A pilot prospective cohort study using experimental quantification of early peripheral nerve regeneration with high-frequency three-dimensional tomographic ultrasound (HFtUS).

Quantification of peripheral nerve regeneration after injury relies upon subjective outcome measures or electrophysiology assessments requiring fully regenerated neurons. Nerve surgeons and researchers lack objective, quantifiable information on the site of surgical repair and regenerative front. To address this need, we developed a quantifiable, visual, clinically available measure of early peripheral nerve regeneration using high-frequency, three-dimensional, tomographic ultrasound (HFtUS). We conducted a prospective, longitudinal study of adult patients with ulnar and/or median nerve injury of the arm undergoing direct epineurial repair within 5 days of injury. Assessment of morphology, volumetric and 3D grey-scale quantification of cross-sectional views were made at baseline up to 15 months post-surgery. Sensory and motor clinical outcome measures and patient reported outcome measures (PROMs) were recorded. Five participants were recruited to the study. Our data demonstrated grey-scale values (an indication of axonal density) increased in distal stumps within 2-4 months after repair, returning to normal as regeneration completed (4-6 months) with concomitant reduction in intraneural volume as surgical oedema resolved. Two patients with abnormal regeneration were characterized by increased intraneural volume and minimal grey-scale change. HFtUS may quantify early peripheral nerve regeneration offering a window of opportunity for surgical intervention where early abnormal regeneration is detected.

The incidence and management of peripheral nerve injury in England (2005-2020).

Peripheral nerve injury (PNI) is a significant health problem that confers lifelong impact on those injured. Current interventions are purely surgical; however, outcomes remain poor. There is a lack of high-quality epidemiological data that is needed to identify populations involved, current healthcare demands, and ensure resources are distributed to the greatest effect, to reduce the injury burden. METHODS: Anonymized hospital episode statistical (HES) data on admitted patient care was obtained from NHS Digital for all National Health Service (NHS) patients sustaining PNI of all body regions between 2005 and 2020. Total numbers of finished consultant episodes (FCEs) or FCEs/100,000 population were used to demonstrate changes in demographic variables, anatomical locations of injury, mechanisms of injury, speciality, and main operation. RESULTS: There was a mean national incidence of 11.2 (95% CI 10.9, 11.6) events per 100,000 population per year. Males were at least twice as likely (p < 0.0001) to sustain a PNI. Upper limb nerves at or distal to the wrist were most commonly injured. Knife injuries increased (p < 0.0001), whereas glass injuries decreased (p < 0.0001). Plastic surgeons increasingly managed PNI (p = 0.002) as opposed to orthopaedic surgeons (p = 0.006) or neurosurgeons (p = 0.001). There was an increase in neurosynthesis (p = 0.022) and graft procedures (p < 0.0001) during the study period. DISCUSSION: PNI is a significant national healthcare problem predominantly affecting distal, upper limb nerves of men of working age. Injury prevention strategies, improved targeted funding and rehabilitation pathways are needed to reduce the injury burden and improve patient care.

Clinical consensus statement: Establishing the roles of locoregional and systemic therapies for the treatment of intermediate-stage hepatocellular carcinoma in Canada.

BACKGROUND: Hepatocellular carcinoma (HCC) a leading cause of cancer mortality worldwide and approximately one-third of patients present with intermediate-stage disease. The treatment landscape of intermediate-stage HCC is rapidly evolving due to developments in local, locoregional and systemic therapies. Treatment recommendations focused on this heterogenous disease stage and that take into account the Canadian reality are lacking. To address this gap, a pan-Canadian group of experts in hepatology, transplant, surgery, radiation therapy, nuclear medicine, interventional radiology, and medical oncology came together to develop consensus recommendations on management of intermediate-stage HCC relevant to the Canadian context. METHODS: A modified Delphi framework was used to develop consensus statements with strengths of recommendation and supporting levels of evidence graded using the AHA/ACC classification system. Tentative consensus statements were drafted based on a systematic search and expert input in a series of iterative feedback cycles and were then circulated via online survey to assess the level of agreement. RESULTS & CONCLUSION: The pre-defined ratification threshold of 80 % agreement was reached for all statements in the areas of multidisciplinary treatment (n = 4), intra-arterial therapy (n = 14), biologics (n = 5), radiation therapy (n = 3), surgical resection and transplantation (n = 7), and percutaneous ablative therapy (n = 4). These generally reflected an expansion in treatment options due to developments in previously established or emergent techniques, introduction of new and more active therapies and increased therapeutic flexibility. These developments have allowed for greater treatment tailoring and personalization as well as a paradigm shift toward strategies with curative intent in a wider range of disease settings.

Explaining With Examples: Lessons Learned From Crowdsourced Introductory Description of Information Visualizations.

Data visualizations have been increasingly used in oral presentations to communicate data patterns to the general public. Clear verbal introductions of visualizations to explain how to interpret the visually encoded information are essential to convey the takeaways and avoid misunderstandings. We contribute a series of studies to investigate how to effectively introduce visualizations to the audience with varying degrees of visualization literacy. We begin with understanding how people are introducing visualizations. We crowdsource 110 introductions of visualizations and categorize them based on their content and structures. From these crowdsourced introductions, we identify different introduction strategies and generate a set of introductions for evaluation. We conduct experiments to systematically compare the effectiveness of different introduction strategies across four visualizations with 1,080 participants. We find that introductions explaining visual encodings with concrete examples are the most effective. Our study provides both qualitative and quantitative insights into how to construct effective verbal introductions of visualizations in presentations, inspiring further research in data storytelling.

Looking Into the Future: The Current and Future State of IR in Canada.

This review explores the priorities and future opportunities of interventional radiology in Canada.

CohortVA: A Visual Analytic System for Interactive Exploration of Cohorts based on Historical Data.

In history research, cohort analysis seeks to identify social structures and figure mobilities by studying the group-based behavior of historical figures. Prior works mainly employ automatic data mining approaches, lacking effective visual explanation. In this paper, we present CohortVA, an interactive visual analytic approach that enables historians to incorporate expertise and insight into the iterative exploration process. The kernel of CohortVA is a novel identification model that generates candidate cohorts and constructs cohort features by means of pre-built knowledge graphs constructed from large-scale history databases. We propose a set of coordinated views to illustrate identified cohorts and features coupled with historical events and figure profiles. Two case studies and interviews with historians demonstrate that CohortVA can greatly enhance the capabilities of cohort identifications, figure authentications, and hypothesis generation.

DPVisCreator: Incorporating Pattern Constraints to Privacy-preserving Visualizations via Differential Privacy.

Data privacy is an essential issue in publishing data visualizations. However, it is challenging to represent multiple data patterns in privacy-preserving visualizations. The prior approaches target specific chart types or perform an anonymization model uniformly without considering the importance of data patterns in visualizations. In this paper, we propose a visual analytics approach that facilitates data custodians to generate multiple private charts while maintaining user-preferred patterns. To this end, we introduce pattern constraints to model users' preferences over data patterns in the dataset and incorporate them into the proposed Bayesian network-based Differential Privacy (DP) model PriVis. A prototype system, DPVisCreator, is developed to assist data custodians in implementing our approach. The effectiveness of our approach is demonstrated with quantitative evaluation of pattern utility under the different levels of privacy protection, case studies, and semi-structured expert interviews.

Simultaneous versus rapid serial interventions in a hybrid operating suite for severely injured patients: a prospective evaluation of differences in RAPTOR techniques and outcomes.

BACKGROUND: Open surgical and percutaneous endovascular procedures aimed at arresting traumatic life-threatening hemorrhage are usually performed in rapid serial fashion by surgeons and interventional radiologists; truly simultaneous procedures require modifications in technique, workflow and team collaboration. The primary objective of this study was to prospectively audit outcomes in patients with ongoing hemorrhage who underwent truly simultaneous open and percutaneous procedures. METHODS: We prospectively evaluated the cases of all severely injured patients who required an open and percutaneous procedure within the hybrid RAPTOR (resuscitation with angiography, percutaneous techniques and operative repair) suite at the Foothills Medical Centre, Calgary, Alberta, Canada, between Apr. 4, 2013, and Dec. 5, 2019. We compared outcomes between the truly simultaneous and rapid serial cases. RESULTS: Thirty-five patients (31 [89%] male, median age 46 yr, median Injury Severity Score 30, blunt mechanism in 26 cases [74%]) underwent a hybrid intervention in the RAPTOR suite to stop ongoing hemorrhage during the study period. Twenty-three patients (66%) had a rapid serial procedure, and 12 (34%) had a truly simultaneous procedure. Demographic characteristics were similar between the 2 groups. Compared to the rapid serial group, a higher proportion of patients in the truly simultaneous group were hemodynamically unstable (11 [92%] v. 13 [56%], p = 0.03) and required damage-control procedures (10 [83%] v. 12 [52%], p = 0.03). The time from hospital arrival to procedure initiation was shorter for the truly simultaneous group (mean 31 min v. 59 min, p = 0.02), and a lower proportion had initial radiologic studies (3 [25%] v. 16 [70%], p = 0.01). The median hospital length of stay, intensive care unit stay and mortality rate were similar between the 2 groups. CONCLUSION: Truly simultaneous open and percutaneous procedures to stop ongoing hemorrhage were unique in both patient and procedural details. For the most severely injured patients, the provision of truly simultaneous modalities is necessary to achieve clinical outcomes equivalent to those of less ill patients.

Iatrogenic Arteriovenous Fistula: A Rare Complication of Pacemaker Implantation.

Severe vascular complications associated with pacemaker implantation are rare. Typically, they are overt, and require immediate resolution. We present 2 patients with insidious presentation of arteriovenous fistulae due to pacemaker implantation that were recognized early post-implantation. Both were repaired endovascularly and had good outcomes post-repair. (Level of Difficulty: Intermediate.).

Renal hemofiltration prevents metabolic acidosis and reduces inflammation during normothermic machine perfusion of the vascularized composite allograft: A preclinical study.

INTRODUCTION: Recent experimental evidence suggests normothermic machine perfusion of the vascularized composite allograft results in improved preservation compared to static cold storage, with less reperfusion injury in the immediate post-operative period. However, metabolic acidosis is a common feature of vascularized composite allograft perfusion, primarily due to the inability to process metabolic by-products. We evaluated the impact of combined limb-kidney perfusion on markers of metabolic acidosis and inflammation in a porcine model. METHODS: Ten paired pig forelimbs were used for this study, grouped as either limb-only (LO, n = 5) perfusion, or limb-kidney (LK, n = 5) perfusion. Infrared thermal imaging was used to determine homogeneity of perfusion. Lactate, bicarbonate, base, pH, and electrolytes, along with an inflammatory profile generated via the quantification of cytokines and cell-free DNA in the perfusate were recorded. RESULTS: The addition of a kidney to a limb perfusion circuit resulted in the rapid stabilization of lactate, bicarbonate, base, and pH. Conversely, the LO circuit became progressively acidotic, correlating in a significant increase in pro-inflammatory cytokines. Global perfusion across the limb was more homogenous with LK compared to LO. CONCLUSION: The addition of a kidney during limb perfusion results in significant improvements in perfusate biochemistry, with no evidence of metabolic acidosis.

A new proposal for secondary surveillance following potentially curative therapy of HCC: alternating MRI and CEUS.

PURPOSE: A high recurrence rate following ablative therapy of hepatocellular carcinoma (HCC) necessitates routine follow-up imaging (secondary surveillance) to facilitate early re-treatment. We evaluate our unique secondary surveillance algorithm (with use of alternating MRI and CEUS) by assessment of the relative diagnostic accuracy of MRI and CEUS in detection of residual/recurrent tumor. Potential benefits of alternating surveillance are compared to the use of MRI alone. MATERIALS AND METHODS: This prospective observational IRB approved study included 231 patients with 354 treated tumors between January 2017 and June 2020. Treated lesions underwent secondary surveillance for a minimum of 7 months and up to 3 years, median follow-up 14 months. Secondary surveillance involved MRI performed at 1 month after treatment, followed by CEUS and MRI at alternate 3-month intervals (i.e., CEUS at month 4, MRI at month 7, etc.), for a total of 2 years. An equivocal finding on one imaging modality triggered expeditious evaluation with the alternate modality. Arterial phase hyperenhancement and washout comprise the classic features of recurrent tumor on both modalities. RESULTS: A total of 746 MRI and 712 CEUS examinations were performed, and a total of 184 tumor recurrences detected, MRI (n = 82) and CEUS (n = 102) (p = 0.19). There was no difference in the sensitivity (71.0-85.0% and 80.9-92.0%), specificity (97.4-99.2% and 98.5-99.9%), and area under the ROC curve (0.85-0.92 and 0.91-0.96) between MRI and CEUS, respectively. 23 of 82 recurrent tumors identified on MRI were equivocal and confirmed with expedited CEUS. 9 equivocal cases on MRI were disproved by expedited CEUS. On CEUS, 1 of the 102 recurrent tumors was equivocal and confirmed on MRI, and 2 equivocal CEUS cases were disproved by MRI. CONCLUSION: MRI and CEUS performed similarly in our secondary surveillance algorithm for HCC in their ability to detect tumor recurrence, and showed no significant difference in their relative diagnostic test accuracy measures. Of greater interest, equivocal results on MRI (typically due to difficulty in distinguishing tumor recurrence from post-treatment change/shunting) were either confirmed or disproven by CEUS in all cases. Secondary surveillance of treated HCC with alternating MRI and CEUS shows equivalent performance of each modality. CEUS resolves equivocal MRI and optimally demonstrates APHE and washout in tumor recurrence.

Arginase Signalling as a Key Player in Chronic Wound Pathophysiology and Healing.

Arginase (ARG) represents an important evolutionarily conserved enzyme that is expressed by multiple cell types in the skin. Arg acts as the mediator of the last step of the urea cycle, thus providing protection against excessive ammonia under homeostatic conditions through the production of L-ornithine and urea. L-ornithine represents the intersection point between the ARG-dependent pathways and the urea cycle, therefore contributing to cell detoxification, proliferation and collagen production. The ARG pathways help balance pro- and anti-inflammatory responses in the context of wound healing. However, local and systemic dysfunctionalities of the ARG pathways have been shown to contribute to the hindrance of the healing process and the occurrence of chronic wounds. This review discusses the functions of ARG in macrophages and fibroblasts while detailing the deleterious implications of a malfunctioning ARG enzyme in chronic skin conditions such as leg ulcers. The review also highlights how ARG links with the microbiota and how this impacts on infected chronic wounds. Lastly, the review depicts chronic wound treatments targeting the ARG pathway, alongside future diagnosis and treatment perspectives.

A Quantitative Systematic Review of Clinical Outcome Measure Use in Peripheral Nerve Injury of the Upper Limb.

BACKGROUND: Peripheral nerve injury (PNI) is common, leading to reduced function, pain, and psychological impact. Treatment has not progressed partly due to inability to compare outcomes between centers managing PNI. Numerous outcome measures exist but there is no consensus on which outcome measures to use nor when. OBJECTIVE: To perform a systematic review in order to describe and classify outcome measures used in PNI. METHODS: A search of Ovid Medline, Ovid Embase, Allied and Complementary Medicine Database (AMED), and CENTRAL (Cochrane Clinical Trials) was conducted. Randomized control trials (RCTs), cohort studies, and case-controlled and case series (≥5 participants) published from inception of the database until 2019 investigating adult patients with a traumatic upper limb PNI in which an outcome measurement was utilized were included. RESULTS: A total of 96 studies were included (15 RCTs, 8 case-control studies, 18 cohort studies, 5 observational studies, and the remainder were case series or retrospective reviews). A total of 56 individual outcome measures were identified, utilized across 28 different countries and 7097 patients. Ten core domains were defined: sensory subjective, sensory objective, motor subjective, motor objective, sensorimotor function, psychology and well-being, disability, quality of life, pain and discomfort, and neurotrophic measures. CONCLUSION: Lack of consensus on outcome measure use hinders comparison of outcomes between nerve injury centers and the development of novel treatments. Development of a core outcome set will help standardize outcome reporting, improve translation of novel treatments from lab to clinical practice, and ensure future research in PNI is more amenable to systematic review and meta-analysis.

Engineering a cell-hydrogel-fibre composite to mimic the structure and function of the tendon synovial sheath.

The repair of tendon injuries is often compromised by post-operative peritendinous adhesions. Placing a physical barrier at the interface between the tendon and the surrounding tissue could potentially solve this problem by reducing adhesion formation. At present, no such system is available for routine use in clinical practice. Here, we propose the development of a bilayer membrane combining a nanofibrous poly(ε-caprolactone) (PCL) electrospun mesh with a layer of self-assembling peptide hydrogel (SAPH) laden with type-B synoviocytes. This bilayer membrane would act as an anti-adhesion system capable of restoring tendon lubrication, while assisting with synovial sheath regeneration. The PCL mesh showed adequate mechanical properties (Young's modulus=19±4 MPa, ultimate tensile stress=9.6±1.7 MPa, failure load=0.5±0.1 N), indicating that the membrane is easy to handle and capable to withstand the frictional forces generated on the tendon's surface during movement (~0.3 N). Morphological analysis confirmed the generation of a mesh with nanosized PCL fibres and small pores (< 3 µm), which prevented fibroblast infiltration to impede extrinsic healing but still allowing diffusion of nutrients and waste. Rheological tests showed that incorporation of SAPH layer allows good lubrication properties when the membrane is articulated against porcine tendon or hypodermis, suggesting that restoration of tendon gliding is possible upon implantation. Moreover, viability and metabolic activity tests indicated that the SAPH was conducive to rabbit synoviocyte growth and proliferation over 28 days of 3D culture, sustaining cell production of specific matrix components, particularly hyaluronic acid. Synoviocyte-laden peptide hydrogel promoted a sustained endogenous production of hyaluronic acid, providing an anti-friction layer that potentially restores the tendon gliding environment.

Aberrant Differentiation of Human Pluripotent Stem Cell-Derived Kidney Precursor Cells inside Mouse Vascularized Bioreactors.

BACKGROUND: Numerous studies have documented the in vitro differentiation of human pluripotent stem cells (hPSCs) into kidney cells. Fewer studies have followed the fates of such kidney precursor cells (KPCs) inside animals, a more life-like setting. Here, we tested the hypothesis that implanting hPSC-derived KPCs into an in vivo milieu surgically engineered to be highly vascular would enhance their maturation into kidney tissues. METHODS: 3D printed chambers containing KPCs were implanted into the thighs of adult immunodeficient mice. In some chambers, an arterial and venous flow-through (AVFT) was surgically fashioned. After 3 weeks and 3 months, implants were studied by histology, using qualitative and quantitative methods. RESULTS: After 3 weeks, chambers containing AVFTs were richer in small vessels than contralateral chambers without AVFTs. Glomeruli with capillary loops and diverse types of tubules were detected in all chambers. At 3 months, chambers contained only rudimentary tubules and glomeruli that appeared avascular. In chambers with AVFTs, prominent areas of muscle-like cells were also detected near tubules and the abnormal tissues immunostained for transforming growth factor ß1. These features have similarities to renal dysplasia, a typical histological signature of human congenital kidney malformations. CONCLUSIONS: This study urges a note of caution regarding the in vivo fates of hPSC-derived kidney precursors, with pathological differentiation appearing to follow a period of increased vascularity.