The role of circulating tumor DNA in melanomas of the uveal tract.

Melanoma of the uveal tract or uveal melanoma (UM) originates from melanocytes of the eye and is the most common intraocular malignancy in adults. Despite considerable advances in diagnostic procedures and treatments, prognosis remains poor in those with advanced disease. Accordingly, although current treatments have an excellent local disease control rate, approximately 50% of patients develop metastatic relapse within 10 years.

Epigenetics in Heart Failure.

Heart failure is a clinical syndrome with rising global incidence and poor prognosis despite improvements in medical therapy. There is increasing research interest in epigenetic therapies for heart failure. Pathological cardiac remodelling may be driven by stress-activated cardiac signalling cascades, and emerging research has shown the involvement of epigenetic signals that regulate transcriptional changes leading to heart failure.

Clinical and basic science aspects of innate lymphoid cells as novel immunotherapeutic targets in cancer treatment.

Immunotherapy has revolutionised cancer treatment over the past decade, demonstrating remarkable efficacy across a broad range of cancer types. However, not all patients or cancer types respond to contemporary clinically-utilised immunotherapeutic strategies, which largely focus on harnessing adaptive immune T cells for cancer treatment. Accordingly, it is increasingly recognised that upstream innate immune pathways, which govern and orchestrate the downstream adaptive immune response, may prove critical in overcoming cancer immunotherapeutic resistance.

Reducing door-to-wire time for ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention by multidisciplinary collaboration: An observational study.

The aim of this study is to reduce door-to-wire time for ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention through multidisciplinary collaboration. Patients over the age of 18who visited the Foshan Sanshui District People's Hospital between 2018 and 2019 and were diagnosed with STEMI were included in this study. Analyses were performed with patients segregated into a pre-intervention interim period (2018) and a post-intervention period (2019) based on the date of admission.

The use of Three-Dimensional Printing in Orthopaedics: a Systematic Review and Meta-analysis.

Objectives: 3D-printing is a rapidly developing technology with applications in orthopaedics including pre-operative planning, intraoperative guides, design of patient specific instruments and prosthetics, and education. Existing literature demonstrates that in the surgical treatment of a wide range of orthopaedic pathology, using 3D printing shows favourable outcomes. Despite this evidence 3D printing is not routinely used in orthopaedic practice.

Mef2d potentiates type-2 immune responses and allergic lung inflammation.

Innate lymphoid cells (ILCs) and adaptive T lymphocytes promote tissue homeostasis and protective immune responses. Their production depends on the transcription factor GATA3, which is further elevated specifically in ILC2s and T helper 2 cells to drive type-2 immunity during tissue repair, allergic disorders, and anti-helminth immunity. The control of this crucial up-regulation is poorly understood.

Emerging roles of type 1 innate lymphoid cells in tumour pathogenesis and cancer immunotherapy.

Innate lymphoid cells (ILCs) are the most recently discovered class of innate immune cells found to have prominent roles in various human immune-related pathologies such as infection and autoimmune diseases. However, their role in cancer was largely unclear until recently, where several emerging studies over the past few years unanimously demonstrate ILCs to be critical players in tumour immunity. Being the innate counterpart of T cells, ILCs are potent cytokine producers through which they orchestrate the overall immune response upstream of adaptive immunity thereby modulating T cell function.

The evolution of poller screws.

Compared to other techniques, poller screws with intramedullary nailing are technically simple, practical, and reproducible for the fixation of metaphyseal fractures. In addition, poller screws do not require special instruments or hardware and are minimally invasive. This review takes a historical perspective to evaluate poller screws holistically.

Novel therapeutic strategies targeting myeloid-derived suppressor cell immunosuppressive mechanisms for cancer treatment.

Cancer is the leading cause of death globally superseded only by cardiovascular diseases, and novel strategies to overcome therapeutic resistance against existing cancer treatments are urgently required. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with potent immunosuppressive capacity against well-established anti-tumour effectors such as natural killer cells (NK cells) and T cells thereby promoting cancer initiation and progression. Critically, MDSCs are readily identified in almost all tumour types and human cancer patients, and numerous studies in the past decade have recognised their role in contributing to therapeutic resistance against all four pillars of modern cancer treatment, namely surgery, chemotherapy, radiotherapy and immunotherapy.

Increased left ventricular remodelling index in paradoxical low-flow severe aortic stenosis with preserved left ventricular ejection fraction compared to normal-flow severe aortic stenosis.

Introduction: Patients with paradoxical low-flow (LF) severe aortic stenosis (AS) despite preserved left ventricular ejection fraction (LVEF) appear distinct from normal-flow (NF) patients, showing worse prognosis, more concentric hypertrophy and smaller left ventricular (LV) cavities. The left ventricular remodelling index (LVRI) has been demonstrated to reliably discriminate between physiologically adapted athlete's heart and pathological LV remodelling.

Methods: We studied patients with index echocardiographic diagnosis of severe AS (aortic valve area <1 cm2) with preserved LVEF (>50%).

Predictors of futile recanalization after endovascular treatment in acute ischemic stroke: a multi-center study.

Background And Objectives: Endovascular thrombectomy (EVT) improves long-term outcomes and decreases mortality in ischemic stroke patients. However, a significant proportion of patients do not benefit from EVT recanalization, a phenomenon known as futile recanalization or reperfusion without functional independence (RFI). In this study, we aim to identify the major stroke risk factors and patient characteristics associated with RFI.

Left ventricular vortex formation time: emerging clinical applications and limitations.

Vortex formation during left ventricular diastolic filling may provide clinically useful insights into cardiac health. In recent years, there has been growing interest in the measurement of vortex formation time (VFT), especially because it is derived noninvasively. There are important applications of VFT in valvular heart disease, athletic physiology, heart failure and hypertrophic cardiomyopathy.

Supermicrosurgery: past, present and future.

Supermicrosurgery was popularised in 1997 and is defined as a technique of microvascular anastomosis for single nerve fascicles and vessels 0.3-0.8 mm in diameter.

7-Day National Institutes of Health Stroke Scale as a surrogate marker predicting ischemic stroke patients' outcome following endovascular therapy.

Background: Early neurological deterioration after endovascular thrombectomy (EVT) is associated with poor prognosis. National Institutes of Health Stroke Scale (NIHSS) score measured at 24 h after EVT may be a better outcome predictor than other methods that focus on changes in NIHSS. Nevertheless, clinical fluctuations in ischemic stroke patients during the immediate phase after symptoms onset are well recognized.

Association between the extension of smoke-free legislation and incident acute myocardial infarctions in Singapore from 2010 to 2019: an interrupted time-series analysis.

Background: We examined the association between smoke-free laws implemented in the outdoors and the common areas of residential apartment blocks and reported acute myocardial infarctions (AMI) in Singapore.

Methods: We used an interrupted time-series design and seasonal autoregressive integrated moving average models to examine the effect of the smoke-free law extensions in 2013 (common areas of residential blocks, covered pedestrian linkways, overhead bridges and within 5 m of bus stops), 2016 (parks) and 2017 (educational institutions, buses and taxis) on the monthly incidence rate of AMIs per 1 000 000 population.

Results: We included 133 868 AMI reports from January 2010 to December 2019.

Predictors of failure of early neurological improvement in early time window following endovascular thrombectomy: a multi-center study.

Background And Objective: Endovascular thrombectomy (EVT) has become the gold standard in the treatment of acute stroke patients. However, not all patients respond well to this treatment despite successful attempts. In this study, we aimed to identify variables associated with the failure of improvements following EVT.

Using Pre-Clinical Studies to Explore the Potential Clinical Uses of Exosomes Secreted from Induced Pluripotent Stem Cell-Derived Mesenchymal Stem cells.

Recent studies of exosomes derived from mesenchymal stem cells (MSCs) have indicated high potential clinical applications in many diseases. However, the limited source of MSCs impedes their clinical research and application. Most recently, induced pluripotent stem cells (iPSCs) have become a promising source of MSCs.

Prophylactic antibiotic use for infective endocarditis: a systematic review and meta-analysis.

Objectives: Infective endocarditis (IE) is a devastating disease with a 50% 1-year mortality rate. In recent years, medical authorities across the globe advised stricter criteria for antibiotic prophylaxis in patients with high risk of IE undergoing dental procedures. Whether such recommendations may increase the risk of IE in at-risk patients must be investigated.

Type 1 and type 2 cytokine-mediated immune orchestration in the tumour microenvironment and their therapeutic potential.

Cancer remains the second leading cause of death worldwide despite modern breakthroughs in medicine, and novel treatments are urgently needed. The revolutionary success of immune checkpoint inhibitors in the past decade serves as proof of concept that the immune system can be effectively harnessed to treat cancer. Cytokines are small signalling proteins with critical roles in orchestrating the immune response and have become an attractive target for immunotherapy.

Emerging roles for IL-25 and IL-33 in colorectal cancer tumorigenesis.

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide, and is largely refractory to current immunotherapeutic interventions. The lack of efficacy of existing cancer immunotherapies in CRC reflects the complex nature of the unique intestinal immune environment, which serves to maintain barrier integrity against pathogens and harmful environmental stimuli while sustaining host-microbe symbiosis during homeostasis. With their expression by barrier epithelial cells, the cytokines interleukin-25 (IL-25) and IL-33 play key roles in intestinal immune responses, and have been associated with inappropriate allergic reactions, autoimmune diseases and cancer pathology.

Air Pollution and Ischaemic Stroke.

Air pollution is a significant contributor of cardiovascular diseases, including ischaemic stroke (IS), with substantial mortality and morbidity. However, associations between air pollution and IS remain unclear. Limited data are available on the relationship between IS and individual air pollutants.

An innate IL-25-ILC2-MDSC axis creates a cancer-permissive microenvironment for mutation-driven intestinal tumorigenesis.

Interleukin-25 (IL-25) and group 2 innate lymphoid cells (ILC2s) defend the host against intestinal helminth infection and are associated with inappropriate allergic reactions. IL-33-activated ILC2s were previously found to augment protective tissue-specific pancreatic cancer immunity. Here, we showed that intestinal IL-25-activated ILC2s created an innate cancer-permissive microenvironment.

Management of a Hot Swollen Joint in the Acute Setting.

Background: The presentation of a hot swollen joint is common in the emergency department, general practice, rheumatology and orthopedic clinics. There is a wide set of differential diagnoses for a hot swollen joint, thus making it difficult to diagnose and manage, especially for junior doctors. Initially, it is pertinent to exclude/diagnose medical and surgical emergencies.

A retrospective analysis of the definitive management of open talus fractures at a major trauma centre, comparing ORIF to FUSION: cohort study and audit of BOAST 4 guidelines.

Purpose: Open talus fractures are notoriously difficult to manage, and they are commonly associated with a high level of complications including non-union, avascular necrosis and infection. Currently, the management of such injuries is based upon BOAST 4 guidelines although there is no suggested definitive management, and thus, definitive management is based upon surgeon preference. The key principles of open talus fracture management which do not vary between surgeons are early debridement, orthoplastic wound care, anatomic reduction and definitive fixation whenever possible.