2024Trial2

Question 1

The incubation periods of travel-related infections are varied. Which of the following travel-related infections has an intermediate (10-21 days) incubation period?

A. Typhoid
B. Tuberculosis
C. Rocky Mountain Spotted Fever
D. Dengue

Answer 1

A. Typhoid

Tuberculosis >21 days
Rocky Mountain Spotted Fever < 10 days
Dengue < 10 days

Question 2

Anifrolumab has recently been PBS listed for use in systemic lupus erythematosus (SLE) in July 2024. Which of the following infections would you need to caution patients against?

A. Herpes Zoster
B. John Cunningham virus (JC virus)
C. Candida albicans
D. Pneumocystis jirovecii

Answer 2

A. Herpes Zoster

Question 3

Which of the following is the most common cause of end-stage renal disease (ESRD) in adults?

A. Hypertension
B. Diabetes mellitus
C. Polycystic kidney disease
D. Glomerulonephritis

Answer 3

B. Diabetes mellitus

Question 4

Which of these is NOT a contraindication to the use of adenosine in the acute treatment of supraventricular tachycardia?

A. Pregnancy
B. Uncontrolled asthma
C. Mobitz I atrioventricular block
D. Wolff-Parkinson-White syndrome

Answer 4

A- pregnancy

can precipitate bronchospasm, can cause bradycardia or higher degree heart block when used in a patient with AV block greater than first degree.
blocking of AV nodal tissue can cause unhindered conduction via the accessory pathway

Question 5

Which of the following statements is FALSE regarding frontotemporal dementia?

A. Frontotemporal dementia encompasses behavioural variant frontotemporal dementia, semantic variant primary progressive aphasia, and non-fluent variant primary progressive aphasia
B. Mutations in C9orf72 are the most common genetic cause of familial frontotemporal dementia and motor neurone disease
C. Transactive-response DNA binding protein-43 (TDP-43) inclusions are not associated with frontotemporal dementia
D. Focal frontal or temporal atrophy is demonstrated in 50-65% of patients on neuroimaging

Answer 5

C. Transactive-response DNA binding protein-43 (TDP-43) inclusions are not associated with frontotemporal dementia

Question 6

Which of the following is correct during pregnancy?

A. Serum total and ionised calcium levels increase during pregnancy
B. Parathyroid hormone levels increase during pregnancy
C. 1,25 dihydroxy vitamin D levels increase significantly during pregnancy
D. Placental 1 alpha hydroxylase activity is more important than maternal renal 1-alpha hydroxylase activity.

Answer 6

C. 1,25 dihydroxy vitamin D levels increase significantly during pregnancy

Question 7

Regulation of iron homeostasis is undertaken by hepcidin. Which of the following is correct about hepcidin?

A. Hepcidin is produced in the nucleus of the hepatocyte and binds to ferroportin in duodenal enterocytes to increase iron protein export

B. Inflammatory markers such as interleukin-6 upregulate the expression of hepcidin

C. Individuals with HFE-associated hereditary haemochromatosis have higher expression of hepcidin

D. Iron refractory iron deficiency anaemia, caused by mutations in TMPRSS6 gene, have low serum hepcidin levels

Answer 7

B. Inflammatory markers such as interleukin-6 upregulate the expression of hepcidin

Question 8

Which of the following statements regarding Burkitt lymphoma is most correct?

A. Diagnosis is made by expression of both MYC and IGH on lymphoma cells assessed by immunohistochemistry (IHC)

B. Diagnosis is made by presence of MYC/IGH fusion within lymphoma cells assessed by fluorescence in-situ hybridisation (FISH)

C. Diagnosis is made by expression of MYC and IGH on lymphoma cells assess my multiparameter flow cytometry (MPFC)

D. Diagnosis is made by identifying both MYC and IGH gene variants within lymphoma cells assessed by next generation sequencing (NGS)

Answer 8

B. Diagnosis is made by presence of MYC/IGH fusion within lymphoma cells assessed by fluorescence in-situ hybridisation (FISH)

BURKITT lymphoma: t(8;14) translocation on the MYC oncogene (on chromosome 8) and IGH oncogene (on chromosome 14)

Question 9

A 30-year-old woman undergoes genetic testing after a family history reveals multiple cases of breast and ovarian cancer. Her genetic test results show a pathogenic variant in the BRCA1 gene. Which of the following best explains the mechanism by which BRCA1 mutations increase cancer risk?

A. Increased DNA methylation leading to gene silencing
B. Defective DNA repair via homologous recombination
C. Enhanced proto-oncogene activation
D. Increased telomerase activity

Answer 9

B. Defective DNA repair via homologous recombination

Question 10

A 40-year-old male presents with recurrent sinopulmonary infections, chronic diarrhea, and failure to thrive. Laboratory tests reveal low levels of all immunoglobulin subclasses, undetectable B cells, and normal T cell counts. Genetic testing identifies a mutation in the BTK gene.

Which of the following best describes the primary immunological defect in this patient?

A. Impaired T cell receptor signaling
B. Defective B cell receptor signaling
C. Inadequate class switch recombination
D. Dysfunctional phagocyte oxidative burst

Answer 10

B. Defective B cell receptor signaling

The BTK (Bruton’s tyrosine kinase) gene mutation causes X-linked agammaglobulinemia (XLA), characterized by a block in B cell development at the pre-B cell stage. This leads to a profound deficiency of B cells and, consequently, very low levels of immunoglobulins. The primary immunological defect is in B cell receptor signaling, which is critical for B cell maturation.

Impaired T cell receptor signaling, inadequate class switch recombination, and dysfunctional phagocyte oxidative burst are not the primary defects associated with BTK mutations.

Question 11

In the treatment of multiple sclerosis, what is the mechanism of action of siponimod?

A. Sphingosine-1-phosphate receptor inhibitor, which acts to inhibit lymphocyte maturation
B. Sphingosine-1-phosphate receptor inhibitor, which acts to inhibit lymphocyte ingress to the central nervous system
C. Sphingosine-1-phosphate receptor inhibitor, which acts to inhibit lymphocyte egress from secondary lymphoid tissues
D. Sphingosine-1-phosphate receptor inhibitor, which acts to promote apoptosis of memory B-cells

Answer 11

C. Sphingosine-1-phosphate receptor inhibitor, which acts to inhibit lymphocyte egress from secondary lymphoid tissues

Question 12

Which of the following is INCORRECT with regards to the pharmacology of phenytoin?

A. It blocks voltage gated sodium channels
B. The therapeutic index is narrow
C. Elimination follows first order kinetics
D. It is a strong inducer of CYP3A4

Answer 12

C. Elimination follows first order kinetics

Question 13

The mechanisms of action of NAC (N-Acetyl Cystine) infusion for paracetamol toxicity include all of the following, EXCEPT

A. Enhances CYP450 metabolism in promoting paracetamol conjugates with glucuronide sulphates
B. Increased glutathione availability
C. Direct binding of NAPQI
D. Provision of inorganic sulphate

Answer 13

A. Enhances CYP450 metabolism in promoting paracetamol conjugates with glucuronide sulphates

NAC increases glutathionine which binds to NAPQI and excretes it

Question 14

Hypermagnesaemia is associated with which of the following complications in patients with diabetes mellitus?

A. Hyperosmolar hyperglycaemic state
B. Hypoglycaemia
C. Macrovascular complications
D. Microvascular complications

Answer 14

D. Microvascular complications

A cross-sectional study of adult patients with diabetes mellitus observed hypermagnesaemia in 4.1% of patients. Hypermagnesaemia was associated with hypertension, hypocalcaemia, nephropathy, and retinopathy

Question 15

Which of the following formulas may be used to calculate a patient’s diffusing capability for carbon monoxide (DLco)?

A. DLco = kco x VA
B. DLco = TLC x kco
C. DLco = FEV1 x VA
D. DLco = kco x FVC

Answer 15

A. DLco = kco x VA

kco = the rate of carbon monoxide uptake. Determined by: the integrity of the alveolar-capillary membrane and, the volume of capillary Hb

VA = estimated alveolar volume. Determined by: the actual number of lung units and, the chest wall function and, the ability of the gas mix to reach all accessible lung during the DLco manoeuvre.

Question 16

Anticholinergic medication properties can be associated with adverse drug reactions such as dry eyes, urinary retention, cognitive impairment and falls.

What is a medication commonly used that has high anticholinergic potency?

A. Amitriptyline 50 mg
B. Haloperidol 0.5 mg
C. Digoxin 62.5 mcg
D. Mirabegron 25 mg

Answer 16

A. Amitriptyline 50 mg

Question 17

Which of the following is LEAST associated with a response to checkpoint inhibitor immunotherapy in solid-organ malignancies?

A. Mutation burden
B. PD-L1 expression
C. Microsatellite instability
D. KRAS mutation

Answer 17

D. KRAS mutation

Question 18

Which of the following terms describes the adherence to prosthetic material, multiplication, and exopolysaccharide elaboration and coalescence by bacteria?

A. Small colony variant formation
B. Biofilm formation
C. Quorum sensing
D. Heteroresistance

Answer 18

B. Biofilm formation

Small colony variant –> subpopulations of bacteria that exhibit slow-growth and atypical colony morphology and biochemical characteristics.

Quorum sensing –> secretion of chemicals to facilitate communication between bacterial cells, which can result in biofilm and/or small colony variant formation.

Heteroresistance= anti-microbial resistant subpopulation of microbes

Question 19

Which of the following best describes the handling of free light chains by the nephron?

A. Not filtered through the glomerulus
B. Freely filtered at the glomerulus and largely reabsorbed through receptor-mediated endocytosis in the proximal tubule
C. Freely filtered at the glomerulus and largely reabsorbed through receptor-mediated endocytosis in the distal tubule
D. Freely filtered at the glomerulus, mostly not reabsorbed in the proximal or distal tubules

Answer 19

B. Freely filtered at the glomerulus and largely reabsorbed through receptor-mediated endocytosis in the proximal tubule

Question 20

A 25-year-old-man is found to have a moderate sized atrial septal defect. With regards to the mean pressure within the pulmonary artery and the ratio of pulmonary arterial to systemic flow (Qp:Qs), compared to a normal individual, he is likely to have:

A. Increased Qp:Qs, decreased pulmonary arterial pressure
B. Increased Qp:Qs, increased pulmonary arterial pressure
C. Decreased Qp:Qs, decreased pulmonary arterial pressure
D. Increased Qp:Qs, unchanged pulmonary arterial pressure

Answer 20

B. Increased Qp:Qs, increased pulmonary arterial pressure

Question 21

Levo-dopa (L-dopa) is always given with a decarboxylase inhibitor. Which of the following is the reason for combination with a decarboxylase inhibitor?

A. It reduces the half-life of oral L-dopa
B. It prevents decarboxylation in the brain
C. It reduces the dose required for a clinical effect
D. It has a direct agonist effect on the dopamine receptors

Answer 21

C. It reduces the dose required for a clinical effect

Question 22

Secretion of urease is an important virulence factor that leads to alkalinisation of urine. Urease-producing bacteria are associated with staghorn calculi and formation of stones.

Which is NOT an example of a urea-splitting organism?

A. Proteus mirabilis
B. Pseudomonas aeruginosa
C. Klebsiella pneumoniae
D. Escherichia coli

Answer 22

D. Escherichia coli

Question 23

A 36-year-old lady with seronegative rheumatoid arthritis has been on biologic therapy with adalimumab for 4 years. She presents for routine clinic review and complains of 3 months of malaise, myalgia, and weight loss. She has a malar rash and some synovitis of the small joints of her hands.

Which of the following is LEAST likely to be informative of a suspected diagnosis of TNF-inhibitor induced Systemic Lupus Erythematosus?

A. Anti-histone antibodies
B. ANA antibodies
C. Anti-dsDNA antibodies
D. Anti-SSA/Ro antibodies

Answer 23

A. Anti-histone antibodies

Induction of autoantibodies by TNF-a therapy is widely known and can cause a clinical SLE syndrome. Most commonly, this is represented by ANA, dsDNA, and ENAs. Anti-histone antibodies may be present in >95% of drug-induced SLE, however are more associated with hydralazine, chlorpromazine, and to a slightly lesser degree with minocycline and propylthiouracil. Reports show anti-histone antibodies in only 17-57% of patients with TNFa induced SLE

Question 24

A 65-year-old man requires emergency surgery for a bowel obstruction. He is on dabigatran for atrial fibrillation, and the surgical team has requested urgent reversal of dabigatran.

Which one of the following statements is most correct regarding idarucizumab administration?

A. Recurrence of plasma concentrations of unbound dabigatran may occur after 2-3 hours, indicating further re-administration of idarucizumab
B. Patients with end-stage renal failure should dose-reduce idarucizumab by 25% to maintain reversal efficacy
C. Elevated activate partial thromboplastin time (aPTT) or diluted thrombin time (dTT) caused by Factor Xa inhibitors can be reduced by idarucizumab
D. Recommencement of dabigatran can occur 24 hours after idarucizumab administration once surgical clearance is obtained

Answer 24

D. Recommencement of dabigatran can occur 24 hours after idarucizumab administration once surgical clearance is obtained

Question 25

Which of the following factors would cause a more favourable shift to the right on the oxyhaemoglobin dissociation curve?

A. Low PCO2
B. High [H+]
C. Methaemoglobinaemia
D. Hypothermia

Answer 25

B. High [H+]

Question 25

Which of the following investigations means coeliac disease is very UNLIKELY as a diagnosis in a patient who does not eat gluten-containing food?

A. Gastroscopy with duodenal biopsies
B. Colonoscopy with terminal Ileal biopsies
C. Tissue Transglutaminase serology with IgA levels
D. Negative HLA DQ2/8 genotyping

Answer 25

D. Negative HLA DQ2/8 genotyping

Question 26

A 73-year-old lady presents to hospital with itchy, tense, fluid-filled blisters. Her background history is significant for hypertension, type 2 diabetes mellitus, mild cognitive impairment, osteoporosis, and cervical cancer. Her medications include amlodipine 10mg daily, metformin extended-release (XR) 1g twice daily, sitagliptin 100mg daily, denosumab 60mg 6 monthly, and vitamin D 1000 IU daily.

The skin lesion is biopsied and she is diagnosed with bullous pemphigoid. Her autoimmune screen for bullous pemphigoid returns negative. Drug-induced bullous pemphigoid is suspected.

Which of the following medications is most likely to be the cause?

A. Amlodipine
B. Metformin
C. Sitagliptin
D. Denosumab

Answer 26

C. Sitagliptin

Question 27

The diagnostic criteria for Common Variable Immunodeficiency (CVID) is a patient who exhibits all of the following, EXCEPT

A. Low IgA or IgM levels
B. Low CD4+ T Cells
C. Low total serum IgG levels
D. Poor or absent response to vaccination

Answer 27

B. Low CD4+ T Cells

Question 28

Which of the following antifungals is sufficiently excreted in its active form into urine to be therapeutic for urinary tract infection?

A. Fluconazole
B. Voriconazole
C. Liposomal amphotericin B
D. Anidulafungin

Answer 28

A. Fluconazole

Fluconazole is the only azole that is excreted into urine in an active form. Other azoles, including voriconazole, posaconazole, itraconazole and isavuconazole, have negligible urinary excretion as an active agent although some have significant renal elimination of inactive metabolites. Conventional amphotericin gets into the urine, but the lipid formulations of amphotericin do not. Echinocandins such as anidulafungin have no urinary penetration.

Question 29

What is the most commonly associated genetic mutation with catecholaminergic polymorphic ventricular tachycardia (CPVT)?

A. RYR2
B. CALM1
C. CASQ3
D. TRDN

Answer 29

A. RYR2

CPVT is an inherited genetic disorder that predisposes to VT/VF typically during exercise or emotional stress. The VT is characteristically bidirectional. The abnormalities caused in CPVT are related to the metabolism and control of Calcium in the cardiac myocyte. All of the above options are genetic mutations identified in CPVT however the most commonly identified mutation is in RYR2 which encodes a protein included in an ion channel known as the ryanodine receptor. Mutation is RYR2 is identified in up to half of all cases.

Question 30

Trastuzumab deruxtecan is a HER2-targeting antibody-drug conjugate that has shown efficacy in both HER2-amplified and HER2-low cancers. Its cytotoxic action on HER2-low cancers is attributed to which of its properties?

A. High drug-to-antibody ratio
B. Potent topoisomerase I inhibitor payload
C. Payload easily crosses the cell membrane
D. Cleavable tetrapeptide-based linker

Answer 30

C. Payload easily crosses the cell membrane

Trastuzumab deruxtecan has a released payload that easily crosses the cell membrane, which allows for a ‘bystander’ cytotoxic effect on neighbouring tumour cells regardless of target (HER2) expression.

Question 31

A 72-year-old man presented with bilateral asymmetrical weakness of hand grip.

On examination, there was loss of muscle bulk on the volar aspect of the forearms and impaired flexion of the distal interphalangeal joints of the fingers.

Impaired function of which muscle is chiefly contributing to the weakness seen?

A. Flexor digitorum profundus
B. Flexor digitorum superficialis
C. Flexor pollicis brevis
D. Flexor pollicis longus

Answer 31

A. Flexor digitorum profundus

Question 32

A 63-year-old man with a history of bipolar affective disorder that is well-controlled using lithium carbonate presents with a one-week history of polyuria and polydipsia. Blood tests show a serum sodium concentration of 151 mmol/L, a serum osmolality of 300 mOsm/L, and a serum lithium concentration of 0.9 mmol/L (stable). Urinalysis shows a urine sodium concentration of 10mmol/L and a urine osmolality of 235 mOsm/L.

A diagnosis of lithium-induced nephrogenic diabetes insipidus is made and the patient is started on amiloride (a potassium-sparing diuretic).

By what mechanism is amiloride effective in the management of lithium-induced diabetes insipidus?

A. Increasing renal sodium losses
B. Reducing circulating blood volume
C. Competing for tubular reabsorption of lithium
D. Increasing lithium clearance by increasing glomerular filtration

Answer 32

C. Competing for tubular reabsorption of lithium

Question 33

Which drug is most associated with nephrolithiasis?

A. Acyclovir
B. Atazanavir
C. Emtricitabine
D. Tenofovir

Answer 33

B. Atazanavir

Question 34

Which statement is most correct regarding vaccine-induced immune thrombotic thrombocytopenia (VITT)?

A. VITT is caused by IgG antibodies that recognize platelet factor 4, which activate platelets via low affinity platelet FcγIIa receptors
B. VITT is caused by IgM antibodies that recognize platelet factor 4, which activate platelets via low affinity platelet FcγIIa receptors
C. VITT is caused by antibodies that recognize platelet factor 4, which leads to platelets sequestration in the spleen via low affinity platelet FcγIIa receptors
D. VITT is caused by antibodies that recognize platelet factor 4 which can be detected using lateral flow immunoassay

Answer 34

A. VITT is caused by IgG antibodies that recognize platelet factor 4, which activate platelets via low affinity platelet FcγIIa receptors

Question 35

Answer 35

Answer: C

Here, the JVP trace demonstrates cannon “A” waves - indicative of AV dissociation and right atrial contraction whilst the tricuspid valve is still closed. The patient has presented with syncope and his ECG demonstrates complete heart block, with complete AV dissociation.

Question 36

Which of the following drugs targets lymphocyte α4β7 integrin, a key mediator of gastrointestinal inflammation implicated in inflammatory bowel disease?

A. Ustekinumab
B. Secukinumab
C. Vedolizumab
D. Golimumab

Answer 36

C. Vedolizumab

Ustekinumab inhibits cytokines IL-12 and IL-23. Secukinumab inhibits IL-17A. Vedolizumab binds to alpha4-beta7-integrin and inhibits adhesion of T lymphocytes to mucosal addressin-cell adhesion molecule‑1 (MAdCAM‑1) expressed in the gastrointestinal tract. Golimumab is a TNF alpha inhibitor.

Question 37

A clinical trial investigates the effectiveness of a new medication, TarMin123, in alleviating chronic back pain in patients with osteoarthritis. The trial includes 150 patients, 50 of whom receive standard treatment with analgesics. Out of the 100 patients treated with TarMin123, 60 experience significant relief from their back pain.

What are the odds of a patient with osteoarthritis receiving significant pain relief from TarMin123?

A. 1.5
B. 3
C. 1
D. 2

Answer 37

A- 1.5

To find the odds, we can use the formula: Odds = Number of successes / Number of failures

Here, the number of patients receiving significant relief (successes) is 60, and the number of patients who did not receive significant relief (failures) is 100 - 60 = 40.

So the odds would be: Odds = 60/ 40 = 1.5

Question 38

Which of the following forms part of the membrane attack complex?

A. C3a
B. C3b
C. C5a
D. C5b

Answer 38

D. C5b

The membrane attack complex consists of C5b, C6, C7, C8 and C9. C3a and C5a are anaphylotoxins, pro-inflammatory peptides formed after C3 and C5 are cleaved during complement cascade activation. C3b is important for opsonization of pathogens and for forming C3 and C5 convertase.

Question 39

Lecanemab is a monoclonal antibody being tested in persons with early Alzheimer’s disease. Which bests describes the immunological target of lecanemab?

A. Amyloid-beta protofibrils
B. Cholinesterase
C. N-methyl-D-aspartate (NMDA) receptor
D. Tau protein

Answer 39

A. Amyloid-beta protofibrils

Question 40

A 74-year-old woman with a stable coronary artery disease and hypertension presents with progressive dyspnoea over 2 months. She has an oxygen saturation of 83% despite 15L/min through a non-rebreather mask. Your examination of the patient is unrevealing apart from central cyanosis. Notably, the emergency department registrar notes that when the patient was laid flat while transferring from the ambulance bed, the patient’s oxygen saturations improved to 96%, which you are able to replicate.

Which of these investigations is most likely to be diagnostic in this patient?

A. Tilt table test
B. Transoesophageal echocardiography with bubble study
C. Contrast chest CT
D. Invasive coronary angiogram

Answer 40

B. Transoesophageal echocardiography with bubble study

This patient has platypnoea orthodeoxia syndrome

Question 41

A 28-year-old female patient with left sided ulcerative colitis sees you in the outpatient clinic. Her recent blood tests include: Haemoglobin 119 g/L, mean corpuscular volume 90 fL, C-reactive protein 9 mg/L, normal renal and liver function tests. A recent faecal calprotectin is 49 mcg/mg (normal < 50mcg/mg).

She is established on azathioprine 2 mg/kg and mesalazine 2 grams daily. She is opening her bowels twice daily with formed stools and no blood. She informs you that she is 6 weeks pregnant.

Which of the following is the most correct action to undertake?

A. Stop azathioprine due to its safety profile in pregnancy and switch to methotrexate
B. Continue with the current treatment regimen
C. Add course of prednisolone 40mg daily, reducing by 5mg per week, to her azathioprine to prevent a colitis flare during this stage of pregnancy
D. Perform a sigmoidoscopy to assess colitis activity before altering any medications

Answer 41

B. Continue with the current treatment regimen

Azathioprine and Mesalazine have a well-established safety profile in pregnant women with UC and should be continued

Question 42

James is a 48-year-old HIV-infected man who presents to the emergency department with confusion and a decreased level of consciousness. He has recently returned from a six-month trip to the Philippines, during which he was not taking his medications. An urgent lumbar puncture and MRI are performed, which show findings concerning for tuberculous meningitis, and he is commenced on empirical treatment.

Which of the following is true regarding the use of adjunctive dexamethasone in addition to standard therapy in the treatment of tuberculous meningitis in HIV-infected adults?

A. Decrease in all-cause mortality at 12 months
B. Decrease in neurologic disability at 12 months
C. Decrease incidence of immune reconstitution inflammatory syndrome during the first 6 months
D. There is no benefit to the use of dexamethasone in this scenario

Answer 42

D. There is no benefit to the use of dexamethasone in this scenario

Question 43

A 20-year-old university student was brought in by her flatmate due to acute confusion and a history of using large amount of nitrous oxide, up to 3L per day.

Clinical examination may have all the following features, EXCEPT

A. Peripheral neuropathy
B. Loss of vibration and proprioception
C. Psychosis
D. Visual loss

Answer 43

D. Visual loss

Chronic nitrous oxide exposure results in dose-dependent inactivation of Vitamin D, which is a co-factor required for methionine synthesis. Methionine is required for DNA synthesis and maintenance of nervous system myelin sheaths. Loss of methionine leads to demyelination in peripheral and/or central nervous system. Sensory deficits, impaired proprioception, and ataxia are common findings.

Question 44

A 65-year-old man presents with weight gain and ankle swelling.

Results of laboratory investigations include: creatinine 75 μmol/L, eGFR 80, serum albumin 18 g/L, 24-hour urine protein 5.6 grams.

Renal biopsy shows thickening of the glomerular basement membrane with silver spikes and granular deposits of IgG and C3 on the subepithelial aspect of the GBM.

PLA2R antibody is strongly positive.

Which of the following is correct?

A. PLA2R positivity strongly suggests underlying malignancy
B. He should be commenced on high dose steroids
C. Rituximab has limited benefit in this disorder
D. A fall in PLA2R antibody level is prognostically important

Answer 44

D. A fall in PLA2R antibody level is prognostically important

This is membranous glomerulonephritis.
PLA2R positivity is suggestive of primary (autoimmune) membranous GN. Although malignancy may still occur in patients with PLA2R antibodies, it is less likely (in contrast THSD7a antibodies are often associated with underlying malignancy).

Question 45

A 35-year-old woman is evaluated for worsening thrombocytopenia; she is pregnant at 36 weeks gestation. Medical history is significant for childhood asthma. Recent platelet counts during have been 50-70 x109/L. Her only medication is a prenatal vitamin.

Which diagnosis is LEAST likely?

A. Immune thrombocytopenia
B. Pre-eclampsia
C. Gestational thrombocytopenia
D. Pseudothrombocytopenia

Answer 45

C. Gestational thrombocytopenia

In 99 percent of people, the platelet count is ≥100,000 /microL

Question 46

A 26-year-old medical student presents for further evaluation of hyperglycaemia noted as part of a clinical skills session where they were learning to measure capillary blood glucose level. On further history, he recalls polyuria and polydipsia over a 6-month period.

An HbA1C was measured with his General Practitioner and came back at 8.2%, but reassuringly ketones were negative at 0.2 mmol/L. A venous blood gas was also performed which demonstrated a normal pH and bicarbonate level. Islet cell antibodies were negative. He has no other medical history other than sensorineural deafness which was diagnosed aged 12 years old. He also reports his mother has a history of diabetes mellitus and sensorineural deafness also and has a diagnosis of maternally inherited diabetes and deafness (MIDD).

Given the history provided, the patient most likely has a diagnosis of which class of diabetes, and what treatment would NOT be first line management?

A. Monogenic diabetes - gliclazide
B. Mitochondrial diabetes - metformin
C. Monogenic diabetes - metformin
D. Mitochondrial diabetes - gliclazide

Answer 46

B. Mitochondrial diabetes - metformin

Though metformin has been the first line agent for use in type 2 diabetes, treatment of mitochondrial diabetes with metformin therapy is generally avoided due to the high risk of lactic acidosis.

Question 47

A 67-year-old female presents complaining of gradual onset pain in her fingers across her proximal inter-phalangeal joints, which is worse during the day-time. Her GP has organised a panel of investigations and noted her erythrocyte sedimentation rate (ESR) was 18 mm/hour (normal <10mm/hour), C-reaction protein (CRP) was 3.7 mg/L (normal <5 mg/L), rheumatoid factor titre 1:13, and anti-nuclear antibody titre 1:160 with a dense fine speckled 70 pattern.

Which is the most likely diagnosis?

A. Systemic lupus erythematosus
B. Sjogren’s syndrome
C. Scleroderma
D. Osteoarthritis

Answer 47

D. Osteoarthritis

Question 48

A 60-year-old male is referred for multidisciplinary assessment following a provisional diagnosis of motor neuron disease.

Which of the following is NOT an indication to commence nocturnal ventilatory support therapy?

A. Forced vital capacity less than 50% of predicted value
B. Maximum inspiratory pressure less than 60% predicted value
C. Severe bulbar dysfunction
D. Orthopnoea

Answer 48

C. Severe bulbar dysfunction

(Severe bulbar dysfunction). Non-invasive ventilation (NIV) can improve symptoms, quality of life and survival for patients with a rapidly progressive neurodegenerative disease such as MND. Declining lung function, including measures of muscle strength, correlate with nocturnal and daytime hypoventilation. Symptoms of dyspnoea, orthopnoea, headache, and fatigue also predict respiratory muscle weakness and are commonly used in clinical practice. Patients with bulbar dysfunction may have respiratory muscle weakness and can be offered NIV if hypoventilation is suspected or confirmed but may be limited in their tolerance of NIV due to secretions and aspiration risk.

Question 49

Which of the following genetic variants can be routinely detected on whole exome sequencing?

A. Balanced chromosome translocations
B. Deep intronic variants
C. Missense variants
D. Triplet repeat expansions

Answer 49

C. Missense variants

Question 50

A 78-year-old male presents with fever and rigors. He denies any urinary symptoms. A mid-stream urine specimen exhibits the following microscopy and culture results.

Microscopy:

White cell count: >100 x 106 cell/L
Red cell count: >100 x 106 cell/L
Epithelial cell count: < 10 x 106 cell/L
Bacteria seen
Culture: >108 CFU/L of Staphylococcus aureus isolated

What is the most appropriate next intervention?

A. Blood culture collection
B. Indwelling catheter insertion
C. Intravenous flucloxacillin commencement
D. Oral cephalexin commencement

Answer 50

A. Blood culture collection

Question 51

An 18-year-old male with a history of well-controlled eczema presents to clinic following an episode of lip swelling, urticaria, and wheeze after ingestion of peanuts.

Which of the following is the most appropriate first line investigation?

A. Specific IgE to peanut
B. Specific IgE to araH2
C. Skin prick testing to tree nut panel and peanut
D. Skin prick testing to peanut

Answer 51

D. Skin prick testing to peanut

Skin prick testing is usually the first line diagnostic test in assessment of suspected IgE mediated food allergy. Specific IgE can be performed but is less preferred (unless there is a reason such as dermatographism or poorly controlled eczema making skin testing difficult to interpret). Skin prick testing should be limited to the suspected allergen: skin prick testing of broad panels without justification can lead to unnecessary avoidance of foods as sensitisation does not necessarily equate to clinical allergy.

Question 52

A 35-year-old woman developed sudden onset of back pain followed by bilateral lower limb weakness and urinary incontinence. On examination, there is flaccid paralysis of both lower limbs with no reflexes able to be elicited and a T8 sensory level with loss of pain and temperature sense but preserved vibration sense and proprioception. The upper limb and cranial nerve examinations were normal.

Which of the following is the most likely diagnosis?

A. Tabes dorsalis
B. Syringomyelia
C. Anterior spinal artery occlusion
D. Demyelination

Answer 52

C. Anterior spinal artery occlusion

Question 53

A 50-year-old man was admitted with abdominal pain and acute kidney injury. A subsequent workup demonstrated the presence of acute pancreatitis and an abdominal CT scan showed multiple renal masses. A kidney biopsy revealed extensive plasma cell infiltrates.

Laboratory results include:

Low C3 (0.39 g/L) and low C4 (0.10 g/L). ANA positive, 1:40. WBC 8.5 x106/L with 10% eosinophilia.

Based on the clinical presentation, what is the most likely diagnosis?

A. Undocumented drug ingestion causing acute allergic interstitial nephritis
B. Myeloma with renal plasmacytomas
C. IgG4-related systemic disease
D. SLE with systemic vasculitis

Answer 53

C. IgG4-related systemic disease

This patient presents with IgG4-related systemic disease. It is characterised by a marked plasma cell infiltrate (typically described in a “storiform” cartwheel pattern) that produces expansile destructive lesions. Autoimmune pancreatitis is frequently seen in conjunction with kidney disease, but all major organs may demonstrate variable involvement. IgG4 is uniquely deposited in the tubules. The classical complement pathway may be activated with a resultant low C3 and C4, and there may be eosinophilia and low-grade ANA titre. A tubulointerstitial and/or membranous nephropathy is typically seen in the kidney, but obstruction can also occur from the large plasma cell aggregates. Myeloma does not activate complement, nor does acute interstitial nephritis (AIN). None of the other choices are associated with systemic and laboratory presentation of IgG4-related systemic disease.

Question 54

A 50-year-old man with metastatic pancreatic cancer presents with nausea and vomiting. He is found to have a malignant bowel obstruction and initial management with dexamethasone, nasogastric tube insertion, and antiemetics is commenced. You are called for advice on how to prescribe his usual oral analgesia.

He usually takes regular long-acting oxycodone 15mg twice daily and PRN immediate release oxycodone 5mg two times a day. His pain has been well managed on this regimen. His renal function is normal. He is not demonstrating any opioid toxicity on your examination today.

You decide to rotate his analgesia to the subcutaneous route.

Which of the following is the best regimen to manage his analgesia?

A. Subcutaneous morphine 5 mg every 4 hours
B. Subcutaneous morphine 2.5 mg every 4 hours
C. Subcutaneous oxycodone 5 mg every 4 hours
D. Subcutaneous oxycodone 5 mg every 4 hours

Answer 54

A. Subcutaneous morphine 5 mg every 4 hours

Question 55

Rebecca is a 65-year-old female with a history of hypertension, osteoarthritis, and recurrent episodes of major depression. For the past four months Rebecca has experienced low mood, anhedonia, disrupted sleep, a lack of energy and poor appetite. Rebecca does not use alcohol or any other recreational substances.

At initial presentation Rebecca was commenced on sertraline 50 mg daily and this was up-titrated to 200 mg over 8 weeks. After minimal improvement sertraline was ceased, duloxetine 60 mg was commenced, and Rebecca commenced concurrent psychological therapy.

Despite this Rebecca still failed to respond after 8 weeks. She was referred to a psychiatrist for treatment resistant depression and they consider antidepressant augmentation.

Which of the following treatments would NOT be considered to augment her current treatment?

A. Quetiapine
B. Liothyronine
C. Valproate
D. Lithium

Answer 55

C. Valproate

There is little evidence for the use of valproate in the treatment of major (unipolar) depression and it does not have an established role in the augmentation of antidepressant therapy. Valproate may be used in bipolar depression because, like lithium, valproate has efficacy in mania in addition to which, empirically it has been shown to be effective for maintenance and prophylaxis with a possible reduction in depressive symptoms long term.

Question 56

A 47-year-old male presents with right hemiparesis with subsequent imaging confirming a left hemisphere middle cerebral artery stroke. Following successful endovascular clot retrieval, further investigation with Holter monitoring was normal. There is no history of hypertension, diabetes mellitus, dyslipidaemia, or smoking. Transthoracic and transoesophageal echocardiography demonstrate the presence of a patent foramen ovale.

Which of the following is NOT true with respect to percutaneous device closure of patent foramen ovale?

A. Device closure in patients with an atrial septal aneurysm is associated with a greater risk reduction compared to the absence of an atrial septal aneurysm
B. A higher ROPE score is associated with a greater likelihood of intracardiac shunt as the precipitant for stroke
C. Cortical stroke on cerebral MRI favours proceeding to patent foramen ovale closure
D. The risk of atrial fibrillation after percutaneous device closure of patent foramen ovale is 0.5% in the first 6 months post-procedure

Answer 56

D. The risk of atrial fibrillation after percutaneous device closure of patent foramen ovale is 0.5% in the first 6 months post-procedure

In patients undergoing PFO device closure the risk of atrial fibrillation is approximately 5% in the early post procedure period.

Question 57

A 20-year-old female presents for investigation of primary amenorrhea. She does not have monthly pelvic pain. She does not have any other symptoms of note and she has no other significant past medical history. She has a normal diet and plays soccer once a week.

On examination, she has a height of 1.74 cm, weight of 62 kg, BMI of 20.5 kg/m2, and Tanner stage 3 for breast and pubic hair development.

Investigations reveal:

Normal EUC, LFT’s, FBC
Corrected calcium 2.35 mmol/l, 25-0H vitamin D 22 nmol/l, PTH 9.8 pmol/l (1.6-6.9)
TSH 12.5 mIU/l (0.4-4.0), fT4 11.1 pmol/l (10-20)
LH 0.1 IU/L (0.5-17), FSH 1.0 IU/L (2.5-10), oestradiol < 30 pmol/L
Cortisol 410 nmol/L, ACTH 6.5 pmol/L (1.0-10.7)
Prolactin 245 mIU/L (100-500)
IGF-1 35 nmol/L (15.0-54.3)
Androgen profile normal
17-OH progesterone 1.6 nmol/L (< 6)
Bone mineral density: Osteopenia at lumbar and femoral sites
MRI pituitary: Normal sized pituitary. No evidence of an adenoma
Which genetic mutation or karyotype if found would be most consistent with her condition?

A. ANOS1 gene mutation (found in Kallman’s syndrome)
B. Menin gene mutation (found in Multiple endocrine neoplasia-1)
C. Karyotype XO- (Turner’s syndrome)
D. AIRE gene mutation (found in Autoimmune polyglandular syndrome Type-1)

Answer 57

A. ANOS1 gene mutation (found in Kallman’s syndrome)

turner syndrome are short
also in turner syndrome get primary ovarian insufficiency (so get raised LH and FSH)

also in autoimmune polyglandular syndrome get primary ovarian insufficiency (raised LH and FSH)

Question 58

Which of the following is NOT a side effect of ibrutinib?

A. Atrial fibrillation
B. Hypertension
C. Arthralgia
D. QTc prolongation

Answer 58

D. QTc prolongation

Bruton tyrosine kinase signalling (BTK) is a critical step for B-cell development and immunoglobulin synthesis. Ibrutinib is an orally bioavailable Bruton tyrosine kinase inhibitor (BTKi) and forms an irreversible covalent bound to BTK at the Cysteine-481 residue

Question 59

A 58-year-old man presents with a neck lump and is diagnosed with lymph node positive squamous cell carcinoma arising from base of tongue. Concurrent chemoradiation is recommended.

Which of the following scenarios is associated with the best prognosis?

A. HPV-positive cancer in a non-smoker
B. ALK gene rearrangement-negative cancer in a non-smoker
C. HPV-positive cancer in an ex-smoker
D. EBV-positive cancer in an ex-smoker

Answer 59

A. HPV-positive cancer in a non-smoker

Question 60

A 60-year-old man presented to the emergency department with painless unilateral vision loss on waking up that morning. He has otherwise been well. His background history includes obesity with obstructive sleep apnoea and erectile dysfunction for which he takes sildenafil.

On examination, he has reduced visual acuity in his right eye and an afferent pupillary defect. Neurological examination is otherwise normal.

You decide to perform fundoscopy and you see the following:
What is the next most appropriate investigation to confirm the diagnosis?

A. ESR and CRP
B. MRI Brain
C. Carotid Doppler Ultrasound
D. Temporal artery biopsy

Answer 60

A. ESR and CRP

Condition: Non-arteritic anterior ischaemic optic neuropathy

This is mostly a clinical diagnosis. ESR and CRP should be done for adults aged greater than 55 years. If these are elevated, then a temporal artery biopsy can be considered if there is a clinical suspicion for GCA. The other investigations are not required.

Question 61

A 29-year-old female who is 5 months post-partum presents to you with 5 kg of weight loss and anxiety since the birth of her child. She is currently exclusively breastfeeding her newborn baby. She had an uncomplicated pregnancy and birth and has no significant past medical history. On examination her heart rate is 109 beats per minute, blood pressure is 125/75 mmHg, and respiratory rate is 18 breaths per minute.

What is your next step in management?

A. Reassurance, this is normal in an exclusively breastfeeding mother
B. Psychologist referral
C. Blood test including TFTs
D. Transthoracic echocardiogram and troponin level

Answer 61

C. Blood test including TFTs

This is likely postpartum thyroiditis as there is no history of previous thyroid disease. Post-partum thyroiditis occurs in 5% of mothers in the generalpopulation. Post-partum thyroiditis most commonly occurs within the first year post-partum. If thyroid function is abnormal then adding on autoantibodies is valuable to ensure it is not an autoimmune disease.

Question 62

Sarah is a 33-year-old female who has been referred to you for bilateral and symmetrical hilar adenopathy. She has a cough and is breathless on exertion. The decision is made to proceed to a linear endobronchial ultrasound, fine needle aspiration and bronchial alveolar lavage (BAL) to investigate sarcoidosis and exclude other diagnoses.

Which investigation results are most in keeping with sarcoidosis?

A. Caseating granulomas with a CD4/CD8 ratio > 4 on BAL
B. Non-caseating granulomas with a CD4/CD8 > 4 ratio on BAL
C. Caseating granulomas with a CD4/CD8 ratio < 4 on BAL
D. Non-caseating granulomas with a CD4/CD8 ratio < 4 on BAL

Answer 62

B. Non-caseating granulomas with a CD4/CD8 > 4 ratio on BAL

CD8 cells are often deplete, thus the CD4/CD8 ratio is typically high. There may also be a lymphocytosis

Question 63

A 61-year-old male presents with recurrent self-limiting abdominal pain. While endoscopic evaluation was unremarkable, CT abdomen shows small and large bowel thickening at the time of acute attack. Stool culture was negative. There is no significant family history.

He has a low C3 and C4 complement levels and undetectable C1 inhibitor levels and function.

Which of the following is most correct?

A. Patient likely carries a SERPING1 gene mutation
B. A trial of high dose H1 and H2 antagonists is a potential treatment option
C. Patient should be screened for potential underlying malignancy
D. Immunoglobulin replacement therapy is a potential treatment option

Answer 63

C. Patient should be screened for potential underlying malignancy

Lymphoproliferative disorders or MGUS identified in 67 percent of cases of acquired C1 inhibitor deficiency. SERPING1 mutations are only found in hereditary angioedema.

Question 64

A 28-year-old male presents with a 2-day history of anal pain, haematochezia, tenesmus, and painful bilateral inguinal lymphadenopathy. He returned from Thailand 4 weeks ago, where he engaged in unprotected insertive and receptive oral and anal intercourse with multiple male partners.

His microbiological investigation results are shown below.

Genital swab HSV-1 PCR: Not detected
Genital swab HSV-2 PCR: Not detected
Rectal swab Chlamydia trachomatis PCR: Detected
Rectal swab Neisseria gonorrhoeae PCR: Not detected
Urine (first-void) Chlamydia trachomatis PCR: Detected
Urine (first-void) Neisseria gonorrhoeae PCR: Not detected
Throat swab Chlamydia trachomatis PCR: Detected
Throat swab Neisseria gonorrhoeae PCR: Not detected
Serum HIV Ab/Ag screen: Non-reactive
Serum syphilis EIA: Non-reactive
What is the most appropriate treatment regimen?

A. Azithromycin 1 g PO statim
B. Azithromycin 1 g PO statim and ceftriaxone 500 mg IM/IV statim
C. Doxycycline 100 mg PO twice daily for 7 days
D. Doxycycline 100 mg PO twice daily for 21 days

Answer 64

D. Doxycycline 100 mg PO twice daily for 21 days

Chlamydia trachomatis serovars cause lymphogranuloma venereum (LGV). which manifests initially as an ulcer (typically painless) at the inoculation site then regional lymphadenitis (typically painful) and/or proctocolitis 2-6 weeks later.

incubation period of 3-14 days.

Complications of LGV can include colorectal fistulae and/or strictures, frozen pelvis, infertility, and lymphoedema (genital elephantiasis).

Chlamydia trachomatis can be detected on PCR testing of genital swab specimens and specific PCR testing for C. trachomatis serovars L1, L2, and L3 should be requested by the clinician if the diagnosis of LGV is suspected based on clinical and/or epidemiological factors.

Doxycycline 100 mg PO BD for 21 days is the preferred treatment regimen for LGV and exhibits a microbiological cure rate of >95%.

Azithromycin 1 g orally once weekly for 3 weeks is an alternative regimen if doxycycline therapy is contraindicated or not tolerated.

Options C and A are the recommended first- and second-line antibiotic regimens respectively for uncomplicated Chlamydia trachomatis infection.

Option B is the first-line antibiotic regimen for uncomplicated, non-pharyngeal Neisseria gonorrhoeae infection.

Question 65

A 51-year-old male presents with arthralgias and myalgias, petechial rash over his lower limbs, and macroscopic haematuria. Autoimmune and haemolysis screens are negative.

Deficiency of which of the following vitamins could account for this presentation?

A. Vitamin A
B. Vitamin B1
C. Vitamin C
D. Vitamin E

Answer 65

Vitamin C

Vitamin C deficiency results in impaired collagen synthesis and scurvy, which manifests as arthralgias and myalgias (due to haemorrhage into the muscles and periosteum), ecchymoses, gingivitis, and impaired wound healing. Neuropathy can also occur.

Vitamin B1 deficiency results in beriberi, which is characterised by peripheral neuropathy with (wet) or without (dry) cardiomyopathy, and Wernicke-Korsakoff syndrome, which is characterised by ataxia, confusion, nystagmus, and ophthalmoplegia, with or without anterograde and retrograde amnesia.

Vitamin E deficiency results in haemolysis, neuropathy (particularly spinocerebellar syndrome and peripheral neuropathy), and, rarely, brown bowel syndrome (due to lipofuscin deposition in the muscularis propria and muscularis mucosa).

Question 66

Mrs. RZ is a 79-year-old woman living at home alone with severe Parkinson’s dementia brought into the emergency department by ambulance following a fall with a left neck of femur fracture. She has services to assist her with self-care (dressing, showering).

Her son (Gary) lives overseas and last spoke to her over a year ago. She has a brother Allan who occasionally visits her but last saw her over 6 months ago and a neighbour Sally who prepares meals for her daily and assists with the laundry. She follows up regularly with her General Practitioner. She has no Enduring Guardian and no Enduring Power of Attorney.

It is found that Mrs. RZ does not to have capacity to decide about medical management and requires an operative fixation of her neck of femur.

Which person is the substitute decision maker for Mrs. RZ?

A. Gary (son)
B. Allan (brother)
C. Sally (neighbour)
D. General practitioner

Answer 66

C. Sally (neighbour)

The person responsible in order of priority is:

1. Appointed Enduring guardian (for medical matters, accommodation) or appointed Enduring Power of Attorney (for financial matters). If the person doesn’t have one then:
2. Spouse and de-facto partner (including same sex partner) with a close and ongoing relationship with the patient. If the person doesn’t have one, then:
3. The patient’s carer-an unpaid carer who organised their care before they went into a nursing home (Note: The carer’s pension does not count as payment). If there is no one in this category, then:
4. Close friend or relative. If the person doesn’t have one then
5. Health professional proposing the treatment can make an application for consent to the Guardianship Division of the NCAT

Question 67

Which of the following is FALSE regarding patients with a renal transplant?

A. Squamous cell carcinoma is the most common cancer following transplantation
B. Cardiovascular, infection-related, and cancer-related deaths are the most common causes of death in patients with a renal transplant
C. New onset diabetes mellitus after transplantation is more likely to occur with the use of tacrolimus than cyclosporine or mycophenolate
D. Recurrent glomerulonephritis is the most common cause of death-censored graft loss

Answer 67

D. Recurrent glomerulonephritis is the most common cause of death-censored graft loss

The most common cause of death-censored graft loss is rejection.

Question 68

A 63-year-old woman is seen in your clinic with a 12-month history of puffy fingers. On further questioning, she describes difficulty with swallowing liquids, finger pallor and pain in the cold, and progressive shortness of breath over the past four weeks.

On examination she has skin thickening and telangiectasia on her face, neck, and chest wall as well on her hands and forearms. She has fine crackles in her lower and mid lung fields. A CT chest shows diffuse NSIP pattern ILD.

Which antibodies would be most consistent with her presentation?

A. ANA 1:1280 speckled pattern with Scl-70 and Ro52 antibodies
B. ANA 1:5120 centromere pattern with a CENP-B antibody
C. ANA 1:1280 homogenous pattern with dsDNA and Smith antibody
D. ANA 1:2560 speckled pattern with an Scl-70 antibody

Answer 68

D. ANA 1:2560 speckled pattern with an Scl-70 antibody

This patient clinically has diffuse systemic sclerosis with rapidly progressive ILD. She would be expected to have an Scl-70 antibody (options A and D). The combination of connective tissue disease ILD with a positive Ro52 antibody portends a more aggressive ILD phenotype, and hence the answer A is preferred to D.

Question 69

All the following patients with cirrhosis would qualify for antibiotic therapy for prophylaxis of spontaneous bacterial peritonitis, EXCEPT

A. 49-year-old male with Child Pugh C cirrhosis secondary to alcohol witha bilirubin level of 65 micromol/L and large volume ascites with an ascitic fluid protein concentration of 10 g/L
B. 70-year-old male with NASH cirrhosis and a previous episode of spontaneous bacterial peritonitis treated with IV ceftriaxone
C. 59-year-old male with cirrhosis secondary to autoimmune hepatitis, large varices on screening endoscopy (though no history of gastrointestinal bleeding), and large volume ascites
D. 65-year-old female with cirrhosis secondary to treated hepatitis C, chronic kidney disease with baseline creatinine of 160 μmol/L, and moderate volume ascites with an ascitic fluid protein concentration of 8 g/L

Answer 69

C. 59-year-old male with cirrhosis secondary to autoimmune hepatitis, large varices on screening endoscopy (though no history of gastrointestinal bleeding), and large volume ascites

Secondary prophylaxis is indicated after a patient experiences the first episode of SBP, by reduced subsequent episodes and all-cause mortality (option B).

Primary prophylaxis is only recommended for patients at high risk for SBP. These patients must have an ascitic fluid protein less than 15g/L, and at least one of:
-impaired renal function (creatinine >110micromol/L, urea >8.9mmol/L OR sodium < 130mmol/L) (option A)
-liver failure with Child Pugh score of 9 or more and serum bilirubin >50 micromol/L (option D)

Antibiotics are indicated in patients with cirrhosis and upper gastrointestinal bleeding; however, option C only has varices without bleeding

Question 70

A novel immunotherapy agent has a number needed to treat (NNT) of 10. The traditional chemotherapy protocol had an NNT of 20. What is the absolute risk reduction with the novel immunotherapy agent relative to the traditional chemotherapy protocol?

A. 5%
B. 10%
C. 50%
D. 100%

Answer 70

A. 5%

The NNT is defined as the reciprocal of the absolute risk reduction, which is defined in the context of the control event rate. Here, the ARR of the immunotherapy is 10% and the chemotherapy protocol is 5%. Hence, 10 - 5 = 5%.

Question 71

Which of the following features is suggestive of an alternate diagnosis to transient global amnesia?

A. Anterograde amnesia
B. Repetitive stereotyped questions
C. Headache
D. Disorientation to self

Answer 71

D. Disorientation to self

Anterograde amnesia is a defining feature and there is an inability to retain new information for more than a few seconds. Retrograde amnesia extends backward for several hours, days, or longer. Patients characteristically ask repetitive stereotyped questions. The average duration of episodes is about six hours. Headache is the most commonly reported associated symptom. There is preservation of alertness and all other cognitive functions (and there should be no disorientation to self). TGA occurs primarily in older adults.

Question 72

A 24-year-old man presents with a maculopapular rash, oral ulcers, and bilateral cervical lymphadenopathy 3 weeks after unprotected sexual intercourse with a casual male partner. He tells you that he has been adherent with daily tenofovir + lamivudine (TDF + 3TC) HIV pre-exposure prophylaxis for the last 9 months.

He had a negative sexual health screen performed while asymptomatic 2 months ago, including HIV and syphilis serology and gonorrhoea and chlamydia nucleic acid testing.

Which of the following is INCORRECT?

A. HIV seroconversion can be excluded as a reason for the current presentation with a 4th generation HIV serology test (combined p24 antigen- HIV antibody assay)
B. A rapid plasma regain (RPR) titre of 128 would be consistent with secondary syphilis
C. If early syphilis is diagnosed, first line treatment is a single dose of benzathine penicillin intramuscularly
D. If early syphilis is diagnosed and treated, this patient should be considered for post-exposure prophylactic doxycycline treatment (DOXY-PEP) to prevent re-infection

Answer 72

A. HIV seroconversion can be excluded as a reason for the current presentation with a 4th generation HIV serology test (combined p24 antigen- HIV antibody assay)

Question 73

A 40-year-old woman with a history of alcohol abuse presents asking for medication to help reduce her drinking. After discussions with her GP, she is commenced on naltrexone.

Which of the following is LEAST correct regarding the use of naltrexone for management of alcohol misuse disorder?

A. Naltrexone should be avoided in individuals using recreational or prescribed opioids
B. Naltrexone is contraindicated in patients with acute hepatitis, liver failure, or elevated liver enzymes
C. Naltrexone is one of the preferred agents for patients who are pregnant or considering pregnancy
D. Naltrexone may cause nausea, headache, and dizziness, and should be stopped if these side effects occur

Answer 73

D. Naltrexone may cause nausea, headache, and dizziness, and should be stopped if these side effects occur

These side effects of naltrexone subside with continued use. The other options are correct.

Question 74

A female cystic fibrosis (CF) carrier wishes to conceive with a male who has tested negative for mutations in the relevant gene. The laboratory advises that the test is 90% sensitive. What is the risk of their child having CF?

A. 1/1000
B. 1/666
C. 1/100
D. 1/440

Answer 74

A. 1/1000

For an AR disorder there is a ¼ risk of affected child if both parents are carriers. The carrier frequency for CF is 1/25.

Facts given in the question:
One parent is a known carrier of CF - carrier risk =1.0
Residual risk that partner is a carrier after test is ~10% of original risk for partner i.e. 1/25 x0.10

In a recessive condition in which neither parent has the disease:
Risk of affected child = (carrier risk of parent) x (carrier risk of partner) x1/4
= (1) x (1/25 x 0.10) x1/4
= 1/1000

Question 75

A 36-year-old male with no past medical history presents to the emergency department due to rapid palpitations. On review his blood pressure is 130/90 mmHg, GCS 15, and peripheral oxygen saturations 96% on room air. He denies any syncope or presyncope however feels like his “heart is thumping all over”.

A 12-lead ECG is obtained as shown below:

Which of the following is the most appropriate next course of action?

A. Administer IV adenosine
B. Sedation and direct current cardioversion
C. Closely observe in emergency on telemetry
D. Load with IV digoxin with concurrent administration of oral flecainide

Answer 75

B. Sedation and direct current cardioversion

This ECG shows a critical finding which is pre-excited atrial fibrillation which is a medical emergency. The characteristic finding is the broad complex tachycardia with variable R-R interval and distinct upsloping of the QRS complexes. The differentials for such an ECG include VT or a supraventricular rhythm with aberrancy. The most inappropriate answer here is to give IV adenosine which can result in ventricular fibrillation by blocking the AV node and forcing conduction down the accessory pathway. The administration of AV nodal blocking agents in general is contraindicated and should only be used under very specialist guidance. Despite looking well and having normal blood pressure, observation is also inappropriate here. The only treatment option in the first instance in patients with pre-excited atrial fibrillation with rapid heart rates is DCCV as it can lead to catastrophic haemodynamic collapse.

Question 76

A 20-year-old man presents with a several month history of fatigue, weakness, nausea, and anorexia. He also complains of light-headedness on standing and thin hair. His family history is notable for his mother who suffers from peripheral neuropathy.

On examination, his heart rate is 88 bpm, respiratory rate 16 breaths/min, SpO2 99% on room air, and temperature 37.5 degrees Celsius. His blood pressure is 123/75 mmHg on lying and 90/60 mmHg on standing.

Investigations are as below (normal reference ranges in parentheses):

Sodium 128 mmol/L (135-145)
Potassium 4.5 mmol/L (3.5-5.2)
Chloride 100 mmol/L (95-110)
Bicarbonate 16 mmol/L (22-32)
Urea 5 mmol/L (4.9-9)
Creatinine 65 μmol/L (65-110)
eGFR >60 ml/min/1.73 m2 (>69)
Haemoglobin 138 g/L (130-189)
WCC 9 x106/L (4-11)
Platelets 190 x106/L (150-400)
Neutrophils 6.2 x106/L (2-8)
Lymphocytes 3.0 x106/L (1-4)
Monocytes 0.8 x106/L (0.2-1)
Eosinophils 0.3 x106/L (< 0.5)
Basophils 0 x106/L (< 0.1)
8am Cortisol 113 nmol/L
8am ACTH 54.1 nmol/L (7.2-63.3)
Of the following options, which is the next best investigation?

A. Dexamethasone suppression test
B. MRI pituitary
C. Very long chain fatty acids
D. Protein electrophoresis and serum free light chain ratio

Answer 76

C. Very long chain fatty acids

This patient presents with symptoms and signs typical for adrenal insufficiency. An associated low morning cortisol and high-normal ACTH on his blood tests are suggestive of primary adrenal insufficiency. The next best step would be to confirm adrenal insufficiency with a short synACTHen test, although this is not a given option. Initial investigation for primary adrenal insufficiency would then be an anti-21-hydroxylase antibody, but this is also not an option. In a male patient with primary adrenal insufficiency, X-linked adrenoleukodystrophy should be considered as a diagnosis, and further clues to this are his thinning hair and his family history, where female carriers are most likely to have mild neurological manifestations. VLCFA is the best option of these answers.

A- A dexamethasone suppression test confirms cortisol excess, not cortisol deficiency.

B- MRI pituitary would be useful to investigate for secondary (pituitary) adrenal insufficiency. D- Although assessing for a paraproteinaemia can be useful for the investigation of postural hypotension, it does not explain the patient’s clinical picture.

Question 77

You request pulmonary function testing for a patient with ‘low volume’ pulmonary haemorrhage. This patient has a history of severe asthma.

What would you expect the Carbon Monoxide Diffusing Capacity (DLCO) to be given the clinical presentation?

A. DLCO is expected to be very high as both conditions typically increase DLCO
B. DLCO is expected to be near normal as DLCO is typically increased by pulmonary haemorrhage and decreased by severe asthma
C. DLCO is expected to be near normal as DLCO is typically decreased by pulmonary haemorrhage and increased by severe asthma
D. DLCO would be very low as both conditions typically reduce the DLCO

Answer 77

A. DLCO is expected to be very high as both conditions typically increase DLCO

Question 78

A 60-year-old man with a history of multiple minimal trauma fractures, type 2 diabetes, and prostatic hypertrophy with mild bladder outflow obstruction is sent by his GP to the emergency department with a new palpable purpuric rash, arthritis, and progressive foot numbness on the background of a 2-month history of nasal blockage, excessive crusting, and epistaxis.

His creatinine is 140 μmol/L and urine shows > 100 red cells and 24-hour urine protein excretion is 1.2 grams. His ANCA is positive with a PR3 antibody.

Which of the following induction protocols would be most appropriate after 3 doses of pulse IV methylprednisolone?

A. Oral cyclophosphamide, 12-month prednisone taper
B. Rituximab 1g x 2 doses, avacopan 30mg BD, 4-week prednisone taper
C. Rituximab 1g x 2 doses, 12-month prednisone taper
D. Azathioprine 2 mg/kg, avacopan 30mg BD, 4-week prednisone taper

Answer 78

B. Rituximab 1g x 2 doses, avacopan 30mg BD, 4-week prednisone taper

This man has major organ (renal, neurological) granulomatosis with polyangiitis (ANCA associated vasculitis). Rituximab is the preferred baseline induction agent rather than cyclophosphamide in view of his PR3 status and bladder outflow obstruction. The ADVOCATE trial (NEJM 2021) demonstrated a steroid sparing effect of avacopan, a novel C5a receptor inhibitor, in ANCA associated vasculitis, making this the best choice for this man whose comorbidities of osteoporosis and diabetes would be worsened with long term corticosteroids

Question 79

Which is of the following agents is NOT routinely used in the treatment of T cell lymphomas?

A. Brentuximab vedotin
B. Rituximab
C. Pralatrexate
D. Prednisone

Answer 79

B. Rituximab

Rituximab is a monoclonal antibody against CD20, an antigen expressed on the majority of normal and malignant B cells. T cell lymphomas are disorders of neoplastic T cells which typically don’t express CD20, thus Rituximab is not routinely used in the treatment of these disorders. CD3 is a pan-T cell marker. CD30 is also expressed on certain T cell lymphoma subtypes (e.g. ALCL) and Brentuximab vedotin is an anti-CD30 antibody drug conjugate commonly used to treat CD30 positive T cell lymphomas. Pralatrexate is a lymphodepleting antimetabolite that is commonly used in relapsed refractory T cell lymphoma. Prednisone is lymphodepleting agent which is used in almost all lymphoma protocols.

Question 80

A 28-year-old man presents is commenced on carbamazepine for epilepsy. Six weeks later he presents with fever, lymphadenopathy, lip swelling, and a widespread purpuric skin rash. His eosinophil count is 2.8 x 109/L and there is liver function test derangement. A diagnosis of DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome is made.

Which of the following drugs would interfere with the immune pathway involved in this reaction and could potentially treat this drug reaction?

A. Bevacizumab (anti-VEGF)
B. Mepolizumab (anti-IL5)
C. Pembrolizumab (anti-PD1)
D. Ocrelizumab (anti-CD20)

Answer 80

B. Mepolizumab (anti-IL5)

Question 81

Which of the following is FALSE about atypical femoral fractures following use of antiresorptive therapy?

A. Atypical femoral fractures are more common in people of Asian background
B. Atypical femoral fractures can be detected on a hip x-ray
C. All patients with an atypical femoral fracture should have imaging of the opposite femur
D. Management of atypical femoral fractures requires operative intervention

Answer 81

D. Management of atypical femoral fractures requires operative intervention

Question 82

A 27-year-old man presented to the emergency department following syncope during a social touch football game. Blood pressure on arrival in the emergency department was 80/50 mmHg. The following 12-lead electrocardiograms were recorded prior and after cardioversion.
Which of the following is the correct diagnosis?

A. Artefact
B. Supraventricular tachycardia with aberrance
C. Ventricular tachycardia
D. Paced tachycardia

Answer 82

B. Supraventricular tachycardia with aberrance

Question 83

A 37-year-old G3P1 woman is currently at 18 weeks gestation and presents with pruritus. She thinks she had some pruritus during her last pregnancy 13 years ago but did not have any treatment for it. She has been taking some herbal medications for her lethargy for the past one month. She is a non-smoker and prior to her pregnancy was drinking alcohol on weekends.

On examination her blood pressure is 117/56 mmHg, SpO2 is 100% on room air, and heart rate is 66 bpm.

Current laboratory results:

Bilirubin 9 μmol/L (< 19)
ALT 82 IU/L (10-35)
AST 85 IU/L (10-35)
GGT 162 IU/L (< 35)
ALP 561 IU/L (30-110)
Bile acids 15 μmol/L (< 8)
Hb 107 g/L (115 - 165)
Platelets 383 x 109/L (150-400)
Last year (non-pregnant) laboratory results:

Bilirubin 10 μmol/L
ALT 80 IU/L
AST 93 IU/L
GGT 191 IU/L
ALP 462 IU/L

Her ANA is 1:160 in a cytoplasmic pattern; Smooth muscle antibody not detected; Liver/Kidney Microsomal Antibody not detected; Anti Mitochondrial antibody 1:80; and HBsAg and Hepatitis C virus antibodies are negative.

Her abdominal ultrasound shows a normal abdominal ultrasound scan, with a normal liver in size and echogenicity, no cholelithiasis or acute cholecystitis, and no abnormal dilatation of the biliary tree. There is a peripancreatic lymph node just superior to the pancreatic head.

What is the most likely cause of her presentation?

A. Drug induced liver injury
B. Intrahepatic cholestasis of pregnancy
C. Autoimmune hepatitis
D. Primary biliary cholangitis

Answer 83

D. Primary biliary cholangitis

Question 84

A 40-year-old lady presents with right foot drop associated with numbness. She has a history of severe asthma which has been refractory to inhaler therapy. More recently, she has been complaining of anosmia and nasal congestion with CT showing chronic rhinosinusitis with nasal polyps. She has significant peripheral blood eosinophilia. ANCA studies return negative.

Which of the following is INCORRECT?

A. ANCA negativity excludes small vessel vasculitis
B. Targeting IL-5 or CD20 is a potential treatment option
C. Patient is at risk of myocarditis
D. Patient should undergo NCS and/or sural nerve biopsy

Answer 84

A. ANCA negativity excludes small vessel vasculitis

ANCA negative eosinophilic granulomatosis with polyangiitis occurs in up to 70% of EGPA, with more active asthma and peripheral neuropathy compared to ANCA positive patients.

Question 85

A 22-year-old woman returns from holiday in Brazil. Three weeks later, she develops fevers occurring every 48 hours, chills, headache, and diarrhoea. On examination, she is confused and jaundiced. Her initial bedside finger-prick blood glucose level is 2.0 mmol/L. Thick and thin blood films demonstrate Plasmodium vivax.

What should her initial treatment be?

A. Artemether and lumefantrine
B. Atovaquone and proguanil
C. Artesunate
D. Primaquine, artemether, and lumefantrine

Answer 85

C. Artesunate

Artesunate, given the patient has severe malaria (confusion, jaundice, hypoglycaemia).

Question 86

Phillip is a 74-year-old male diagnosed with Parkinson’s disease 8 years previously. He has been referred for deep brain stimulation for motor fluctuations refractory to medical therapy.

Which of the below factors will predict a good response to the procedure?

A. Good preoperative response to levodopa
B. Minimal preoperative levodopa-related motor complications
C. Higher preoperative Unified Parkinson’s Disease Rating Scale (UPDRS) score
D. Lower preoperative levodopa equivalent daily dose

Answer 86

A. Good preoperative response to levodopa

Question 87

A 78-year-old man arrives with a two-day history of generalised headache and confusion whilst on an anti-amyloid drug trial. He is on no other regular medications. There has been no history of trauma. His blood pressure is 165/60 mmHg and aside from disorientation, his neurological examination is unremarkable. His WCC is 9 x109/L and CRP 10 mg/L. Renal function and full blood count are at his baseline. A chest X-ray, urine microscopy and culture, and non-contrast CT brain are unremarkable.

What would be the next most appropriate form of neuroimaging?

A. MRI brain
B. CT angiogram Circle of Willis
C. CT perfusion
D. Amyloid PET

Answer 87

A. MRI brain

Given this patient is on an anti-amyloid monoclonal, and CXR, bloods and urine MCS are unremarkable, it would be important to exclude amyloid-related imaging abnormalities (ARIA). MRI brain is the most appropriate investigation of ARIA to look for oedema or haemorrhage - not an amyloid PET. The presentation is not typical for a stroke given the absence of other focal neurological deficits; hence a CT angiogram or CT perfusion would not be appropriate.

Question 88

Answer 88

C. Hyperaldosteronism

Question 89

Which of the following signs or symptoms is LEAST associated with catatonic schizophrenia?

A. Posturing
B. Feeling dead inside
C. Repeating the interviewer’s speech
D. Staring

Answer 89

B. Feeling dead inside

Feeling dead inside is a nihilistic delusion most often associated with a psychotic depression, whilst posturing, repetition of speech and staring are classically associated with catatonia.

Question 90

Which of the following clinical syndromes is correctly identified?

A. Tachycardia, mydriasis, urinary retention, diaphoresis → cholinergic toxicity
B. Tachycardia, hypertension, diaphoresis, urinary incontinence → sympathomimetic syndrome
C. Mydriasis, bradycardia, hypotension → alpha2-agonist syndrome
D. Insomnia, diarrhea, hallucination, tachycardia, hypertension → opioid withdrawal syndrome

Answer 90

D. Insomnia, diarrhea, hallucination, tachycardia, hypertension → opioid withdrawal syndrome

Cholingeric poisoning ( SLUDGE) - salivation, lacrimation, urination, defecation, GI hyper motility, and emesis

sympathomimetic syndrome includes tachycardia, hypertension, mydriasis, and diaphoresis. Urinary retention

Alpha2-receptor agonism essentially produces a sympatholytic syndrome. Clonidine and other imidazoles are alpha2-agonists that act presynaptically to inhibit sympathetic outflow from the CNS. Alpha2-agonists therefore produce miosis, bradycardia, and hypotension. Alpha2-agonist poisoning also produces a depressed mental status, respiratory depression, and coma.

Question 91

A 24-year-old woman with childhood-onset asthma presents to clinic with subacute worsening shortness of breath on exertion, dry cough, chest tightness at rest, and increasing salbutamol usage up to 10 times daily. She has had five courses of prednisone in the last year, each consisting of three to five days of prednisone 50mg daily.

She is wheezy to auscultation with an FEV1 of 60% of the predicted value and an FVC of 95% of the predicted value.

Her regular asthma therapy is ciclesonide 160 μg two puffs twice daily via spacer, tiotropium via Respimat 2.5 μg two inhalations daily, and montelukast 10 mg orally daily.

She is atopic, with skin-prick reactivity to pollens, cats, dust mite and Aspergillus fumigatus, and her total serum IgE is 247 IU/L, with specific IgE reactivity to Aspergillus. Her peripheral blood eosinophil count is 0.6 x 109/L.

The fraction of exhaled nitric oxide (FeNO) is 56 ppb and the Asthma Control Questionnaire (ACQ-5) score is 3.4. Her CT chest shows only mild hyperinflation and some mosaicism of lung density.

What is the most appropriate intervention?

A. Long-term low dose oral corticosteroid therapy
B. Long-term itraconazole therapy
C. Inhaled long-acting β-agonist therapy
D. IL-5 antagonist therapy

Answer 91

C. Inhaled long-acting β-agonist therapy

This young patient with Aspergillus-sensitised asthma is deliberately presented as being severe with persistent symptoms, impaired lung function and frequent exacerbations. Low dose, long-term oral corticosteroid is a treatment of last resort in asthma patients without allergic bronchopulmonary aspergillosis (ABPA); this woman’s largely normal CT excludes the latter condition. Itraconazole doesn’t have a role in asthma outside the setting of a patient with ABPA already on long-term OCS. She may well be a candidate for IL-5 antagonist therapy in the future but needs to have been on inhaled long-acting, β-agonist therapy and high-dose ICS for at least a year before such therapy could be considered. She is not on an inhaled long-acting β-agonist and, given her symptom burden and airflow obstruction, should start one.

Question 92

A 62-year-old man is brought to the emergency department after being found on the floor at home by concerned neighbours who have not seen him for a few days. Upon arrival he is disoriented and agitated at times. He has no headache. No focal neurological deficit other than gait ataxia is identified on further neurological examination. He is afebrile.

His past medical history includes, hypertension, type 2 diabetes mellitus, coronary artery disease managed in the past with coronary artery stents (on regular aspirin), and alcohol dependence.

Biochemistry at the time of admission is notable for a serum sodium of 129 mmol/L, a peripheral white cell count of 12 x106/L, normocytic anaemia (Hb 98 g/L), and a CRP of 40 mg/L. No acute pathology is seen on a non-contrast CT scan of the brain.

Which of the following diagnoses is most likely?

A. Acute ischaemic stroke
B. Bacterial meningitis
C. Wernicke encephalopathy
D. Autoimmune encephalitis

Answer 92

C. Wernicke encephalopathy

Question 93

A 28-year-old lady presents for investigation of infertility after 18 months of failing to fall pregnant. Her background includes severe reflux managed with a proton pump inhibitor. On screening blood tests, it is noted she has hypercalcaemia with a corrected calcium 2.80 mmol/L (2.1-2.55) with a normal PTH 6.8 pmol/L (1.6-6.9).

What diagnosis would explain her presentation?

A. Primary hyperparathyroidism
B. Peutz-Jegher’s syndrome
C. MEN2 syndrome
D. MEN1 syndrome

Answer 93

D. MEN1 syndrome

Presentation hinting at prolactinoma (infertility), gastrinoma (severe reflux in a young patient), and parathyroid adenoma, all tumours associated with MEN1.

Whilst primary hyperparathyroidism is associated with MEN2A classical (medullary thyroid cancer, phaeochromocytoma, primary hyperparathyroidism), the other features are not suggestive.
The two characteristic manifestations of Peutz-Jeghers syndrome are mucocutaneous macules and multiple hamartomatous gastrointestinal polyps.

Whilst the stem suggests the patient has primary hyperparathyroidism, this diagnosis alone does not explain the full presentation.

Question 94

A 76-year-old retired postal worker with an ECOG of 0 has been diagnosed with metastatic prostate cancer after presenting with a symptomatic pathological fracture of the rib. His serum prostate-specific antigen (PSA) level was elevated at 221 ng/mL, and CT and radionuclide bone scan showed widespread bony lesions (>10 lesions) in his axial and appendicular skeleton. Biopsy of a lesion confirms prostatic adenocarcinoma. He is commenced on androgen deprivation therapy, which he tolerates well. He is not a candidate for taxane-based chemotherapy due to pre-existing peripheral neuropathy from diabetes mellitus.

Answer 94

Apalutamide

Combination treatment with ADT is standard, particularly for high volume disease, with either triplet therapy (docetaxel chemotherapy plus a novel androgen receptor pathway inhibitor (ARPI) e.g. darolutamide or abiraterone), or combination with either chemotherapy or a novel ARPI, of which there are multiple options including apalutamide, darolutamide, enzalutamide or abiraterone. Given the contraindication to docetaxel based chemotherapy (peripheral neuropathy), addition of the ARPI apalutamide is appropriate as demonstrated in the TITAN trial.

Question 95

A 49-year-old post-menopausal woman presents after 6 months of vague abdominal pain and discomfort. She has a history of early breast cancer diagnosed and treated successfully at age 41 and has poorly controlled hypertension. CT of her abdomen reveals omental thickening, ascites and an adnexal mass, and her serum CA-125 level is elevated. A biopsy
of the omental lesion reveals high grade serous carcinoma. She undergoes neo-adjuvant platinum-based chemotherapy with a good clinical response on imaging, and proceeds to debulking surgery, where all visible macroscopic disease is removed (R0 resection), and she completes the remaining adjuvant platinum-based chemotherapy, with no recurrence of disease on imaging. Her CA-125 has normalised. A mainstream genetic test reveals the woman carries a pathogenic variant in BRCA1 gene.

Answer 95

Answer: Olaparib

Vignette describes advanced ovarian cancer, FIGO stage at least IIIB. She has a good response to standard first-line therapy, and the question asks about maintenance treatment options. Given her BRCA1 mutation, she is an appropriate candidate for maintenance therapy with a PARP inhibitor, based on the SOLO1 trial, demonstrating a significant benefit to progression free survival. Combination with olaparib and bevacizumab (although not given as an option here) is also supported with the results of PAOLA-1, as would maintenance treatment with bevacizumab (based upon older trials ICON7, GOG-218), though the magnitude of benefit would generally support PARP inhibitor use in the first-line. Furthermore, her poorly controlled hypertension would be a relative contraindication to bevacizumab us

Question 96

A 56-year-old woman who was born in China, with no significant smoking history, presents with a 3-month history of cough, dyspnoea, and weight loss. She has no other significant medical history, and currently works as a medical centre receptionist. Investigations reveal multiple lesions in both lung fields up to 22mm in diameter, with enlarged mediastinal nodal disease, and sclerotic lesions in her bilateral ribs and pelvis. A CT brain in unremarkable. Biopsy of one of the lung lesions reveals an adenocarcinoma of pulmonary origin. Immunohistochemistry staining reveals a PD-L1 of 60%. Molecular testing identifies a deletion in exon 19 of the gene encoding epidermal growth factor receptor (EGFR), and no rearrangement in anaplastic lymphoma kinase (ALK) or c-ROS oncogene 1 (ROS1).

Answer 96

Answer: Osimertinib

This clinical scenario describes a classic example of stage IV non-small cell lung cancer with an EGFR driver mutation, arising in a female non-smoker of Asian descent. First-line therapy when an activating mutation of EGFR (exon 19 deletion or point mutation in exon 21 L858R) is an EGFR tyrosine kinase inhibitor. The current standard, based upon the FLAURA trial, is the third generation osimertinib, which also treats the common resistance mutation T790M, rather than using a first or second generation TKI (e.g. gefitinib, erlotinib) and treating with osimertinib second-line if a resistance mechanism is identified. Immunotherapy is not used in the first-line setting for NSCLC with a driver mutation.

Question 97

A 58-year-old male forklift driver presents with 2 months of constipation. Investigation and workup reveals a descending colon lesion, with multiple liver and lung lesions. Biopsy of a liver lesion reveals colorectal adenocarcinoma with proficient mismatch-repair (MMR) staining. He has a history of intermittent reflux but is not on any regular medications. He is commenced on chemotherapy with infusional fluorouracil, leucovorin and oxaliplatin, which he tolerates well. A molecular test of the biopsied lesion reveals no mutations in the KRAS or NRAS genes within exons 2, 3 or 4, and no BRAF V600E mutation.

Answer 97

Answer: Cetuximab

Scenario describes metastatic left-sided colorectal cancer, with proficient MMR staining and RAS wild-type. Standard first-line therapy is the FOLFOX regimen (described in the scenario), with the addition of a biological agent dependent on the RAS mutation status. Given there are no mutation in the stated RAS genes or BRAF mutations, an EGFR monoclonal antibody (cetuximab or panitumumab) can be added to his treatment, particularly given the left-sided tumour. Bevacizumab is reserved for patients with an EGFR or BRAF mutation, where EGFR monoclonal antibodies are detrimental, or right-sided tumours