Non-technical summary K+ -Cl − cotransporters (KCCs) play a fundamental role in epithelial cell function, both in the context of ionic homeostasis and also in cell morphology, cell division and locomotion. Unlike other ubiquitously expressed KCC isoforms, expression of KCC2 is widely considered to be restricted to neurons. Here we report a novel finding that KCC2 is widely expressed in several human cancer cell lines including the cervical cancer cell line (SiHa). Our data establish that KCC2 expression and function is not restricted to neurons and that KCC2 serves to increase cervical cancer progression via an ion transport-independent mechanism.Abstract K + -Cl − cotransporters (KCCs) play a fundamental role in epithelial cell function, both in the context of ionic homeostasis and also in cell morphology, cell division and locomotion. Unlike other ubiquitously expressed KCC isoforms, expression of KCC2 is widely considered to be restricted to neurons, where it is responsible for maintaining a low intracellular chloride concentration to drive hyperpolarising postsynaptic responses to the inhibitory neurotransmitters GABA and glycine. Here we report a novel finding that KCC2 is widely expressed in several human cancer cell lines including the cervical cancer cell line (SiHa). Membrane biotinylation assays and immunostaining showed that endogenous KCC2 is located on the cell membrane of SiHa cells. To elucidate the role of KCC2 in cervical tumuorigenesis, SiHa cells with stable overexpression or knockdown of KCC2 were employed. Overexpression of KCC2 had no significant effect on cell proliferation but dramatically suppressed cell spreading and stress fibre organization, while knockdown of KCC2 showed opposite effects. In addition, insulin-like growth factor 1 (IGF-1)-induced cell migration and invasiveness were significantly increased by overexpression of KCC2. KCC2-induced cell migration and invasion were not dependent on KCC2 transport function since overexpression of an activity-deficient mutant KCC2 still increased IGF-1-induced cell migration and invasion. Moreover, overexpression of KCC2 significantly diminished the number of focal adhesions, while knockdown of KCC2 increased their number. Taken together, our data establish that KCC2 expression and function are not restricted to neurons and that KCC2 serves to increase cervical tumourigenesis via an ion transport-independent mechanism.

Cardio-oncology is an emerging subspecialty arising from the need for multidisciplinary collaboration to address the increasing prominence of cardiovascular disease (CVD) among cancer patients. This overview outlines the case for establishing cardio-oncology services and defines the ways in which these services benefit cancer patients. The primary objective of cardio-oncology is to manage CVDs in order to allow cancer patients to complete the best cancer treatments safely and with minimal interruption. In the decades since the first discovery of heart failure induced by anthracycline chemotherapy, both cardiovascular and oncological science have advanced considerably. Cardio-oncology services aim to bring together expertise from these two fast moving fields in order to provide optimal evidence-based care for cancer patients with CVDs. Here we discuss the basis of cardio-oncology services by presenting their rationale and key components, as well as their essential roles in education, training and research. At each stage of the cancer care pathway, a cardio-oncology service can add value by ensuring cancer patients have timely access to specialist care backed up by cutting edge diagnostic tools and treatment options, as well as holistic supports. We highlight areas of recent and upcoming developments in the field that are likely to change established clinical practice. Improved cardiac imaging modalities can detect chemotherapy-related cardiac dysfunction earlier and are also essential for the prompt diagnosis of an expanding range of cardiovascular effects complicating newer cancer therapeutics, such as immune checkpoint inhibitors and other targeted therapies. Modern cancer therapy has dramatically improved cancer survival and as such CVD is becoming one of the principal determinants of overall outcome for cancer patients. A dedicated cardio-oncology service can facilitate the optimisation of cardiovascular treatment and enable the completion of cancer therapy. A multidisciplinary collaborative approach is key to achieving these objectives.

Purpose of reviewCardiovascular comorbidity among cancer patients is a growing clinical problem with the dramatic improvements in cancer survival. Cardio-oncology has developed as a new medical field dedicated to addressing the complex issues faced by patients who have both cancer and cardiovascular disease. This article explains to the reader what cardio-oncology services provide and the nature of cardiovascular problems caused by the growing array of modern cancer therapies. Recent findingsThe list of potentially cardiotoxic cancer therapeutic agents is ever growing and dedicated cardio-oncology experts are required to tackle cardiovascular complications with minimal delay to necessary cancer therapy. Cardio-oncology services originated in academic centres but are now being set up around the world in all hospitals and clinics that provide care to cancer patients. Cardio-oncology plays an increasingly active role at every stage of cancer therapy including baseline risk assessment pretreatment, surveillance and prevention during treatment, response to acute complications and assessment in survivors post cardiotoxic treatments. New treatment strategies exist to optimize cancer treatment so it can be completed safely.

We describe the case of an 86-year-old man with a background of severe left ventricular dysfunction and ischaemic cardiomyopathy who, having been optimised for heart failure therapy in hospital, unexpectedly deteriorated again with hypotension and progressive renal failure over the course of 2 days. Common causes of decompensation were ruled out and a bedside echocardiogram unexpectedly diagnosed new pericardial effusion with tamponade physiology. The patient underwent urgent pericardiocentesis and 890 mL of haemorrhagic fluid was drained. Common causes for haemopericardium were ruled out, and the spontaneous haemopericardium was thought to be related to introduction of rivaroxaban anticoagulation. The patient made a full recovery and was well 2 months following discharge. This case highlights the challenges of diagnosing cardiac tamponade in the presence of more common disorders that share similar non-specific clinical features. In addition, this case adds to growing evidence that therapy with direct oral anticoagulants can be complicated by spontaneous haemopericardium, especially when coadministered with other agents that affect clotting, renal dysfunction and cytochrome P3A5 inhibitors.

Background Implantation of a device is usually required in cardiac sarcoidosis (CS) patients presenting with advanced conduction abnormalities or ventricular arrhythmias. A cardiac resynchronisation therapy (CRT) device is often chosen in patients with concomitant left ventricular systolic impairment. The role of CRT in CS is not well established. Purpose To describe the cohort of CS patients with CRT device in situ in our hospital focusing on the short-term effect in serial echocardiography and long-term outcomes on morbidity and mortality. Methods All consecutive CS patients with a CRT device in situ were identified in our CS database (2005–2022). A confident CS diagnosis was provided after review of all relevant clinical and imaging baseline data in our CS multi-disciplinary meeting and a consensus decision for CRT-D implantation was made based on international guidelines. All patients were followed up for at least 6 months with serial echocardiography. Serial data regarding symptoms, rhythm disturbance and echocardiographic parameters were obtained and comparisons were performed using Wilcoxon signed rank test. Results A total of 51 CS patients with CRT-D were identified (mean age: 57±10 years old). Patients were male predominant (64.7%) and Caucasian in origin (86.2%). Extra-cardiac sarcoidosis was confirmed histologically in 33 (64.7%) patients. The prevalence of smoking, diabetes, hypertension and ischaemic heart disease was 27.5%, 21.6%, 49.0% and 7.8% respectively. At the time of device implantation or during follow-up, 43 (84.3%) patients were found to have active cardiac sarcoidosis on cardiac PET. Post CRT implantation there was a significant difference in LV ejection fraction (35.9±15.0% vs 42.2±14.1%, p<0.001), LV end-systolic diameter (4.90±1.46 cm vs 4.62±1.32 cm, p=0.012) and LV end-diastolic diameter (5.99±1.18 cm vs 5.66±1.06 cm, p<0.001). No significant changes were observed in the right ventricular function (p=0.09) and severity of mitral regurgitation (p=0.40). There was one patient who experienced acute heart failure decompensation admission within six months of CRT-D implantation. The New York Heart Association (NYHA) class improved in 26 patients (51.0%), worsened in 4 (7.8%) patients and remained the same in 21 (41.2%) patients at 6 months post CRT-implantation. During the mean follow up of 47.6 months, the composite end-point of death and cardiac transplantation was reached in 9 (17.6%) patients (8 deaths and 1 cardiac transplantation). 5 patients had major complications including a large haematoma, a small atrio-septal defect, haemothorax, device associated endocarditis and lead fracture. Minor wound infections were seen in 3 patients and 4 patients received inappropriate shock or anti-tachycardia pacing. Conclusions CRT in cardiac sarcoidosis patients is associated with short-term improvement in LV remodelling and functional status but over a four year follow up, morbidity and mortality are common. Funding Acknowledgement Type of funding sources: None.