Surgery (Austin & Northern Health) - Research Publications
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ItemThe Optimal Target and Connectivity for Deep Brain Stimulation in Lennox-Gastaut Syndrome(WILEY, 2022-04-28)OBJECTIVE: Deep brain stimulation (DBS) can reduce seizures in Lennox-Gastaut syndrome (LGS). However, little is known about the optimal target and whether efficacy depends on connectivity of the stimulation site. Using outcome data from the ESTEL trial, we aimed to determine the optimal target and connectivity for DBS in LGS. METHODS: A total of 20 patients underwent bilateral DBS of the thalamic centromedian nucleus (CM). Outcome was percentage seizure reduction from baseline after 3 months of DBS, defined using three measures (monthly seizure diaries, 24-hour scalp electroencephalography [EEG], and a novel diary-EEG composite). Probabilistic stimulation mapping identified thalamic locations associated with higher/lower efficacy. Two substitute diffusion MRI datasets (a normative dataset from healthy subjects and a "disease-matched" dataset from a separate group of LGS patients) were used to calculate structural connectivity between DBS sites and a map of areas known to express epileptic activity in LGS, derived from our previous EEG-fMRI research. RESULTS: Results were similar across the three outcome measures. Stimulation was most efficacious in the anterior and inferolateral "parvocellular" CM border, extending into the ventral lateral nucleus (posterior subdivision). There was a positive association between diary-EEG composite seizure reduction and connectivity to areas of a priori EEG-fMRI activation, including premotor and prefrontal cortex, putamen, and pontine brainstem. In contrast, outcomes were not associated with baseline clinical variables. INTERPRETATION: Efficacious CM-DBS for LGS is linked to stimulation of the parvocellular CM and the adjacent ventral lateral nucleus, and is associated with connectivity to, and thus likely modulation of, the "secondary epileptic network" underlying the shared electroclinical manifestations of LGS. ANN NEUROL 2022;92:61-74.
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ItemNo Preview AvailableIntimal macrophages develop from circulating monocytes during vasculitis.(Wiley, 2022)OBJECTIVE: Vasculitis is characterised by inflammation of the blood vessels. While all layers of the vessel can be affected, inflammation within the intimal layer can trigger thrombosis and arterial occlusion and is therefore of particular clinical concern. Given this pathological role, we have examined how intimal inflammation develops by exploring which (and how) macrophages come to populate this normally immune-privileged site during vasculitis. METHODS: We have addressed this question for Kawasaki disease (KD), which is a type of vasculitis in children that typically involves the coronary arteries. We used confocal microscopy and flow cytometry to characterise the macrophages that populate the coronary artery intima in KD patient samples and in a mouse model of KD, and furthermore, have applied an adoptive transfer system to trace how these intimal macrophages develop. RESULTS: In KD patients, intimal hyperplasia coincided with marked macrophage infiltration of the coronary artery intima. Phenotypic analysis revealed that these 'intimal macrophages' did not express markers of resident cardiac macrophages, such as Lyve-1, and instead, were uniformly positive for the chemokine receptor Ccr2, suggesting a monocytic lineage. In support of this origin, we show that circulating monocytes directly invade the intima via transluminal migration during established disease, coinciding with the activation of endothelial cells lining the coronary arteries. CONCLUSIONS: During KD, intimal macrophages develop from circulating monocytes that infiltrate the inflamed coronary artery intima by transluminal migration.
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ItemDeveloping a spinal cord injury research strategy using a structured process of evidence review and stakeholder dialogue. Part III: outcomes(NATURE PUBLISHING GROUP, 2015-10-01)STUDY DESIGN: Focus Group. OBJECTIVES: To develop a unified, regional spinal cord injury (SCI) research strategy for Australia and New Zealand. SETTING: Australia. METHODS: A 1-day structured stakeholder dialogue was convened in 2013 in Melbourne, Australia, by the National Trauma Research Institute in collaboration with the SCI Network of Australia and New Zealand. Twenty-three experts participated, representing local and international research, clinical, consumer, advocacy, government policy and funding perspectives. Preparatory work synthesised evidence and articulated draft principles and options as a starting point for discussion. RESULTS: A regional SCI research strategy was proposed, whose objectives can be summarised under four themes. (1) Collaborative networks and strategic partnerships to increase efficiency, reduce duplication, build capacity and optimise research funding. (2) Research priority setting and coordination to manage competing studies. (3) Mechanisms for greater consumer engagement in research. (4) Resources and infrastructure to further develop SCI data registries, evaluate research translation and assess alignment of research strategy with stakeholder interests. These are consistent with contemporary international SCI research strategy development activities. CONCLUSION: This first step in a regional SCI research strategy has articulated objectives for further development by the wider SCI research community. The initiative has also reinforced the importance of coordinated, collective action in optimising outcomes following SCI.
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ItemExpanding traditional tendon-based techniques with nerve transfers for the restoration of upper limb function in tetraplegia: a prospective case series(ELSEVIER SCIENCE INC, 2019-08-17)BACKGROUND: Loss of upper extremity function after cervical spinal cord injury greatly affects independence, including social, vocational, and community engagement. Nerve transfer surgery offers an exciting new option for the reanimation of upper limb function in tetraplegia. The aim of this study was to evaluate the outcomes of nerve transfer surgery used for the reanimation of upper limb function in tetraplegia. METHODS: In this prospective case series, we consecutively recruited people of any age with early (<18 months post-injury) cervical spinal cord injury of motor level C5 and below, who had been referred to a single centre for upper extremity reanimation and were deemed suitable for nerve transfer. All participants underwent single or multiple nerve transfers in one or both upper limbs, sometimes combined with tendon transfers, for restoration of elbow extension, grasp, pinch, and hand opening. Participants were assessed at 12 months and 24 months post-surgery. Primary outcome measures were the action research arm test (ARAT), grasp release test (GRT), and spinal cord independence measure (SCIM). FINDINGS: Between April 14, 2014, and Nov 22, 2018, we recruited 16 participants (27 limbs) with traumatic spinal cord injury, among whom 59 nerve transfers were done. In ten participants (12 limbs), nerve transfers were combined with tendon transfers. 24-month follow-up data were unavailable for three patients (five limbs). At 24 months, significant improvements from baseline in median ARAT total score (34·0 [IQR 24·0-38·3] at 24 months vs 16·5 [12·0-22·0] at baseline, p<0·0001) and GRT total score (125·2 [65·1-154·4] vs 35·0 [21·0-52·3], p<0·0001) were observed. Mean total SCIM score and mobility in the room and toilet SCIM score improved by more than the minimal detectable change and the minimal clinically important difference, and the mean self-care SCIM score improved by more than the minimal detectable change between baseline and 24 months. Median Medical Research Council strength grades were 3 (IQR 2-3) for triceps and 4 (IQR 4-4) for digital extensor muscles after 24 months. Mean grasp strength at 24 months was 3·2 kg (SD 1·5) in participants who underwent distal nerve transfers (n=5), 2·8 kg (3·2) in those who had proximal nerve transfers (n=9), and 3·9 kg (2·4) in those who had tendon transfers (n=8). There were six adverse events related to the surgery, none of which had any ongoing functional consequences. INTERPRETATION: Early nerve transfer surgery is a safe and effective addition to surgical techniques for upper limb reanimation in tetraplegia. Nerve transfers can lead to significant functional improvement and can be successfully combined with tendon transfers to maximise functional benefits. FUNDING: Institute for Safety, Compensation, and Recovery Research (Australia).
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ItemTransfer of the supinator nerve to the posterior interosseous nerve for hand opening in tetraplegia through an anterior approach(SAGE PUBLICATIONS LTD, 2021-03-05)We report a retrospective series of 44 transfers in 26 patients in whom a functioning supinator nerve was transferred to a paralyzed posterior interosseous nerve through a single, anterior approach to re-animate hand opening in mid-cervical tetraplegia. Eighteen patients underwent concurrent nerve or tendon transfers to re-animate grasp and/or pinch through the same anterior incision. We evaluated the strength of the innervated muscle at mean follow-up of 24 months (range 12-27). The strength attained in our patients was equivalent to the strength after the transfer through a posterior approach reported in the literature. Nineteen of our patients were satisfied with the hand opening procedure. First webspace opening was the only variable to correlate with patient satisfaction. We conclude that the anterior approach yields similar results to the posterior approach and has the advantage of allowing easier access for simultaneously performing nerve or tendon transfers to reconstruct grasp and pinch.Level of evidence: IV.
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ItemPredicting strength outcomes for upper limb nerve transfer surgery in tetraplegia(SAGE Publications, 2022-12)We report a retrospective study of 112 nerve transfers in 39 participants to investigate predictors of strength outcomes after nerve transfer surgery for upper limb reanimation in tetraplegia. We measured clinical and pre- and intraoperative neurophysiological assessment variables and compared them with strength outcomes 2 years after nerve transfer surgery. We found statistically significant improvement in Medical Research Council strength grades after nerve transfer surgery with lower cervical spine injuries (between one and two grades), lower donor nerve stimulation thresholds (half of a grade), greater motor evoked potential activity in recipient nerves (half of a grade) and greater muscle responses to intraoperative stimulation of donor (half of a grade) and recipient nerves (half of a grade).Level of evidence: III.
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ItemSocial Determinants Contribute to Disparities in Test Positivity, Morbidity and Mortality: Data from a Multi-Ethnic Cohort of 1094 GU Cancer Patients Undergoing Assessment for COVID-19(MDPI, 2022-09-01)Background: The COVID-19 pandemic exploits existing inequalities in the social determinants of health (SDOH) that influence disease burden and access to healthcare. The role of health behaviours and socioeconomic status in genitourinary (GU) malignancy has also been highlighted. Our aim was to evaluate predictors of patient-level and neighbourhood-level factors contributing to disparities in COVID-19 outcomes in GU cancer patients. Methods: Demographic information and co-morbidities for patients screened for COVID-19 across the Mount Sinai Health System (MSHS) up to 10 June 2020 were included. Descriptive analyses and ensemble feature selection were performed to describe the relationships between these predictors and the outcomes of positive SARS-CoV-2 RT-PCR test, COVID-19-related hospitalisation, intubation and death. Results: Out of 47,379 tested individuals, 1094 had a history of GU cancer diagnosis; of these, 192 tested positive for SARS-CoV-2. Ensemble feature selection identified social determinants including zip code, race/ethnicity, age, smoking status and English as the preferred first language—being the majority of significant predictors for each of this study’s four COVID-19-related outcomes: a positive test, hospitalisation, intubation and death. Patient and neighbourhood level SDOH including zip code/ NYC borough, age, race/ethnicity, smoking status, and English as preferred language are amongst the most significant predictors of these clinically relevant outcomes for COVID-19 patients. Conclusion: Our results highlight the importance of these SDOH and the need to integrate SDOH in patient electronic medical records (EMR) with the goal to identify at-risk groups. This study’s results have implications for COVID-19 research priorities, public health goals, and policy implementations.
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ItemValidation of a Novel Patient Specific CT-Morphometric Technique for Quantifying Bone Graft Resorption Following the Latarjet Procedure.(MDPI AG, 2022-09-20)Bone graft resorption following the Latarjet procedure has received considerable concern. Current methods quantifying bone graft resorption rely on two-dimensional (2D) CT-scans or three-dimensional (3D) techniques, which do not represent the whole graft volume/resorption (i.e., 2D assessment) or expose patients to additional radiation (i.e., 3D assessment) as this technique relies on early postoperative CT-scans. The aim of the present study was to develop and validate a patient-specific, CT-morphometric technique combining image registration with 3D CT-reconstruction to quantify bone graft resorption following the Latarjet procedure for recurrent anterior shoulder instability. Pre-operative and final follow-up CT-scans were segmented to digitally reconstruct 3D scapula geometries. A virtual Latarjet procedure was then conducted to model the timepoint-0 graft volume, which was compared with the final follow-up graft volume. Graft resorption at final follow-up was highly correlated to the 2D gold standard-technique by Zhu (Kendall tau coefficient = 0.73; p < 0.001). The new technique was also found to have excellent inter- and intra-rater reliability (ICC values, 0.931 and 0.991; both p < 0.001). The main finding of this study is that the technique presented is a valid and reliable method that provides the advantage of 3D-assessment of graft resorption at long-term follow-up without the need of an early postoperative CT-scan.
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ItemCase Report: Midshaft clavicle fracture with concomitant high grade (Type V) acromioclavicular joint dislocation.(Frontiers Media SA, 2022)INTRODUCTION: Concomitant acromioclavicular joint dislocation and midshaft clavicle fracture are rare injuries, generally resulting from high energy trauma, with limited previous experience in management. CASE: A 30 year old male presented following a pushbike accident. He had suffered a head on collision with another cyclist. Radiographic examination demonstrated a displaced midshaft clavicle fracture with a Rockwood Type V acromioclavicular joint dislocation. Operative management was undertaken using a dual plating technique. At six month follow up the patient demonstrated full range of motion and had no pain. CONCLUSION: Appropriate radiographic evaluation and careful intraoperative assessment are required using the principles of management for acromioclavicular joint injuries, along with stabilization of the mid-clavicular fracture to reduce the risk of non-union.
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ItemRole of PSMA PET-guided metastases-directed therapy in oligometastatic recurrent prostate cancer(FRONTIERS MEDIA SA, 2022-08-18)Oligometastatic prostate cancer (OMPC) has been proposed as an intermediary state between localised disease and widespread metastases, with varying definitions including 1, 3, or ≤5 visceral or bone metastasis. Traditional definitions of OMPC are based on staging with conventional imaging, such as computerised tomography (CT) and whole-body bone scan (WBBS). Novel imaging modalities such as prostate-specific membrane antigen positron emission tomography (PSMA PET) have improved diagnostic utility in detecting early metastatic prostate cancer (PC) metastases compared with conventional imaging. Specifically, meta-analytical data suggest that PSMA PET is sensitive in detecting oligometastatic disease in patients with biochemical recurrence (BCR) post-radical treatment of PC. Recent trials have evaluated PSMA PET-guided metastases-directed therapy (MDT) in oligometastatic recurrent disease, typically with salvage surgery or radiotherapy (RT). To date, these preliminary studies demonstrate promising results, potentially delaying the need for systemic therapy. We aim to report a comprehensive, multidisciplinary review of PSMA-guided MDT in OMPC. In this review, we highlight the utility of PMSA PET in biochemically recurrent disease and impact of PSMA PET on the definition of oligometastatic disease and outline data pertaining to PSMA-guided MDT.