Study protocol for VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer, a UK multicentre randomised controlled trial with an internal pilot (the VIOLET study)

INTRODUCTION: Lung cancer is a leading cause of cancer deaths worldwide and surgery remains the main treatment for early stage disease. Prior to the introduction of video-assisted thoracoscopic surgery (VATS), lung resection for cancer was undertaken through an open thoracotomy. To date, the evidence base supporting the different surgical approaches is based on non-randomised studies, small randomised trials and is focused mainly on short-term in-hospital outcomes. METHODS AND ANALYSIS: The VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer study is a UK multicentre parallel group randomised controlled trial (RCT) with blinding of outcome assessors and participants (to hospital discharge) comparing the effectiveness, cost-effectiveness and acceptability of VATS lobectomy versus open lobectomy for treatment of lung cancer. We will test the hypothesis that VATS lobectomy is superior to open lobectomy with respect to self-reported physical function 5 weeks after randomisation (approximately 1 month after surgery). Secondary outcomes include assessment of efficacy (hospital stay, pain, proportion and time to uptake of chemotherapy), measures of safety (adverse health events), oncological outcomes (proportion of patients upstaged to pathologic N2 (pN2) disease and disease-free survival), overall survival and health related quality of life to 1 year. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment. ETHICS AND DISSEMINATION: This trial has been approved by the UK (Dulwich) National Research Ethics Service Committee London. Findings will be written-up as methodology papers for conference presentation, and publication in peer-reviewed journals. Many aspects of the feasibility work will inform surgical RCTs in general and these will be reported at methodology meetings. We will also link with lung cancer clinical studies groups. The patient and public involvement group that works with the Respiratory Biomedical Research Unit at the Brompton Hospital will help identify how we can best publicise the findings

A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (TRANSFORM)

Rationale: Single-center randomized controlled trials of the Zephyr endobronchial valve (EBV) treatment have demonstrated benefit in severe heterogeneous emphysema. This is the first multicenter study evaluating this treatment approach. Objectives: To evaluate the efficacy and safety of Zephyr EBVs in patients with heterogeneous emphysema and absence of collateral ventilation. Methods: This was a prospective, multicenter 2:1 randomized controlled trial of EBVs plus standard of care or standard of care alone (SoC). Primary outcome at 3 months post-procedure was the percentage of subjects with FEV1 improvement from baseline of 12% or greater. Changes in FEV1, residual volume, 6-minute-walk distance, St. George's Respiratory Questionnaire score, and modified Medical Research Council score were assessed at 3 and 6 months, and target lobe volume reduction on chest computed tomography at 3 months. Measurements and Main Results: Ninety seven subjects were randomized toEBV(n = 65) or SoC(n = 32). At 3 months, 55.4% of EBV and 6.5% of SoC subjects had an FEV1 improvement of 12% or more (P <0.001). Improvements were maintained at 6 months: EBV 56.3% versus SoC 3.2% (P <0.001), with a mean +/- SD change in FEV1 at 6 months of 20.7 +/- 29.6% and -8.6 +/- 13.0%, respectively. A total of 89.8% of EBV subjects had target lobe volume reduction greater than or equal to 350 ml, mean 1.09 +/- 0.62 L (P <0.001). Between-group differences for changes at 6 months were statistically and clinically significant: Delta EBV-SoC for residual volume, -700 ml; 6-minute-walk distance, +78.7 m; St. George's Respiratory Questionnaire score, -6.5 points; modified Medical Research Council dyspnea score, -0.6 points; and BODE(body mass index, airflow obstruction, dyspnea, and exercise capacity) index, 21.8 points (all P <0.05). Pneumothorax was the most common adverse event, occurring in 19 of 65 (29.2%) of EBV subjects. Conclusions: EBV treatment in hyperinflated patients with heterogeneous emphysema without collateral ventilation resulted in clinically meaningful benefits in lung function, dyspnea, exercise tolerance, and quality of life, with an acceptable safety profile

Risk Prediction for Acute Kidney Injury in Acute Medical Admissions in the UK

Background Acute Kidney Injury (AKI) is associated with adverse outcomes; identifying patients who are at risk of developing AKI in hospital may lead to targeted prevention. This approach is advocated in national guidelines but is not well studied in acutely unwell medical patients. We therefore aimed to undertake a UK-wide study in acute medical units (AMUs) with the following aims: to define the proportion of acutely unwell medical patients who develop hospital-acquired AKI (hAKI); to determine risk factors associated with the development of hAKI; and to assess the feasibility of using these risk factors to develop an AKI risk prediction score. Methods In September 2016, a prospective multicentre cohort study across 72 UK AMUs was undertaken. Data were collected from all patients who presented over a 24-hour period. Chronic dialysis, community-acquired AKI (cAKI) and those with fewer than two creatinine measurements were subsequently excluded. The primary outcome was the development of h-AKI. Results 2,446 individuals were admitted to the AMUs of the 72 participating centres. 384 patients (16%) sustained AKI of whom 287 (75%) were cAKI and 97 (25%) were hAKI. After exclusions, 1,235 participants remained in whom chronic kidney disease (OR 3.08, 95% CI 1.96-4.83), diuretic prescription (OR 2.33, 95% CI 1.5-3.65), a lower haemoglobin concentration and an elevated serum bilirubin were independently associated with development of hAKI. Multivariable model discrimination was moderate (c-statistic 0.75), and this did not support the development of a robust clinical risk prediction score. Mortality was higher in those with hAKI (adjusted OR 5.22; 95% CI 2.23-12.20). Conclusion AKI in AMUs is common and associated with worse outcomes, with the majority of cases community acquired. The smaller proportion of hAKI cases, only moderate discrimination of prognostic risk factor modelling and the resource implications of widespread application of an AKI clinical risk score across all AMU admissions suggests that this approach is not currently justified. More targeted risk assessment or automated methods of calculating individual risk may be more appropriate alternatives

Better clinical outcomes in hospitalized COVID-19 minority patients with accompanying gastrointestinal symptoms

BACKGROUND AND AIMS: The novel coronavirus (SARS-CoV-2) is highly contagious pathogen that primarily causes respiratory illnesses. Howerver, multiple gastrointestinal (GI) symptoms have been reported in Coronavirus Disease of 2019 (COVID-19). We conducted a retrospective cohort study of inpatients with COVID-19 at the George Washington University Hospital (GWUH) to assess the prevalence of GI symptoms and their association with clinical outcomes. METHODS: We reviewed the charts of 401 adults admitted to GWUH with positive SARS-CoV-2 tests from February 24 to May 21, 2020, ultimately including 382 inpatients. RESULTS: 87% of our cohort was African American or Latinx. 59% of patients reported at least one GI symptom, with diarrhea being the most common (29%). Patients with GI symptoms were slightly younger (58 +/- 15.8 vs. 65 +/- 16.9, p = 0.0005), have higher body mass index (31.5 +/- Standard Deviation of 8.7 vs. 28 +/- 8.2, p = 0.0001), and more likely to be Latinx (34 vs. 27, p = 0.01). Patients who presented with abdominal pain, nausea, vomiting, or diarrhea had significantly lower rates of death during hospitalization compared to those who did not present those symptoms (Odds Ratio 0.48, 95% Confidence Interval 0.28-0.8, p = 0.004). CONCLUSIONS: Our study suggests that GI symptoms portend a less-severe clinical course of COVID-19 which may reflect a different disease phenotype and lower overall immune response. Additional research should focus on more robust symptom reporting and longer follow-up

Design of the Superconducting AC and DC Distribution for the ASCEND Demonstrator at Airbus

The ground-based Advanced Superconducting and Cryogenic Experimental power train Demonstrator (ASCEND) at Airbus intends to demonstrate the potential and feasibility of a cryogenic and superconducting powertrain as a breakthrough electric propulsion solution on future electric aircraft. A direct current distribution network is used in a propulsion chain to transfer 500 kW of power from the source to an electrical converter, which transforms the power into an alternating voltage/current to drive a superconducting motor. The working point of 1,700 A and 300 V is chosen for safety and installation reasons by operating at relatively low voltage. The direct current (DC) bus of ASCEND will be formed by a pair of high-temperature superconducting CORC cables inserted into a 10-meter-long narrow cryostat, resulting in a compact and lightweight solution. The 2-meter-long alternating current (AC) bus between the inverter and the electric motor is formed by a three-phase CORC cable. The challenge associated with 500 Hz operation in which a balance between AC loss in the cable and the size and mass of the system needs to be found, will be outlined. The AC and DC buses include several devices that connect the liquid nitrogen cooled power cables with the other system components that, in the case of the room temperature generator, operate at significantly higher temperatures. These devices thus include conduction-cooled current leads that are dimensioned to minimize the heat inleak from the warm to the cold environment. An overview of the design of the AC and DC buses and connecting devices will be provided and some of the design and operational challenges will be outlined.</p

Anterior crucial ligament rupture: self-healing through dynamic intraligamentary stabilization technique

PURPOSE: Surgery involving arthroscopic reconstruction of the injured ligament is the gold standard treatment for torn anterior cruciate ligament (ACL). Recent studies support the hypothesis of biological self-healing of ruptured ACL. The aim of the study is to evaluate, in an animal model, the efficacy of a new technique, dynamic intraligamentary stabilization that utilizes biological self-healing for repair of acute ACL ruptures. METHODS: The ACL in 11 adult female white alpine sheep was transected and in 8 sheep reconstructed by dynamic intraligamentary stabilization. To enhance the healing potential, microfracturing and collagen were used in all animals. The contralateral, non-operated knees served as controls. At 3 months postkilling, all animals were submitted to magnetic resonance imaging and biomechanical and histological evaluation. RESULTS: No surgery-related complications were observed. Postoperatively, all animals regularly used the operated leg with full weight bearing and no lameness. At the time of killing, all animals exhibited radiological and histological healing of the transacted ACL. Biomechanical tests confirmed successful restoration of anteroposterior translation in the dynamic intraligamentary stabilization knees. Histological examination revealed dense scar tissue at the ends of the transected ligaments exhibiting hypercellularity and hypervascularization. CONCLUSION: The dynamic intraligamentary stabilization technique successfully induced self-healing of ruptured ACL in a sheep model. Knee joints remained stable during the healing period allowing free range of motion and full weight bearing, and no signs of osteoarthritis or other intraarticular damage in the follow up were observed