as the "pelvic waddle." Modern 3-dimensional (3D) gait analysis serves an important tool to objectively analyze the different components of this characteristic gait preoperatively and postoperatively and is an objective measure of postoperative improvement.This study demonstrates the use of 3D gait analysis preoperatively and postoperatively in a cohort of 4 consecutive patients with HGS treated surgically at a single tertiary referral center and utilize this to objectively evaluate outcome of surgical treatment in these patients. This has not been reported previously in a cohort of patients. METHODS: This is a prospective analysis of patients with HGS who underwent surgical intervention for spondylolisthesis at a single institution. Patient demographics, clinical, and radiologic assessment were recorded, and all patients underwent 3D gait analysis before and after surgical intervention. Kinetic, kinematic, and spatial parameters were recorded preoperatively and postoperatively for all patients. This allowed the outcome of change in gait deviation index, before and after surgical treatment, to be evaluated. RESULTS: We were able to review complete records of 4 adolescent patients who underwent surgical treatment for HGS. Mean age at surgery was 13.5 years with a minimum follow-up of 2.5 years postoperatively (average 40 mo). Preoperative gait analysis revealed marked posterior pelvic tilt in 2 patients, reduced hip and knee extension in all 4 patients and external foot progression in 3 of the 4 patients. Along with an observed improvement in gait, there was an objective improvement in gait parameters postoperatively in all 4 patients. Gait deviation index score improved significantly from 78.9 to 101.3 (mean). CONCLUSIONS: Preoperative gait abnormalities exist in HGS and can be objectively analyzed with gait analysis. Surgical intervention may successfully resolve these gait abnormalities and gait analysis is a useful tool to assess the outcome of surgery and quantify an otherwise intangible benefit of surgical intervention. LEVEL OF EVIDENCE: Level IV-case series.

Minimizing the need for high dependency unit support in adolescent idiopathic scoliosis surgery. Is enhanced recovery and the multidisciplinary team key?

Current trends in the surgical treatment of patients with adolescent idiopathic scoliosis (AIS) involve the use of high dependency unit (HDU) in the postoperative period. The British Scoliosis Society also recommends the availability of HDU support in the postoperative period for these patients. However, this practice may lead to unexpected theatre cancellations due to lack of availability of HDU bed on the day of surgery. We also hypothesize that this practice may eventually lead to longer inpatient stay for the patients. All AIS patients at our unit are managed on a paediatric ward postoperatively, without HDU support. The primary aim of the study therefore is to evaluate whether operating on AIS patients without HDU support is well tolerated practice. Secondary aims were to evaluate patient related outcomes, including length of stay (LOS), and postoperative analgesia requirements. Adolescents aged 12-17 years with idiopathic scoliosis deformity who were treated with posterior instrumented scoliosis (PIS) correction were included in this prospective cohort study. The study period was between 12 November 2012 and 6 August 2018. Twenty-two patients were included in the HDU group and 33 patients in the non-HDU group. These were two matched cohort groups. Data were collected on complication rates, LOS, analgesic requirements, time to bowel opening, and attainment of physiotherapy goals in the immediate postoperative period. Statistical analysis was performed using statistical software R (3.4.3). There were no complications in the non-HDU group and one pneumothorax in the HDU group. There was a significant reduction in the LOS from 7.4 days (SD ±2.3, CI 0.012) days, to 5.8 (SD ±1.4, CI 0.01) days in the non-HDU group (P = 0.0001). There was no significant difference statistically or clinically in opiate usage between the HDU group, 115 mg (SD ±60.7, CI 0.8) and the non-HDU group 116 mg (SD ±55.8, CI 0.6) (P = 0.609). However, there was an improvement in pain scores in the non-HDU group where oral analgesics only were used (P = 0.002). A cost saving of £2038.80 per AIS case was made in the non-HDU group. AIS surgery can be performed safely without the need for HDU support in healthy adolescents. An oral analgesia-based enhanced recovery regime compares favourably to patient-controlled analgesia (PCA) and indicates these patients can be managed safely with strong multidisciplinary support on a paediatric ward.

Magnetically controlled growing rods in the treatment of early onset scoliosis: a single centre experience of 44 patients with mean follow-up of 4.1 years.

AIMS: Magnetically controlled growing rods (MCGR) have been gaining popularity in the management of early-onset scoliosis (EOS) over the past decade. We present our experience with the first 44 MCGR consecutive cases treated at our institution. METHODS: This is a retrospective review of consecutive cases of MCGR performed in our institution between 2012 and 2018. This cohort consisted of 44 children (25 females and 19 males), with a mean age of 7.9 years (3.7 to 13.6). There were 41 primary cases and three revisions from other rod systems. The majority (38 children) had dual rods. The group represents a mixed aetiology including idiopathic (20), neuromuscular (13), syndromic (9), and congenital (2). The mean follow-up was 4.1 years, with a minimum of two years. Nine children graduated to definitive fusion. We evaluated radiological parameters of deformity correction (Cobb angle), and spinal growth (T1-T12 and T1-S1 heights), as well as complications during the course of treatment. RESULTS: The mean Cobb angles pre-operatively, postoperatively, and at last follow-up were 70° (53 to 103), 35° (15 to 71) and 39° (15 to 65) respectively (p < 0.001). Further, there was a mean of 14° (-6 to 27) of additional Cobb angle correction upon graduation from MCGR to definitive fusion. Both T1-T12 and T1-S1 showed significant increase in heights of 27 mm and 45 mm respectively at last follow-up (p < 0.001). Ten children (23%) developed 18 complications requiring 21 unplanned operations. Independent risk factors for developing a complication were single rod constructs and previous revision surgery. CONCLUSION: MCGR has the benefit of avoiding multiple surgeries, and is an effective tool in treatment of early-onset scoliosis. It also maintains the flexibility of the spine, allowing further correction at the time of definitive fusion.Cite this article: Bone Joint Open 2020;1-7:405-414.

A novel technique for the subfascial insertion of magnetically controlled growing rods - The Alder Hey technique.

PURPOSE: In this study, we would like to describe a novel technique for subfascial insertion of magnetically controlled growing rods using chest drain during surgery for early-onset scoliosis. MATERIALS AND METHODS: Posterior approach, surgical dissection to the spine is performed exposing the relevant anatomy to allow placement of pedicle screws always in the distal construct and pedicle screws or hooks in the proximal construct. To allow easy passage of the Magnetic Expansion Control (MAGEC) rod, as well as easy maneuvering of the rod in either the cranial to caudal direction, we use a chest drain of size 24 French diameter as a tunnel. This allows surgeons to fit the nonflexible part of MAGEC rod in the middle of the deformity and cut to length passed through the chest drain from a cranial to caudal position and then chest drain is removed. RESULTS: A total of 40 children with early-onset scoliosis had insertion of MAGEC rods using this technique. There were 21 female and 19 male patients. Early-onset scoliosis etiology is idiopathic in 20 patients, neuromuscular in 16 patients, and others in 4 patients. Median age across all groups was 7 years (range 4-13) at the time of surgery. Follow-up ranged from 11 to 56 months with a median of 24 months. CONCLUSION: The use of a chest drain during subfascial passage of magnetically controlled growing rod is a safe, reliable, reproducible novel technique. This shortens overall time of surgery in our experience.

A multicentre retrospective review of muscle necrosis of the leg following spinal surgery with motor evoked potential monitoring: a cause for concern?

PURPOSE: There are very few reported cases of compartment syndrome of the leg following spinal surgery via a posterior approach. An association between compartment syndrome and muscle over-activity via nerve stimulation during evoked potential monitoring was first suggested in 2003. No further reports have suggested this link. We present a multicentre retrospective review of a series of five patients who developed compartment syndrome of the leg following spinal surgery via a posterior approach, whilst un-paralysed and with combined sensory (SSEP)/motor evoked potential (MEP) monitoring with an aim of highlighting this possible causative factor. METHODS: All data were collected contemporaneously and retrospective analysis was performed. We then arranged for a multidisciplinary review of the cases including surgeons, anaesthetists, radiologists, neurophysiologists and theatre and ward nursing staff. Finally, the literature was reviewed. RESULTS: All patients were operated on by three different surgeons, on different operating tables/mattresses in the prone position. The common factors were un-paralysed patients having motor/sensory monitoring, mechanical calf pumps and total intravenous anaesthesia. Three patients underwent surgical decompression of their compartments and two were treated expectantly. Three patients had confirmed intra-compartmental changes on MRI consistent with compartment syndrome and one had intra-compartmental pressure monitoring which confirmed the diagnosis. CONCLUSIONS: Previous cases in the literature have related to mal-positioning on the Jackson table or use of the knee-chest position for surgery. This was not the case for our patients; therefore, we suspect an association between overactive muscle stimulation and muscle necrosis. Further experimental studies investigating this link are required.

High content and high throughput screening to assess the angiogenic and neurogenic actions of mesenchymal stem cells in vitro.

Mesenchymal stem cells are universally regarded across many fields of medicine, as one of the most promising cell types for use in cell-based therapies. Although not yet fully understood, the therapeutic effects of these cells are largely attributed to the trophic actions of growth factors and cytokines present in the cell secretome. Specifically, the angiogenic and neurogenic properties of these cells make them attractive for the repair of vascularised and innervated tissues. In this study, we investigate the effect of mesenchymal stem cell conditioned media on in vitro assays of angiogenesis and nerve growth. We describe the use of two state of the art high content and high throughput cell analysis systems and compare them against manual analysis techniques. Mesenchymal stem cell secretomes stimulated angiogenesis and nerve growth in vitro in a donor dependant manner. Levels of neuroregulin, platelet-derived growth factor-AA and glial-derived neurotrophic factor, positively correlated with the observed angiogenic effects of these cells. High content and high throughput cell analysis systems such as the ones used in this study, may provide rapid screening tools to assist not only with patient selection but the identification of predictive therapeutic markers to support clinical outcome monitoring for patients treated with stem cell therapies.

Does walking change the Romberg sign?

The Romberg sign helps demonstrate loss of postural control as a result of severely compromised proprioception. There is still no standard approach to applying the Romberg test in clinical neurology and the criteria for and interpretation of an abnormal result continue to be debated. The value of this sign and its adaptation when walking was evaluated. Detailed clinical examination of 50 consecutive patients of cervical myelopathy was performed prospectively. For the walking Romberg sign, patients were asked to walk 5 m with their eyes open. This was repeated with their eyes closed. Swaying, feeling of instability or inability to complete the walk with eyes closed was interpreted as a positive walking Romberg sign. This test was compared to common clinical signs to evaluate its relevance. Whilst the Hoffman's reflex (79%) was the most prevalent sign seen, the walking Romberg sign was actually present in 74.5% of the cases. The traditional Romberg test was positive in 17 cases and 16 of these had the walking Romberg positive as well. Another 21 patients had a positive walking Romberg test. Though not statistically significant, the mean 30 m walking times were slower in patients with traditional Romberg test than in those with positive walking Romberg test and fastest in those with neither of these tests positive. The combination of either Hoffman's reflex and/or walking Romberg was positive in 96% of patients. The walking Romberg sign is more useful than the traditional Romberg test as it shows evidence of a proprioceptive gait deficit in significantly more patients with cervical myelopathy than is found on conventional neurological examination. The combination of Hoffman's reflex and walking Romberg sign has a potential as useful screening tests to detect clinically significant cervical myelopathy.

Histology and pathology of the human intervertebral disc.

The intervertebral disc is a highly organized matrix laid down by relatively few cells in a specific manner. The central gelatinous nucleus pulposus is contained within the more collagenous anulus fibrosus laterally and the cartilage end plates inferiorly and superiorly. The anulus consists of concentric rings or lamellae, with fibers in the outer lamellae continuing into the longitudinal ligaments and vertebral bodies. This arrangement allows the discs to facilitate movement and flexibility within what would be an otherwise rigid spine. At birth, the human disc has some vascular supply within both the cartilage end plates and the anulus fibrosus, but these vessels soon recede, leaving the disc with little direct blood supply in the healthy adult. With increasing age, water is lost from the matrix, and the proteoglycan content also changes and diminishes. The disc-particularly the nucleus-becomes less gelatinous and more fibrous, and cracks and fissures eventually form. More blood vessels begin to grow into the disc from the outer areas of the anulus. There is an increase in cell proliferation and formation of cell clusters as well as an increase in cell death. The cartilage end plate undergoes thinning, altered cell density, formation of fissures, and sclerosis of the subchondral bone. These changes are similar to those seen in degenerative disc disease, causing discussion as to whether aging and degeneration are separate processes or the same process occurring over a different timescale. Additional disorders involving the intervertebral disc can demonstrate other changes in morphology. Discs from patients with spinal deformities such as scoliosis have ectopic calcification in the cartilage end plate and sometimes in the disc itself. Cells in these discs and cells from patients with spondylolisthesis have been found to have very long cell processes. Cells in herniated discs appear to have a higher degree of cellular senescence than cells in nonherniated discs and produce a greater abundance of matrix metalloproteinases. The role that abnormalities play in the etiopathogenesis of different disorders is not always clear. Disorders may be caused by a genetic predisposition or a tissue response to an insult or altered mechanical environment. Whatever the initial cause, a change in the morphology of the tissue is likely to alter the physiologic and mechanical functioning of the tissue.

Traction radiography performed under general anesthetic: a new technique for assessing idiopathic scoliosis curves.

STUDY DESIGN: A prospective review of 24 patients with late-onset idiopathic scoliosis. OBJECTIVES.: To compare curve flexibility measured using supine bending radiography and traction radiography; to examine the correlation of each technique with postoperative correction; and to determine the influence of each technique on the decision to perform concomitant anterior release surgery with posterior instrumentation. SUMMARY OF BACKGROUND DATA: Assessment of curve flexibility is important in decision making before surgical correction of scoliosis. Supine bending radiographs are presently the gold standard technique by which flexibility is assessed, but their reliability has been questioned. No literature has shown a conclusively superior role for traction radiography in assessing idiopathic scoliosis curves. METHODS: Each patient had erect anteroposterior radiographs and supine bending radiographs. On the day of surgery, traction radiography was performed under general anesthetic. The correction obtained in the Cobb angle between the bending and traction radiographs was compared. The influence of the traction radiography on the decision for anterior release surgery and its correlation with postoperative result was examined. RESULTS: Traction radiography demonstrated significantly greater curve flexibility than supine bending radiographs (P < 0.001). Eleven of 13 patients planned for anterior release surgery and posterior instrumentation avoided anterior release after review of the traction radiography. No significant difference was demonstrated between the traction radiography and postoperative correction (P = 0.13). CONCLUSION: Traction radiography is superior to supine bending radiography in assessing curve mobility before surgery. This method benefits patients by allowing them to avoid anterior release surgery and helps predict postoperative correction.

Clinical and radiographic predictors of scoliosis in patients with myelomeningocele.

BACKGROUND: The prevalence of scoliosis in patients with myelomeningocele has been reported to be as high as 80% to 90% in some studies. However, those studies included patients with both congenital and developmental curves. The variation in the patient population as well as the definition of scoliosis in those studies made it difficult to predict the true prevalence of scoliosis in these patients. The purpose of the present study was to identify clinical and radiographic factors that may predict the onset of developmental scoliosis in patients with myelomeningocele. METHODS: A retrospective review of the charts and radiographs of all patients with a diagnosis of myelomeningocele who were seen in our clinic between 1990 and 1995 was performed. The criteria for inclusion in the study included a diagnosis of myelomeningocele or lipomeningocele, an age of more than ten years at the time of the review, serial documentation of motor power, and radiographic documentation of spinal deformity primarily in the coronal plane. The radiographs were examined to assess the degree of scoliosis and to document the last intact laminar arch. The relationship between the degree of scoliosis and the last intact laminar arch was evaluated. Statistical analysis was performed to assess the association between scoliosis and the clinical motor level, the ambulatory status, spasticity, motor asymmetry, and hip instability. RESULTS: One hundred and forty-one patients satisfied the criteria for inclusion in the study. Seventy-four patients (52%) had scoliosis. The average duration of follow-up was 9.4 years (range, three to thirty years), and the average age of the patients was nineteen years (range, ten to forty-two years). Scoliosis developed before the age of nine years in forty-three patients and after the age of nine years in thirty-one patients, with new curves continuing to develop until the age of fifteen years. Curves of <20 degrees degrees often resolved. The clinical motor level, ambulatory status, and last intact laminar arch were all found to be predictive factors for the development of scoliosis in these patients. CONCLUSIONS: In the population of patients with myelomeningocele, the term scoliosis should be reserved for curves of >20 degrees. New curves may continue to develop until the age of fifteen years. The level of the last intact laminar arch is a useful early predictor of the development of scoliosis in these patients.

Spinal trauma: therapy--options and outcomes.

The management of patients with spinal trauma is based on the following goals: (1) the preservation of life; (2) preserving and maximising the neurological function; and (3) providing a stable, painless vertebral column. There have been advances in both non operative as well operative modalities of treatment of patients with spinal injuries. These advances have led to renewed interest in the management of a spinally injured patient. However, despite these advances controversies exist regarding the classification of these fractures, the use of pharmacological intervention, the timing of surgical intervention and indeed the use of surgical intervention itself in the management of these fractures. Most of these controversies surround the treatment of thoracic and lumbar fractures. The purpose of this article is to provide an over view of the therapy options available in the treatment of these fractures. The article shall also look at some of the controversies surrounding the management of these fractures.