Hemostatic Profiles of Patients Who Underwent Transcatheter Versus Surgical Aortic Valve Replacement Versus Percutaneous Coronary Intervention.

Guidelines for transcatheter aortic valve replacement (TAVR) antithrombotic prophylaxis are extrapolated predominantly from percutaneous coronary intervention (PCI) data. Here, we examined temporal coagulation changes occurring in the early perioperative period to determine the pathobiologic validity of this supposition. This was a prospective observational study of consecutive patients who underwent transfemoral TAVR (n = 27), PCI (n = 12), or surgical aortic valve replacement (SAVR) requiring cardiopulmonary bypass and cross-clamping (n = 12). Blood samples were taken at 4 time points: T1 (baseline), after general anesthesia or sedation; T2, after heparin administration; T3, at the end of the procedure; and T4, 6 hours after the procedure. The samples were assessed concurrently using standard laboratory coagulation tests and viscoelastic tests of whole blood clotting, including the latest generation thromboelastometry (ROTEM sigma) and thromboelastometry (TEG 6s). Patients in the TAVR cohort were older and a had lower baseline hemoglobin level than patients in the PCI and SAVR cohorts. The baseline platelet function was similar between the TAVR and PCI cohorts and impaired in the SAVR cohort Figure S1. The baseline hemostatic measures were comparable among cohorts. Regarding the per-patient change from baseline, the TAVR cohort showed an overall more prothrombotic state than the other cohorts, with the most marked differences from the SAVR cohort after intraoperative heparin administration and from the PCI cohorts 6 hours after the procedure. In addition, the ROTEM and TEG parameters were well correlated but not interchangeable. In conclusion, patients who underwent TAVR have a more prothrombotic hemostatic profile than PCI and SAVR patients. These findings question the current guidelines that extrapolate antithrombotic regimens from PCI to TAVR settings.

Pelvic Exenteration for the Treatment of Locally Advanced Vulvar Cancer in South West Wales.

The treatment of locally advanced vulvar carcinoma (LAVC) represents a major challenge. We investigated the role of pelvic exenteration as a treatment of LAVC. Women who underwent pelvic exenteration for primary and recurrent LAVC in our centre between 2001 and 2019 were included. Among the 19 women included during the study period, 14 women (73.7%) had primary LAVC while 5 women (26.3%) had recurrent disease. Surgical resection margins were microscopically clear (R0) in 94.7% of patients-14/14 undergoing primary treatment and 4/5 undergoing treatment for recurrent disease. Complete closure of the wound was achieved in 100% of women, with no wound left to heal by secondary intention. Tumour size was a predictor of requiring myocutaneous flap reconstruction, with all tumours less than 40 mm undergoing primary closure, while almost all tumours 40 mm diameter or greater (14/15 women) required flap reconstruction (p = 0.001). The 30-day major morbidity rate was 42% and there was no perioperative death. The mean overall survival was 144.8 months (2-206 months), with 1-, 2- and 5-year survival rates of 89.5%, 75.1% and 66.7%, respectively. In our centre, a primary surgical approach to the management of LAVC has resulted in good survival outcomes with acceptable morbidity rates.

Fluid resuscitation after cardiac surgery in the intensive care unit: A bi-national survey of clinician practice. (The FRACS-ICU clinician survey).

Context and Aims: To describe current fluid and vasopressor practices after cardiac surgery in Australia and New Zealand cardiothoracic intensive care units (ICU). Design and Setting: This web-based survey was conducted in cardiothoracic ICUs in Australia and New Zealand. Methods: Intensivists, cardiac surgeons, and anesthetists were contacted to complete the online survey that asked questions regarding first and second choice fluids and vasopressors and the tools and factors that influenced these choices. Results: There were 96 respondents including 51 intensivists, 27 anesthetists, and 18 cardiac surgeons. Balanced crystalloids were the most preferred fluids (70%) followed by 4% albumin (18%) overall and among intensivists and anesthetists; however, cardiac surgeons (41%) preferred 4% albumin as their first choice. The most preferred second choice was 4% albumin (74%). Among vasopressors, noradrenaline was the preferred first choice (93%) and vasopressin the preferred second choice (80%). 53% initiated blood transfusion at a hemoglobin threshold of 70 g/L. Clinical acumen and mean arterial pressure were the most commonly used modalities in determining the need for fluids. Conclusions: There is practice variation in preference for fluids used in cardiac surgical patients in Australia and New Zealand; however, balanced crystalloids and 4% albumin were the most popular choices. In contrast, there is broad agreement with the use of noradrenaline and vasopressin as first and second-line vasopressors. These data will inform the design of future studies that aim to investigate hemodynamic management post cardiac surgery.

Evaluation of latest viscoelastic coagulation assays in the transcatheter aortic valve implantation setting.

BACKGROUND: Point of care viscoelastic measures with thromboelastography (TEG; Haemonetics Corporation, Switzerland) and thromboelastometry (ROTEM, Tem Innovations GmbH, Germany) now supersede laboratory assays in the perioperative assessment and management of coagulation. To the best of our knowledge, this sophisticated coagulation assessment has not been performed to characterise thrombotic changes in the transcatheter aortic valve implantation (TAVI) setting, nor have the two latest iteration cartridge-based systems been directly compared in the elective perioperative period. METHODS: Patients undergoing TAVI were prospectively recruited. Samples (n=44) were obtained at four timepoints (postinduction of anaesthesia, postheparin (100 IU/kg), postprotamine (1 mg/100 IU heparin) and 6 hours postoperatively). Each sample was concurrently assessed with standard laboratory tests (prothrombin time/international normalised ratio, activated partial thromboplastin time, thrombin clotting time, platelet count and direct fibrinogen, ROTEMSigma and TEG6s). RESULTS: Clot strength showed a statistically significant increase postheparin/TAVI deployment. When considering the subgroup of samples taken following the administration heparin, the heparinase channel of the TEG6s did not yield clotting strength results in 55% of samples and clotting time exceeded the upper limit of normal in 70% of samples. It was retrospectively recognised that the arachidonic acid channel of the TEG6s Platelet Mapping Cartridge had been decommissioned prohibiting assessment of aspirin effect. CONCLUSIONS: This study demonstrated a small intraprocedural prothrombotic change of uncertain clinical importance during the transcatheter aortic valve procedure. Further comparison with percutaneous coronary intervention and aortic valve replacement cohorts are needed to assess the merits of current antithrombotic guidelines, which are extrapolated from the PCI setting. The heparin effect was more consistently quantified by ROTEM.

Implementing clinical guidelines into practice: The Osteoarthritis Self-management and Independent-living Support (OASIS) group-A service evaluation.

INTRODUCTION: Arthritis is a common diagnosis for people presenting to healthcare reporting joint pain and stiffness. It is estimated that around 10 million people in the United Kingdom are thought to have arthritis. National Guidance states that patients with osteoarthritis should be offered three core treatments: information, exercise and weight loss advice. The Osteoarthritis Self-management and Independent-living Support (OASIS) group is a programme of progressive exercise and educational advice. METHODS: This service evaluation was to determine if the OASIS group was improving functional and reported pain-level outcomes of patients with lower limb osteoarthritis between 2016 and 2018. Routinely collected data were analysed to determine its effects on a number of functional and self-reported outcomes. Ethical approval was not required following local National Health Service (NHS) Trust approval (Reference e2020-08). RESULTS: During the 3-year period of the review between 2016 and 2018, a total of 339 patients were invited to attend the OASIS group. A total of 196 (57.8%) patients improved their overall pain score. Of the patients who attended all six sessions, 96.7% (174) improved in at least one of the functional outcome measures, and 90% (162) improved in at least two functional outcomes. CONCLUSION: On evaluation of the OASIS group, it has shown to be effective at improving pain and functional performance of patients with lower limb osteoarthritis, whilst remaining cost-effective. In comparison with other similar initiatives, the results are comparable, and it is implemented over a shorter time period, enhancing the cost-effectiveness for the NHS.

Antibody drug conjugates against the receptor for advanced glycation end products (RAGE), a novel therapeutic target in endometrial cancer.

BACKGROUND: The treatment of endometrial cancer (EC), the most common gynecological cancer, is currently hampered by the toxicity of current cytotoxic agents, meaning novel therapeutic approaches are urgently required. METHODS: A cohort of 161 patients was evaluated for the expression of the receptor for advanced glycation end products (RAGE) in endometrial tissues. The present study also incorporates a variety of in vitro methodologies within multiple cell lines to evaluate RAGE expression and antibody-drug conjugate efficacy, internalisation and intercellular trafficking. Additionally, we undertook in vivo bio-distribution and toxicity evaluation to determine the suitability of our chosen therapeutic approach, together with efficacy studies in a mouse xenograft model of disease. RESULTS: We have identified an association between over-expression of the receptor for advanced glycation end products (RAGE) and EC (H-score = Healthy: 0.46, SD 0.26; Type I EC: 2.67, SD 1.39; Type II EC: 2.20, SD 1.34; ANOVA, p < 0.0001). Furthermore, increased expression was negatively correlated with patient survival (Spearman's Rank Order Correlation: ρ = - 0.3914, p < 0.05). To exploit this association, we developed novel RAGE-targeting antibody drug conjugates (ADC) and demonstrated the efficacy of this approach. RAGE-targeting ADCs were up to 100-fold more efficacious in EC cells compared to non-malignant cells and up to 200-fold more cytotoxic than drug treatment alone. Additionally, RAGE-targeting ADCs were not toxic in an in vivo pre-clinical mouse model, and significantly reduced tumour growth in a xenograft mouse model of disease. CONCLUSIONS: These data, together with important design considerations implied by the present study, suggest RAGE-ADCs could be translated to novel therapeutics for EC patients.

Routine X-rays for suspected frozen shoulder offer little over diagnosis based on history and clinical examination alone.

INTRODUCTION: Frozen shoulder is a common condition, and current guidelines state that it is a diagnosis of exclusion. Along with a history and clinical examination, routine X-ray is mandated, to rule out any "masquerading" pathology such as fracture, dislocation, metastatic lesions or severe osteoarthritis. Despite the certainty of the guidelines there is a lack of evidence to support the use of routine X-rays in this situation. METHODS: A retrospective review was performed of all X-rays obtained in the diagnosis of frozen shoulder between February 2014 and August 2017 in an integrated musculoskeletal interface service. Results were screened and the prevalence of masquerading pathology was determined. RESULTS: A total of 350 shoulder X-rays that had been performed for patients with a provisional diagnosis of frozen shoulder were reviewed. Of these, 213 were from female patients (60.9%), the mean age was 57.7 (standard deviation 10.4) years and 342 (97.7%) did not have any concerning features. Six (1.7%) had severe osteoarthritis, one (0.3%) had a fracture and one (0.3%) had a lucency. All eight patients with masquerading pathology had findings from the history and clinical examination which would have warranted an X-ray, regardless of a differential diagnosis of frozen shoulder. CONCLUSIONS: The findings of this retrospective review of a large number of X-rays do not support the requirement of a routine X-ray to rule out masquerading pathology to confirm the diagnosis. The data suggest that it is unnecessary for patients without a relevant clinical history suggestive of serious or masquerading pathology to undergo routine imaging.