Everyday Medicine with Dr Luke

Hypermobile joints were noted by Hippocrates as long ago as 400 BCE and are common, occurring in about 10-25 % of the population. In a minority of patients’ pain and injury results suggest that the clinical findings may reflect a condition referred to as hypermobility spectrum disorder, a polygenic connective tissue syndrome affecting between 1:500 to 1:600 people. This syndrome involves extreme joint flexibility often associated with joint pains, tends to run in families and is more common amongst females. Hypermobility spectrum disorder has been redefined separately from the more stringent diagnostic criteria required for the diagnosis of more extreme hypermobility syndromes such as Ehlers-Danlos syndrome, Marfans disease, Loeys-Dietz or Osteogenesis imperfecta syndromes. In relation to the above-mentioned syndromes in 1901 a Danish doctor, Dr Lauritz-Edvard Ehlers presented a case of hypermobility, and a similar case was subsequently presented by French physician Dr Henri-Alexandre Danlos in 1908. The name Ehlers-Danlos syndrome (EDS) wasn’t proposed until many years later in 1936 by Englishman Dr Parkes-Weber. We now recognize 13 types of Ehlers-Danlos syndrome with hypermobile EDS as the most common and myopathic EDS, Spondylodysplastic classical EDS and brittle cornea syndrome as just some of the others. About 1: 3500 to 1: 5000 people have EDS. Both dominant and recessive inheritance patterns are noted. Frequent joint and ligament injuries including sprains and dislocations may occur and joint stiffness, clumsiness, fatigue dizziness and associated bowel and bladder complaints are often cited. Another well-known hypermobility disorder Marfans syndrome is rare affecting about 1 in 5000 and in three-quarters of cases, inheritance is autosomal dominant with the defective fibrillin gene resulting in tall individuals with slender limbs, fingers and toes, cardiac defects including aortic dissections, aortic root aneurysms and valvular incompetence, lens dislocations as well as the high arched palate, crowded teeth and abnormal sternum development (pectus excavatum or pectus carinatum ). A quarter of cases experience a new gene mutation with no family pedigree identified. These hypermobility conditions have common abnormalities in collagen structure and function. Whilst genetic studies are available in some cases of hypermobility (but not hypermobility spectrum disorder), the criteria for diagnosis referred to as The Beighton criteria are essentially clinical and includes a Beighton score reflecting joint extensibility and mobility combined with arthralgia over 3 months, dislocations and subluxations, soft tissue lesions such as epicondylitis, tenosynovitis and bursitis, Marfanoid habitus and abnormal skin with striae, hyperextensibility, thin skin and papyraceous scarring. No cure is currently known for these syndromes which are managed symptomatically. Fortunately, societies such as the Ehlers-Danlos Society and physicians such as Assoc Professor Chris O’Callaghan from Melbourne’s Austin Health are the most helpful resources and I welcome you to the interview with Chris to expand our understanding of this subject today. References: Assoc Professor Chris O’Callaghan: www.austin.org.au The Ehlers Danlos Society: www.ehlers-danlos.com Ehlers-Danlos syndromes: www.nhs.uk

Acid-Base theory is often considered a difficult subject. As long ago as 1962, Creese et al wrote in the Lancet … “There is a bewildering variety of pseudoscientific jargon in medical writing on this subject “My suspicion is that some degree of confusion and thus avoidance of the subject continues to this day. Hopefully, this podcast conversation will resonate with some of our listeners and smooth out any misunderstandings should they exist. As a background, Bronsted and Lowrys definitions of acids and bases are as follows: A base is a substance that accepts a proton (a hydrogen ion) an acid is a compound that dissociates in water to release a proton. A strong acid is one that readily dissociates in water to release a proton (eg HCL), and a weak acid does not readily dissociate in water (uric acid). pH is the negative logarithm of the hydrogen ion concentration to the base 10. Thus, the negative logarithm of 0.0000001 which may be expressed as 10 to the power of -7 is 7. The reason blood and cellular pH are so important is that their stability is essential to the integrity of enzymes, metabolic processes, and cell membrane potential. Homeostasis holds our blood pH tightly between 7.35 and 7.45 with an intracellular pH of 6.8. Where does the acid come from? Acid production results from the production of CO2 by metabolism of glucose, fatty acids, and amino acids. CO2 combines with water and is converted to carbonic acid -H2CO3 by carbonic anhydrase and then dissociates to H+ and HCO3-. That enzyme carbonic anhydrase pops up everywhere. Acid production also results from anaerobic glucose metabolism whereby glucose is converted to H+ and lactate in ketogenesis as well as from the catabolism of the amino acids: methionine and cysteine. Which organs play a major role in the maintenance of pH? Both the lungs and kidneys play critical roles in acid-base balance. We exhale CO2 from the lungs effectively blowing off acid but may also retain CO 2 by underventilation. The kidneys have the potential to excrete or absorb bicarbonate and to excrete or reabsorb protons (hydrogen ions) influencing and compensating for pH disturbance through an intricate juggling of these two. The excretion of protons is by combination with ammonia from the metabolism of muscle glutamine or in combination with monohydrogen phosphate. These ingenious biological systems may be influenced by multiple disease processes and respiratory forms of acidosis and alkalosis as well as metabolic processes leading to acidosis and alkalosis are well recognised. Whilst arterial blood gas assessment is used in critical care units to determine the degree of oxygenation, adequacy of ventilation, and the presence and severity of acid-base disturbances in the body, arterial puncture may result in complications, and the difficulty in acquiring arterial blood may delay care. Venous blood gas (VBG) is a more accessible alternative to ABG sampling and correlates well with arterial sampling in pH measurement (slightly lower in venous sample) and HCO3 - (1.41 mmol/l higher in venous) with pCO2 approximately 5.6 mmHg higher in venous blood. These differences may be exaggerated however in circulatory failure. In this podcast with ICU physician Associate Professor Adrian Regli, we will explore the subject further, delve into some of the typical metabolic and respiratory disturbances we are likely to encounter as clinicians and also review some handy rules of thumb to draw upon in practical acid-base interpretation. Currently, Adrian works as an ICU consultant at Fiona Stanley Hospital Perth. Please welcome Adrian to the Podcast. References Assoc Professor Adrian Regli - via Google Oh’s Intensive Care Manual, Bersten et al 6 th ED, Butterworth Medical Biochemistry at a Glance, Salway,3rd ED, Wiley-Blackwell Acid-Base Disorders in the Critically Ill Patient, Achanti et al CJASN, Sept 2022

Clinical problems related to the integument are very common and contribute up to 15% of all general practitioner presentations. Humans are predisposed to a multitude of skin diseases ranging from acne and atopic dermatitis to psoriasis, autoimmune diseases such as SLE, vasculitis, skin cancers, viral exanthems, drug eruptions and external manifestations of internal disease - which in the gastroenterology world have erythema nodosum and pyoderma gangrenosum as interesting examples of these. Given our love affair with the sun it’s not surprising to learn that skin cancer will affect 2 in 3 Australians in their lifetime. About 2000 Australians die each year from melanoma and non-melanoma skin cancer - 800 more than the number of people dying from car accidents annually in Australia bringing into perspective the impact of this disease alone. Inflammatory skin diseases such as acne and eczema are also very common. They are a cause of serious morbidity, both physical as well as psychological – a child with severe eczema has a burden of disease that is worse than a child with diabetes. Have you ever had itchy skin? This is one of the most distressing symptoms one may experience.The mental health issues of patients with skin disease can be severe. A recent meta-analysis of patients with alopecia areata for example found that up to 17% of those patients required professional help for symptoms of anxiety and depression. A skin problem is very visible and yet, in the hierarchy of “medical student teaching” – dermatology is treated almost as an optional extra. In recent years advances in skin management have been significant especially following the discovery of TNF inhibitors such as Adalimumab used in dermatology for moderate to severe psoriasis as well as in both rheumatology and gastroenterology. In this podcast I was curious to learn more about dermatological management, the new horizons of treatment, possible role for AI in assisting diagnosis as well as to be reminded of key tips that would be useful in primary care. It was a real honour to discover Melbourne dermatologist Dr Alvin Chong, founder of an internationally acclaimed podcast called Spot Diagnosis that has been ground-breaking in bringing the specialty of dermatology to general practice and medical students. Alvin has established himself as a key educator in this field and has received accolades from the RACGP recognising his achievements and contribution to education. Alvin has public appointments as Visiting Dermatologist and Director of Dermatological Education at St Vincent’s Hospital Melbourne and Head of Transplant Dermatology Clinic at Skin Health Institute. He is Adjunct Associate Professor at the University of Melbourne. Please welcome Alvin to the Podcast. References: Dr Alvin Chong ⁠http://spotdiagnosis.org.au/⁠ ⁠https://www.skinhealthinstitute.org.au/page/370/spotdiagnosis⁠

Clinical problems related to the integument are very common and contribute up to 15% of all general practitioner presentations. Humans are predisposed to a multitude of skin diseases ranging from acne and atopic dermatitis to psoriasis, autoimmune diseases such as SLE, vasculitis, skin cancers, viral exanthems, drug eruptions and external manifestations of internal disease - which in the gastroenterology world have erythema nodosum and pyoderma gangrenosum as interesting examples of these.  Given our love affair with the sun it’s not surprising to learn that skin cancer will affect 2 in 3 Australians in their lifetime. About 2000 Australians die each year from melanoma and non-melanoma skin cancer - 800 more than the number of people dying from car accidents annually in Australia bringing into perspective the impact of this disease alone. Inflammatory skin diseases such as acne and eczema are also very common. They are a cause of serious morbidity, both physical as well as psychological – a child with severe eczema has a burden of disease that is worse than a child with diabetes. Have you ever had itchy skin? This is one of the most distressing symptoms one may experience.The mental health issues of patients with skin disease can be severe. A recent meta-analysis of patients with alopecia areata for example found that up to 17% of those patients required professional help for symptoms of anxiety and depression. A skin problem is very visible and yet, in the hierarchy of “medical student teaching” – dermatology is treated almost as an optional extra.  In recent years advances in skin management have been significant especially following the discovery of TNF inhibitors such as Adalimumab used in dermatology for moderate to severe psoriasis as well as in both rheumatology and gastroenterology.  In this podcast I was curious to learn more about dermatological management, the new horizons of treatment, possible role for AI in assisting diagnosis as well as to be reminded of key tips that would be useful in primary care. It was a real honour to discover Melbourne dermatologist Dr Alvin Chong, founder of an internationally acclaimed podcast called Spot Diagnosis that has been ground-breaking in bringing the specialty of dermatology to general practice and medical students. Alvin has established himself as a key educator in this field and has received accolades from the RACGP recognising his achievements and contribution to education. Alvin has public appointments as Visiting Dermatologist and Director of Dermatological Education at St Vincent’s Hospital Melbourne and Head of Transplant Dermatology Clinic at Skin Health Institute. He is Adjunct Associate Professor at the University of Melbourne.  Please welcome Alvin to the Podcast.   References: Dr Alvin Chong http://spotdiagnosis.org.au/ https://www.skinhealthinstitute.org.au/page/370/spotdiagnosis

From the RACGP Health of the Nation report; depression, anxiety, and sleep disturbances are amongst the most commonly seen presentations of mental disorders in general practice. About 1 in 8 people in the world live with a mental disorder which often involves significant disturbances in thinking, emotional regulation, or behaviour.  Globally it is estimated that 5% of adults suffer from depression, affecting women a little more than men.  Anxiety disorders affect a similar number of people, characterised by excessive fear, and worry and related behavioural disturbances.  Bipolar disease is characterised by periods of depressive episodes alternating with periods where manic symptoms prevail. Affecting less than 1 % of the population, suicide risk is increased.  Addiction disorders embrace a long list of destructive habits. Post traumatic stress disorder (PTSD), schizophrenia, disruptive behaviour, and dissocial disorders as well as neurodevelopmental disorders are amongst the many conditions presenting clinically and often requiring psychiatric assessment.  I was also interested to discover more about the adverse effects of social media on teenage and young adults’ mental health and in this podcast, and was curious to explore some of the mental health conditions presenting commonly in primary practice and to understand the place of therapies available. It was a privilege to interview psychiatrist Dr Usman Riaz for this episode. Dr Muhammad Usman Riaz is a fellow of The Royal Australian and New Zealand College of Psychiatrists and has sub-specialised in addiction psychiatry. He Holds a Master of Public Health with a major in Occupational Health and Safety from Monash University and Master of Psychiatry from the University of Melbourne. He is Director of Medical Service at The Langmore Centre in Berwick operated by St John of God Hospital. Please welcome Usman to the conversation. REFERENCES: Dr Usman Riaz-www.sjog.org.au World Health Organization-Mental Disorders. Who.int Selective Serotonin Reuptake Inhibitors-Stat Pearls www.ncbi.nlm.nih.gov ⁠www.beyondblue.org.au⁠

From the RACGP Health of the Nation report; depression, anxiety, and sleep disturbances are amongst the most commonly seen presentations of mental disorders in general practice. About 1 in 8 people in the world live with a mental disorder which often involves significant disturbances in thinking, emotional regulation, or behaviour.  Globally it is estimated that 5% of adults suffer from depression, affecting women a little more than men.  Anxiety disorders affect a similar number of people, characterised by excessive fear, and worry and related behavioural disturbances.  Bipolar disease is characterised by periods of depressive episodes alternating with periods where manic symptoms prevail. Affecting less than 1 % of the population, suicide risk is increased.  Addiction disorders embrace a long list of destructive habits. Post traumatic stress disorder (PTSD), schizophrenia, disruptive behaviour, and dissocial disorders as well as neurodevelopmental disorders are amongst the many conditions presenting clinically and often requiring psychiatric assessment.  I was also interested to discover more about the adverse effects of social media on teenage and young adults’ mental health and in this podcast, and was curious to explore some of the mental health conditions presenting commonly in primary practice and to understand the place of therapies available. It was a privilege to interview psychiatrist Dr Usman Riaz for this episode. Dr Muhammad Usman Riaz is a fellow of The Royal Australian and New Zealand College of Psychiatrists and has sub-specialised in addiction psychiatry. He Holds a Master of Public Health with a major in Occupational Health and Safety from Monash University and Master of Psychiatry from the University of Melbourne. He is Director of Medical Service at The Langmore Centre in Berwick operated by St John of God Hospital. Please welcome Usman to the conversation. REFERENCES: Dr Usman Riaz-www.sjog.org.au World Health Organization-Mental Disorders. Who.int Selective Serotonin Reuptake Inhibitors-Stat Pearls www.ncbi.nlm.nih.gov www.beyondblue.org.au

Over the past decade there has been an emergence of literature pointing to potential clinical benefits for a range of disease states through the adoption of slow breathing techniques. The popularity worldwide of the Wim Hof method adopted from eastern techniques has done much to pique interest.  Notably the belief and practice of controlling one’s breath to both restore and enhance health is not new however and has been practised for thousands of years amongst Eastern cultures. Pranayama or Yogic breathing as well as Kundalini are well-known ancient practices of controlled breathing and exists in various forms often in conjunction with meditation. A system of breathing developed in the 1900s by the Ukranian doctor Konstantin Buteyko claimed to successfully treat patients diagnosed with respiratory and circulatory disease possibly through reducing ventilatory dead space, increased tidal volume and by inducing favourable effects on the autonomic nervous system. Practised slow nasal breathing has been shown to extract 20 % more oxygen from each breath enhancing athletic performance. Slow and controlled breathing through the nose with a respiration rate of between 6 and 10 per minute appears to be optimal for enhancing the Bohr effect. Getting there requires practice and adoption of nasal breathing techniques. The latter also delivers more Nitrous oxide, an important vasodilator which in relation to this subject is produced by the paranasal sinuses. Nasal breathing also filters and humidifies the air we breathe. In this podcast I was interested to explore this fascinating subject with breathing expert, physiotherapist and snow skier Mr Allan Abbott. Allan has broadened his expertise with qualifications in physical education, ergonomics and acupuncture. He runs numerous seminars on breathing for performance including Athletes Master Classes incorporating high altitude training through his company Health Innovations Australia and has established the “Breathe Light Breathe Right” as well as the ‘Sleep Well be Well” programs.  Allan subscribes to a notion that  breathing, sleep, diet, exercise and mindfulness are the major components to optimal health. Please welcome Allan to the podcast. References: Mr Allan Abbott.oxygenadvantage.com and ⁠www.healthinnovations⁠ .net.au Breath- The New Science of a Lost Art. Penguin Books. July 20,2021.James Nestor The Physiological effects of slow breathing in the health human. Russo et al. ⁠www.ncbi.nlm.nih.gov⁠ How Breath-Control Can Change Your Life : A systematic review on Psycho-Physiological Correlates of Slow Breathing. Zaccaro et al.2018. www.frontiersin.org. 

Over the past decade there has been an emergence of literature pointing to potential clinical benefits for a range of disease states through the adoption of slow breathing techniques. The popularity worldwide of the Wim Hof method adopted from eastern techniques has done much to pique interest.  Notably the belief and practice of controlling one’s breath to both restore and enhance health is not new however and has been practised for thousands of years amongst Eastern cultures. Pranayama or Yogic breathing as well as Kundalini are well-known ancient practices of controlled breathing and exists in various forms often in conjunction with meditation. A system of breathing developed in the 1900s by the Ukranian doctor Konstantin Buteyko claimed to successfully treat patients diagnosed with respiratory and circulatory disease possibly through reducing ventilatory dead space, increased tidal volume and by inducing favourable effects on the autonomic nervous system. Practised slow nasal breathing has been shown to extract 20 % more oxygen from each breath enhancing athletic performance. Slow and controlled breathing through the nose with a respiration rate of between 6 and 10 per minute appears to be optimal for enhancing the Bohr effect. Getting there requires practice and adoption of nasal breathing techniques. The latter also delivers more Nitrous oxide, an important vasodilator which in relation to this subject is produced by the paranasal sinuses. Nasal breathing also filters and humidifies the air we breathe. In this podcast I was interested to explore this fascinating subject with breathing expert, physiotherapist and snow skier Mr Allan Abbott. Allan has broadened his expertise with qualifications in physical education, ergonomics and acupuncture. He runs numerous seminars on breathing for performance including Athletes Master Classes incorporating high altitude training through his company Health Innovations Australia and has established the “Breathe Light Breathe Right” as well as the ‘Sleep Well be Well” programs.  Allan subscribes to a notion that  breathing, sleep, diet, exercise and mindfulness are the major components to optimal health. Please welcome Allan to the podcast. References: Mr Allan Abbott.oxygenadvantage.com and www.healthinnovations .net.au Breath- The New Science of a Lost Art. Penguin Books. July 20,2021.James Nestor The Physiological effects of slow breathing in the health human. Russo et al. www.ncbi.nlm.nih.gov How Breath-Control Can Change Your Life : A systematic review on Psycho-Physiological Correlates of Slow Breathing. Zaccaro et al.2018. www.frontiersin.org. 

Emotional intelligence (EI) also known as EQ, is the ability to perceive, understand and manage emotions in positive ways to communicate effectively, empathise with others, overcome challenges and defuse conflict as well as to relieve stress. Emotional intelligence helps build stronger relationships, achieve personal career goals, and interact more positively at work. It gives us an ability to join intelligence, empathy, and emotions to enhance thought and understanding of interpersonal dynamics, guiding our thinking and behaviour. For as in Shakespeare’s Hamlet - 'there is nothing either good nor bad but thinking makes it so'. The term EI first appeared in writing in 1964 and was popularised by Daniel Goleman in his book titled Emotional Intelligence published in 1995 in which he applied the concept especially to business defining the term as an array of skills and characteristics that drive leadership and performance. EI is commonly defined by four domains or attributes including: 1. Self-Awareness-Understanding what you are feeling and why and appreciating your strengths and weaknesses. 2. Self-Management- The ability to control impulsive feelings and behaviours, adapt to changing circumstances and manage emotions in healthy ways. This is also referred to as self-regulation and points to a positive outlook and achievement. 3. Social awareness -Including the concept of empathy which helps us understand the emotions, needs and concerns of others. Developing social awareness allows us to recognise the power dynamics in a group or organisation. 4. Relationship management-Which encompasses conflict management, coaching and mentorship and encourages the development of teamwork through inspirational leadership. There are several excellent books on the subject of emotional intelligence including: Achieving Emotional Literacy by Claude Steiner, 'How Emotions are Made' by Lisa Feldman Barrett, Emotional Agility by Susan David and Daniel Goleman’s Emotional Intelligence. I was curious to explore this topic in more detail and was privileged recently to meet Shawn Price who is an expert in this field. Shawn initially trained as a mathematician but was drawn to the study of psychology and especially emotional intelligence recognising its important application to both business, families, and individuals. Shawn now manages his company Positive Intelligence from where he coaches and consults privately as well as being engaged by industry and large organisations to run workshops and lecture programs on this important subject. Please welcome Shawn to the podcast. References: Shawn Price: Positive Intelligence. www.positiveintelligence.com.au Emotional Intelligence, Daniel Goleman. ISBN:9780553804911 Emotional Intelligence; www.helpguide.org/ Segal, Robinson and Shubin Emotional Intelligence has 12 Elements. Which do you need to work on? Harvard Business Review. Feb 06,2017. Goleman and Boyatzis

We are dedicating this podcast to the memory of Professor Lawrie Powell, both a gentleman, mentor and giant in the field of hepatology and whose very significant contributions to our understanding of hemochromatosis laid down a firm foundation of knowledge and insight for everyone practicing internal medicine. It is upon his shoulders that much further research in the field of hemochromatosis and hepatology generally has prospered. Haemochromatosis is the most common autosomal recessive disorder in Caucasians with an incidence of about 1 :260 and carriage of about 1: 10. Untreated the excess iron storage from hemochromatosis may lead to cirrhosis and hepatocellular carcinoma, diabetes, cardiomyopathy, hypogonadism, arthritis, bronzing of the skin and render some susceptibility to siderophilic bacteria including some vibrio and Yersinia species. The consequences of iron overload are exacerbated by preexisting condition such as NASH and alcohol associated liver disease.  A key breakthrough in the understanding of hemochromatosis came with the discovery of a negative regulatory protein coded for by the HAMP gene on chromosome 19 called Hepcidin. Hepcidin serves as a counterregulatory protein. As iron absorption and stores increase Hepcidin levels in healthy individuals also increase leading to decreased iron absorption and restoration of normal iron levels. Hepcidin appears to work by internalization and degradation of Ferroportin thereby inhibiting iron absorption across the basolateral membrane of enterocytes as serum iron levels climb.  A transferrin receptor on the surface of hepatocytes relays information concerning serum iron concentration as part of this elaborate feedback mechanism.  Mutations of the so-called High Iron -or Hemostatic Iron Regulator -HFE gene on the short arm of chromosome 6 modulate the expression of Hepcidin, effectively blocking the elaborate feedback mechanism that senses serum iron and leading to inappropriately lowered levels of Hepcidin production as iron levels climb. This defect underlies the problem of excess iron absorption in Hemochromatosis with the consequent adverse physiologic effects mentioned above.  The gene mutation responsible for Hemochromatosis is thought to have arisen some 6000 years ago within Viking or Celtic communities possibly protecting against iron deficiency states when resources were scarce.  Treatment by regular phlebotomy remains the preferred method of management and screening for HCC in cases of established cirrhosis is mandatory. I was honored to further this conversation about hemochromatosis with Professor Darrell Crawford, one of my mentors from Queensland in a previous life. Darrell has both the reputation for being an excellent hepatologist as well as having significant international standing in the field of liver disease and has published widely. He has held leadership positions within the national and international professional societies relevant to his discipline including GESA and the University of Queensland including as the Acting Deputy Executive Dean and Head, School of Medicine where he has played a key role in reshaping the medical program and medical faculty at the University of Queensland. Please welcome Darrell to the podcast. Treatment by regular phlebotomy remains the preferred method of management and screening for HCC in cases of established cirrhosis is mandatory. References: Professor Darrell Crawford-medicine.uq.edu.au,  Queensland Gastroenterology Greenberger’s Current Diagnosis and Treatment, 4th Ed, Friedman et al, McGraw Hill Lange Principles of Medical Biochemistry, 3Rd Ed, Meisenberg and Simmons, Elsevier Saunders

The corner stone of cardiovascular disease prevention is the identification of high-risk asymptomatic individuals. In this regard coronary artery calcium is a highly specific marker of atherosclerosis and can be quantified using non contrast CT scanning which provides an accurate measure of atherosclerotic burden. Coronary artery disease is the single leading cause of disease morbidity and mortality in Australia and is responsible for approximately one in 10 deaths furthermore half the individuals with coronary artery disease will present with a myocardial infarction or death. The compelling reason for undertaking coronary artery calcium scoring is to identify asymptomatic at-risk individuals who are likely to benefit from early detection, risk factor intervention and treatment of coronary artery disease. In Australia risk assessment is recommended using the National Vascular Disease Prevention Alliance tool based on the Framingham Risk Equation. This risk stratification is drawn upon to guide the decision for calcium scoring which according to the Cardiac Society of Australia and New Zealand is recommended for asymptomatic intermediate risk patients or where there may be other strong evidence supporting its ability to improve cardiovascular risk assessment. High risk individuals may be better assessed by means of stress testing. The calcium score is determined by non-contrast CT scanning and is complete within about ten minutes delivering just a little over 1 mSv of radiation equivalent to the annual background radiation we are exposed to. Using the Agatston method the volume and density of calcium is calculated and computed as a score. Again drawing upon The Cardiac society of Australia and New Zealand calcium scores may be interpreted as follows: A measurement of 0 is very low risk of coronary disease, a score of 1-100 is low risk, a measure of 101-400 is considered moderate risk and a patient lying within the 75th percentile of this group is at moderately high risk. Measurement over 400 denotes a high risk. Multiple studies including the Multiethnic Study of Atherosclerosis (MESA) have confirmed the long-term prognostic value of CT calcium scores with over ten years of prospective follow up. The value of calcium scoring lies in its ability to improve the accuracy of risk prediction. It helps to identify individuals who may benefit from more aggressive primary prevention measures; including the use of low dose aspirin that may otherwise not be recommended for primary prevention, as well as aggressive lipid management with statin therapies. Given the importance of detecting asymptomatic coronary heart disease I was interested in pursuing the conversation further with one of the US expert cardiologists Dr Alistair Fyfe who has been practicing cardiology for over 38 years after graduation from the University of Tasmania. Alistair has worked in Canada as well as the United States and is in Dallas, Texas where he has affiliations with Medical City Dallas and White The Heart Hospital Baylor Plano and is Medical Director of Blue Cross and Blue Shield of Illinois, Montana, New Mexico Oklahoma, and Texas not bad for a home-grown lad. He is currently busy writing a contributing chapter to a soon to be published book titled: "The Implementation of Personalised Precision Medicine”, which, if I know Alistair will be excellent and a must read. Given his expertise I was curious to learn a little more about its application and how a measured coronary calcium score should influence our approach to patient management. I know you will find this conversation with Alistair very interesting. Please welcome him to the podcast. References: Dr Alistair Fyfe - on google and LinkedIn Coronary artery calcium in primary prevention Chuah.www1.racgp.org.au When not to use calcium scoring www.ausdoc.com.au Polonsky et al. Coronary artery calcium score and risk classification for coronary heart disease prediction.

Headache is an extremely common symptom, and collectively, headache disorders rank among the most prevalent nervous system disorders. Approximately 95% of the general population have experienced a headache at some point in their lives, with a one-year prevalence rate of about one in every two adults. Headache accounts for up to 1 in 10 general practitioner consultations, remains a frequent reason for neurology referrals, and in Europe, constitutes up to 4% of emergency department visits, with migraine being the most common type. The World Health Organization includes headache among the top ten causes of disability. While the impact on the economy and an individual’s quality of life may be challenging to quantify, in the case of migraine, up to 75% of patients report functional disability during an attack, and about 50% require the assistance of family and friends. Headaches do not discriminate; they affect people of all ages, races, and socioeconomic statuses, but they are more common in women. Headaches are generally categorized as acute or chronic. Acute headaches may be new and severe, potentially indicating critical intracranial pathology like an aneurysm or meningitis. Chronic headaches are typically classified into primary types such as migraine, cluster, and tension-type, or secondary, which could reflect intracranial pathology or result from conditions like cervical spondylosis, dental and ocular disorders, sinusitis, hypertension, depression, TMJ dysfunction, temporal arteritis, medication side effects, and others. When consulting with patients, inquiring about the onset of the headache, its frequency and type, duration, recent changes in characteristics, intensity, location, pain quality, associated symptoms like nausea and vomiting, factors that worsen or alleviate it, as well as the presence of neurological symptoms such as visual and sensory changes or alterations in speech, can all aid in establishing a diagnosis. Migraine often demonstrates a complex polygenic pattern of inheritance, and in the case of familial hemiplegic migraine, it exhibits an autosomal dominant pattern of inheritance. In my conversation with expert headache and movement disorder specialist Dr. Michael Eller from Richmond Neurology, I was keen to delve deeper into the realm of chronic primary headaches—specifically, migraine and cluster types. The evolving understanding of the pathophysiology of these headaches and the developing treatment approaches, focusing on inhibiting the neurotransmitter called Calcitonin gene-related peptide, is fascinating. This peptide is inhibited by the 5-HT1D and 1B receptor agonist effect of the triptans, as well as by a new family of CGRP-targeting drugs and monoclonal antibodies developed for the preventive treatment of migraine. Michael completed his medical degree at the University of Sydney in 2003 following a Bachelor of Science and Arts. He has interests in archaeology, neuroscience, infectious disease, and indigenous health. Additionally, he has volunteered as an aid worker in remote locations, including PNG, and underwent training from 2012 to 2014 at The University of California, San Francisco, under Professor Peter Goadsby. I believe you will find this conversation quite engaging. Please welcome Michael to the podcast. References: Dr. Michael Eller: Richmond Neurology - richmondneurology.com.au Headache disorders: differentiating and managing the common subtypes, Ahmed - ncbi.nlm.nih.gov Current Medical Diagnosis and Treatment.2019: Papadakis, McPhee et al, McGraw Hill Education, Lange

The World Health Organisation estimates that between 2030 and 2050, climate change is anticipated to result in approximately 250,000 additional deaths annually. These fatalities may arise from issues such as malnutrition, and heat stress, as well as diseases like malaria and infectious diarrhoea. The impact of a planet warming at a recorded rate of 0.08 degrees centigrade per decade since 1880, accelerating to 0.18 degrees centigrade since 1981, poses threats to human lives and health across multiple dimensions. It's important to note that this statement does not delve into the detrimental potential such warming has on other species. Factors crucial to human survival—such as clean air, safe drinking water, a nutritious food supply, and secure shelter—are all imperilled in a world grappling with climate change. In this podcast, my intention was not to focus on the specific science of global warming and subsequent climate change, but rather on the associated health consequences. Despite the numerous pledges made by countries in various climate forums, global emissions in 2022 are projected to reach an unprecedented peak. However, there is a positive note to highlight—Australia managed to reduce its emissions by 1.9% in 2021. The historical responsibility for emissions lies significantly with the United States, followed by China, Russia, and Brazil. Undoubtedly intertwined with atmospheric emissions and consequent climate change is the world's population, which is growing at an alarming rate. Thomas Malthus, in his Essay on 'the principle of population' in the 1800s, once predicted its unsustainability. Today, with a population exceeding 8 billion, the United Nations forecasts a peak population of about 10.4 billion by the 2080s, noting that the "peak baby" phase has already been reached, leading to a measurable slowdown in population growth. Time will undoubtedly affirm the accuracy of these figures in history. It's crucial to mention that an expanding population, particularly a growing wealthier middle class in many countries worldwide, is likely to result in increased greenhouse gas emissions, heightened resource consumption, and will test humanity's capacity to solve ecological problems arising from the collective global burden we carry. My curiosity to delve deeper into this subject led me to invite Professor Richard Eckard to join the podcast and further enrich the discussion. Richard, a Professor of Sustainable Agriculture at The University of Melbourne and Director of The Primary Industries Climate Challenges Centre is a globally recognised authority on sustainable agricultural production. His focus includes carbon-neutral agriculture and agricultural adaptation to climate change. Richard's significant contributions encompass developing the initial greenhouse gas accounting tools for agriculture. Moreover, his research forms the scientific foundation for six carbon offset methods currently employed in Australia. Serving as a science advisor to various governments and international organisations such as the Australian, New Zealand, and UK governments, the International Livestock Research Institute, the Food and Agriculture Organisation of the United Nations, and the European Union, Richard provides invaluable counsel on climate change adaptation and mitigation in agriculture. Additionally, he represents Australia in the Global Research Alliance on Agricultural Greenhouse Gases. Please welcome Richard to the podcast. References: • Professor Richard Eckard: rjeckard@unimelb.edu.au • www.who.int/health-topics/climate-change • "The Weather Makers" by Tim Flannery, Text Publishing • National Geographic (multiple references)

Acid-Base theory is often considered a difficult subject. As long ago as 1962, Creese et al wrote in the Lancet … “There is a bewildering variety of pseudoscientific jargon in medical writing on this subject “My suspicion is that some degree of confusion and thus avoidance of the subject continues to this day. Hopefully, this podcast conversation will resonate with some of our listeners and smooth out any misunderstandings should they exist. As a background, Bronsted and Lowrys definitions of acids and bases are as follows: A base is a substance that accepts a proton (a hydrogen ion) an acid is a compound that dissociates in water to release a proton. A strong acid is one that readily dissociates in water to release a proton (eg HCL), and a weak acid does not readily dissociate in water (uric acid). pH is the negative logarithm of the hydrogen ion concentration to the base 10. Thus, the negative logarithm of 0.0000001 which may be expressed as 10 to the power of -7 is 7. The reason blood and cellular pH are so important is that their stability is essential to the integrity of enzymes, metabolic processes, and cell membrane potential. Homeostasis holds our blood pH tightly between 7.35 and 7.45 with an intracellular pH of 6.8. Where does the acid come from? Acid production results from the production of CO2 by metabolism of glucose, fatty acids, and amino acids. CO2 combines with water and is converted to carbonic acid -H2CO3 by carbonic anhydrase and then dissociates to H+ and HCO3-. That enzyme carbonic anhydrase pops up everywhere. Acid production also results from anaerobic glucose metabolism whereby glucose is converted to H+ and lactate in ketogenesis as well as from the catabolism of the amino acids: methionine and cysteine. Which organs play a major role in the maintenance of pH? Both the lungs and kidneys play critical roles in acid-base balance. We exhale CO2 from the lungs effectively blowing off acid but may also retain CO 2 by underventilation. The kidneys have the potential to excrete or absorb bicarbonate and to excrete or reabsorb protons (hydrogen ions) influencing and compensating for pH disturbance through an intricate juggling of these two. The excretion of protons is by combination with ammonia from the metabolism of muscle glutamine or in combination with monohydrogen phosphate. These ingenious biological systems may be influenced by multiple disease processes and respiratory forms of acidosis and alkalosis as well as metabolic processes leading to acidosis and alkalosis are well recognised. Whilst arterial blood gas assessment is used in critical care units to determine the degree of oxygenation, adequacy of ventilation, and the presence and severity of acid-base disturbances in the body, arterial puncture may result in complications, and the difficulty in acquiring arterial blood may delay care. Venous blood gas (VBG) is a more accessible alternative to ABG sampling and correlates well with arterial sampling in pH measurement (slightly lower in venous sample) and HCO3 - (1.41 mmol/l higher in venous) with pCO2 approximately 5.6 mmHg higher in venous blood. These differences may be exaggerated however in circulatory failure. In this podcast with ICU physician Associate Professor Adrian Regli, we will explore the subject further, delve into some of the typical metabolic and respiratory disturbances we are likely to encounter as clinicians and also review some handy rules of thumb to draw upon in practical acid-base interpretation. Currently, Adrian works as an ICU consultant at Fiona Stanley Hospital Perth. Please welcome Adrian to the Podcast. References Assoc Professor Adrian Regli - via Google Oh’s Intensive Care Manual, Bersten et al 6 th ED, Butterworth Medical Biochemistry at a Glance, Salway,3rd ED, Wiley-Blackwell Acid-Base Disorders in the Critically Ill Patient, Achanti et al CJASN, Sept 2022

Recently a team from the Monash Department of Diabetes published in the Nature Journal ‘ Signal Transduction and Targeted Therapy ‘ how their research could lead to the regeneration of insulin in pancreatic stem cells. As their findings could potentially benefit the 130,000 Type I diabetics in Australia and 30 per cent of Type II diabetics who are insulin dependent it received significant media attention. Diabetes is the fastest-growing illness in Australia and about 500 million people have diabetes worldwide with the potential complications of cardiovascular disease, renal failure, cerebrovascular disease, neuropathy, retinopathy, and lower limb amputation.   Associate Professor Neale Cohen who is the director of diabetes clinical research at the Baker Heart and diabetes institute believes the research shows great potential. Currently, the research is being conducted by a carefully selected team lead by Professor Sam El-Osta and including Dr Ishant Khurana and Dr Al-Hasani and we will be discussing their work and objectives further with Ishant in this podcast.  The research has discovered how to reawaken stem-like cells in the diabetic pancreas. Using an inhibitor of the protein called EZH2 which induces histone H3 lysine 27 trimethylation that functions to silence the insulin gene, insulin expression may be reawakened. If successful, the research will not only lead to a method for avoiding islet cell transplantation but possibly the need for exogenous insulin therapy altogether which is very exciting.  I was curious to have this research explained in more detail and to discover how close the investigative team were to success using these groundbreaking epigenetic strategies.  Please join me in welcoming Dr Ishant Khurana to the podcast.    References:  Dr Ishant Khurana: https ://research.monash.edu  Twitter: https://twitter.com/IshantKhuranaAU Nature journal, Signal Transduction and Targeted Therapy titled: Inhibition of pancreatic EZH2 restores progenitor insulin in T1D donor. DOI: 10.1038/s41392-022-01034-7 

Leukemias are malignant progressive disease in which the bone marrow and other blood-forming organs produce increased numbers of immature or abnormal leucocytes. This is thought to occur after somatically acquired genetic mutations lead to dysregulation and clonal expansion of progenitor cells. Whilst most leukemias involve white blood cells, occasionally other cells are the primary leukemia cells such as red blood cells or platelets.   As disease progression occurs, suppression of normal blood cell production leads to anemia and cytopenia with a host of attendant symptoms and clinical consequences.   There are 14 new diagnoses of Leukaemia per day in Australia accounting for about 5200 diagnoses yearly and making up about 3.2 % of all new cancer diagnoses per year. Leukaemia is responsible for over 2100 deaths annually.  Men are slightly more likely to be affected in a 60: 40 split with women. By the age of 85 years, one has a 1: 50 chance of this diagnosis. With current treatment approaches overall 5-year survival sits at about 64 % but this figure is influenced by the subtype of Leukaemia diagnosed with aggressive forms of Leukaemia such as AML carrying a much worse prognosis than a diagnosis such as CLL which may run an indolent course for many years.  Dividing adult Leukaemia into acute and chronic classification is most helpful and this podcast will approach the topic similarly over two episodes.  The acute Leukaemias encompass acute myeloid leukemia (30 % of adult Leukaemia), acute lymphoblastic Leukaemia and Leukaemia's of ambiguous origin.  The chronic Leukaemias include Chronic Myeloid Leukaemia (CML) and Chronic lymphocytic leukemia (CLL)  This is another vast subject, and it was a real honour to invite Professor Jake Shortt to the podcast. Jake is the Head of Haematology Research at the School of Clinical Sciences and clinical lead at Monash Haematology for Myeloid Leukaemia, myelodysplasia and T-cell lymphoma. He is the Principal Investigator on a range of clinical trials for T-cell lymphoma and myeloid malignancies, conducted through the Monash Haematology clinical trials unit and the recipient of a Medical Research Future Fund Career Development Fellowship. His work in the School of Clinical Sciences is focused on strategies incorporating epigenetic drugs with immunotherapy in haematological cancers, particularly Lymphoma and Multiple Myeloma. Jake heads the Blood Cancer Therapeutics laboratory within the Monash Health Translation Precinct and somehow also finds the time to be Chair of the Laboratory Sciences Working Party of the Australasian Leukaemia and Lymphoma Group (ALLG) and Deputy Chair of their Scientific Advisory Committee.   Please welcome Professor Jake Shortt to the podcast.  References :   Haematology and Oncology Subspecialty Consult, 4th Ed, Cashen and Van Tine, Wolters Kluwer, Ch 31  ⁠www.leukaemia⁠.org.au  www.cancer.org.au  www.monashhealth.org/services/haematology/jake-shortt/

Leukemias are malignant progressive disease in which the bone marrow and other blood-forming organs produce increased numbers of immature or abnormal leucocytes. This is thought to occur after somatically acquired genetic mutations lead to dysregulation and clonal expansion of progenitor cells. Whilst most leukemias involve white blood cells, occasionally other cells are the primary leukemia cells such as red blood cells or platelets.   As disease progression occurs, suppression of normal blood cell production leads to anemia and cytopenia with a host of attendant symptoms and clinical consequences.   There are 14 new diagnoses of Leukaemia per day in Australia accounting for about 5200 diagnoses yearly and making up about 3.2 % of all new cancer diagnoses per year. Leukaemia is responsible for over 2100 deaths annually.  Men are slightly more likely to be affected in a 60: 40 split with women. By the age of 85 years, one has a 1: 50 chance of this diagnosis. With current treatment approaches overall 5-year survival sits at about 64 % but this figure is influenced by the subtype of Leukaemia diagnosed with aggressive forms of Leukaemia such as AML carrying a much worse prognosis than a diagnosis such as CLL which may run an indolent course for many years.  Dividing adult Leukaemia into acute and chronic classification is most helpful and this podcast will approach the topic similarly over two episodes.  The acute Leukaemias encompass acute myeloid leukemia (30 % of adult Leukaemia), acute lymphoblastic Leukaemia and Leukaemia's of ambiguous origin.  The chronic Leukaemias include Chronic Myeloid Leukaemia (CML) and Chronic lymphocytic leukemia (CLL)  This is another vast subject, and it was a real honour to invite Professor Jake Shortt to the podcast. Jake is the Head of Haematology Research at the School of Clinical Sciences and clinical lead at Monash Haematology for Myeloid Leukaemia, myelodysplasia and T-cell lymphoma. He is the Principal Investigator on a range of clinical trials for T-cell lymphoma and myeloid malignancies, conducted through the Monash Haematology clinical trials unit and the recipient of a Medical Research Future Fund Career Development Fellowship. His work in the School of Clinical Sciences is focused on strategies incorporating epigenetic drugs with immunotherapy in haematological cancers, particularly Lymphoma and Multiple Myeloma. Jake heads the Blood Cancer Therapeutics laboratory within the Monash Health Translation Precinct and somehow also finds the time to be Chair of the Laboratory Sciences Working Party of the Australasian Leukaemia and Lymphoma Group (ALLG) and Deputy Chair of their Scientific Advisory Committee.   Please welcome Professor Jake Shortt to the podcast.    References :   Haematology and Oncology Subspecialty Consult, 4th Ed, Cashen and Van Tine, Wolters Kluwer, Ch 31  www.leukaemia.org.au  www.cancer.org.au  www.monashhealth.org/services/haematology/jake-shortt/

Pilates is a form of low-impact exercise that aims to strengthen muscles while improving postural alignment and flexibility. It can be practised with or without equipment and the movements reinforce slow precise actions and breath control. The exercises strengthen and stabilise the core which is the body's foundation allowing one to move efficiently while improving posture flexibility and mobility. This method of exercise is based on the rehabilitation work of Joseph Pilates, born in Dusseldorf in 1883. Joseph Pilates believed that injuries were caused by imbalances in the body and by habitual patterns of imperfect movement and hypothesised that an overcompensation or overdevelopment of another area occurred when a person had a weakness or misaligned area in order to achieve the functional movements desired. He felt it was critical to correct the misalignment and to re-educate the body to prevent recurrence. His studio in New York allowed him to develop over 600 exercises over his career and he invented various pieces of apparatus to assist with the execution of these in particular his so-called reformer and cadillac with pulleys and springs allowing his method initially called Contrology to be practised with precision and exact repetition. Joseph Pilates died in 1967 before his method now called Pilates became well known and widely accepted. Today, decades later his approach has gained significant popularity with over 3000 studios in Australia and some 380,000 Australians practising Pilates either regularly or occasionally. His method has been widely adopted by physiotherapists in Australia, North America and Europe with increasing popularity is a testament to its amazing benefits. Recently I had the pleasure of being introduced to Samantha Wood whilst she was blitzing it at a surfing location in Fiji with her tall athletic partner Jeff. They were both limber, flexible and in the moment and she was immediately recognised as the author of Pilates for Rehabilitation which has become a bible of Pilates based exercises and a comprehensive guide for therapists offering rehabilitation from orthopaedic injuries. Samantha began her career as a physiotherapist and after a serendipitous meeting with Pilates guru Rael Isacowitz she developed a passion for Pilates and is now world renown in her field lecturing internationally, conducting workshops and convening body and mind retreats as well as running a busy Pilates and PT clinic at The Cypress Center in Pacific Palisades Los Angeles California. I was very grateful that she was available for this interview to discuss Pilates further, as I believe we should all be familiar with the method and recognise the outstanding benefits it offers our patients. Please welcome Samantha to the podcast. References: Samantha Wood-Cypress Center-Pacific Palisades, Los Angeles. www.samanthawoodphysio.com Pilates for Rehabilitation -Samantha Wood. Human Kinetics www.HumanKinetics.com To be a guest on the show or provide some feedback, I’d love to hear from you: manager@gihealth.com.au.Dr Luke Crantock MBBS, FRACP, is a gastroenterologist in practice for over 25 years. He is the founder of The Centre for GI Health, based in Melbourne, Australia, and is passionate about educating General Practitioners and patients on disease prevention and how to manage and improve their digestive health.

Lipids are essential for cell function and healthy metabolism however clinical analysis of a patient’s lipid profile also addresses one of the fundamental drivers of atherosclerotic cardiovascular disease responsible for 25 % of all deaths in Australia. Modification of abnormal serum lipid levels by lifestyle and pharmacologic intervention aims to achieve healthy coronary circulation reducing new atheroma formation and stabilizing preexisting atheromatous plaques. Atheroma develops when cholesterol esters and triglycerides enter the vascular intima inducing local inflammation. Macrophages recruited to the inflammation engulf the cholesterol esters by phagocytosis. Stuffed with cholesterol these cells are referred to as foam cells. The inflammatory cascade is accentuated and recruits more inflammatory cells some of whom perish over time and calcium deposition and fibrosis develops within a forming plaque. Plaque enlargement may distort vascular anatomy expanding into the vessel lumen impeding blood flow and inducing ischaemia however not all plaques impact in this way and even large developing plaques may form in a way that does not disrupt blood flow. Instability in a growing plaque however may lead to rupture and the initiation of an acute thrombotic event. Whilst hyperlipidemia underscores atheroma pathogenesis this complex and life-threatening process is also adversely influenced by cigarette smoking, hypertension, genetics, and poor glycaemic control. Having a clear understanding of lipid physiology allows us to appreciate both atheroma formation and how cardiovascular risk may be modified. One of the key points is that as lipids are water insoluble and they must be transported in specialized vesicles. These are called lipoproteins when produced by the liver for entry into the circulation and micelles for entry into the biliary system and subsequently the gastrointestinal tract. Chylomicrons are the specialized vesicles produced by gut enterocytes to transport lipids from the digestive tract via lymphatics ultimately into the circulation. Current Australian guidelines for lipid management recommend: Total Cholesterol < 4 mmol/l if high risk, < 5 .5 mmol/l for general population LDL < 1.8 mmol/l for high risk, < 2.0mmol/l general population Triglycerides < 2 mmol/l HDL > 1.0 mmol/l Lowering LDL cholesterol by 1mmol/l reduces the incidence of major vascular events (non-fatal myocardial infarction, coronary death, coronary revascularization, or stroke) by about one fifth. With 11 fewer vascular events per 1000 treated over 5 years. Similarly, triglyceride reduction per 1 mmol/l is associated with about half this cardiovascular risk reduction. Interventions that are utilized to modify the cardiac risk associated with lipids include: Dietary manipulation Pharmacologic modification of lipid synthesis or absorption Multiple epidemiological studies have demonstrated a greater incidence of coronary artery disease linked to non-HDL cholesterol and elevated serum triglycerides as well as a protective benefit from high HDL levels which includes when triglycerides and LDL levels are high and a lowering of CVD risk even when optimal triglyceride and non HDL cholesterol levels are achieved. Given the critical importance of cardiovascular risk modification it was a pleasure to invite cardiologist Dr Brett Forge to the following two episodes of this podcast to expand on this fascinating subject. References: Basic and Clinical Pharmacology 14th ed -Bertram G. Katzung, LANGE Books, Ch 35. Principles of Medical Biochemistry, Eisenberg & Simmons,3Rd Ed, Elsevier Saunders, Ch 23 Ganong’s Review of Medical Physiology, Barrett et al,25 th Ed, LANGE Books, Ch 26 Dietary Fat and Risk of Cardiovascular Disease: Recent Controversies and Advances, Annual Review of Nutrition, Vol. 37:423-446, Wang & Hu Dietary Cholesterol and the Lack of Evidence in Cardiovascular Disease, Nutrients 2018Jun;10(6):780 Ghada A. Soliman

Lipids are essential for cell function and healthy metabolism however clinical analysis of a patient’s lipid profile also addresses one of the fundamental drivers of atherosclerotic cardiovascular disease responsible for 25 % of all deaths in Australia. Modification of abnormal serum lipid levels by lifestyle and pharmacologic intervention aims to achieve a healthy coronary circulation reducing new atheroma formation and stabilizing preexisting atheromatous plaques. Atheroma develops when cholesterol esters and triglycerides enter the vascular intima inducing local inflammation. Macrophages recruited to the inflammation engulf the cholesterol esters by phagocytosis. Stuffed with cholesterol these cells are referred to as foam cells. The inflammatory cascade is accentuated and recruits more inflammatory cells some of whom perish overtime and calcium deposition and fibrosis develops within a forming plaque. Plaque enlargement may distort vascular anatomy expanding into the vessel lumen impeding blood flow and inducing ischaemia however not all plaques impact in this way and even large developing plaques may form in a way that does not disrupt blood flow. Instability in a growing plaque however may lead to rupture and the initiation of an acute thrombotic event. Whilst hyperlipidemia underscores atheroma pathogenesis this complex and life-threatening process is also adversely influenced by cigarette smoking, hypertension, genetics, and poor glycaemic control. Having a clear understanding of lipid physiology allows us to appreciate both atheroma formation and how cardiovascular risk may be modified. One of the key points is that as lipids are water insoluble and they must be transported in specialized vesicles. These are called lipoproteins when produced by the liver for entry into the circulation and micelles for entry into the biliary system and subsequently the gastrointestinal tract. Chylomicrons are the specialized vesicles produced by gut enterocytes to transport lipids from the digestive tract via lymphatics ultimately into the circulation. Current Australian guidelines for lipid management recommend: Total Cholesterol < 4 mmol/l if high risk, < 5 .5 mmol/l for general population LDL < 1.8 mmol/l for high risk, < 2.0mmol/l general population Triglycerides < 2 mmol/l HDL > 1.0 mmol/l Lowering LDL cholesterol by 1mmol/l reduces the incidence of major vascular events (non-fatal myocardial infarction, coronary death, coronary revascularization, or stroke) by about one fifth. With 11 fewer vascular events per1000 treated over 5 years. Similarly, triglyceride reduction per 1 mmol/l is associated with about half this cardiovascular risk reduction. Interventions that are utilized to modify the cardiac risk associated with lipids include: Dietary manipulation Pharmacologic modification of lipid synthesis or absorption Multiple epidemiological studies have demonstrated a greater incidence of coronary artery disease linked to non-HDL cholesterol and elevated serum triglycerides as well as a protective benefit from high HDL levels which includes when triglycerides and LDL levels are high and a lowering of CVD risk even when optimal triglyceride and non HDL cholesterol levels are achieved. Given the critical importance of cardiovascular risk modification it was a pleasure to invite cardiologist Dr Brett Forge to the following two episodes of this podcast to expand on this fascinating subject. References: Basic and Clinical Pharmacology 14th ed - Bertram G. Katzung, LANGE Books, Ch35. Principles of Medical Biochemistry, Eisenberg & Simmons, 3rd Ed, Elsevier Saunders, Ch 23 Ganong’s Review of Medical Physiology, Barrett et al, 25th Ed, LANGE Books, Ch26 Dietary Fat and Risk of Cardiovascular Disease: Recent Controversies and Advances, Annual Review of Nutrition, Vol.37:423-446, Wang & Hu Dietary Cholesterol and the Lack of Evidence in Cardiovascular Disease,Nutrients 2018 Jun; 10(6):780 Ghada A. Soliman