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Long-term survival and clinical implications of allogeneic stem cell transplantation in relapse/refractory lymphoma: A 20-year Singapore experience

Over the past few decades, a wide array of novel therapies has become available for the treatment of relapsed/refractory (R/R) lymphoma. Despite these advancements, outcomes and the durability of disease control remain poor for many patients. While autologous hematopoietic stem cell transplantation (auto-HSCT) may be appropriate for some lymphoma...

AL amyloidosis: Singapore Myeloma Study Group consensus guidelines on diagnosis, treatment and management

Amyloidosis refers to disorders characterised by the deposition of insoluble amyloid fibrils, which are pathogenic,1 resulting in organ dysfunction. Amyloidoses differ in the protein precursor undergoing aggregation and downstream target organs implicated. Consequently, clinical manifestations are varied, from localised amyloidosis in Alzheimer’s disease, to systemic amyloidosis such as immunoglobulin...

Clinical utility of PET/MRI in multiple myeloma

Multiple myeloma (MM) is a haematological malignancy characterised by abnormal accumulation of malignant plasma cells and is associated with anaemia, renal impairment, hypercalcemia and bone lesions. A sensitive method to detect bone lesions is crucial as it could determine the decision to start treatment. In this era, the International...

Improving management of AL amyloidosis

In this issue of the Annals, Tan et al. on behalf of Singapore Myeloma Study Group presented the consensus guidelines on light chain (AL) amyloidosis.1 This is an encouraging effort as AL amyloidosis is a rare disease, with diagnostic and therapeutic challenges.  A comprehensive review examining its pathophysiology, diagnostic...

Incorporating assessment of fibrinogen gene polymorphisms and bleeding risk in patients treated with direct oral anticoagulants

Direct oral anticoagulants (DOACs) have become entrenched as the dominant anticoagulant over the last decade for patients with venous thrombosis and atrial fibrillation.1 Compared to warfarin, bleeding risk is similar or lower for patients on DOACs but clinically relevant bleeding is still a risk, especially for patients with impaired...

Erdheim-Chester disease: Imaging spectrum of multisystemic manifestations

Dear Editor, Erdheim-Chester disease (ECD) is a rare non-Langerhans histiocytosis, usually affecting middle-aged to older adults. It is a multisystemic disease with protean clinical manifestations. It can involve single or multiple organs, and presentations range from asymptomatic lesions detected incidentally on imaging to severe organ dysfunction. Hence, accurate and timely...

Impact of aortic annular size and valve type on haemodynamics and clinical outcomes after transcatheter aortic valve implantation

The management of severe aortic stenosis (AS) in patients with small aortic annulus (SAA) represents a therapeutic challenge due to the increased mortality and major adverse cardiac events (MACE) seen in this group of patients even after surgical aortic valve replacement (SAVR).1,2 In recent times, the role of transcatheter aortic...

Antiphospholipid and other autoantibodies in COVID-19 patients: A Singapore series

Dear Editor, Thrombosis is an unexpected complication of COVID-19 initially reported in 3 patients from China.1 These patients tested positive for immunoglobulin (Ig) A anticardiolipin (ACA), IgG anti-β2-glycoprotein I antibodies (aβ2GPI) and IgA aβ2GPI, though not for the lupus anticoagulant (LAC). In a Singapore study comprising 47,527 patients, 19 (0.04%) developed...

Safety and efficacy of combined antiplatelet and low-dose rivaroxaban in patients with chronic limb threatening ischaemia in Singapore

Dear Editor, Peripheral artery disease (PAD) is characterised by the debilitating atherosclerotic occlusion of arteries in the lower extremities, with chronic limb threatening ischaemia (CLTI) representing the most advanced stage of this disease process. Left untreated, these sequelae will invariably progress to major lower extremity amputation (LEA) and premature death....

Haemoglobin H disease and outcomes in Singapore

Dear Editor, Haemoglobin H (HbH) disease is a haemoglobinopathy affecting 3 of 4 α-globin genes on chromosome 16. It results from the deletion of 2 linked α-globin genes (α0-thalassaemia) on one chromosome and either a single α-globin gene deletion (--/-α) or non-deletional gene mutation (--/αTα) on the other chromosome.  The...

A Case Report of Neutrophilic Eccrine Hidradenitis in a Patient Receiving Chemotherapy for Acute Myeloid Leukaemia

Neutrophilic eccrine hidradenitis (NEH) is a neutrophilic dermatosis primarily affecting the eccrine glands and occurs most commonly in patients undergoing chemotherapy for a malignancy. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

A Study of Idiopathic Thrombocytopenic Purpura (ITP) Patients over a Ten-year Period

Idiopathic thrombocytopenic purpura (ITP) is an immunoregulatory disorder in which antibodies damage platelets leading to their removal by cells of the reticuloendothelial system (RES). This occurs mainly in the spleen which is also the primary site of synthesis of these antiplatelet antibodies. This article is available only as a PDF....

The Sixth SGH Lecture—Singapore: A New Venice of the 21st Century

Venice is one of the legendary cities of the world. Its beauty and physical setting make Venice unique. For almost 800 years, from 1000 AD to 1797, the Venetians were a separate people. This article is available only as a PDF. Please click on “Download PDF” on top to view...

Childhood Leukaemia: Towards an Integrated Psychosocial Intervention Programme in Singapore

In the last two decades there has been a surge of interest concerning the psychosocial correlates of life-threatening illnesses. Research in this area has focused especially on cancer and the possible link between immunology and psychological factors. This article is available only as a PDF. Please click on “Download PDF”...

Medicine and Surgery—History, Change and Challenge

Mr Koh Yong Guan, guest-of-honour; Dr Tan Ser Kiat, Master, Academy of Medicine; Dr K C Tan, Chairman, Chapter of Surgeons; Dr Robert Jalleh from Malaysia; Dr Idral Darwis from Indonesia; Dr P B Chacha, my esteemed partner; Dr John Isaac, Master of Ceremonies; fellow academicians, practitioners and friends,...

Current Continuing Medical Education Provision in Singapore

It was in 1994 that as an overseas fellow of the College, I received a letter from Dr Peter Toghill, Director of Continuing Medical Education (CME), Royal College of Physicians of London, stating that the three Royal Colleges of Physicians in the UK have agreed to joint recommendation on...

Early 21st Century Professional Practice: Change and Challenge

Today is a day of rejoicing for all of you, graduates, parents, relatives and loved ones. I can share in your joy and also a sense of relief that you have passed the first and for some, the second professional exam in your career. This article is available only as...

9th Seah Cheng Siang Memorial Lecture: Gastric Cancer—Where are we now?

The last two decades have witnessed dramatic changes in the understanding of gastric cancer: a rapid decline in global incidence, its association with Helicobacter pylori gastritis, and the new information regarding its molecular biology. Nevertheless, gastric cancer remains the second commonest cancer in the world in terms of morbidity...

A Case Report of Adult T-Cell Leukaemia/Lymphoma (ATLL)

Our patient was a 71-year-old Chinese man who presented with a 6-year history of recurrent papular erythematous eruptions to the dermatologist. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

New Treatment and Research Strategies for the Improvement of Care of Cleft Lip and Palate Patients in the New Millennium

I have chosen as the title of my keynote address “New Treatment and Research Strategies for the Improvement of the Care of Cleft Lip and Palate Patients”. The reason for this is that despite the tremendous strides we have made over the past 50 years in the management of...

Newer Thrombolytic Agents

First-generation fibrinolytic agents (streptokinase and urokinase) are effective thrombolytic drugs, but are not fibrin specific as they also have the property to convert circulating plasminogen to plasmin when given at therapeutic doses. Because the plasminogen in the thrombus is in equilibrium with the plasminogen pool in plasma, the plasminogen...

Young Investigator’s Award: Induction of Apoptosis Following Traumatic Head Injury in Humans

The outlook for sufferers of severe head trauma is extremely poor. Some 20% of patients died before significant treatment can be administered, and nearly one quarter of patients end in a vegetative state with little potential for further progress. This article is available only as a PDF. Please click on...

3rd Yahya Cohen Lecture: The Role of the Myofibroblast-Like Cell in Hepatocellular Carcinoma—Host Defence?

It is indeed a great honour for me to be named the third Yahya Cohen lecturer and I would like to express my deepest thanks and appreciation to the Academy of Medicine Singapore for having selected me for this award. At this lecture, I would like to share with...

9th Chapter of Surgeons’ Lecture: The Orthopaedic Surgeon: Historical Perspective, Ethical Considerations and the Future

The legacy of caring and humanitarianism has been the mission of the medical profession since the founding of Singapore by Sir Stamford Raffles in 1819. To this small fishing village in the Riau Archipelago on the southern tip of the Malay Peninsula came traders and entrepreneurs from China, India...

1998 Distinguished Academician Lecture: Hepatic Resection— A Western Perspective

Although debridement of portions of liver that prolapsed through war wounds was recorded from distant times, attempts at resection of a solid liver tumour were first reported in the latter part of the 19th century. When one considers the enormous challenges faced by surgeons of the time, without the...

1998 Runme Shaw Memorial Lecture: Somatic Evolution of Cancer

The interpretation of cancer as a somatic evolutionary process involving genetic mutation followed by selection, goes back to the early years of this century. Boveri’s hypothesis put forward in 1914 that cancer was associated with abnormalities of the chromosomes and Tyzzer and Strong’s experiments of transplantable tumours in 1916...

14th Gordon Arthur Ransome Oration: Continuity and Change

Deputy Prime Minister Lee Hsien Loong, Datuk Dr Yeoh Poh Hong, Dr Chee Yam Cheng, distinguished guests, ladies and gentlemen, I am deeply honoured to be invited to deliver the 14th Gordon Arthur Ransome Oration, following in the footsteps of previous illustrious speakers. I am particularly honoured that you...

The Future of Medicine from the Standpoint of the Practising Paediatrician

From the time of recorded history of medicine, the doctor whether he be the ancient healer or the modern medical practitioner, the doctor had practised the art and science, on the basis of curing the patient when he has an illness. The doctor is sought out when the patient...

Activated Protein C Resistance: A Study Among 60 Thromboembolic Patients in the Singapore Population

In 1993, Dahlback and colleagues described a new hereditary thrombophilia state-activated protein C resistance (AK-R). Further studies showed this to be the commonest genetic cause of thrombophilia. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

Address by the Master, Academy of Medicine, Singapore at the 2000 Annual Induction Dinner—Learn the Past, Ensure the Future

I am delighted to share this celebratory occasion with you. It is a time for congratulations all round not only to our new Fellows but also to their families and friends. No specialist trains by himself. This article is available only as a PDF. Please click on “Download PDF” on...

Response by the Representative of Inductees, Academy of Medicine, Singapore at the 2000 Annual Induction Ceremony—A Call to Patient Advocacy

I count myself fortunate to be allowed to join the ranks of the Academy. On behalf of my fellow inductees, may I extend a word of thanks for this honour. Thank you, also, for allowing me the privilege of delivering this Reply. This article is available only as a PDF....

Address by the Master, Academy of Medicine, Singapore at the 2000 Annual Induction Ceremony—The EQ & IQ of Specialist Doctors

First, let me warmly welcome you to this pristine auditorium with its well preserved ceiling architectural details. Probably none of the new Fellows is old enough to remember that this was the old Allen and Farris Lecture Theatres of the Faculty of Medicine when it was at Sepoy Lines...

8th SGH Lecture: Genomics, Talent and the Development of the Life Sciences Industry in Singapore

In a few months’ time, one of the most significant advances, possibly the most significant advance ever in the history of biology and medicine, will be achieved with the rolling out of the first draft of the map detailing the entire Human Genome. This article is available only as a...

Pseudomembranous Tracheobronchitis Caused by Aspergillus in a Patient after Peripheral Blood Stem Cell Transplantation

Pseudomembranous tracheobronchitis caused by Aspergillus is a rare and lethal variant of invasive aspergillosis. It has been reported in a few series of immunocompromised patients. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

3rd Tan Tock Seng Hospital Oration: The Changing Fabric of Medicine—An Ethical and Social Revolution

The legacy of Tan Tock Seng Hospital began with the founding of the Pauper Hospital in Pearl’s Hill in 1844. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

Management of Growth Arrest with Tissue-engineered Cells

Before I go on to the scientific aspects of my talk, I would like to pay tribute to Dr Yahya Cohen. Dr Cohen was born in Singapore of Jewish parents. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

Philadelphia Positive Acute Lymphoblastic Leukaemia (ALL): Clinico-Haematologic Characteristics, Molecular Analyses and 3-year Follow Up—A Single Institution Study

A number of specific chromosome abnormalities are associated with acute lymphoblastic leukaemia (ALL). The commonest in adults with B lineage ALL is the Philadelphia (Ph) chromosome t(9;22)(q34;q11). This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

10th Chapter of Surgeons’ Lecture: The Challenges in Surgery—Past, Present and Future, and in Search of the 4Cs

Firstly may I thank the Academy of Medicine and the Chapter of Surgeons for giving me this great privilege and honour to deliver the final lecture of the century for our series of Chapter of Surgeons lectures to close the 20th century and begin a new dawn in the...

Opening Address by Dr Chee Yam Cheng, Master, Academy of Medicine, Singapore at the 33rd Annual Combined Surgical Meeting on 4 November 1999 at the COMB Auditorium

It is a pleasure to be present with you all at your 33rd Annual Combined Surgical Meeting for 1999 with less than 60 days to go into the new millennium. I applaud your organising committee under Dr Sarbjit Singh for a comprehensive and exciting programme which I trust you...

Thrombotic and Haemorrhagic Complications in Patients with Mechanical Heart Valve Prostheses Attending the Singapore General Hospital Anticoagulation Clinic

Patients with mechanical heart-valve prosthesis receive lifelong anticoagulation. The management of these patients taking oral anticoagulants is aimed at achieving and maintaining adequate levels of anticoagulation to prevent thrombotic manifestations and at the same time to keep the risk of severe haemorrhagic complications to the minimum. This article is available...

Funding and Future Diagnosis Related Group Development

Supplement on Casemix Conference Singapore 2001 held on 17-19 August 2001 in Singapore This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

Clinical Pathways or Case Management

Supplement on Casemix Conference Singapore 2001 held on 17-19 August 2001 in Singapore This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

Getting Clinicians Involved: The Australian Experience

Supplement on Casemix Conference Singapore 2001 held on 17-19 August 2001 in Singapore This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

The 4th Tan Tock Seng Hospital Oration: Challenge for the Medical Profession in the 21st Century

I am greatly honoured to speak at the 4th TTSH Oration following such distinguished luminaries like Dr Chew Chin Hin, Dr Chen Ai Ju and Professor N Balachandran. I also wish to thank all of you who are present this evening. This article is available only as a PDF. Please...

Treatment of Acute Promyelocytic Leukaemia Using a Combination of All-trans Retinoic Acid and Chemotherapy

Acute promyelocytic leukaemia (APL), or acute myeloid leukaemia (AML)-M3 under the French-American-British (FAB) classification, is characterised by the following: a distinct expansion of promyelocytes and immature myeloblasts in the bone marrow; balanced reciprocal translocation between the long arms of chromosome 15 and 17, t(15;17) which results in apposition of...

Alternate Modes of Financing Health Care Technology

Alternative financing of health care delivery is one of the most vexing problems facing medicine today. Intensive care in many ways is a perfect example of the core problems facing policymakers responsible for financing health care. This article is available only as a PDF. Please click on “Download PDF” on...

2nd Chapter of Paediatricians Lecture: The Future of Paediatrics in Singapore

When I was first invited to give this 2nd Chapter of Paediatricians Lecture by the Chapter, my obvious answer was no. I could think of quite a few other paediatricians more qualified and appropriate as speakers and hoped that my emphatic no would work. This article is available only as...

10th Seah Cheng Siang Memorial Lecture: Going Places—A Rheumatological Odyssey

I am greatly honoured to deliver the 10th Seah Cheng Siang memorial lecture. I came into direct contact with Professor Seah in January 1965 when I joined the then Thomson Road General Hospital as his senior registrar. This article is available only as a PDF. Please click on “Download PDF”...

5th Yahya Cohen Lecture: Angiosomes and Extension of Skin Flaps—Anatomic Study and Clinical Implications

I would like to express my gratitude to the Chapter of Surgeons and the Academy of Medicine, Singapore for the honour of presenting this 5th Yahya Cohen Lecture. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

11th Chapter of Surgeons Lecture—The Art of Letting Go

These observations were made by a Persian mathematician some 900 years ago. His sentiments are self-evident but no less easy to accept especially for operating surgeons. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

15th Gordon Arthur Ransome Oration: A Journey of Care—Mission Impossible?

I am deeply honoured by the invitation to deliver the 15th Sir Gordon Arthur Ransome Oration. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

The Runme Shaw Memorial Lecture 2000—Treating VIPs in Washington

My lecture is about people, power, illness, and the patient-physician relationship. It is the personality of the politician or official, the ego elevation conferred by power, the repression of the thought of illness, and the combination of these factors, which leads to subversion of the patient-doctor relationship when a...

12th Chapter of Surgeons Lecture: Shifting Paradigms in the Management of Breast Cancer—A Surgical Perspective

The recorded history of breast cancer management spans four millennia. This story about breast cancer management is also one about change, about resistance to and acceptance of change. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

CD4 Lymphocyte Enumeration in Patients with Human Immunodeficiency Virus Infection Using Three-Colour and Four-Colour Dual-Platform Flow Cytometry: An Inter-Laboratory Comparative Evaluation

Clinical flow cytometry provides a precise technology for the multiparameter analysis of the morphological (scatter) and immunofluorescence properties of stained leukocyte populations, as well as their percentages and absolute counts, at the single-cell level. Flow cytometry is commonly used for the identification of human lymphocyte subsets, a process referred...

Deep Vein Thrombosis is Not Rare in Asia—The Singapore General Hospital Experience

Deep vein thrombosis (DVT), pulmonary embolism (PE), the postphlebitic syndrome and recurrent venous thromboembolism (VTE) are important and often preventable causes of early morbidity or death and of long-term disability in western populations. The reported annual incidence of VTE is about 2 per 10,000 persons in Scotland. This article is...

High-dose Therapy followed by Autologous Haematopoietic Stem Cell Transplantation in Multiple Myeloma

Multiple myeloma (MM) is a disorder in which malignant plasma cells accumulate in the bone marrow and produce an immunoglobulin, usually monoclonal IgG or IgA. The incidence of MM in Singapore is 1 to 2 per 100,000 per year with a median age of 65 to 70 years at...

New Aspects of the Blood Coagulation Cascade, Anticoagulants and Vein Thrombosis in Asia

Injury to blood vessels triggers haemostasis, a process that has evolved to achieve two superficially incompatible outcomes: arresting blood loss while protecting vessel patency and blood flow to distal organs. Contributors to haemostasis include subendothelial tissues and endothelial cells, blood platelets, tissue factor, plasma clotting factors and their physiological...

5th Tan Tock Seng Hospital Oration: Advances for Life

I am honoured and privileged to have been invited to deliver the 5th Tan Tock Seng Hospital (TTSH) Oration at the Opening of your 9th Annual Scientific Meeting. When I was invited, I hesitated for a moment as I have not been in active practice for quite a while,...

6th Yahya Cohen Lecture: Visual Experience During Cataract Surgery

What a patient can see during his or her surgery can be a cause of anxiety for the patient. It may cause additional stress to what for most patients is already a traumatic event. This article is available only as a PDF. Please click on “Download PDF” on top to...

Four Pregnancies in Two Patients with Essential Thrombocythaemia—A Case Report

Essential thrombocythaemia (ET) is a rare myeloproliferative disease which manifests with an elevated platelet count. It presents predominantly in the middle-aged population, occurring slightly more frequently in women than men. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

Idiopathic Thrombocytopenia in Pregnancy

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which platelets are sensitised with an antiplatelet autoantibody and then destroyed by the reticuloendothelial system.1 Hence, it is also known as primary autoimmune thrombocytopenic purpura. There are two forms of ITP—acute and chronic. This article is available only as a PDF....

Thrombophilia in Pregnancy

A clear understanding of thrombophilia is becoming increasingly important in the practice of high-risk obstetrics. In addition to their role in thromboembolic disease, there is increasing evidence linking thrombophilia and adverse pregnancy outcomes such as pre-eclampsia, intrauterine growth restriction, placental abruption and recurrent pregnancy loss. This article is available only...

Management of Haematologic Malignancies in Pregnancy

Malignancy complicates the course of about 1 in 1000 pregnancies and is the second leading cause of death in women of reproductive age. The most commonly diagnosed malignancies during pregnancy are breast cancer, cervical carcinoma, Hodgkin’s lymphoma and melanoma. This article is available only as a PDF. Please click on...

Pregnancy in Women with Idiopathic Thrombocytopaenic Purpura

Idiopathic thrombocytopaenic purpura (ITP) is the most common autoimmune haematological disorder in pregnancy. The pathophysiology of the disease is peripheral destruction of platelets mediated by antiplatelet antibodies. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

Clinical Update on Deep Vein Thrombosis in Singapore

Deep vein thrombosis (DVT), and its acute complication–pulmonary embolism (PE), is one of the most important preventable causes of death in hospital patients. It also contributes to significant morbidity in terms of post-phleblitic syndrome and chronic venous ulcers. This article is available only as a PDF. Please click on “Download...

Case Report on Recombinant Coagulation Factor VIIa in the Treatment of Three Haemophilia A Patients with Inhibitors in Singapore

Development of inhibitors against factor VIII is one of the main complications in the treatment of haemophiliacs. Inhibitors block the procoagulant effects of factor VIII and prevent the successful arrest of bleeding episodes when administered to these haemophiliacs. This article is available only as a PDF. Please click on “Download...

Evaluation on the Use of a Portable Unit Versus the Laboratory for the Monitoring of International Normalized Ratio (INR) in Orally Anticoagulated Patients

Oral anticoagulation therapy is used for a number of conditions, namely deep venous thrombosis, pulmonary embolism, mechanical heart valves, embolic stroke as well as atrial fibrillation. Patients receiving this therapy are carefully monitored in order to maintain the intensity of anticoagulation in the appropriate therapeutic range. This article is available...

Is Healthcare Competition Healthy?

There are many problems which all Health Ministers worry about. But we can generally boil them down to one common problem: “money no enough”. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

Clinical Profile and Treatment Outcome of Livedoid Vasculitis: A Case Series

Livedoid vasculitis is a clinicopathological entity that has variously been referred to as atrophie blanche, livedoid vasculopathy or segmental hyalinising vasculitis. It presents with purpuric lesions and recurrent, painful ulcerations of the lower limbs which result in depressed, atrophic white scars. This article is available only as a PDF. Please...

Neonatology In Singapore: The Way We Were, The Way Forward

Over a span of 35 years of my working life, I have witnessed the growth of, and also grown together with, neonatology in Singapore. As I look at the present-day status of neonatology, it gives me a sense of achievement and accomplishment. This article is available only as a PDF....

Significance of the Lateral Epiphysis of the Acetabulum to Hip Joint Stability

Developmental dysplasia of the hip (DDH) remains one of the most difficult disorders to understand and treat in Paediatric Orthopaedics. The aetiology have not been clearly understood and therefore the management remains controversial. This article is available only as a PDF. Please click on “Download PDF” on top to view...

Craniofacial Anomalies: Clinical and Molecular Perspectives

Cleidocranial dysplasia is an autosomal dominant skeletal disorder characterized by short stature, brachycephaly, delayed closure of the fontanelles and sutures, Wormian bones, midface hypoplasia, unerupted teeth, supernumerary permanent teeth, aplasia or hypoplasia of the clavicles, and other skeletal anomalies, such as hypoplastic iliac wings and brachydactyly. This article is available...

Autoimmune Liver Disease in Children

Autoimmune liver disorders are inflammatory liver diseases characterised histologically by a dense mononuclear cell infiltrate, including plasma cells, in the portal tract (Fig. 1) and serologically by the presence of non-organ and liver-specific autoantibodies and increased levels of immunoglobulin G (IgG), in the absence of a known aetiology. They...

HIV/AIDS in Children

The human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) epidemic in Asia has grown from a handful of cases to a major public health threat with wide-ranging medical, social and economic consequences. First gaining foothold among intravenous drug users and commercial sex workers, HIV quickly spreads to...

Speech By Mr Lim Hng Kiang, Minister For Health and Second Minister for Finance, at the Opening Ceremony of the 36th Singapore-Malaysia Congress of Medicine on Thursday, 1 August 2002 at 1810 Hours at Raffles City Convention Centre

It gives me great pleasure to join you this evening at the 36th Singapore Malaysia Congress of Medicine and the 36th Annual Combined Surgical Meeting of the Chapter of Surgeons, Academy of Medicine, Singapore. This article is available only as a PDF. Please click on “Download PDF” on top to...

Trauma-induced coagulopathy: Mechanisms and clinical management

Globally, trauma accounts for the highest number of mortalities in adolescents and young adults up to 49 years old.1 Of these deaths, a large percentage is attributable to exsanguination.2 Trauma-induced coagulopathy (TIC) occurs in 25–35% of hospitalised severe trauma patients and is associated with increased incidence of bleeding, blood...

Coagulopathy related to trauma: Is it time for a goal-directed approach?

Trauma represents a leading cause of death globally, and post-traumatic haemorrhage accounts for 40% of early mortality in spite of recent improvements in modern trauma care.1 Post-traumatic haemorrhage occurs primarily from direct injury to blood vessels, leading to exsanguination and hypovolaemic shock depending on the type and calibre of...

Inaugural College of Obstetricians & Gynaecologists Lecture: Recent Developments in Obstetric Care and Maternal Fetal Medicine in Singapore

Has it done any good to pregnancy outcome as promised? This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

Citation on Dr Andrew Chew Guan Kuan for Admission to Honorary Fellowship on 19 August 2004

It is indeed a great pleasure and honour to present to you Dr Andrew Chew Guan Khuan, who is already a Fellow of the Academy, for conferment of Honorary Fellowship of the Academy of Medicine, Singapore, the highest honour the Academy can bestow on any of its Fellows. Dr...

Citation on Sir Donald Irvine – 17th Gordon Arthur Ransome Orator

It is my pleasure and privilege to introduce Sir Donald Irvine as the 17th Gordon Arthur Ransome Orator. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

Address by Master, Academy of Medicine, Singapore at the Opening Ceremony of the 38th Singapore-Malaysia Congress of Medicine and Induction Ceremony

It is my pleasure to welcome you to the Opening Ceremony of the 38th Singapore-Malaysia Congress of Medicine with participation of the Hong Kong Academy of Medicine and Induction Comitia of the Academy of Medicine, Singapore. This article is available only as a PDF. Please click on “Download PDF” on...

1st College of Physicians Lecture: The Role of Internal Medicine as a Specialty in the Era of Subspecialisation

It humbles me to accept the invitation to give this lecture, the First College of Physicians Lecture, titled “The Role of Internal Medicine as a Specialty in the Era of Subspecialisation”. I believe I am given this honour as I am one of the few of a seemingly dying...

15th Chapter of Surgeons Lecture: Surgeon of the New Millennium – Surgeon, Scientist and Scholar

Next year, we celebrate a hundred years of medical education in Singapore. We have come a long way since 1821 – from a small, sleepy medical outpost catering to the British Armed Forces in the Far East, to an excellent state-of-the-art medical hub. This article is available only as a...

Standards and Revalidation or Recertification

In my Gordon Arthur Ransome Oration and other papers, I have described the nature and development of patient-centred professionalism, the key features of which are summarised in Figure 1. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

Continuing Professional Development – a Surrogate for Recertification?

The Hong Kong Academy of Medicine is a statutory body set up in 1993 with the objectives of fostering the development of postgraduate medical education and continuing medical education, the study and practice of medicine and its specialties, and medical research. It is concerned with the standard of specialist...

Teaching and Learning of Professionalism in Medical Schools

There is now worldwide consensus that the elements of medical professionalism need to be enhanced and explicitly taught in medical schools. Medical schools in the United Kingdom (UK) have recently published a model for a core ethics curriculum. This article is available only as a PDF. Please click on “Download...

The Challenge of Teaching Professionalism

For the past 25 years, professionalisation, industrialisation, large-scale infusions of technology into the healthcare system and consumerism, to name a few factors, have definitely contributed to changes in the healthcare environment. At the same time, society has moved from modernity to post-modernity with the adoption of pluralism, relativism and...

2004 Runme Shaw Memorial Lecture: Professionalism – A Concept in Need of Nurturing

It is a great honour to be invited to deliver the Runme Shaw Memorial Lecture. I am grateful to the Runme Shaw Foundation for their support of this lecture. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

17th Gordon Arthur Ransome Oration: Patient-centred Professionalism

When sickness strikes we all need doctors. People everywhere know that the quality of medical care can affect the outcome and possible consequences of illness, and at times mean the difference between life and death. This article is available only as a PDF. Please click on “Download PDF” on top...

The Role of Public Health and Occupational Physicians in the New Millennium

I want to thank the Chapter and organisers for honouring me with this kind invitation to speak to you. This millennium is only 4 years old, and yet I cannot see beyond the next decade, with things moving so rapidly. This article is available only as a PDF. Please click...

Flap Prefabrication – The Bridge Between Conventional Flaps and Tissue-engineered Flaps

Flap prefabrication is one of the most exciting areas in Plastic Surgery because of its bridging role between conventional reconstructive surgery and tissue engineering. Using this technique, tissues such as bone, cartilage, skin and muscle can be pre-assembled to form precise composites that will fit any defect. This article is...

Clinico-pathological Analysis of Myelodysplastic Syndromes According to French-American-British Classification and International Prognostic Scoring System

Myelodysplastic syndromes (MDS) are a heterogeneous group of acquired clonal haemopoietic stem cell disorders characterised by ineffective haematopoiesis and peripheral cytopenia. The natural history ranges from the indolent forms spanning years to those with rapid evolution to blast transformation. This article is available only as a PDF. Please click on...

In vitro Biological Characteristics of Human Cord Blood-derived Megakaryocytes

Haematopoietic stem cell transplantation (HSCT) is now a well-established therapeutic modality for a broadening spectrum of medical problems. Umbilical cord blood (CB) has emerged as an alternative source of HSCT in recent years due to the lack of a human leukocyte antigen (HLA)-identical sibling donor in the majority of...

Unrelated Umbilical Cord Blood Transplantation in Children and Adults

Allogeneic haematopoietic stem cell transplantation (HSCT) is an established form of treatment for many high-risk haematological malignancies and marrow failure syndromes. The use of HSCT is still limited by the availability of human leukocyte antigen (HLA) matched donors, even though unrelated donor registries have markedly improved the chances of...

Haematopoietic Graft Engineering

Haematopoietic stem cell transplantation (HSCT) has become an established modality for the treatment of cancer and diseases of the bone marrow and immunological system. Such transplants effect their cures through 3 main avenues: namely, eradication of disease through intensive chemo/radiotherapy, replacement of defective blood-forming cells with normal haematopoietic progenitors...

Stem Cells: Current Usage and Future Potentials

In recent years, the term “haematopoeitic stem cell transplantation” has replaced “bone marrow transplantation”. It is more precise and emphasises the “haematopoeitic stem cell” as the key element. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

Refining Clinical Practice: Transforming Science Research into the Art of Medicine

I am humbled by the invitation given to me by Changi General Hospital to deliver this lecture at your 5th Annual Scientific Meeting with the theme “Frontiers of Medicine”. Thank you very much for the honour accorded me. Your CEO, Mr Udairam, and your CMB, Prof Fock Kwong Ming,...

14th Chapter of Surgeons Lecture: Back to Basics

I am happy to be among old friends. As surgeons, we share a kindred spirit. I wish to thank the Academy for the honour of giving this lecture. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

A Rare Case of Porphyria

Porphyrias are a rare and intriguing group of metabolic disorders. We report a case of congenital erythropoietic porphyria, one of the infrequent forms of porphyria. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

Extensive Calcinosis Cutis in Relapsed Acute Lymphoblastic Leukaemia

Calcinosis cutis is characterised by the aberrant deposition of calcium salts in the skin. In metastatic calcinosis cutis, calcium salts are precipitated in normal tissue as a result of an underlying defect in calcium and/or phosphate metabolism. This article is available only as a PDF. Please click on “Download PDF”...

3rd College of Physicians’ Lecture – Translational Research: From Bench to Bedside and From Bedside to Bench; Incorporating a Clinical Research Journey in IgA Nephritis (1976 to 2006)

In our quest to pursue knowledge regarding a patient’s illness or seek a cure for the disease, as doctors we have to derive the necessary answers through physical examination of the patient and investigations either at the bedside or the laboratory. We engage in research activities into the patient’s...

16th Seah Cheng Siang Memorial Lecture – The Changing Face of Cardiology Practice, Training and Research in Singapore

Professor Seah Cheng Siang was one of the most illustrious physicians of his era. During his professional career, he held the following positions: Head, Department of Medicine, Thomson Road General Hospital (1960-71); Head, Department of Medicine III at the Singapore General Hospital (1971-87); Master of the Academy of Medicine...

3rd FY Khoo Memorial Lecture – Education, Professionalism, Outsourcing and the Future of Radiology

Radiology is undergoing unprecedented changes. Not only is the technology evolving rapidly, providing images of breathtaking anatomical clarity, but functional information has also become a reality. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

10th Yahya Cohen Memorial Lecture: Clinical Predictors in Obstructive Sleep Apnoea Patients with Computer-assisted Quantitative Videoendoscopic Upper Airway Analysis

Obstructive sleep apnoea (OSA) is a common disease, which is estimated to affect up to 2% of middle-aged women and 4% of middle-aged men.1 Various attempts have been made to obtain predictive indicators of OSA, ranging from clinical predictors using body mass index (BMI), Malampatti score2 and tonsil size...

New Treatments for Atopic Dermatitis – Facts, Comparisons and Uncertainties

Atopic dermatitis is associated with asthma and allergic rhinitis, and presents with a typical morphology and distribution. Eighty-four per cent of cases of atopic dermatitis are mild, 14% moderate, and 2% severe.1 There are 10 randomised controlled trials, and 1 systematic review addressing the appropriate frequency of application of...

Clinical Experience with Three Combination Regimens for the Treatment of High-risk Febrile Neutropenia

Cancer patients who become severely neutropenic as a result of intensive myelosuppressive chemotherapy are at high risk for developing life-threatening infections, and unless they are treated at the first sign of infection, the rate of mortality is high. Because of the defect in the inflammatory response, the classic signs...

5th College of Physicians Lecture – A Physician’s Odyssey: Recollections and Reflections

Allow me to thank you Mr President and your Council for asking me to deliver the 5th College of Physicians Lecture. Your President has suggested that with over 50 years of association with Medicine, the title be “In the Service of the Medical Profession”. This article is available only as...

Brachytherapy – One Man’s Meat, A Personal Journey in Radiation Oncology

Dr Tan Kim Ping, Chairman for the Dr FY Khoo Memorial Lecture, Ladies and Gentlemen – It is a signal honour for me to deliver this Lecture, the second since the Inaugural Lecture last year. Sadly, it has been renamed a Memorial Lecture, as Dr FY Khoo passed away...

Retinal and Cardiovascular Diseases: The “Common Soil” Theory

There is increasing evidence that retinal and cardiovascular diseases share a “common soil”. Risk factors for cardiovascular disease, such as hypertension, diabetes, hyperlipidaemia and cigarette smoking, are known to influence the development of a range of retinal diseases, including hypertensive retinopathy, diabetic retinopathy, retinal vein and artery occlusion, retinal...

4th FY Khoo Memorial Lecture 2008: Nasopharyngeal Cancer Workgroup – The Past, The Present and The Future

Thank you Madam Chairman. First, I would like to thank the Singapore Radiological Society and the College of Radiologists, Academy of Medicine Singapore for giving me the honor of delivering this the 4th FY Khoo Memorial Lecture, 2008. This article is available only as a PDF. Please click on “Download...

3rd College of Paediatrics and Child Health Lecture – The Past, the Present and the Shape of Things to Come…

In the post-war days of the 1950s, Singapore children were faced with problems of malnutrition and infectious diseases. There was poverty, overcrowded housing and lack of hygiene, and the social conditions were apparently appalling. This article is available only as a PDF. Please click on “Download PDF” on top to...

Use of Antibiotics in a Haematology Ward – An Audit

Rising rates of antibiotic resistance prompted a review of antibiotic use policies hospitalwide. The Department of Haematology established a new set of consensus guidelines in 2002 for antibiotic use in febrile neutropenia. We were tasked by the hospital’s Pharmacy and Therapeutics Committee to audit adherence to the guidelines. This article...

The Role of Electrophysiology in the Diagnosis and Management of Cervical Spondylotic Myelopathy

Cervical spondylosis is an extremely common condition managed by both physicians and surgeons in daily clinical practice. Cervical spondylotic myelopathy (CSM), resulting from longstanding degenerative impingement of the spinal cord and nerve roots by osteo-cartilagineous elements, is managed by conservative or surgical methods.1 While surgery is often performed in...

Demands and Challenges of Modern Medicine

I am deeply honoured by the invitation to deliver the 16th Tun Dr Ismail Oration and I wish to thank the Master and Council of the Academy of Medicine of Malaysia for this rare privilege of addressing a distinguished gathering such as this, as previous illustrious orators had done...

Happenings in Histopathology – A Post-World War II Perspective

During the past few decades, there have been many significant developments in the practice of histopathology, the specialty that is also referred to as anatomic pathology, surgical pathology, or simply as pathology without qualification. Those selected for review are grouped under 4 headings: new techniques, organisational developments, ethical and...

Tumour Interstitial Fluid Pressure May Regulate Angiogenic Factors in Osteosarcoma

Solid tumours have states of raised interstitial fluid pressure (IFP) that cause significant changes to their physiology.1-3 We have previously shown that human osteosarcomas respond to this raised IFP by increasing their proliferative state. This proliferative state results in increased sensitivity to chemotherapy – a finding noted both in...

Surgical Training – The Challenge of Change

President of the College of Surgeons, distinguished guests, friends, ladies and gentlemen. It is a great honour and a unique privilege for me to be invited to deliver a named lecture for a third time. Twenty years ago, I gave the first overseas Joint Lecture of the Academy and...

Preparedness for Terrorism: Managing Nuclear, Biological and Chemical Threats

Preparedness for terrorism in the 21st century includes addressing the management of nuclear, biological and chemical (NBC) terrorism events. Understanding the terrorist threat and detecting clues that an attack has occurred are critical to reducing morbidity and mortality in the next decade. While high explosive events (bomb and blast)...

An Unusual Cause of Lymphadenopathy and Rash

A 38-year-old Chinese man who was previously well, presented with one month of fever and a non-pruritic rash involving the face, trunk and upper limbs. There was no oral, ocular or genital involvement. He denied weight loss, night sweats, fatigue or easy bruising and there was no history of...

5th College of Surgeons Lectureship: Surgery beyond Scalpels

The training of surgeons composed of two aspects: (1) Clinical skill and competence; (2) The ‘soft’ skill and ‘art’ of surgery. With the gradual introduction of residency programme into the surgical discipline, hopefully our clinical training will be more systematic, closely supervised, monitored, assessed and reassessed, and structured. This article...

The Evolution of Radiology from Paraclinical to Clinical

I would like to thank the Academy of Medicine and the Singapore Radiological Society for giving me the honour of delivering this year’s F Y Khoo’s Memorial Lecture. I believe that I am one of the few radiologists in Singapore who had the privilege of working with Dr F...

Bone Marrow Cytogenetics Workup: Application of Lean Management System to Determine if Additional Cell Workup is Helpful and Necessary to Analysis

Cytogenetic studies are important to the diagnosis and monitoring of various haematopoietic disorders such as myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), lymphoproliferative disease (LPD), and multiple myeloma (MM). It can also provide a prognosis to a...

A Case of Congenital Haemolytic Anaemia and Thrombocytopenia

A 20-month-old boy came from Bangladesh to Singapore for medical consultation. He presented with progressive pallor, easy bruising, intermittent dark-coloured urine, and failure to thrive since birth. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

Prospective Audit of Febrile Neutropenia Management at a Tertiary University Hospital in Singapore

Febrile neutropenia (FN) is considered a medical emergency and remains a major cause of morbidity and mortality in Oncology and Haematology units worldwide. A study analysing pooled FN data from 115 US academic medical centres between 1995 and 2000 showed that the overall in-hospital mortality was 9.5%, whereas pooled...

3rd College of Surgeons Lecture — Bringing up Surgeons

I am greatly honoured to be given the privilege of delivering the 3rd College of Surgeons Lecture, especially when I have retired from surgery for 3 years. I am not in a position to contribute anything significant to your knowledge. There is an old Chinese saying that learning is...

Management of Antiplatelet Therapy During Acute Percutaneous Coronary Intervention: New Strategies and Therapeutics

Platelet adhesion, activation, and aggregation are stimulated during an acute coronary syndrome (ACS), the result of intimal injury due to rupture of an atherosclerotic plaque. This triggers a cascade of events leading to the catastrophic formation of an occlusive clot. Antiplatelet agents assume the cornerstone role in modern pharmacotherapy...

12th Yahya Cohen Memorial Lecture – The Cellular and Molecular Basis of Radiation-induced Sensori-neural Hearing Loss

Radiation-induced sensori-neural hearing loss (SNHL) has long been recognised as a complication of radiotherapy (RT) for head and neck tumours, if the auditory pathways had been included in the radiation fields. In Singapore, nasopharyngeal carcinoma (NPC) is common and the prevalence of SNHL after radiotherapy for NPC has been...

11th Yahya Cohen Memorial Lecture – An In vivo Comparative Study of the Ability of Derived Mesenchymal Stem Cells in the Treatment of Partial Growth Arrest

It has been my greatest pleasure and honour to accept this, the 11th Yahya Cohen Memorial Lectureship on the anniversary of a half century of the Academy of Medicine. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

Immunophenotypic, Cytogenetic and Clinical Features of 113 Acute Lymphoblastic Leukaemia Patients in China

Acute lymphoblastic leukaemia (ALL) is a heterogeneous disease with abnormal proliferation and accumulation of immature lymphoblasts within the bone marrow (BM), peripheral blood and lymphoid tissues, and is composed of different genetic, biological, and clinically relevant subtypes. Morphological and cytochemical methods were the main tools for diagnosis and classification...

Non-haem Iron-mediated Oxidative Stress in Haemoglobin E Beta-thalassaemia

Thalassaemia is a genetic haemoglobinopathy in which the production of normal haemoglobin is partly or completely suppressed because of a defective synthesis of 1 or more of its component globin chains. In haemoglobin (Hb) E beta-thalassaemia, an individual inherits 1 gene for Hb E from 1 parent and 1...

Thrombocytopenia and its Related Factors: A Hospital-based, Cross-sectional Study

Thrombocytopenia is a common clinical problem found in laboratory results during health examinations. Blood platelets play an essential role in haemostasis, thrombosis and coagulation of blood. This article is available only as a PDF. Please click on “Download PDF” on top to view the full article.

Challenges and Pitfalls in the Introduction of Pharmacogenetics for Cancer

Pharmacogenetics, by definition, refers to the study of genetic differences in metabolic pathways which can affect an individual’s responses to drugs in terms of both therapeutic and adverse effects. In recent years, there have been several success stories such as HER2 for trastuzumab in breast cancer and VKORC1/CYP2C9 for...

7th College of Physicians Lecture — The Changing Face of Medicine, Medicine – Past, Present and Future

When we think about medicine, just like we do about other things in life in the past and the present, we usually reflect on the good old days. On hindsight, the past always seems brighter than the present. Sometimes, it is worth looking back to see how things have...

15th Yahya Cohen Memorial Lecture – The Relationship between the Air-bone Gap and the Size of Superior Semicircular Canal Dehiscence

Superior semicircular canal dehiscence (SSCD) can result in a characteristic constellation of vestibular and auditory features, including autophony, oscillopsia, and vertigo, and characteristic eye movements induced by sound and pressure changes. Patients with SSCD also show lowered thresholds for vestibular-evoked myogenic potentials (VEMPs) and a heightened sensitivity to bone-conducted...

5th Chao Tze Cheng Memorial Lecture—Recent Developments in Informed Consent

The question of informed consent is a concern of recent origin and has engaged the mind of the medical profession here for only some 5 decades now. The term ‘informed consent’ is very much of American origin and the British have termed it as ‘a duty to warn’. This...

7th Tan Tock Seng Oration: Surgical Excellence at TTSH—100 Years on and onward

Mr SR Nathan, our guest of honour, Mr Gan Kim Yong, Minister for Health, Madam Kay Kuok, Chairman of NHG Board, Board members, colleagues, distinguished guests, friends, ladies and gentlemen, I am greatly humbled by the honour and privilege to deliver the 7th TTSH Oration this evening. The sixth...

8th FY Khoo Memorial Lecture 2012 —Why Radiologists Need Philosophy

Firstly, I wish to thank the Singapore Radiological Society and the College of Radiologists, Singapore for deeply honouring me with the invitation to give the FY Khoo Memorial Lecture for this year’s Annual Scientific Meeting. Today, I will present you an argument that radiologists should be conscious of philosophy...

6th College of Surgeons Lecture The Philosophy of Balance: The Art of Healing

With the rise of high tech medicine, and emphasis on the scientific aspects of medicine, there is danger that we may lose the balanced approach to healing, and lose the benefit of the traditional medical wisdom and emotional support to improve the care of our patients. This article is available...

2013 Runme Shaw Memorial Lecture: Clinical Applications of Stem Cells in Modern Medicine—21st Century and Beyond

The rapid advancement of biomedical research in the recent years was propelled by a series of groundbreaking technological inventions and breakthrough discoveries. In this lecture, I will discuss about the scientific achievements that led to different eras of intense research with profound impact on biomedicine, focusing on the use...

22nd Gordon Arthur Ransome Oration: Is Medicine Still an Art?

Distinguished guests and colleagues in medicine, I am deeply honoured to have been invited to deliver this 22nd oration in honour of Sir Gordon Arthur Ransome, and also humbled when I peruse the list of outstanding previous orators. This article is available only as a PDF. Please click on “Download...

24th Seah Cheng Siang Lecture: Seeing Better, Doing Better—Evolution and Application of Gastrointestinal (GI) Endoscopy

Man’s innate curiosity to study the internal organs of the human body dates back to the time of Hippocrates where basic speculums were invented to peer into the buccal cavity and vagina. The first instruments used to intubate the oesophagus and stomach in the 16th and 17th centuries were...

Medical management of PAD: Expand or consolidate?

In this issue of the Annals, a rapid review of adherence to evidence-based medical treatment highlights an important and underappreciated aspect of the management of patients with peripheral arterial disease (PAD). It is easy, upon meeting a patient, to prescribe appropriate medication in an outpatient setting and believe that...

Severe COVID-19 and coagulopathy: A systematic review and meta-analysis

Manifestations of the coronavirus disease 2019 (COVID-19) span a wide clinical spectrum, from asymptomatic carriers to critical illness with a wide range of complications. Our understanding of the pathophysiology of the disease process is still evolving. As part of the host response to viraemia, it has been postulated that...

Estimating the impact of COVID-19-induced coagulopathy

The current coronavirus disease 2019 (COVID-19) pandemic has exerted significant strain on healthcare worldwide. Mostly asymptomatic or mildly symptomatic, COVID-19 caused by SARS-CoV-2 is described as a thrombo-inflammatory syndrome,1 with severe respiratory illness occurring in about 13% of affected patients. This can rapidly transform into a life-threatening condition in...