Positioning Imatinib for Pulmonary Arterial Hypertension: A Dose Finding Phase 2 Study.

Rationale: Imatinib 400mg daily reduces pulmonary vascular resistance and improves exercise capacity in patients with pulmonary arterial hypertension. Concerns about safety and tolerability limit its use.

Objectives: To identify a safe and tolerated dose of oral imatinib between 100mg and 400mg daily and evaluate its efficacy.

From Microcirculation to Aging-Related Diseases: A Focus on Endothelial SIRT1.

Silent information regulator sirtuin 1 (SIRT1) is an NAD+-dependent deacetylase with potent anti-arterial aging activities. Its protective function in aging-related diseases has been extensively studied. In the microcirculation, SIRT1 plays a crucial role in preventing microcirculatory endothelial senescence by suppressing inflammation and oxidative stress while promoting mitochondrial function and optimizing autophagy.

Fluorogenic platinum(IV) complexes as potential predictors for the design of hypoxia-activated platinum(IV) prodrugs.

Hypoxia (low-oxygen) is one of the most common characteristics of solid tumours. Exploiting tumour hypoxia to reductively activate Pt(IV) prodrugs has the potential to deliver toxic Pt(II) selectively and thus overcome the systemic toxicity issues of traditional Pt(II) therapies. However, our current understanding of the behaviour of Pt(IV) prodrugs in hypoxia is limited.

Dexmedetomidine improves pulmonary outcomes in thoracic surgery under one-lung ventilation: A meta-analysis.

Introduction: Dexmedetomidine improves intrapulmonary shunt in thoracic surgery and minimizes inflammatory response during one-lung ventilation (OLV). However, it is unclear whether such benefits translate into less postoperative pulmonary complications (PPCs). Our objective was to determine the impact of dexmedetomidine on the incidence of PPCs after thoracic surgery.

Medicines and Healthcare products Regulatory Agency's "Consultation on proposals for legislative changes for clinical trials": a response from the Trials Methodology Research Partnership Adaptive Designs Working Group, with a focus on data sharing.

In the UK, the Medicines and Healthcare products Regulatory Agency consulted on proposals "to improve and strengthen the UK clinical trials legislation to help us make the UK the best place to research and develop safe and innovative medicines". The purpose of the consultation was to help finalise the proposals and contribute to the drafting of secondary legislation. We discussed these proposals as members of the Trials Methodology Research Partnership Adaptive Designs Working Group, which is jointly funded by the Medical Research Council and the National Institute for Health and Care Research.

Continuous Positive Airway Pressure plus Mandibular Advancement Therapy (PAPMAT): study protocol for an adaptive randomised crossover trial comparing the benefits and costs of combining two established treatments for obstructive sleep apnoea.

Background: Obstructive sleep apnoea (OSA) involves repeated breathing pauses during sleep due to upper airway obstruction. It causes excessive daytime sleepiness and has other health impacts. Continuous positive airway pressure (CPAP) therapy is effective first line treatment for moderate to severe OSA.

A Double-Blind, Randomized, Placebo-controlled Trial of Long-Term Doxycycline Therapy on Exacerbation Rate in Patients with Stable Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of morbidity and mortality, and preventing them is a key treatment target. Long-term macrolide treatment is effective at reducing exacerbations, but there is a paucity of evidence for other antibiotic classes. To assess whether 12-month use of doxycycline reduces the exacerbation rate in people with COPD.

Efficacy and effectiveness of inactivated vaccines against symptomatic COVID-19, severe COVID-19, and COVID-19 clinical outcomes in the general population: a systematic review and meta-analysis.

Background: Inactivated, whole-virion vaccines have been used extensively in the SARS-CoV-2 pandemic. Its efficacy and effectiveness across regions have not been systematically evaluated. Efficacy refers to how well a vaccine performs in a controlled environment.

Artificial intelligence and end user tools to develop a nurse duty roster scheduling system.

Objectives: A nurse duty roster is usually prepared monthly in a hospital ward. It is common for nurses to make duty shift requests prior to scheduling. A ward manager normally spends more than a working day to manually prepare and subsequently to optimally adjust the schedule upon staff requests and hospital policies.

Positioning imatinib for pulmonary arterial hypertension: A phase I/II design comprising dose finding and single-arm efficacy.

Pulmonary arterial hypertension is an unmet clinical need. Imatinib, a tyrosine kinase inhibitor, 200 to 400 mg daily reduces pulmonary artery pressure and increases functional capacity in this patient group, but is generally poorly tolerated at the higher dose. We have designed an open-label, single-arm clinical study to investigate whether there is a tolerated dose of imatinib that can be better targeted to patients who will benefit.

Patient-Derived Nasopharyngeal Cancer Organoids for Disease Modeling and Radiation Dose Optimization.

Effective radiation treatment (RT) for recurrent nasopharyngeal cancers (NPC), featuring an intrinsic hypoxic sub-volume, remains a clinical challenge. Lack of disease-specific models of NPC, together with difficulties in establishing patient derived xenograft (PDX) models, have further hindered development of personalized therapeutic options. Herein, we established two NPC organoid lines from recurrent NPC PDX models and further characterized and compared these models with original patient tumors using RNA sequencing analysis.

Simplified sigmoidal curve fitting for a 6 MV FFF photon beam of the Halcyon to determine the field size for beam commissioning and quality assurance.

Background: An O-ring gantry-type linear accelerator (LINAC) with a 6-MV flattening filter-free (FFF) photon beam, Halcyon, includes a reference beam that contains representative information such as the percent depth dose, profile and output factor for commissioning and quality assurance. However, because it does not provide information about the field size, we proposed a method to determine all field sizes according to all depths for radiation therapy using simplified sigmoidal curve fitting (SCF).

Methods: After mathematical definition of the SCF using four coefficients, the defined curves were fitted to both the reference data (RD) and the measured data (MD).

A stochastically curtailed two-arm randomised phase II trial design for binary outcomes.

Randomised controlled trials are considered the gold standard in trial design. However, phase II oncology trials with a binary outcome are often single-arm. Although a number of reasons exist for choosing a single-arm trial, the primary reason is that single-arm designs require fewer participants than their randomised equivalents.

Targeted Retreatment of Incompletely Recovered Chronic Obstructive Pulmonary Disease Exacerbations with Ciprofloxacin. A Double-Blind, Randomized, Placebo-controlled, Multicenter, Phase III Clinical Trial.

Chronic obstructive pulmonary disease (COPD) exacerbations are prone to nonrecovery, but there are no data about the effectiveness of retreatment for these prolonged events. We examined whether further therapy with ciprofloxacin for incompletely resolved COPD exacerbations prolonged the time until the next event. To assess whether incompletely recovered COPD exacerbations benefit from additional treatment with ciprofloxacin, at Day 14.

Two new approaches for the visualisation of models for network meta-analysis.

Background: Meta-analysis is a useful tool for combining evidence from multiple studies to estimate a pooled treatment effect. An extension of meta-analysis, network meta-analysis, is becoming more commonly used as a way to simultaneously compare multiple treatments in a single analysis. Despite the variety of approaches available for presenting fitted models, ascertaining an intuitive understanding of these models is often difficult.

Development and validation of an imaging and clinical scoring system to predict early mortality in spontaneous ruptured hepatocellular carcinoma treated with transarterial embolization.

Purpose: To develop and validate a scoring system using a combination of imaging and clinical parameters to predict 30-day mortality in ruptured HCC (rHCC) patients after transarterial embolization (TAE).

Methods: 98 consecutive patients with rHCC who underwent abdominal CT and subsequent TAE between January 2007 and December 2016 were retrospectively reviewed. The CT scans were reviewed by two radiologists blinded to the patient outcome.

Tumor Segmentation in Contrast-Enhanced Magnetic Resonance Imaging for Nasopharyngeal Carcinoma: Deep Learning with Convolutional Neural Network.

Objectives: To evaluate the application of a deep learning architecture, based on the convolutional neural network (CNN) technique, to perform automatic tumor segmentation of magnetic resonance imaging (MRI) for nasopharyngeal carcinoma (NPC).

Materials And Methods: In this prospective study, 87 MRI containing tumor regions were acquired from newly diagnosed NPC patients. These 87 MRI were augmented to >60,000 images.

Failure Analysis for Ultrasound Machines in a Radiology Department after Implementation of Predictive Maintenance Method.

Objective: The objective of the study was to perform quantitative failure and fault analysis to the diagnostic ultrasound (US) scanners in a radiology department after the implementation of the predictive maintenance (PdM) method; to study the reduction trend of machine failure; to understand machine operating parameters affecting the failure; to further optimize the method to maximize the machine clinically service time.

Materials And Methods: The PdM method has been implemented to the 5 US machines since 2013. Log books were used to record machine failures and their root causes together with the time spent on repair, all of which were retrieved, categorized, and analyzed for the period between 2013 and 2016.

Opportunistic screening for osteoporosis in abdominal computed tomography for Chinese population.

Unlabelled: This study assessed the possibility of diagnosing and excluding osteoporosis with routine abdominal CT scans in a Chinese population who underwent both DXA and CT for unrelated reasons. Statistical correlation was made between the HU measured of the spine on CT and various parameters on DXA. Diagnostic cutoff points in terms of HU were established for the diagnosis (≤ 136 HU) and exclusion (≥ 175 HU) of osteoporosis on sagittal reformatted images.

Comparison of image quality and radiation exposure between conventional imaging and gemstone spectral imaging in abdominal CT examination.

Objective: To compare patients' image quality and radiation exposure between gemstone spectral imaging (GSI) with rapid kV switching technique and conventional polychromatic imaging (CPI) performed in abdominal CT examinations.

Methods: Adult patients who were referred to abdominal CT from October 2015 to March 2016 were enrolled. Unenhanced CT with CPI mode and tri-phase (arterial/portal/delayed phase) contrast-enhanced scan with GSI mode were performed with different protocols respectively.

Percutaneous cholecystostomy for high-risk patients with acute cholangitis.

Percutaneous cholecystostomy (PC) is a well-established treatment for acute cholecystitis. We investigate the performance and role of PC in managing acute cholangitis.Retrospective review on all patients who underwent PC for acute cholangitis between January 2012 and June 2017 at a major regional hospital in Hong Kong.