Evaluation of Real and Perceived Risk to Health Care Workers Caring for Patients With the Omicron Variant of the SARS-CoV-2 Virus in Surgery and Obstetrics.

OBJECTIVES: The Omicron variant of the SARS-CoV-2 virus is described as more contagious than previous variants. We sought to assess risk to health care workers (HCWs) caring for patients with COVID-19 in surgical/obstetrical settings, and the perception of risk among this group. METHODS: From January to April 2022, reverse transcription polymerase chain reaction was used to detect the presence of SARS-CoV-2 viral ribonucleic acid in patient, environmental (floor, equipment, passive air) samples, and HCWs' masks (inside surface) during urgent surgery or obstetrical delivery for patients with SARS-CoV-2 infection. The primary outcome was the proportion of HCWs' masks testing positive. Results were compared with our previous cross-sectional study involving obstetrical/surgical patients with earlier variants (2020-2021). HCWs completed a risk perception electronic questionnaire. RESULTS: Eleven patients were included: 3 vaginal births and 8 surgeries. In total, 5/108 samples (5%) tested positive (SARS-CoV-2 Omicron) viral ribonucleic acid: 2/5 endotracheal tubes, 1/22 floor samples, 1/4 patient masks, and 1 nasal probe. No samples from the HCWs' masks (0/35), surgical equipment (0/10), and air (0/11) tested positive. No significant differences were found between the Omicron and 2020/21 patient groups' positivity rates (Mann-Whitney U test, P = 0.838) or the level of viral load from the nasopharyngeal swabs (P = 0.405). Nurses had a higher risk perception than physicians (P = 0.038). CONCLUSION: No significant difference in contamination rates was found between SARS-CoV-2 Omicron BA.1 and previous variants in surgical/obstetrical settings. This is reassuring as no HCW mask was positive and no HCW tested positive for COVID-19 post-exposure.

Literature review on the use of methoxyflurane in the management of pain in cancer-related procedures.

INTRODUCTION: Self-administered methoxyflurane, also known as Penthrox, at a sub-anesthetic dose is a short-term, fast-acting, and safe analgesic that may provide suitable pain relief for cancer patients. This review aims to compile the existing evidence on methoxyflurane and its efficacy in reducing pain during cancer-related procedures. METHODS: A literature search was conducted through OVID Medline and Embase. The search was limited to articles published between 2012 and 2021 and studies were included if they assessed the efficacy of methoxyflurane to reduce pain in cancer-related procedures. All types of cancer were included. RESULTS: The literature search yielded seven studies published between 2012 and 2021. The studies analyzed assessed methoxyflurane use in prostate biopsy, colonoscopy, removal of brachytherapy rods, and bone marrow biopsy. Various research designs were employed, including three randomized controlled trials, two prospective observational studies, one retrospective, and one non-randomized controlled trial. In all, methoxyflurane has a demonstrated ability to reduce pain in these procedures. CONCLUSION: In the limited studies available in evaluating the efficacy of methoxyflurane for reducing procedural pain during cancer-related procedures, all have demonstrated clinical equivalency or superiority. Pain relief appears to be equivalent however methoxyflurane overcomes the standard limitations of respiratory sedation and has demonstrated quicker procedural recovery times than traditional sedation methods. The accumulated data to date supports the use of methoxyflurane which can supplement or supplant current methods of analgesia in cancer-related procedures.

Quality of life issues in patients with bone metastases: A systematic review.

INTRODUCTION: Bones are frequent sites of metastatic disease, observed in 30-75% of advanced cancer patients. Quality of life (QoL) is an important endpoint in studies evaluating the treatments of bone metastases (BM), and many patient-reported outcome tools are available. The primary objective of this systematic review was to compile a list of QoL issues relevant to BM and its interventions. The secondary objective was to identify common tools used to assess QoL in patients with BM, and the QoL issues they fail to address. METHODS: A search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases between 1946 and 27 January 2023 with the keywords "bone metastases", "quality of life", and "patient reported outcomes". Specific QoL issues in original research studies and the QoL tools used were extracted. RESULTS: The review identified the QoL issues most prevalent to BM in the literature. Physical and functional issues observed in patients included pain, interference with ambulation and daily activities, and fatigue. Psychological symptoms, such as helplessness, depression, and anxiety were also common. These issues interfered with patients' relationships and social activities. Items not mentioned in existing QoL tools were related to newer treatments of BM, such as pain flare, flu-like symptoms, and jaw pain due to osteonecrosis. CONCLUSIONS: This systematic review highlights that QoL issues for patients with BM have expanded over time due to advances in BM-directed treatments. If they are relevant, additional treatment-related QoL issues identified need to be validated prospectively by patients and added to current assessment tools.

Comparison of major spine navigation platforms based on key performance metrics: a meta-analysis of 16,040 screws.

PURPOSE: The objective of this meta-analysis is to compare available computer-assisted navigation platforms by key performance metrics including pedicle screw placement accuracy, operative time, neurological complications, and blood loss. METHODS: A systematic review was conducted using major databases for articles comparing pedicle screw accuracy of computer-assisted navigation to conventional (freehand or fluoroscopy) controls via post-operative computed tomography. Outcome data were extracted and pooled by random-effects model for analysis. RESULTS: All navigation platforms demonstrated significant reduction in risk of breach, with Stryker demonstrating the highest accuracy compared to controls (OR 0.16 95% CI 0.06 to 0.41, P < 0.00001, I2 = 0%) followed by Medtronic. There were no significant differences in accuracy or most surgical outcome measures between platforms; however, BrainLab demonstrated significantly faster operative time compared to Medtronic by 30 min (95% CI - 63.27 to - 2.47, P = 0.03, I2 = 74%). Together, there was significantly lower risk of major breach in the navigation group compared to controls (OR 0.42, 95% CI 0.27-0.63, P < 0.0001, I2 = 56%). CONCLUSIONS: When comparing between platforms, Stryker demonstrated the highest accuracy, and Brainlab the shortest operative time, both followed by Medtronic. No significant difference was found between platforms regarding neurologic complications or blood loss. Overall, our results demonstrated a 60% reduction in risk of major breach utilizing computer-assisted navigation, coinciding with previous studies, and supporting its validity. This study is the first to directly compare available navigation platforms offering insight for further investigation and aiding in the institutional procurement of platforms. LEVEL 3 EVIDENCE: Meta-analysis of Level 3 studies.

Key Stakeholder Perceptions of Standard vs. Total Cost of Ownership: A Procurement Analysis for Orthopaedic-Powered Instruments.

This study compares standard procurement methodology (SPM) with total cost of ownership (TCO) methodology for the procurement of orthopaedic-powered instruments. The authors conducted semi-structured standardized interviews with key hospital procurement stakeholders following consolidated criteria for reporting qualitative research. Of the 33 hospital procurement stakeholders interviewed, all (100%) reported that SPM would be easier to use than TCO. However, only six (18%) preferred SPM over TCO. Barriers to the adoption of TCO emerged as a theme. Creating TCO frameworks can help to simplify the process for procurement agents and facilitate its adoption in the healthcare sector.

An antisense circular RNA circSCRIB enhances cancer progression by suppressing parental gene splicing and translation.

Circular RNAs (circRNAs) represent a large group of non-coding RNAs that are widely detected in mammalian cells. Although most circRNAs are generated in a sense orientation, there is a group of circRNAs that are synthesized in an antisense orientation. High-throughput analysis of breast cancer specimens revealed a significant enrichment of 209 antisense circRNAs. The tumor suppressor SCRIB was shown to potentially produce thirteen circRNAs, three of which are in an antisense orientation. Among these three circRNAs, circSCRIB (hsa_circ_0001831) was the most enriched in the breast cancer panel. This antisense SCRIB circRNA was shown to span one intron and two exons. We hypothesized that this circRNA could decrease pre-mRNA splicing and mRNA translation. To test this, we generated a hsa_circ_0001831 expression construct. We found that there was decreased SCRIB mRNA production but increased cancer cell proliferation, migration, and invasion. In comparison, an exonic sequence construct did not affect mRNA splicing but decreased protein translation, leading to increased E-cadherin expression and decreased expression of N-cadherin and vimentin. Thus, there was increased cell migration, invasion, proliferation, colony formation, and tumorigenesis. Our study suggests a novel modulatory role of antisense circRNAs on their parental transcripts. This may represent a promising approach for developing circRNA-directed therapy.

Validation of the Subgroups for Targeted Treatment for Back (STarT Back) screening tool at a tertiary care centre.

BACKGROUND: The Subgroups for Targeted Treatment for Back (STarT Back) tool is a screening questionnaire developed to identify modifiable risk factors for back pain disability in primary care. Given the ability of this tool to assist with early identification of patients at high risk, we examined its concurrent convergent and known-group construct validity in tertiary care. METHODS: This was a case-control study of adult (age > 18 yr) patients with and without an active work-related compensation claim recruited from an academic health centre between August 2017 and May 2019. Patients in the study group were assessed by a physiotherapist and an orthopedic surgeon in a spine specialty program designed to assess and treat workplace injuries. The control group included patients referred to an orthopedic spine surgeon in a publicly funded specialty clinic where an advanced practice physiotherapist determined the need for surgical consultation. We used the Roland-Morris Disability Questionnaire (RMDQ) and the Hospital Anxiety and Depression Scale (HADS) to determine the convergent and known-group construct validity of the STarT Back tool. RESULTS: Fifty case and 50 control participants were included. We observed moderate to high association between the STarT Back total score, psychosocial subscore and risk categories and the RMDQ and HADS scores in the expected direction (p < 0.001). A significant association was observed between risk group allocation and depression (area under the curve values > 80), having a compensable injury and work status (p = 0.002-0.001). CONCLUSION: The STarT Back tool was able to differentiate between patients with and without a compensable injury and patients with different levels of work status. The tool has acceptable convergent and known-group construct validity and can assist in clinical decision-making in a tertiary care setting where adjunct psychologic management may be indicated.

Surgeon clinical practice variation and patient preferences during the informed consent discussion: a mixed-methods analysis in lumbar spine surgery.

Background: Patients with lumbar disc herniation may greatly benefit from microdiscectomy. Although spine surgeons performing microdiscectomy routinely obtain informed consent, the potential adverse events they disclose often vary. Moreover, little is known about what disclosures are deemed most valuable by patients. The aim of this mixed-methods study was to determine practice variations among spine surgeons in regard to the disclosure of potential adverse events during informed consent discussions for lumbar microdiscectomy and to determine which topics patients perceived to be valuable in the consent discussion. Methods: A survey evaluating the frequency with which spine surgeons disclose 15 potential adverse events related to lumbar microdiscectomy during informed consent discussions was distributed among Canadian Spine Society members. Additionally, semistructured interviews were conducted with preoperative patients, postoperative patients, attending spine surgeons, spine fellows and orthopedic residents. Interview transcripts were analyzed using thematic analysis with open coding. Results: Fifty-one Canadian Spine Society members completed the survey. The number of potential adverse events not routinely discussed was greater among orthopedic surgeons than among neurosurgeons (relative risk 1.83; 95% confidence interval 1.22-2.73; p = 0.003). Three preoperative patients, 7 postoperative patients, 6 attending spine surgeons, 3 spine fellows and 5 orthopedic residents participated in the semistructured interviews. The interviews identified gaps in information provided to patients, particularly on topics relating to postoperative care such as expected recovery time, activity restrictions and need for a caregiver. Conclusion: There is variation in the disclosure of potential adverse events during informed consent discussions for lumbar microdiscectomy among Canadian spine surgeons. Patients desire more information regarding their postoperative care. Further research should focus on developing guidelines to reduce practice variation and optimize the effectiveness of consent discussions.

Contexte: Les patients atteints d'une hernie discale lombaire pourraient profiter grandement d'une microdiscectomie. Bien que les chirurgiens spécialistes de la colonne vertébrale réalisant des microdiscectomies obtiennent toujours le consentement éclairé du patient, les événements indésirables potentiels présentés varient souvent. De plus, on en connaît peu sur les informations les plus importantes du point de vue des patients. L'objectif de cette étude à méthodes mixtes était de déterminer les différentes pratiques des chirurgiens en ce qui a trait à la présentation des événements indésirables potentiels pendant les discussions sur le consentement éclairé pour les microdiscectomies lombaires et de déterminer les sujets les plus importants pour les patients pendant ces discussions. Méthodes: Un sondage sur la fréquence à laquelle les chirurgiens présentent 15 événements indésirables potentiels associés à la microdiscectomie lombaire pendant les discussions sur le consentement éclairé a été distribué aux membres de la Société canadienne du rachis. De plus, des entretiens semi-dirigés ont été réalisés auprès de patients en période préopératoire, de patients en période postopératoire, de chirurgiens spécialistes de la colonne vertébrale, de fellows en chirurgie spinale et de résidents en chirurgie orthopédique. Des analyses thématiques utilisant un code ouvert ont été réalisées sur les transcriptions des entretiens. Résultats: Cinquante-et-un membres de la Société canadienne du rachis ont répondu au sondage. Le nombre d'événements indésirables potentiels non systématiquement mentionnés était plus élevé chez les chirurgiens orthopédiques que chez les neurochirurgiens (risque relatif 1,83; intervalle de confiance de 95 % 1,22­2,73; p = 0,003). Dans les entretiens semi-dirigés, on a recueilli les commentaires de 3 patients en période préopératoire, de 7 patients en période postopératoire, de 6 chirurgiens spécialistes de la colonne vertébrale, de 3 fellows en chirurgie spinale et de 5 résidents en chirurgie orthopédique. Les entretiens ont révélé des lacunes dans l'information transmise aux patients, particulièrement sur les soins postopératoires, comme le temps de récupération attendu, les restrictions quant aux activités et la nécessité d'un soignant. Conclusion: On a trouvé une variation dans la présentation des événements indésirables potentiels pendant les discussions sur le consentement éclairé pour les microdiscectomies lombaires chez les chirurgiens spécialistes de la colonne vertébrale au Canada. Les patients veulent en savoir plus sur les soins postopératoires. Des lignes directrices devraient être établies pour réduire les différences entre les pratiques et optimiser l'efficacité des discussions sur le consentement.

Utilization of Spinal Intra-operative Three-dimensional Navigation by Canadian Surgeons and Trainees: A Population-based Time Trend Study.

BACKGROUND: Computer-assisted navigation (CAN) improves the accuracy of spinal instrumentation in vertebral fractures and degenerative spine disease; however, it is not widely adopted because of lack of training, high capital costs, workflow hindrances, and accuracy concerns. We characterize shifts in the use of spinal CAN over time and across disciplines in a single-payer health system, and assess the impact of intra-operative CAN on trainee proficiency across Canada. METHODS: A prospectively maintained Ontario database of patients undergoing spinal instrumentation from 2005 to 2014 was reviewed retrospectively. Data were collected on treated pathology, spine region, surgical approach, institution type, and surgeon specialty. Trainee proficiency with CAN was assessed using an electronic questionnaire distributed across 15 Canadian orthopedic surgical and neurosurgical programs. RESULTS: In our provincial cohort, 16.8% of instrumented fusions were CAN-guided. Navigation was used more frequently in academic institutions (15.9% vs. 12.3%, p<0.001) and by neurosurgeons than orthopedic surgeons (21.0% vs. 12.4%, p<0.001). Of residents and fellows 34.1% were fully comfortable using spinal CAN, greater for neurosurgical than orthopedic surgical trainees (48.1% vs. 11.8%, p=0.008). The use of CAN increased self-reported proficiency in thoracic instrumentation for all trainees by 11.0% (p=0.036), and in atlantoaxial instrumentation for orthopedic trainees by 18.0% (p=0.014). CONCLUSIONS: Spinal CAN is used most frequently by neurosurgeons and in academic centers. Most spine surgical trainees are not fully comfortable with the use of CAN, but report an increase in technical comfort with CAN guidance particularly for thoracic instrumentation. Increased education in spinal CAN for trainees, particularly at the fellowship stage and, specifically, for orthopedic surgery, may improve adoption.

CONTEXTE: La chirurgie assistée par ordinateur (CAO) permet d'améliorer la précision de l'exploration instrumentale employée dans le cas de fractures vertébrales et de maladies dégénératives de la colonne vertébrale. Cela dit, elle n'a pas encore été adoptée à grande échelle en raison d'un manque de formation, de coûts d'immobilisation considérables, d'obstacles liés à l'organisation du travail et de doutes quant à son exactitude. C'est dans cette perspective que nous voulons décrire, parmi divers champs de pratique, les transformations se rapportant au fil du temps à l'utilisation de la CAO de la colonne vertébral dans le cadre d'un régime de santé universel à payeur unique. Qui plus est, nous voulons aussi évaluer l'impact de la CAO en ce qui a trait aux compétences des stagiaires partout au Canada. MÉTHODES: Pour ce faire, nous avons passé en revue de façon rétrospective une base de données tenue à jour prospectivement au sujet de patients ontariens ayant été soumis de 2005 à 2014 à une exploration instrumentale de la colonne vertébrale. Les données obtenues portaient sur le type de pathologie traitée, sur la région de la colonne vertébrale visée, sur l'approche chirurgicale privilégiée, sur le type d'établissement et sur la spécialité du chirurgien ayant intervenu. Les compétences des stagiaires en matière de CAO ont également été évaluées à l'aide d'un questionnaire en ligne diffusé au sein de 15 programmes canadiens de chirurgie orthopédique et de neurochirurgie. RÉSULTATS: En tout, 16,8 % des fusions instrumentées réalisées au sein de notre cohorte ontarienne l'ont été à l'aide de la technique de la CAO. Cette dernière a été utilisée plus fréquemment dans des établissements d'enseignement universitaire (15,9 % par opposition à 12,3 % pour les autres; p<0,001) mais aussi plus souvent par des neurochirurgiens (21,0 % par opposition à 12,4 % par des chirurgiens orthopédiques; p<0,001). En outre, 34,1 % des résidents et des médecins suivant une formation complémentaire étaient parfaitement à l'aise dans l'utilisation de la CAO de la colonne vertébrale (48,1 % de ceux se spécialisant en neurochirurgie par opposition à 11,8 % de ceux se spécialisant en chirurgie orthopédique; p = 0,008). L'utilisation de la CAO a par ailleurs entraîné une augmentation, auto-déclarée, de 11,0 % de l'aptitude à faire usage de l'exploration instrumentale thoracique chez tous les stagiaires (p = 0,036); dans le cas de l'exploration instrumentale atlanto-axiale, cette augmentation a été de 18,0 % (p = 0,014) chez les stagiaires en chirurgie orthopédique. CONCLUSIONS: La CAO de la colonne vertébrale est employée le plus souvent par les neurochirurgiens dans des établissements d'enseignement universitaire. La plupart des stagiaires en chirurgie de la colonne vertébrale ne sont pas entièrement à l'aise en ce qui concerne l'utilisation de la CAO. Toutefois, ils ont signalé une augmentation de leur aisance à utiliser la CAO et à bénéficier de son assistance, en particulier dans des cas d'exploration instrumentale thoracique. En somme, une plus ample formation en matière de CAO de la colonne vertébrale offerte aux stagiaires, particulièrement à ceux suivant une formation complémentaire et dans le champ de la chirurgie orthopédique, pourrait favoriser son adoption.

Advancing spinal fellowship training: an international multi-centre educational perspective.

PURPOSE: The purpose of this article is to review the importance of contemporary spine surgery fellowships and educational strategies to assist with fellowship design and delivery. METHODS: Spine surgery fellowship includes trainees from orthopaedic and neurosurgical backgrounds and is increasingly indicated for individuals wishing to pursue spine surgery as a career, recognizing how spinal surgery evolved significantly in scope and complexity. We combine expert opinion with a review of the literature and international experience to expound spine fellowship training. RESULTS: Contemporary learning techniques include boot camps at the start of fellowship which may reinforce previous clinical learning and help prepare fellows for their new clinical roles. There is good evidence that surgical specialty training boot camps improve clinical skills, knowledge and trainee confidence prior to embarking upon new clinical roles with increasing levels of responsibility. Furthermore, as simulation techniques and technologies take on an increasing role in medical and surgical training, we found evidence that trainees' operative skills and knowledge can improve with simulated operations, even if just carried out briefly. Finally, we found evidence to suggest a role for establishing competence-based objectives for training in specific operative and technical procedures. Competence-based objectives are helpful for trainees and trainers to highlight gaps in a trainee's skill set that may then be addressed during training. CONCLUSIONS: Spinal fellowships may benefit from certain contemporary strategies that assist design and delivery of training in a safe environment. Interpersonal factors that promote healthy teamwork may contribute to an environment conducive to learning. These slides can be retrieved under Electronic Supplementary Material.

Proteostasis as a therapeutic target in glomerular injury associated with mutant α-actinin-4.

Mutations in α-actinin-4 (actinin-4) result in hereditary focal segmental glomerulosclerosis (FSGS) in humans. Actinin-4 mutants induce podocyte injury because of dysregulation of the cytoskeleton and proteotoxicity. Injury may be associated with endoplasmic reticulum (ER) stress and polyubiquitination of proteins. We assessed if the chemical chaperone 4-phenylbutyrate (4-PBA) can ameliorate the proteotoxicity of an actinin-4 mutant. Actinin-4 K255E, which causes FSGS in humans (K256E in the mouse), showed enhanced ubiquitination, accelerated degradation, aggregate formation, and enhanced association with filamentous (F)-actin in glomerular epithelial cells (GECs). The mutant disrupted ER function and stimulated autophagy. 4-PBA reduced actinin-4 K256E aggregation and its tight association with F-actin. Transgenic mice that express actinin-4 K256E in podocytes develop podocyte injury, proteinuria, and FSGS in association with glomerular ER stress. Treatment of these mice with 4-PBA in the drinking water over a 10-wk period significantly reduced albuminuria and ER stress. Another drug, celastrol, which enhanced expression of ER and cytosolic chaperones in GECs, tended to reduce actinin-4 aggregation but did not decrease the tight association of actinin-4 K256E with F-actin and did not reduce albuminuria in actinin-4 K256E transgenic mice. Thus, chemical chaperones, such as 4-PBA, may represent a novel therapeutic approach to certain hereditary glomerular diseases.

Comparison of the effect of two different bone-targeted radiofrequency ablation (RFA) systems alone and in combination with percutaneous vertebroplasty (PVP) on the biomechanical stability of the metastatic spine.

INTRODUCTION: Radiofrequency ablation (RFA) and percutaneous vertebroplasty (PVP) are used independently and in combination to treat metastatically involved vertebrae with the aim of relieving pain, reducing tumour burden and providing bony mechanical stabilization. PURPOSE: The aim of this work was to characterize the effect of two bone-targeted RFA devices, alone and in combination with PVP, to improve strength and mechanical stability in vertebrae with osteolytic metastatic disease. METHODS: Simulated spinal metastases (n = 12) were treated with one of two bone-targeted RFA devices (bipolar cooled or bone coil RF electrodes), followed by PVP. Under axial compressive loading, spinal canal narrowing was measured in the intact specimen, after tumour simulation, post-RFA and post-PVP. RESULTS: RFA alone resulted in successful tumour shrinkage and cavitation, but further increased canal narrowing under loading. RFA combined with PVP significantly reduced posterior wall stability in samples where sufficient tumour shrinkage and cavitation were coupled with a pattern of cement deposition which extended to posterior vertebral body. CONCLUSIONS: RFA combined with cement deposition in the posterior vertebral body demonstrates significantly more stable vertebrae under axial loading.

Versican 3'-untranslated region (3'UTR) promotes dermal wound repair and fibroblast migration by regulating miRNA activity.

Versican is an extracellular chondroitin sulfate proteoglycan which functions as a structural molecule but can also regulate a variety of cellular activities. This study was designed to explore the roles of versican in the process of dermal wound repair. To elevate levels of versican, we ectopically expressed the versican 3'-untranslated region (3'UTR) as a competitive endogenous RNA to modulate expression of versican. We demonstrated that wounds closed faster in transgenic mice expressing the versican 3'UTR, as compared to those in wildtype mice. We stably expressed versican 3'UTR in NIH3T3 fibroblasts and found that the 3'UTR-transfected cells showed increased migratory capacity relative to vector-transfected cells. Interestingly, we found that the 3'UTRs of versican and ß-catenin shared common microRNAs (miRNAs) including miR-185, miR-203*, miR-690, miR-680, and miR-434-3p. Luciferase assays showed that all of these miRNAs could target the 3'UTRs of both versican and ß-catenin, when the luciferase constructs contained fragments harboring the miRNA binding sites. As a consequence, expression of both versican and ß-catenin was up-regulated, which was confirmed in vitro and in vivo. Transfection with small interfering RNAs (siRNAs) targeting the versican 3'UTR abolished the 3'UTR's effects on cell migration and invasion. Taken together, these results demonstrate that versican plays important roles in wound repair and that versican messenger RNAs (mRNAs) could compete with endogenous RNAs for regulating miRNA functions.

MicroRNA miR-24 enhances tumor invasion and metastasis by targeting PTPN9 and PTPRF to promote EGF signaling.

MicroRNAs are known to play regulatory roles in gene expression associated with cancer development. We analyzed levels of the microRNA miR-24 in patients with breast carcinoma and found that miR-24 was higher in breast carcinoma samples than in benign breast tissues. We generated constructs expressing miR-24 and studied its functions using both in vitro and in vivo techniques. We found that the ectopic expression of miR-24 promoted breast cancer cell invasion and migration. In vivo experiments in mice indicated that the expression of miR-24 enhanced tumor growth, invasion into local tissues, metastasis to lung tissues and decreased overall mouse survival. In the miR-24-expressing cells and tumors, EGFR was highly phosphorylated, whereas expression of the phosphatases tyrosine-protein phosphatase non-receptor type 9 (PTPN9) and receptor-type tyrosine-protein phosphatase F (PTPRF) were repressed. We confirmed that miR-24 could directly target both PTPN9 and PTPRF. Consistent with this, we found that the levels of phosphorylated epidermal growth factor receptor (pEGFR) were higher whereas the levels of PTPN9 and PTPRF were lower in the patients with metastatic breast carcinoma. Ectopic expression of PTPN9 and PTPRF decreased pEGFR levels, cell invasion, migration and tumor metastasis. Furthermore, we found that MMP2, MMP11, pErk, and ADAM15 were upregulated, whereas TIMP2 was downregulated; all of which supported the roles of miR-24 in tumor invasion and metastasis. Our results suggest that miR-24 plays a key role in breast cancer invasion and metastasis. miR-24 could potentially be a target for cancer intervention.

An institutional ethnography of chronic pain management in family medicine (COPE) study protocol.

BACKGROUND: Patients with chronic conditions and multiple comorbidities represent a growing challenge for health care globally. Improved coordination of care is considered essential for providing more effective and cost-efficient care for these patients with complex needs. Osteoarthritis is one of the most common and debilitating chronic conditions, is the most frequent cause of chronic pain yet osteoarthritis care is often poorly-coordinated. Primary care is usually the first contact for patients requiring relief from chronic pain. Our previous work suggests discordance between the policy goals of improving patient care and the experience of osteoarthritis patients. We plan to investigate the empirical context of the primary care setting by focusing on primary physicians' conceptualizations and performance of their work in treating complex patients with chronic pain. This will allow for an exploration of how primary health care is - or could be - integrated with other services that play an important role in health care delivery. METHODS: Our study is an Institutional Ethnography of pain management in family medicine, to be carried out in three phases over 3 years from 2014/15 to 2018. Over the first year we will undertake approximately 80 key informant interviews with primary care physicians, other health care providers, policymakers and clinical experts. In the second year we will focus on mobilizing our networks from year one to assist in the collection of key texts which shape the current context of care. These texts will be analyzed by the research team. In the final year of the study we will focus on synthesizing our findings in order to map the social relations informing care. As is standard and optimal in qualitative research, analysis will be concurrent with data collection. DISCUSSION: Our study will allow us to identify how the work of coordinating care across multiple settings is accomplished, in practice as well as discursively and textually. Ultimately, we will identify links between everyday experience of care for patients with chronic pain, and broader discourses related to health care system inefficiencies, integration and patient-centred care. An expected outcome of this study will be the development of new, or augmentation of existing, models of care, that are based in the local realities of primary care practice.

Versican 3'-untranslated region (3'-UTR) functions as a ceRNA in inducing the development of hepatocellular carcinoma by regulating miRNA activity.

This study was designed to explore the role of versican in the development of hepatocellular carcinoma (HCC). Ectopic expression of the versican 3'-untranslated region (3'-UTR) was studied as a competitive endogenous RNA for regulating miRNA functions. We used this approach to modulate the expression of versican and its related proteins in 3'-UTR transgenic mice and in the liver cancer cell line HepG2, stably transfected with the 3'-UTR or a control vector. We demonstrated that transgenic mice expressing the versican 3'-UTR developed HCC and increased expression of versican isoforms V0 and V1. HepG2 cells transfected with versican 3'-UTR displayed increased proliferation, survival, migration, invasion, colony formation, and enhanced endothelial cell growth, but decreased apoptosis. We found that versican 3'-UTR could bind to miRNAs miR-133a, miR-199a*, miR-144, and miR-431 and also interacted with CD34 and fibronectin. As a consequence, expression of versican, CD34, and fibronectin was up-regulated by ectopic transfection of the versican 3'-UTR, which was confirmed in HepG2 cells and in transgenic mice as compared with wild-type controls. Transfection with siRNAs targeting the versican 3'-UTR abolished the effects of the 3'-UTR. Taken together, these results demonstrate that versican V0 and V1 isoforms play important roles in HCC development and that versican mRNAs compete with endogenous RNAs in regulating miRNA functions.

Improving access to emergent spinal care through knowledge translation: an ethnographic study.

BACKGROUND: For patients and family members, access to timely specialty medical care for emergent spinal conditions is a significant stressor to an already serious condition. Timing to surgical care for emergent spinal conditions such as spinal trauma is an important predictor of outcome. However, few studies have explored ethnographically the views of surgeons and other key stakeholders on issues related to patient access and care for emergent spine conditions. The primary study objective was to determine the challenges to the provision of timely care as well as to identify areas of opportunities to enhance care delivery. METHODS: An ethnographic study of key administrative and clinical care providers involved in the triage and care of patients referred through CritiCall Ontario was undertaken utilizing standard methods of qualitative inquiry. This comprised 21 interviews with people involved in varying capacities with the provision of emergent spinal care, as well as qualitative observations on an orthopaedic/neurosurgical ward, in operating theatres, and at CritiCall Ontario's call centre. RESULTS: Several themes were identified and organized into categories that range from inter-professional collaboration through to issues of hospital-level resources and the role of relationships between hospitals and external organizations at the provincial level. Underlying many of these issues is the nature of the medically complex emergent spine patient and the scientific evidentiary base upon which best practice care is delivered. Through the implementation of knowledge translation strategies facilitated from this research, a reduction of patient transfers out of province was observed in the one-year period following program implementation. CONCLUSIONS: Our findings suggest that competing priorities at both the hospital and provincial level create challenges in the delivery of spinal care. Key stakeholders recognized spinal care as aligning with multiple priorities such as emergent/critical care, medical through surgical, acute through rehabilitative, disease-based (i.e. trauma, cancer), and wait times initiatives. However, despite newly implemented strategies, there continues to be increasing trends over time in the number of spinal CritiCall Ontario referrals. This reinforces the need for ongoing inter-professional efforts in care delivery that take into account the institutional contexts that may constrain individual or team efforts.

Health-related quality of life following decompression compared to decompression and fusion for degenerative lumbar spondylolisthesis: a Canadian multicentre study.

BACKGROUND: Decompression alone (D) is a well-accepted treatment for patients with lumbar spinal stenosis (LSS) causing neurogenic claudication; however, D is controversial in patients with LSS who have degenerative spondylolisthesis (DLS). Our goal was to compare the outcome of anatomy-preserving D with decompression and fusion (DF) for patients with grade I DLS. We compared patients with DLS who had elective primary 1-2 level spinal D at 1 centre with a cohort who had 1-2 level spinal DF at 5 other centres. METHODS: Patients followed for at least 2 years were included. Primary analysis included comparison of change in SF-36 physical component summary (PCS) scores and the proportion of patients achieving minimal clinically important difference (MCID) and substantial clinical benefit (SCB). RESULTS: There was no significant difference in baseline SF-36 scores between the groups. The average change in PCS score was 10.4 versus 11.4 (p = 0.61) for the D and DF groups, respectively. Sixty-seven percent of the D group and 71% of the DF group attained MCID, while 64% of both D and DF groups attained SCB. There was no significant difference between D and DF for change in PCS score (p = 0.74) or likelihood of reaching MCID (p = 0.81) or SCB (p = 0.85) after adjusting for other variables. CONCLUSION: In select patients with DLS, the outcome of D is comparable to DF at a minimum of 2 years.

CONTEXTE: La décompression seule est un traitement bien accepté pour la sténose lombaire (SL) causant une claudication neurogène. Son utilisation ne fait cependant pas l'unanimité chez les patients atteints de SL qui souffrent d'un spondylolisthésis dégénératif (SLD). Notre objectif était de comparer l'issue d'une décompression avec préservation anatomique à celle d'une décompression-arthrodèse (DA) chez des patients atteints de SLD de grade 1. Nous avons comparé les patients atteints de SLD ayant subi une décompression élective primaire de niveau 1­2 dans un centre à une cohorte ayant subi une DA de niveau 1­2 effectuée dans 5 autres centres. MÉTHODES: Nous avons inclus les patients qui ont été suivis pendant au moins 2 ans. L'analyse primaire comportait une comparaison des changements aux scores sommaires pour la composante physique (CP) du questionnaire SF-36 et la proportion de patients ayant obtenu une différence minimale cliniquement importante (DMCI) et en ayant tiré un bienfait clinique substantiel (BCS). RÉSULTATS: Il n'y avait pas de différence significative entre les scores SF-36 des 2 groupes au départ. Le changement moyen du score pour la CP a été de 10,4 c. 11,4 (p = 0,61) dans les groupes soumis à la décompression et à la DA, respectivement. Soixante-sept pour cent des patients du groupe soumis à la décompression et 71 % du groupe soumis à la DA ont obtenu une DMCI, tandis que 64 % des 2 groupes ont obtenu un BCS. On n'a noté aucune différence significative entre les groupes soumis à la décompression et à la DA pour ce qui est du changement du score pour la CP (p = 0,74) ou de la probabilité d'obtenir une DMCI (p = 0,81) ou un BCS (p = 0,85) après ajustement pour tenir compte d'autres variables. CONCLUSION: Chez certains patients souffrant de SLD, l'issue de la décompression est comparable à celle de la DA après une période minimale de 2 ans.

Selective Induction of Molecular Assembly to Tissue-Level Anisotropy on Peptide-Based Optoelectronic Cardiac Biointerfaces.

The conduction efficiency of ions in excitable tissues and of charged species in organic conjugated materials both benefit from having ordered domains and anisotropic pathways. In this study, a photocurrent-generating cardiac biointerface is presented, particularly for investigating the sensitivity of cardiomyocytes to geometrically comply to biomacromolecular cues differentially assembled on a conductive nanogrooved substrate. Through a polymeric surface-templated approach, photoconductive substrates with symmetric peptide-quaterthiophene (4T)-peptide units assembled as 1D nanostructures on nanoimprinted polyalkylthiophene (P3HT) surface are developed. The 4T-based peptides studied here can form 1D nanostructures on prepatterned polyalkylthiophene substrates, as directed by hydrogen bonding, aromatic interactions between 4T and P3HT, and physical confinement on the nanogrooves. It is observed that smaller 4T-peptide units that can achieve a higher degree of assembly order within the polymeric templates serve as a more efficient driver of cardiac cytoskeletal anisotropy than merely presenting aligned -RGD bioadhesive epitopes on a nanotopographic surface. These results unravel some insights on how cardiomyocytes perceive submicrometer dimensionality, local molecular order, and characteristics of surface cues in their immediate environment. Overall, the work offers a cardiac patterning platform that presents the possibility of a gene modification-free cardiac photostimulation approach while controlling the conduction directionality of the biotic and abiotic components.

Risk Stratification in a Tertiary Care Spine Centre: Comparison Between STarTBack and OSPRO-YF Screening Tools.

Purpose: STarT Back Screening Tool and OSPRO-YF scales have been reported to be accurate tools for estimating risk for the development of persistent pain or prolonged disability in primary care settings. We performed a comparison of construct convergent and known-group validity and ceiling floor effect (CFE) of these tools using a common sample of patients seen at a tertiary care spine centre. Methods: This was a cross-sectional study of patients with and without a work-related back injury. The Hospital Anxiety and Depression Scale (HADS) was used as the reference outcome measure for convergent validity. For known-group validity, we examined the ability of the scales to differentiate between different levels of compensation, presence of non-organic signs, and work status. The CFE values were calculated. Results: Fifty consecutive injured workers were included along with 50 patients without an active compensation claim related to their low back pain. STarTBack and OSPRO-YF had moderate to high associations with the depression component of the HADS (0.69 to 0.77 respectively) with a statistically significant difference in favour of the OSPRO-YF. STarTBack's risk stratification categories were able to differentiate patients with a compensable injury, non-organic signs, and inability to work (p values ranging from 0.002 to < 0.001). The physical activity and work fear-avoidance beliefs constructs of the OSPRO-YF consistently outperformed other yellow flag constructs (p values ranging from 0.008 to < 0.001). The psychological sub-score of STarTBack showed a ceiling effect. There was a floor effect for the negative affect domain of OSPRO-YF. Neither total score had a floor or ceiling effect. Conclusions: STarTBack and OSPRO-YF are short screening tools with acceptable convergent and known-group construct validity and no floor or ceiling effect of their total score. Both tools could assist with the identification, evaluation, and management of psychological distress in patients presenting to tertiary care spine centres.

Objectif : l'outil de dépistage STarT Back et les échelles OSPRO-YF sont considérés comme des mécanismes précis pour estimer le risque d'apparition d'une douleur persistante ou d'une invalidité prolongée en soins primaires. Les chercheurs ont comparé la validité convergente de construit, la validité des groupes connus et l'effet plafond-plancher (EPP) de ces outils auprès d'un échantillon commun de patients suivis dans un centre tertiaire du rachis. Méthodologie : étude transversale de patients atteints ou non d'une blessure dorsale liée au travail. Les chercheurs ont utilisé l'échelle HADS (anxiété et dépression à l'hôpital) comme mesure de référence des résultats pour déterminer la validité convergente. Pour ce qui est de la validité des groupes connus, ils ont examiné la capacité des échelles à distinguer les divers taux d'indemnisation, la présence de signes non organiques et la situation d'emploi et ont calculé les valeurs de l'EPP. Résultats : cinquante (50) travailleurs blessés consécutifs ont participé à l'étude, de même que 50 patients n'ayant pas de réclamation d'indemnisation active liée à leur douleur lombaire. Les outils STarTBack et OSPRO-YF étaient dotés d'associations modérées à élevées avec l'élément « depression ¼ de l'échelle HADS (0,69 à 0,77. respectivement), et la différence en faveur de l'échelle OSPRO-YF était statistiquement significative. Les catégories de stratification du risque de l'outil STarTBack pouvaient distinguer les patients atteints d'une blessure justifiant une indemnisation, les signes non organiques et l'incapacité de travailler (valeurs p de 0,002 à < 0,001). Les construits de l'activité physique et des comportements d'appréhension ou d'évitement de l'échelle OSPRO-YF étaient constamment supérieurs aux autres construits de drapeau jaune (valeurs p de 0,008 à < 0,001). Le sous-score psychologique de l'outil STarTBack avait un effet plafond, tandis que le domaine d'affect négatif de l'échelle OSPRO-YF avait un effet plancher. Aucun des scores totaux n'avait d'effet plancher ou plafond. Conclusions : STarTBack et OSPRO-YF sont de courts outils de dépistage à la validité de construit convergente et de groupes connus et dont le score total n'a ni effet plancher ni effet plafond. Les deux outils pourraient contribuer à déterminer, à évaluer et à prendre en charge la détresse psychologique chez les parents qui consultent dans un centre tertiaire du rachis.