Yarning to reduce take own leave events in First Nations patients presenting to the Emergency Department-presenting the qualitative themes and co-design of the Deadly RED project.

ISSUE ADDRESSED: The Deadly RED redesign and implementation research aimed to improve take own leave (TOL) rates within a Queensland emergency department by providing a culturally competent care pathway. METHODOLOGY: A mixed methods pre/post evaluation of the feasibility, acceptability and usability of the Deadly RED pathway for First Nations patients presenting to ED was performed. This pathway combined early welcome and information sharing, introduction of screening and follow up for patients who TOL and enhanced access to alternative community healthcare. Yarning circles facilitated co-design of research protocols and tools while a purposefully designed research Yarn enhanced understanding of the 'story' of the people. Qualitative analysis of Yarns allowed deductive themes to be extracted. A Participatory Action Research (PAR) approach and Indigenous research methodology involving First Nations people in design, knowledge sharing and joint ownership of results was used. RESULTS: Common themes from the 85 yarns included the negative impact of long waiting times and positive impact from wholistic care. Unique themes identified included interpretation of waiting room placement and paracetamol prescription as a dismissal. Knowledge dissemination from yarning drove improvements in communications and processes to promote treatment completion resulting in elimination of these themes in post implementation yarns. Eighteen patients who had TOL were included in the post implementation yarns, however only eight of these believed that their treatment was incomplete. CONCLUSION: The use of yarning for consumer engagement has allowed deeper understanding of the reasons for TOL in First Nations emergency patients. The reciprocal knowledge sharing has guided targeted improvements in wholistic emergency care and communication resulting in First Nations patients feeling their care is complete even when the 'number' reports otherwise. SO WHAT?: Indigenous Research methodology including yarning with First Nations patients suggests alternative engagement methods to guide enhanced quality of care monitoring for ED presentations.

Evaluating patients presenting to the emergency department after syncope: validation of the Canadian Syncope Risk Score.

BACKGROUND: Syncope is a common problem but can have any of a broad range of underlying causes. Initial evaluation of the patient in the emergency department often does not identify a specific cause, and the cornerstone of management is reliable risk stratification with clinical decision rules. OBJECTIVES: The primary objective is to validate the utility and safety of the Canadian Syncope Risk Score (CSRS) as a clinical decision rule when assessing patients who present with syncope to Australian emergency departments. Our secondary objective is to evaluate the economic benefits of diverting patients with syncope at low risk of serious adverse events from admission to hospital. METHODS AND ANALYSIS: Prospective, observational study. Patients aged 18 years or more who present to the emergency department (ED) after syncope in the preceding 24 hours and have returned to their baseline state will be enrolled. Patients will be contacted by telephone to determine whether they have experienced any adverse events within 30 days of their initial presentation to the ED. The CSRS will be applied retrospectively to determine the relationship between whether patients were admitted to hospital or discharged home and the reporting of serious adverse events for each CSRS risk level. We will also undertake a cost-effectiveness analysis from the health care perspective. ETHICS APPROVAL: Prince Charles Hospital Human Research Ethics Committee (reference, HREC/17/QPCH/48). DISSEMINATION OF RESULTS: Outcomes will be disseminated by Queensland Health and the funding body via social media, presented at local and national emergency medicine conferences, and published in international emergency medicine and health economics journals. CLINICAL TRIALS REGISTRATION: Not applicable.

Endoscopic-Assisted Radial Forearm Free Flap Harvest: A Novel Technique to Reduce Donor Site Morbidity.

BACKGROUND: The radial forearm free flap (RFFF) remains a workhorse flap but can have significant donor site morbidity. The authors developed a novel technique for endoscopic-assisted RFFF (ERFFF) harvest and hypothesized improved donor site morbidity. METHODS: A retrospective cohort study was conducted evaluating patients who underwent ERFFF or RFFF by a single surgeon for head and neck reconstruction between November 2011 and July 2016; outcomes and complications were compared. A telephone survey was conducted to assess patient satisfaction with donor site appearance and function. RESULTS: Twenty-seven ERFFF and 13 RFFF harvests were performed. The cephalic vein was less commonly incorporated in ERFFF patients compared with RFFF patients (3.70 and 38.46%, respectively, p = 0.0095). ERFFF patients had lower rates of wound healing complications (0% vs. 15.38%, p = 0.10) and perfusion-related complications than RFFF patients (3.70% vs. 23.08%, p = 0.092). Fewer ERFFF patients reported a desire for a more normal appearance (42.86% vs. 71.43%, p = 0.361). The ERFFF group had a higher functional score (64.29% vs. 44.44%, p = 0.101), reporting lower rates of associated discomfort (35.71% vs. 85.71%, p = 0.063). None of the differences in rates of complications or patient-reported outcomes between the groups reached statistical significance. CONCLUSION: ERFFF is safe and effective alternative to RFFF, with similar operative time, similar pedicle safety, and elimination of the lengthy forearm incision. Unnecessary cephalic vein dissection can be avoided with endoscopic visualization of the venae comitantes. Further research with a larger sample size and better standardization is needed to assess effects on donor-site morbidity.

Applying the Keystone Design Perforator Island Flap Concept in a Variety of Anatomic Locations: A Review of 60 Consecutive Cases by a Single Surgeon.

BACKGROUND: The keystone design perforator island flap has been gaining popularity for reconstruction of cutaneous defects. Published experience of this technique in North America is limited predominantly to the trunk and extremities; our study aims to demonstrate expanding applications. METHODS: Retrospective chart review was conducted on all patients who underwent keystone flap reconstruction by a single surgeon. Outcomes of interest were wound healing complications (WHC) and surgical site infections (SSI). Mean follow up time was 24.4 months. RESULTS: Sixty consecutive flaps were performed with an overall WHC rate of 26.7% and SSI rate of 11.7%. Reconstructed sites included 25 lower extremity, 20 trunk, 5 upper extremity, and 10 head and neck. Flap size averaged 405.6 cm (range 16-2303). Wound healing complications were associated with coronary artery disease (P = 0.04) and traumatic defects (P = 0.043). Surgical site infections were associated with coronary artery disease (P = 0.02) and flap size of 251 to 500 cm (P = 0.039), although this association was not seen among flaps greater than 500 cm. Although more common in lower extremity reconstructions, no statistically significant associations between flap location and WHC (P = 0.055) or SSI (P = 0.29) were identified. There were no reconstructive failures and no patients required reoperation. CONCLUSIONS: This series demonstrates the versatility of the keystone flap in a wide variety of anatomic locations, with similar complication rates to those previously reported and no reoperations. Flap design was frequently modified based on the anatomical topography and adjacent subunits. To our knowledge, this is the largest and most diverse North American series of keystone flap reconstructions to date.

Novel Technique for Treatment of Calcaneal Tuberosity Fractures.

Calcaneal tuberosity fractures comprise only 1% to 2% of all calcaneal fractures. Treatment of these injuries has traditionally included open reduction and internal fixation with various means including lag screws, suture anchors, and K-wires. This article reports on a series of cases treated with excision of the tuberosity fragment with repair of the Achilles tendon supplemented by a flexor hallucis longus tendon transfer.

Th2 differentiation is necessary for soft tissue fibrosis and lymphatic dysfunction resulting from lymphedema.

Lymphedema is a dreaded complication of cancer treatment. However, despite the fact that >5 million Americans are affected by this disorder, the development of effective treatments is limited by the fact that the pathology of lymphedema remains unknown. The purpose of these studies was to determine the role of inflammatory responses in lymphedema pathology. Using mouse models of lymphedema, as well as clinical lymphedema specimens, we show that lymphatic stasis results in a CD4 T-cell inflammation and T-helper 2 (Th2) differentiation. Using mice deficient in T cells or CD4 cells, we show that this inflammatory response is necessary for the pathological changes of lymphedema, including fibrosis, adipose deposition, and lymphatic dysfunction. Further, we show that inhibition of Th2 differentiation using interleukin-4 (IL-4) or IL-13 blockade prevents initiation and progression of lymphedema by decreasing tissue fibrosis and significantly improving lymphatic function, independent of lymphangiogenic growth factors. We show that CD4 inflammation is a critical regulator of tissue fibrosis and lymphatic dysfunction in lymphedema and that inhibition of Th2 differentiation markedly improves lymphatic function independent of lymphangiogenic cytokine expression. Notably, preventing and/or reversing the development of pathological tissue changes that occur in lymphedema may be a viable treatment strategy for this disorder.

Evaluation of a pathway to address take own leave events for First Nations peoples presenting for emergency care: The Deadly RED project.

OBJECTIVE: The 'Deadly RED' project primarily aimed to improve culturally competent care to reduce the number of First Nations patients presenting to a Queensland ED who 'Take own leave' (TOL). The secondary aim was to evaluate the implementation project. METHODS: A pre/post-test quasi experimental study design using mixed methods was co-designed with adherence to Indigenous research considerations. Quantitative analysis of First Nations presentations before and after Deadly RED implementation was performed using SPSS. Qualitative analysis of transcribed research yarns in NVIVO was coded and themed for analysis. Staff experiences and perspectives were collated using electronically distributed surveys and process audits were performed. RESULTS: A total of 1096 First Nations presentations June to August 2021 and 1167 in the matched 2022 post-implementation period were analysed. Significantly more patients were recorded as TOL post-implementation (13.0% pre vs 21.3% post) and representations rates were unchanged. Forty-six staff surveyed identified improvements in all parameters including cultural appropriateness and quality of care. Qualitative analysis of 85 research yarns revealed themes migrated to increasingly acceptable, accessible, and usable care. Notably, 45% of the First Nation's patients recorded as TOL self-reported that their treatment was complete. The study was feasible as 80% of packs distributed and 73% follow-up screening after TOL. CONCLUSIONS: The Deadly RED evaluation revealed significant discrepancies in the reported data points of TOL and the 'story' of the First Nations persons experience of appropriate and completed care. Staff awareness and cultural capability improved significantly, and yarning allowed knowledge translation and improvements in communication which contributed to a better healthcare experience for First Nations patients attending our ED.

Clinical guideline on the third generation minimally invasive surgery for hallux valgus.

Minimally invasive surgery for hallux valgus correction, has been attracting great interests in the recent decades, due to the potential benefits of less pain, decreased recovery times, smaller scars with better cosmesis, and improved early post-operative range of motion. The most recent developments in minimally invasive surgery have evolved into the third generation with modifications of the chevron-type osteotomy. This evidence-based clinical guideline of the third generation minimally invasive surgery for hallux valgus is initiated and developed collectively by the Foot and Ankle Committee of Orthopedic Branch of Chinese Medical Doctor Association, Foot and Ankle Committee of Sports Medicine Branch of Chinese Medical Doctor Association, and Foot and Ankle Expert Committee of Orthopedic Branch of the Chinese Association of the Integrative Medicine. This clinical guideline provides recommendations for indications, contraindications, operative planning and techniques, post-operative management, management of complications, and prognosis of the third generation minimally invasive surgery for hallux valgus. The Translational Potential of this Article This comprehensive guideline aims to establish standardized recommendations for the indications, contraindications, operative techniques, and post-operative management of the third generation minimally invasive surgery for hallux valgus. By adhering to this guideline, the success rate of the procedure could be maximized. This comprehensive guideline serves as a valuable reference for practitioners interested in or preparing to perform minimally invasive surgery for hallux valgus.

HIF-1α coordinates lymphangiogenesis during wound healing and in response to inflammation.

This study aimed to investigate the mechanisms that coordinate lymphangiogenesis. Using mouse models of lymphatic regeneration and inflammatory lymphangiogenesis, we explored the hypothesis that hypoxia inducible factor-α (HIF-1α) is a central regulator of lymphangiogenesis. We show that HIF-1α inhibition by small molecule inhibitors (YC-1 and 2-methyoxyestradiol) results in delayed lymphatic repair, decreased local vascular endothelial growth factor-C (VEGF-C) expression, reduced numbers of VEGF-C(+) cells, and reductions in inflammatory lymphangiogenesis. Using transgenic HIF-1α/luciferase mice to image HIF-1α expression in real time in addition to Western blot analysis and pimonidazole staining for cellular hypoxia, we demonstrate that hypoxia stabilizes HIF-1α during initial stages of wound repair (1-2 wk); whereas inflammation secondary to gradients of lymphatic fluid stasis stabilizes HIF-1α thereafter (3-6 wk). In addition, we show that CD4(+) cell-mediated inflammation is necessary for this response and regulates HIF-1α expression by macrophages, as CD4-deficient or CD4-depleted mice demonstrate 2-fold reductions in HIF-1α expression as compared to wild-types. In summary, we show that HIF-1α is a critical coordinator of lymphangiogenesis by regulating the expression of lymphangiogenic cytokines as part of an early response mechanism to hypoxia, inflammation, and lymphatic fluid stasis.

Orthognathic Surgery to Enhance the Smile.

An esthetic smile is an integral feature of beauty. Improvement of the smile can be achieved by a combination of orthognathic surgery, orthodontics, and cosmetic dentistry. Preoperative evaluation serves to address a patient's surgical goals; it allows a surgeon to perform a detailed facial analysis and identify patients who are contraindicated for surgery. LeFort I and bilateral sagittal split osteotomy are performed to minimize the risk of complications. Injuries to the inferior alveolar nerve are the most common complication after orthognathic surgery, in which 90% of patients experience transient sensory disturbance of the lower lip in the postoperative period.

Economic evaluation of applying the Canadian Syncope Risk Score in an Australian emergency department.

OBJECTIVE: To evaluate the Canadian Syncope Risk Score (CSRS) in syncope patients presenting to the ED from an economic perspective, using very-low and low-risk patients (CSRS -3 to 0) as a threshold for avoiding hospital admissions. METHODS: A decision-analytic model, specifically a decision-tree, was developed to evaluate application of the CSRS. A hypothetical cohort of 1000 patients was modelled based on characteristics and outcome of patients enrolled in a clinical validation study performed alongside this evaluation. Several analytic based approaches were used to handle model outputs and uncertainties. RESULTS: For a cohort of 1000 patients, applying the CSRS was associated with 169 less inpatient admissions from the ED, when compared to usual care. There was also a cost-saving of $8255 per admitted patient, when the CSRS was applied, compared to usual care. Adopting the CSRS was the optimal approach in all scenario analyses and was robust to changes in model parameters. More than three-quarters (78.6%) of all model simulations showed that applying the CSRS is a cost-saving approach to managing syncope. There was high confidence in all results, with the approach using the CSRS reducing the costs and number of syncope-related hospital admissions. CONCLUSIONS: Compared to usual care, applying the CSRS appeared as a cost-effective strategy. This new evidence will help decision-makers choose cost-effective approaches for the management of patients presenting to the ED with syncope, as they search for efficient ways to maximise health gain from a finite budget.

Influence of the Synthetic Cannabinoid Agonist on Normal and Inflamed Cartilage: An In Vitro Study.

Medical marijuana (versus Marijuana derivatives) has been reported to possess analgesic, immunomodulatory, and anti-inflammatory properties. Recent studies in animal models of arthritis showed that cannabinoids, a group of compounds produced from marijuana, may attenuate joint damage. However, whether marijuana byproducts can suppress osteoarthritis (OA)-associated cartilage degradation has not been previously reported. In this study, human chondrocytes were isolated from healthy articular cartilage, expanded in vitro, and subjected to pellet culture in a chondrogenic medium to form cartilage tissues. We first examined the influence of marijuana byproducts on normal cartilage by treating chondrocyte-derived tissues with a synthetic cannabinoid agonist, Win-55,212-2 (Win), at different concentrations ranging from 0.01 to 10 µM. After treatment, the tissue phenotype was assessed using glycosaminoglycan (GAG) assay and real-time PCR. Next, cartilage tissues were pre-treated with interleukin-1ß (IL-1ß) to generate an inflamed phenotype and then cultured with Win to assess its therapeutic potential. The results showed that at concentrations lower than 1 µM, Win treatment did not significantly impair chondrocyte growth or cartilage formation capacity, but at a high level (>10 µM), it remarkably suppressed cell proliferation. Interestingly, under the condition of IL-1ß pre-treatment, Win was able to partially preserve the cartilage matrix and decrease the production of interleukin-6, although the protective effect was mild. Taken together, our results indicated that the variable effects of Win on chondrocytes occur in a concentration-dependent manner. Whether cannabinoid derivatives can be used to treat cartilage degradation or can alter other structural changes in OA deserve further investigation.

Toll-like receptor deficiency worsens inflammation and lymphedema after lymphatic injury.

Mechanisms regulating lymphedema pathogenesis remain unknown. Recently, we have shown that lymphatic fluid stasis increases endogenous danger signal expression, and these molecules influence lymphatic repair (Zampbell JC, et al. Am J Physiol Cell Physiol 300: C1107-C1121, 2011). Endogenous danger signals activate Toll-like receptors (TLR) 2, 4, and 9 and induce homeostatic or harmful responses, depending on physiological context. The purpose of this study was to determine the role of TLRs in regulating tissue responses to lymphatic fluid stasis. A surgical model of lymphedema was used in which wild-type or TLR2, 4, or 9 knockout (KO) mice underwent tail lymphatic excision. Six weeks postoperatively, TLR KOs demonstrated markedly increased tail edema compared with wild-type animals (50-200% increase; P < 0.01), and this effect was most pronounced in TLR4 KOs (P < 0.01). TLR deficiency resulted in decreased interstitial and lymphatic transport, abnormal lymphatic architecture, and fewer capillary lymphatics (40-50% decrease; P < 0.001). Lymphedematous tissues of TLR KOs demonstrated increased leukocyte infiltration (P < 0.001 for TLR4 KOs), including higher numbers of infiltrating CD3+ cells (P < 0.05, TLR4 and TLR9 KO), yet decreased infiltrating F4/80+ macrophages (P < 0.05, all groups). Furthermore, analysis of isolated macrophages revealed twofold reductions in VEGF-C (P < 0.01) and LYVE-1 (P < 0.05) mRNA from TLR2-deficient animals. Finally, TLR deficiency was associated with increased collagen type I deposition and increased transforming growth factor-ß1 expression (P < 0.01, TLR4 and TLR9 KO), contributing to dermal fibrosis. In conclusion, TLR deficiency worsens tissue responses to lymphatic fluid stasis and is associated with decreased lymphangiogenesis, increased fibrosis, and reduced macrophage infiltration. These findings suggest a role for innate immune responses, including TLR signaling, in lymphatic repair and lymphedema pathogenesis.

Lymphatic function is regulated by a coordinated expression of lymphangiogenic and anti-lymphangiogenic cytokines.

Lymphangiogenic cytokines such as vascular endothelial growth factor-C (VEGF-C) are critically required for lymphatic regeneration; however, in some circumstances, lymphatic function is impaired despite normal or elevated levels of these cytokines. The recent identification of anti-lymphangiogenic molecules such as interferon-γ (IFN-γ), transforming growth factor-ß1, and endostatin has led us to hypothesize that impaired lymphatic function may represent a dysregulated balance in the expression of pro/anti-lymphangiogenic stimuli. We observed that nude mice have significantly improved lymphatic function compared with wild-type mice in a tail model of lymphedema. We show that gradients of lymphatic fluid stasis regulate the expression of lymphangiogenic cytokines (VEGF-A, VEGF-C, and hepatocyte growth factor) and that paradoxically the expression of these molecules is increased in wild-type mice. More importantly, we show that as a consequence of T-cell-mediated inflammation, these same gradients also regulate expression patterns of anti-lymphangiogenic molecules corresponding temporally and spatially with impaired lymphatic function in wild-type mice. We show that neutralization of IFN-γ significantly increases inflammatory lymph node lymphangiogenesis independently of changes in VEGF-A or VEGF-C expression, suggesting that alterations in the balance of pro- and anti-lymphangiogenic cytokine expression can regulate lymphatic vessel formation. In conclusion, we show that gradients of lymphatic fluid stasis regulate not only the expression of pro-lymphangiogenic cytokines but also potent suppressors of lymphangiogenesis as a consequence of T-cell inflammation and that modulation of the balance between these stimuli can regulate lymphatic function.

Temporal and spatial patterns of endogenous danger signal expression after wound healing and in response to lymphedema.

While acute tissue injury potently induces endogenous danger signal expression, the role of these molecules in chronic wound healing and lymphedema is undefined. The purpose of this study was to determine the spatial and temporal expression patterns of the endogenous danger signals high-mobility group box 1 (HMGB1) and heat shock protein (HSP)70 during wound healing and chronic lymphatic fluid stasis. In a surgical mouse tail model of tissue injury and lymphedema, HMGB1 and HSP70 expression occurred along a spatial gradient relative to the site of injury, with peak expression at the wound and greater than twofold reduced expression within 5 mm (P < 0.05). Expression primarily occurred in cells native to injured tissue. In particular, HMGB1 was highly expressed by lymphatic endothelial cells (>40% positivity; twofold increase in chronic inflammation, P < 0.001). We found similar findings using a peritoneal inflammation model. Interestingly, upregulation of HMGB1 (2.2-fold), HSP70 (1.4-fold), and nuclear factor (NF)-κß activation persisted at least 6 wk postoperatively only in lymphedematous tissues. Similarly, we found upregulation of endogenous danger signals in soft tissue of the arm after axillary lymphadenectomy in a mouse model and in matched biopsy samples obtained from patients with secondary lymphedema comparing normal to lymphedematous arms (2.4-fold increased HMGB1, 1.9-fold increased HSP70; P < 0.01). Finally, HMGB1 blockade significantly reduced inflammatory lymphangiogenesis within inflamed draining lymph nodes (35% reduction, P < 0.01). In conclusion, HMGB1 and HSP70 are expressed along spatial gradients and upregulated in chronic lymphatic fluid stasis. Furthermore, acute expression of endogenous danger signals may play a role in inflammatory lymphangiogenesis.

Blockade of transforming growth factor-beta1 accelerates lymphatic regeneration during wound repair.

Lymphedema is a complication of cancer treatment occurring in approximately 50% of patients who undergo lymph node resection. Despite its prevalence, the etiology of this disorder remains unknown. In this study, we determined the effect of soft tissue fibrosis on lymphatic function and the role of transforming growth factor (TGF)-ß1 in the regulation of this response. We determined TGF-ß expression patterns in matched biopsy specimens collected from lymphedematous and normal limbs of patients with secondary lymphedema. To determine the role of TGF-ß in regulating tissue fibrosis, we used a mouse model of lymphedema and inhibited TGF-ß function either systemically with a monoclonal antibody or locally by using a soluble, defective TGF-ß receptor. Lymphedematous tissue demonstrated a nearly threefold increase in the number of cells that stained for TGF-ß1. TGF-ß inhibition markedly decreased tissue fibrosis, increased lymphangiogenesis, and improved lymphatic function compared with controls. In addition, inhibition of TGF-ß not only decreased TGF-ß expression in lymphedematous tissues, but also diminished inflammation, migration of T-helper type 2 (Th2) cells, and expression of profibrotic Th2 cytokines. Similarly, systemic depletion of T-cells markedly decreased TGF-ß expression in tail tissues. Inhibition of TGF-ß function promoted lymphatic regeneration, decreased tissue fibrosis, decreased chronic inflammation and Th2 cell migration, and improved lymphatic function. The use of these strategies may represent a novel means of preventing lymphedema after lymph node resection.

p21cip/WAF is a key regulator of long-term radiation damage in mesenchyme-derived tissues.

This study aimed to determine the mechanisms responsible for long-term tissue damage following radiation injury. We irradiated p21-knockout (p21(-/-)) and wild-type (WT) mice and determined the long-term deleterious effects of this intervention on mesenchyme-derived tissues. In addition, we explored the mechanisms of radiation-induced mesenchymal stem cell (MSC) dysfunction in isolated bone marrow-derived cells. p21 expression was chronically elevated >200-fold in irradiated tissues. Loss of p21 function resulted in a >4-fold increase in the number of skin MSCs remaining after radiation. p21(-/-) mice had significantly less radiation damage, including 6-fold less scarring, 40% increased growth potential, and 4-fold more hypertrophic chondrocytes in the epiphyseal plate (P<0.01). Irradiated p21(-/-) MSCs had 4-fold increased potential for bone or fat differentiation, 4-fold greater proliferation rate, and nearly 7-fold lower senescence as compared to WT MSCs (P<0.01). Ectopic expression of p21 in knockout cells decreased proliferation and differentiation potential and recapitulated the WT phenotype. Loss of p21 function markedly decreases the deleterious effects of radiation injury in mesenchyme-derived tissues and preserves tissue-derived MSCs. In addition, p21 is a critical regulator of MSC proliferation, differentiation, and senescence both at baseline and in response to radiation.

Adipose-derived stem cells promote lymphangiogenesis in response to VEGF-C stimulation or TGF-ß1 inhibition.

AIMS: Recent studies have demonstrated that augmentation of lymphangiogenesis and tissue engineering hold promise as a treatment for lymphedema. The purpose of this study was to determine whether adipose-derived stem cells (ASCs) can be used in lymphatic tissue-engineering by altering the balance between pro- and anti-lymphangiogenic cytokines. MATERIALS & METHODS: ASCs were harvested and cultured in media with or without recombinant VEGF-C for 48 h. ASCs were then implanted in mice using Matrigel plugs. Additional groups of animals were implanted with ASCs transfected with a dominant-negative TGF-ß1 receptor-II adenovirus with or without VEGF-C stimulation, since TGF-ß1 has been shown to have potent antilymphangiogenic effects. Lymphangiogenesis, lymphatic differentiation and cellular proliferation were assessed. RESULTS: Stimulation of ASCs with VEGF-C in vitro significantly increased expression of VEGF-A, VEGF-C and Prox-1. ASCs stimulated with VEGF-C prior to implantation induced a significant (threefold increase) lymphangiogenic response as compared with control groups (unstimulated ASCs or empty Matrigel plugs; p < 0.01). This effect was significantly potentiated when TGF-ß1 signaling was inhibited using the dominant-negative TGF-ß1 receptor-II virus (4.5-fold increase; p < 0.01). Stimulation of ASCs with VEGF-C resulted in a marked increase in the number of donor ASCs (twofold; p < 0.01) and increased the number of proliferating cells (sevenfold; p < 0.01) surrounding the Matrigel. ASCs stimulated with VEGF-C expressed podoplanin, a lymphangiogenic cell marker, whereas unstimulated cells did not. CONCLUSION: Short-term stimulation of ASCs with VEGF-C results in increased expression of VEGF-A, VEGF-C and Prox-1 in vitro and is associated with a marked increase lymphangiogenic response after in vivo implantation. This lymphangiogenic response is significantly potentiated by blocking TGF-ß1 function. Furthermore, stimulation of ASCs with VEGF-C markedly increases cellular proliferation and cellular survival after in vivo implantation and stimulated cells express podoplanin, a lymphangiogenic cell marker.

Updates on Lisfranc Complex Injuries.

Lisfranc injuries are a disruption of one or more of the tarsometatarsal joints and have an estimated incidence of 1/55 000 people. However, the total number of Lisfranc injuries could be underreported, because almost 20% of these injuries are initially missed. Because of the relative infrequency of these injuries, the current literature is inconsistent in regard to proper treatment. This article provides a review of Lisfranc complex injuries including relevant anatomy, diagnosis, treatment, classifications, operative approaches, and outcomes and complications. Based on existing evidence, it also proposes an algorithm the authors prefer for the evaluation and treatment of Lisfranc complex injuries.

External validation of the Canadian Syncope Risk Score for patients presenting with undifferentiated syncope to the emergency department.

OBJECTIVE: To validate the accuracy and safety of the Canadian Syncope Risk Score (CSRS) for patients presenting with syncope. METHODS: Single centre prospective observational study in Brisbane, Australia. Adults presenting to the ED with syncope within the last 24 h were recruited after applying exclusion criteria. Study was conducted over 1 year, from March 2018 to March 2019. Thirty-day serious adverse events (SAE) were reported based on the original derivation study and standardised outcome reporting for syncope. Individual patient CSRS was calculated and correlated with 30-day SAE and disposition status from ED. RESULTS: Two hundred and eighty-three patients were recruited to the study. Average age was 55.6 years (SD 22.7 years), 37.1% being male with a 39.9% admission rate. Thirty-day SAE occurred in seven patients (2.5%) and no recorded deaths. The CSRS performed with a sensitivity of 71.4% (95% confidence interval [CI] 30.3-94.9%), specificity 72.8% (95% CI 67.1-77.9%) for a threshold score of 1 or higher. CONCLUSION: Syncope patients in our study were predominantly very low to low risk (72%). The prevalence of 30-day SAE was low, majority occurring following hospital discharge. Sensitivity estimates for CSRS was lower than the derivation study but lacked robustness with wide CIs because of a small sample size and number of events observed. However, the CSRS did not miss any clinically relevant outcomes in low risk patients making it potentially useful in aiding their disposition. Larger validation studies in Australia are encouraged to further test the diagnostic accuracy of the CSRS.