Long-term outcomes of liver transplantation for homozygous familial hypercholesterolaemia in Australia and New Zealand.

Background And Aims: Homozygous familial hypercholesterolaemia (FH) causes severe cardiovascular disease from childhood. Conventional drug therapy is usually ineffective; lipoprotein apheresis (LA) is often required. Liver transplantation (LT) can correct the metabolic defect but is considered a treatment of last resort.

The Adrenal Vein Sampling Outcomes Study (AVOS): success rates following adrenalectomy for unilateral primary aldosteronism.

The objective was to determine the clinical and biochemical success rates and assess the nature of follow-up after adrenalectomy in patients with unilateral primary aldosteronism (PA), subtyped by adrenal vein sampling (AVS) in West Australia (WA) using the Primary Aldosteronism Surgical Outcome (PASO) criteria. Clinical and biochemical outcomes were retrospectively evaluated in patients with unilateral PA who underwent adrenalectomy according to AVS between September 2017 and September 2020. Pre- and post-surgical data were collected using a standardised questionnaire, review of clinic letters and examination of private and public pathology results and radiological reports.

A variant in the fibronectin (FN1) gene, rs1250229-T, is associated with decreased risk of coronary artery disease in familial hypercholesterolaemia.

Background: Increased risk of coronary artery disease (CAD) in familial hypercholesterolaemia (FH) is modified by factors beyond defects in the low-density lipoprotein receptor pathway. The rs1250229-T single nucleotide polymorphism (SNP) in the FN1 gene is associated with CAD in genome-wide association studies and is in linkage disequilibrium with another SNP (rs1250259-T) in FN1 that is associated with decrease fibronectin secretion.

Objective: We investigated whether rs1250229-T was also associated with prevalent CAD in patients with genetically confirmed FH.

Detecting patients with Cushing's syndrome: The importance of initial test selection.

Background And Objectives: The recommended initial tests for suspected Cushing's syndrome are late-night salivary cortisol (LNSC), 24-hour urinary free cortisol (UFC) and the 1 mg overnight dexamethasone suppression test (ONDST). These tests have higher sensitivity and specificity than serum cortisol. The aim of this study was to determine the relative frequency of these requested tests in primary care.

Approach to the diagnosis of secondary hypertension in adults.

Presentations that should raise suspicion of secondary hypertension include early-onset, severe or resistant hypertension. A suggestive family history or clinical clues can point to a specific secondary cause. The most common causes and associations are renal disease, primary aldosteronism and obstructive sleep apnoea.

Contemporary perspectives on the genetics and clinical use of lipoprotein(a) in preventive cardiology.

Purpose Of Review: The pathogenicity of lipoprotein(a) [Lp(a)] as a risk factor for atherosclerotic cardiovascular disease (ASCVD) is well evidenced and recognized by international consensus-based guidelines. However, the measurement of Lp(a) is not routine clinical practice. Therapeutic agents targeting Lp(a) are now progressing through randomised clinical trials, and it is timely for clinicians to familiarize themselves with this complex and enigmatic lipoprotein particle.

Lipoprotein apheresis and PCSK9 inhibitors for severe familial hypercholesterolaemia: Experience from Australia and New Zealand.

Introduction: Severe familial hypercholesterolaemia (FH) causes premature disability and death due to atherosclerotic cardiovascular disease and is refractory to standard lipid-lowering therapies. Lipoprotein apheresis (LA) has long been a standard of care for patients with severe FH, but is invasive, expensive and time-consuming for patients and their caregivers. Newer drug therapies, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, may reduce the need for LA.

Widening the spectrum of genetic testing in familial hypercholesterolaemia: Will it translate into better patient and population outcomes?

Familial hypercholesterolaemia (FH) is caused by pathogenic variants in LDLR, APOB or PCSK9. Impaired low-density lipoprotein (LDL) receptor function leads to decreased LDL catabolism and premature atherosclerotic cardiovascular disease (ASCVD). Thousands of LDLR variants are known, but assignation of pathogenicity requires accurate phenotyping, family studies and assessment of LDL receptor function.

Pharmacokinetics of flucloxacillin during prolonged intermittent renal replacement therapy in a 76-year-old man.

Prolonged intermittent renal replacement therapy (PIRRT) use has been increasing in critically ill patients with kidney dysfunction. PIRRT can affect the pharmacokinetics of many drugs, although no data is available to guide flucloxacillin dosing in this clinical scenario. Herein, we describe the pharmacokinetics of flucloxacillin, given at 1 g every 4 h during PIRRT, in a 76-year-old, critically ill patient with a methicillin-susceptible (MSSA) prosthetic joint infection complicated by bacteraemia.

Pharmacokinetics of Benzylpenicillin (Penicillin G) during Prolonged Intermittent Renal Replacement Therapy.

Prolonged intermittent renal replacement therapy (PIRRT) is an increasingly adopted method of renal replacement in critically ill patients. Like continuous renal replacement therapy, PIRRT can alter the pharmacokinetics (PK) of many drugs. In this setting, dosing data for antibiotics like benzylpenicillin are lacking.

Clinical guidance on the contemporary use of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies.

There is now significant evidence for the benefits of lowering low-density lipoprotein cholesterol (LDL-c) to reduce the risk of atherosclerotic cardiovascular disease (ASCVD). Although statins are the most widely prescribed lipid-lowering therapy that effectively lower LDL-c, especially in combination with ezetimibe, some patients require adjunctive therapy to further lower LDL-c and mitigate attendant risk of ASCVD. The gap can be filled by proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies whose use is currently supported by two recent cardiovascular outcome studies and new treatment guidelines.

PCSK9 inhibition 2018: riding a new wave of coronary prevention.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a hepatic enzyme that regulates the low-density lipoprotein cholesterol (LDL-c) receptor and thus circulating LDL-c levels. With overwhelming evidence now supporting the reduction in LDL-c to lower the risk of cardiovascular disease, PCSK9 inhibitors represent an important therapeutic target, particularly in high-risk populations. Here, we summarise and update the science of PCSK9, including its discovery and the development of various inhibitors, including the now approved monoclonal antibodies.

The challenge of improving the diagnostic yield from metanephrine testing in suspected phaeochromocytoma and paraganglioma.

Background Plasma-free metanephrines (PFM) or urinary fractionated metanephrines (UFM) are the preferred biochemical tests for the diagnosis of phaeochromocytoma and paraganglioma (PPGL). Borderline increased results should be followed up to either exclude or confirm diagnosis. Methods We extracted all PFM and UFM results reported by our laboratory over a six-month period from the laboratory information system.

Improved technical success and radiation safety of adrenal vein sampling using rapid, semi-quantitative point-of-care cortisol measurement.

Unlabelled: Objective Primary aldosteronism is a curable cause of hypertension which can be treated surgically or medically depending on the findings of adrenal vein sampling studies. Adrenal vein sampling studies are technically demanding with a high failure rate in many centres. The use of intraprocedural cortisol measurement could improve the success rates of adrenal vein sampling but may be impracticable due to cost and effects on procedural duration.

Rare cause of adrenal insufficiency.

A 72-year-old man presented with weight loss, night sweats and haemoptysis and was hypotensive. CT imaging showed rapidly enlarging bilateral adrenal masses, and he was found to have primary adrenal insufficiency. An adrenal gland biopsy revealed the rare diagnosis of primary adrenal lymphoma.

PCSK9 in context: A contemporary review of an important biological target for the prevention and treatment of atherosclerotic cardiovascular disease.

The identification of the critical role of proprotein convertase subtilisin/kexin type 9 (PCSK9) has rapidly led to the development of PCSK9 inhibition with monoclonal antibodies (mAbs). PCSK9 mAbs are already in limited clinical use and are the subject of major cardiovascular outcomes trials, which, if universally positive, could see much wider clinical application of these agents. Patients with familial hypercholesterolaemia are the most obvious candidates for these drugs, but other patients with elevated cardiovascular risk, statin intolerance or hyperlipoproteinaemia(a) may also benefit.

Isolated brachydactyly type E and idiopathic pancreatitis in a patient presenting to a lipid disorders clinic.

An 18-year-old female tertiary student was referred to a lipid clinic with hypertriglyceridaemia discovered after presentation with acute pancreatitis. The patient's only medication was l-thyroxine for treatment of hypothyroidism. She was overweight, normotensive, with unremarkable facies.

Ten years of lipoprotein apheresis for familial hypercholesterolemia in Malaysia: A creative approach by a cardiologist in a developing country.

Background: Familial hypercholesterolemia (FH) leads to premature coronary artery disease and aortic stenosis, with undertreated severe forms causing death at a young age. Lipoprotein apheresis (LA) is often required for lowering low-density lipoprotein cholesterol levels in severe FH.

Objectives: The objective of this study was to present the first experiences with LA in Malaysia, between 2004 and 2014.

Anacetrapib for the treatment of dyslipidaemia: the last bastion of the cholesteryl ester transfer protein inhibitors?

Introduction: Inhibition of cholesteryl ester transfer protein (CETP) has emerged as a potential way to decrease cardiovascular risk by raising high density lipoprotein (HDL) cholesterol and lowering low density lipoprotein (LDL) cholesterol concentrations. However, high profile withdrawals of several CETP inhibitors have cast doubt over this hypothesis. Despite this concern, anacetrapib appears to be safe, well-tolerated and delivers a substantial increases in HDL cholesterol and reductions in LDL cholesterol as monotherapy and when combined with a statin.

Evolocumab in the treatment of dyslipidemia: pre-clinical and clinical pharmacology.

Introduction: Statins are the mainstay of lipid-lowering therapies targeted at reducing cardiovascular risk. However, they do not completely obviate risk, not all patients tolerate them, and they are not sufficiently effective in patients with very high plasma levels of low-density lipoprotein-cholesterol (LDL-C) such as those with familial hypercholesterolemia (FH) or patients with elevated plasma levels of lipoprotein(a) [Lp(a)]. Recent advances in the understanding of lipoprotein metabolism have led to the development of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors including evolocumab , which lowers plasma levels of LDL-C by 50 - 75% as monotherapy or in combination with statin therapy.