Involvement of Kindlin-1 in cutaneous squamous cell carcinoma.

Kindler syndrome (KS) is a rare genodermatosis resulting from loss-of-function mutations in FERMT1, the gene that encodes Kindlin-1. KS patients have a high propensity to develop aggressive and metastatic cutaneous squamous cell carcinoma (cSCC). Here we show in non-KS-associated patients that elevation of FERMT1 expression is increased in actinic keratoses compared to normal skin, with a further increase in cSCC supporting a pro-tumorigenic role in this population. In contrast, we show that loss of Kindlin-1 leads to increased SCC tumor growth in vivo and in 3D spheroids, which was associated with the development of a hypoxic tumor environment and increased glycolysis. The metalloproteinase Mmp13 was upregulated in Kindlin-1-depleted tumors, and increased expression of MMP13 was responsible for driving increased invasion of the Kindlin-1-depleted SCC cells. These results provide evidence that Kindlin-1 loss in SCC can promote invasion through the upregulation of MMP13, and offer novel insights into how Kindlin-1 loss leads to the development of a hypoxic environment that is permissive for tumor growth.

Evaluation of routine proximal bone analysis for microbiology and histopathology in diabetes-related foot infections and osteomyelitis.

PURPOSE: The value of proximal bone analysis for surgical clearance of infection remains debated. Real-world practice traditionally utilized proximal bone microbiology rather than histopathology to diagnose residual diabetes-related osteomyelitis of the foot (DFO) post-amputation. We assessed the concordance between proximal bone microbiology and histopathology in determining residual infection and their predictability for revision operation in DFO and diabetes-related foot infection (DFI). METHODOLOGY: A single-centre retrospective study was conducted between June and December 2020 at a tertiary institution. We recruited patients with diabetes mellitus who had minor amputations for DFO and DFI and analyzed their proximal bone microbiology, histopathology and outcomes at 6 months. RESULTS: Eighty-four patients were recruited; 64 (76.2%) were male. The mean age was 69.3 years. The mean HbA1c was 8.6%. Seventy-seven operations were performed for DFO and 17 for DFI. Negative microbiology showed complete concordance with histopathology; and none had revision operation (P = 0.99). Positive microbiology had 9.8% concordance with histopathology (P = 0.99). Positive histopathology was associated with a higher rate of revision operation (80% vs. 12.5%; P = 0.01). High preoperative C-reactive protein was associated with residual DFO (P = 0.02) and revision operation (P = 0.01). CONCLUSION: Positive histopathology was more reliable for determining significant residual DFO and predicting revision operation. Positive microbiology was valuable for guiding antibiotic selection. We suggest routine proximal bone analysis for both histopathology and microbiology to optimize the treatment of DFO and DFI.

A case series of first rib resection patients assessed with a novel MRI protocol for neurogenic thoracic outlet syndrome.

Selecting patients who will benefit from first rib resection for neurogenic thoracic outlet syndrome (nTOS) is made difficult by the variety of overlap symptoms with other musculoskeletal, neurogenic and psychological disease. A single diagnostic test is not available, and the diagnosis is typically made based on clinical findings and history. This case series assessed the utility of magnetic resonance imaging (MRI), with the patient's arm placed in a symptom provoking position above the head, as a component of diagnosis nTOS and selection of patients to offer surgery. Outcomes from first rib resection were assessed using the guidelines of The Society for Vascular Surgery for Thoracic Outlet Syndrome. The cases demonstrate that the loss of perineural fat signal on MRI of the brachial plexus with the arm in the provocative position is a useful tool for assessing patients who would benefit from first rib resection for nTOS.

Variable sensitivity multimaterial robotic e-skin combining electronic and ionic conductivity using electrical impedance tomography.

Electronic skins (e-skins) aim to replicate the capabilities of human skin by integrating electronic components and advanced materials into a flexible, thin, and stretchable substrate. Electrical impedance tomography (EIT) has recently been adopted in the area of e-skin thanks to its robustness and simplicity of fabrication compared to previous methods. However, the most common EIT configurations have limitations in terms of low sensitivities in areas far from the electrodes. Here we combine two piezoresistive materials with different conductivities and charge carriers, creating anisotropy in the sensitive part of the e-skin. The bottom layer consists of an ionically conducting hydrogel, while the top layer is a self-healing composite that conducts electrons through a percolating carbon black network. By changing the pattern of the top layer, the resulting distribution of currents in the e-skin can be tuned to locally adapt the sensitivity. This approach can be used to biomimetically adjust the sensitivities of different regions of the skin. It was demonstrated how the sensitivity increased by 500% and the localization error reduced by 40% compared to the homogeneous case, eliminating the lower sensitivity regions. This principle enables integrating the various sensing capabilities of our skins into complex 3D geometries. In addition, both layers of the developed e-skin have self-healing capabilities, showing no statistically significant difference in localization performance before the damage and after healing. The self-healing bilayer e-skin could recover full sensing capabilities after healing of severe damage.

Compressed vessels bias red blood cell partitioning at bifurcations in a hematocrit-dependent manner: Implications in tumor blood flow.

The tumor microenvironment is abnormal and associated with tumor tissue hypoxia, immunosuppression, and poor response to treatment. One important abnormality present in tumors is vessel compression. Vessel decompression has been shown to increase survival rates in animal models via enhanced and more homogeneous oxygenation. However, our knowledge of the biophysical mechanisms linking tumor decompression to improved tumor oxygenation is limited. In this study, we propose a computational model to investigate the impact of vessel compression on red blood cell (RBC) dynamics in tumor vascular networks. Our results demonstrate that vessel compression can alter RBC partitioning at bifurcations in a hematocrit-dependent and flow rate-independent manner. We identify RBC focusing due to cross-streamline migration as the mechanism responsible and characterize the spatiotemporal recovery dynamics controlling downstream partitioning. Based on this knowledge, we formulate a reduced-order model that will help future research to elucidate how these effects propagate at a whole vascular network level. These findings contribute to the mechanistic understanding of hemodilution in tumor vascular networks and oxygen homogenization following pharmacological solid tumor decompression.

Incidence, Management, and Outcomes of Aortic Graft Infection.

BACKGROUND: Infection complicates 1% of aortic grafts, and although uncommon, the associated morbidity and mortality are significant. We sought to determine risk factors for aortic graft infection (AGI), the long-term outcomes in patients managed both nonoperatively and via explantation. METHODS: This observational study reviewed sequential aortic grafts (thoracic or abdominal) inserted via open or endovascular means between 2000 and 2017. We used Cox proportional hazards regression analyses to compare risk factors between groups who did and did not acquire an AGI and recorded method of management, morbidity, mortality, and duration to adverse event. RESULTS: There were 883 aortic repairs, 49% were endovascular. 17.2% were for ruptured aneurysms, 1.1% for symptomatic aneurysms, 1.4% for type B dissections, and 0.5% for occlusive disease. Twelve patients presented with AGI, of which ten had their index procedure performed at our institution (AGI incidence of 1.1%). There was no difference in rates of AGI between open and endovascular repairs (0.9 vs. 1.4%, P = 0.24). AGI was significantly associated with emergency aortic repair (HR 3.63, 95% CI 1.13-11.57, P = 0.03), septic process requiring in-patient management during follow-up (HR 5.44, 95% CI 1.21-24.26, P = 0.02), and suprarenal clamping during open repair (HR 5.21, 95% CI 1.00-26.99, P = 0.05). Four patients were managed with explantation and revascularization (3 extra-anatomical bypasses) and remained well at a median follow-up of 46 months. Of the 8 patients managed nonoperatively, 4 died at an average of 13.5 days after representation, and the other 4 remained well on oral antibiotics at a median follow-up of 26.5 months. No patient suffered limb loss, and there was no change in the rate of infection over the period. CONCLUSIONS: Incidence of AGI remains low but is associated with significant mortality. Patients with aortic grafts in situ require aggressive treatment of septic foci to prevent graft infection.

Development of the surgical science examination of the Royal Australasian College of Surgeons surgical education and training programme: putting the chicken before the egg.

Basic science knowledge is a foundational element of surgical practice. Increasing surgical specialization may merit a reconsideration of the 'whole-body' approach to basic science curriculum in favour of specialty specific depth. The conundrum of depth or breadth of basic science curriculum is currently being addressed by the Royal Australasian College of Surgeons, which introduced a new surgical education and training programme for nine surgical specialties in 2008. This paper describes an innovative solution to the design of a basic science curriculum in the nine different surgical specialty streams of this programme. The task was to develop a curriculum and rigorous assessment in basic sciences to meet the needs of the training programme, for implementation within the first year. A number of political/cultural and technical issues were identified as critical to success. To achieve a robust assessment within the required time frame attention was paid to engagement, governance, curriculum definition, assessment development, and implementation. The pragmatic solution to curriculum and assessment was to use the existing assessment items and blueprint to determine a new curriculum definition and assessment. The resulting curriculum comprises a generic component, undertaken by all trainees, and specialty specific components. In a time critical environment, a pragmatic solution to curriculum, applied with predetermined, structured and meticulous methodology, allowed explicit definition of breadth for the generic basic science curriculum for surgical training in Australia and New Zealand. Implicit definition of specialty specific-basic science curricula was through the creation of a blueprinted assessment.

Follow-up costs increase the cost disparity between endovascular and open abdominal aortic aneurysm repair.

OBJECTIVE: This study compared the hospital and follow-up costs of patients who have undergone endovascular (EVAR) or open (OR) elective abdominal aortic aneurysm repair. METHODS: The records of 195 patients (EVAR, n = 55; OR, n = 140) who underwent elective aortic aneurysm repair between 1995 and 2004 were reviewed. Primary costing data were analyzed for 54 EVAR and 135 OR patients. Hospital costs were divided into preoperative, operative, and postoperative costs. Follow-up costs for EVAR patients were recorded, with a median follow-up time of 12 months. RESULTS: Mean preoperative costs were slightly higher in the EVAR group (AU $961/US $733 vs AU $869/US $663; not significant). Operative costs were significantly higher in the EVAR group (AU $16,124/US $12,297 vs AU $6077/US $4635; P < .001); this was entirely due to the increased cost of the endograft (AU $10,181/US $7,765 for EVAR vs AU $476/US $363 for OR). Postoperative costs were significantly reduced in the EVAR group (AU $4719/US $3599 vs AU $11,491/US $8,764; P < .001). Total hospital costs were significantly greater in the EVAR group (AU $21,804/US $16,631 vs AU $18,437/US $14,063; P < .001). The increase in total hospital costs was due to a significant difference in graft costs, which was not offset by reduced postoperative costs. The average follow-up cost per year after EVAR was AU $1316/US $999. At 1 year of follow-up, EVAR remained significantly more expensive than OR (AU $23,120/US $17,640 vs AU $18,510/US $14,122; P < .001); this cost discrepancy increased with a longer follow-up. CONCLUSIONS: EVAR results in significantly greater hospital costs compared with OR, despite reduced hospital and intensive care unit stays. The inclusion of follow-up costs further increases the cost disparity between EVAR and OR. Because EVAR requires lifelong surveillance and has a high rate of reintervention, follow-up costs must be included in any cost comparison of EVAR and OR. The economic cost, as well as the efficacy, of new technologies such as EVAR must be addressed before their widespread use is advocated.