The effect of eConsult on the provision of orthopaedic services in Nunavut.

To assess the effect of eConsultation in providing Orthopaedic Surgery specialist service to patients in Nunavut. A cross-sectional study of 161 Orthopaedic Surgery consultations received from primary care providers (PCPs) in Nunavut via the Champlain Building Access to Specialist service through eConsult (BASETM) service over the 2-year period from January 2017 to December 2018. Data captured were: reason for consultation, impact of advice on referral, perceived value to the PCPs and time spent. eConsult avoided unnecessary in-person consultation 62% of the time while catching 5% of the referrals that would have otherwise been missed. PCP referral behaviour was modified 48% of the time. 94% of eConsults were rated as valuable to PCPs in their practice and 100% of eConsults resulted in actionable advice. Further, eConsults took an average of 15.4 minutes of specialist time to complete, and the mean time from referral to response was 1.4 days. eConsultation spares unnecessary consultation to Orthopaedic Surgery, catches important referrals that would have otherwise been missed, decreases wait time, and may reduce cost in remote healthcare systems such as Nunavut.

Access to orthopedic specialist service in Ontario via eConsult.

BACKGROUND: Increasing strain on public health resources in Canada, in particular with respect to accessing specialist care, necessitates the exploration of alternative models of care. The aim of this study was to assess the efficacy of electronic consultation (eConsult) in providing orthopedic surgery specialist service to patients in the Champlain Local Health Integration Network (LHIN) of Ontario. METHODS: This was a cross-sectional review of all 564 Champlain LHIN orthopedic surgery referral requests received via the Champlain Building Access to Specialist service through the eConsult (BASE) system in 2017. Primary outcome measures were impact on primary care provider (PCP) referral pattern and time to receive orthopedic consultation. RESULTS: eConsult prevented unnecessary in-person consultation 64% of the time, while PCP referral decisions were modified 51% of the time. Of all eConsults, 94% were rated as valuable to PCPs in their practice and 97% of eConsults resulted in actionable advice. eConsults took an average of 14.5 minutes of specialist time to complete, and the mean time from referral to response was 3.7 days. CONCLUSION: The eConsult system spares unnecessary consultation to orthopedic surgery; catches important referrals that would have otherwise been missed; saves time for patients, PCPs and orthopedic surgeons; and improves efficiency in a socialized health care system.

2021 Frank Stinchfield Award: A novel cemented hip hemiarthroplasty infection model with real-time in vivo imaging in rats : an animal study.

AIMS: The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time. METHODS: Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces. RESULTS: All animals tolerated surgery well, with preservation of gait mechanics and weightbearing in control individuals. Postoperative in vivo imaging demonstrated predictable evolution of infection with logarithmic signal decay coinciding with abscess formation. Postmortem mCT qualitative volumetric analysis showed high contact area and both cement-bone and cement-implant interdigitation. FE-SEM revealed biofilm formation on the prosthetic head. CONCLUSION: This study demonstrates the utility of a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Inoculation with bioluminescent bacteria allows for non-invasive, real-time monitoring of infection. Cite this article: Bone Joint J 2021;103-B(7 Supple B):9-16.

Urinary metabolite prognostic biomarker panel for pancreatic ductal adenocarcinomas.

BACKGROUND: Patients with pancreatic ductal adenocarcinoma (PDAC) have a very low survival rate and surgical resection is the only curative intent treatment available. However, the majority of patients relapse after surgery and identification of biomarkers for accurate prognostication of PDAC patients is required. We have recently identified a six biomarker (i.e., trigonelline, glycolate, hippurate, creatine, myoinositol and hydroxyacetone) urinary metabolite panel with very high potential to diagnose PDAC (Int J Cancer 2021;148:1508-18). This study aimed to assess the prognostic ability of these previously identified diagnostic metabolites in the urine of PDAC patients. METHODS: Metabolite data from 88 PDAC patients was statistically assessed for their prognostic ability. RESULTS: A panel of three metabolites (i.e., trigonelline, hippurate and myoinositol) was able to stratify patients with good- or poor-prognosis based on overall survival. The PDAC patients with abnormal levels of 2 or more metabolites in their urine demonstrated significantly lower survival compared to patients with abnormal levels of one or less metabolites. CONCLUSION: These results demonstrate that the selected three metabolite panel could be used to stratify patients based on their prognostic outcomes and if independently validated may lead to the development of a urinary prognostic biomarker test for PDAC. GENERAL SIGNIFICANCE: This study highlights the potential of using 1H-nuclear magnetic resonance spectroscopy for the identification of novel metabolites which can prognosticate cancer patients.

A unique urinary metabolomic signature for the detection of pancreatic ductal adenocarcinoma.

Our study aimed to identify a urinary metabolite panel for the detection/diagnosis of pancreatic ductal adenocarcinoma (PDAC). PDAC continues to have poor survival outcomes. One of the major reasons for poor prognosis is the advanced stage of the disease at diagnosis. Hence, identification of a novel and cost-effective biomarker signature for early detection/diagnosis of PDAC could lead to better survival outcomes. Untargeted metabolomics was employed to identify a novel metabolite-based biomarker signature for PDAC diagnosis. Urinary metabolites from 92 PDAC patients (56 discovery cohort and 36 validation cohort) were compared with 56 healthy volunteers using 1 H nuclear magnetic resonance spectroscopy. Multivariate (partial-least squares discriminate analysis) and univariate (Mann-Whitney's U-test) analyses were performed to identify a metabolite panel which can be used to detect PDAC. The selected metabolites were further validated for their diagnostic potential using the area under the receiver operating characteristic (AUROC) curve. Statistical analysis identified a six-metabolite panel (trigonelline, glycolate, hippurate, creatine, myoinositol and hydroxyacetone), which demonstrated high potential to diagnose PDAC, with AUROC of 0.933 and 0.864 in the discovery and validation cohort, respectively. Notably, the identified panel also demonstrated very high potential to diagnose early-stage (I and II) PDAC patients with AUROC of 0.897. These results demonstrate that the selected metabolite signature could be used to detect PDAC and will pave the way for the development of a urinary test for detection/diagnosis of PDAC.

Fatal Cerebral Fat Embolism After Pelvic and Multiple Long Bone Fractures without Associated Lung Injury: A Case Report.

CASE: A 29-year-old motor vehicle collision passenger presented with fractures of the pelvic ring, bilateral femurs, and right tibia/fibula. All fractures were stabilized with external fixation and fixed definitively 48 hours later. Postoperatively, the patient suffered rapid clinical decline. Emergent head computed tomography (CT) demonstrated tonsillar herniation with loss of gray-white matter differentiation. Although respiratory status remained uncompromised throughout presentation, pathology revealed extensive cerebral fat embolism. CONCLUSION: Fat embolism can traverse the lungs without eliciting an inflammatory response, radiographic infiltrate, or impairing gas exchange. This may lead to a clinically silent, fatal cerebral fat embolism in an intubated, sedated patient.

Imaging modalities in the diagnosis of pancreatic adenocarcinoma: A systematic review and meta-analysis of sensitivity, specificity and diagnostic accuracy.

BACKGROUND: Pancreatic cancer, primarily pancreatic ductal adenocarcinoma (PDAC), accounts for 2.4% of cancer diagnoses and 5.8% of cancer death annually. Early diagnoses can improve 5-year survival in PDAC. The aim of this systematic review was to determine the sensitivity, specificity and diagnostic accuracy values for MRI, CT, PET&PET/CT, EUS and transabdominal ultrasound (TAUS) in the diagnosis of PDAC. METHODS: A systematic review was undertaken to identify studies reporting sensitivity, specificity and/or diagnostic accuracy for the diagnosis of PDAC with MRI, CT, PET, EUS or TAUS. Proportional meta-analysis was performed for each modality. RESULTS: A total of 5399 patients, 3567 with PDAC, from 52 studies were included. The sensitivity, specificity and diagnostic accuracy were 93% (95% CI=88-96), 89% (95% CI=82-94) and 90% (95% CI=86-94) for MRI; 90% (95% CI=87-93), 87% (95% CI=79-93) and 89% (95% CI=85-93) for CT; 89% (95% CI=85-93), 70% (95% CI=54-84) and 84% (95% CI=79-89) for PET; 91% (95% CI=87-94), 86% (95% CI=81-91) and 89% (95% CI=87-92) for EUS; and 88% (95% CI=86-90), 94% (95% CI=87-98) and 91% (95% C=87-93) for TAUS. CONCLUSION: This review concludes all modalities, except for PET, are equivalent within 95% confidence intervals for the diagnosis of PDAC.

Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels.

The spatial presentation of mechanical information is a key parameter for cell behavior. We have developed a method of polymerization control in which the differential diffusion distance of unreacted cross-linker and monomer into a prepolymerized hydrogel sink results in a tunable stiffness gradient at the cell-matrix interface. This simple, low-cost, robust method was used to produce polyacrylamide hydrogels with stiffness gradients of 0.5, 1.7, 2.9, 4.5, 6.8, and 8.2 kPa/mm, spanning the in vivo physiological and pathological mechanical landscape. Importantly, three of these gradients were found to be nondurotactic for human adipose-derived stem cells (hASCs), allowing the presentation of a continuous range of stiffnesses in a single well without the confounding effect of differential cell migration. Using these nondurotactic gradient gels, stiffness-dependent hASC morphology, migration, and differentiation were studied. Finally, the mechanosensitive proteins YAP, Lamin A/C, Lamin B, MRTF-A, and MRTF-B were analyzed on these gradients, providing higher-resolution data on stiffness-dependent expression and localization.

Limitations in predicting outcome following primary ACL reconstruction with single-bundle hamstring autograft - A systematic review.

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) is one of the most well studied and performed procedures in the world. Thus, it would be useful to develop a tool to predict patient outcomes post-operatively to allow clinicians to optimise management. PURPOSE: To identify and summarise factors predictive of graft failure and patient-reported outcome (PROM) measures at minimum two years after ACLR with single-bundle quadruple hamstring autograft via the anteromedial portal technique. METHODS: Studies reporting IKDC, KOOS, Lysholm and graft failure in ACLR were systematically reviewed. A methodological score was applied to these studies, with those above the mean analysed further. Only those reporting primary predictors of patient outcomes following ACLR were included. RESULTS: Twenty-six studies satisfied our inclusion criteria. Fourteen scored above the mean 20 Downs and Black score (18.4) and were considered higher level evidence. The higher quality papers reported that younger age, female sex, higher BMI, smoking history and activity levels predicted poorer outcomes. High-grade tears of the menisci or full-thickness cartilage defects were identified as predictors of poorer PROMs. None of the factors investigated by more than a single paper were unanimously significant in predicting the outcome of ACLR. CONCLUSIONS: The evidence surrounding predictors of outcome was inconsistent in design, methodology and reporting of results, hindering our ability to draw conclusions regarding the validity of the reported relationships. However, this systematic review identified several patient demographics, concomitant injuries, and surgical factors that could be investigated further in future prospective studies to create a definitive predictive model.

The extracellular microscape governs mesenchymal stem cell fate.

Each cell forever interacts with its extracellular matrix (ECM); a stem cell relies on this interaction to guide differentiation. The stiffness, nanotopography, protein composition, stress and strain inherent to any given ECM influences stem cell lineage commitment. This interaction is dynamic, multidimensional and reciprocally evolving through time, and from this concerted exchange the macroscopic tissues that comprise living organisms are formed. Mesenchymal stem cells can give rise to bone, cartilage, tendon and muscle; thus attempts to manipulate their differentiation must heed the physical properties of incredibly complex native microenvironments to realize regenerative goals.

Resection of colorectal liver metastases and extra-hepatic disease: a systematic review and proportional meta-analysis of survival outcomes.

BACKGROUND: Colorectal cancer (CRC) accounts for 9.7% of all cancers with 1.4 million new cases diagnosed each year. 19-31% of CRC patients develop colorectal liver metastases (CRLM), and 23-38% develop extra-hepatic disease (EHD). The aim of this systematic review was to determine overall survival (OS) in patients resected for CRLM and known EHD. METHODS: A systematic review was undertaken to identify studies reporting OS after resection for CRLM in the presence of EHD. Proportional meta-analyses and relative risk of death before five years were assessed between patient groups. RESULTS: A total of 15,144 patients with CRLM (2308 with EHD) from 52 studies were included. Three and 5-year OS were 58% and 26% for lung, 37% and 17% for peritoneum, and 35% and 15% for lymph nodes, respectively. The combined relative risk of death by five years was 1.49 (95% CI = 1.34-1.66) for lung, 1.59 (95% CI = 1.16-2.17) for peritoneal and 1.70 (95% CI = 1.57-1.84) for lymph node EHD, in favour of resection in the absence of EHD. CONCLUSION: This review supports attempts at R0 resection in selected patients and rejects the notion that EHD is an absolute contraindication to resection.