BPT Trial Exam Questions 1 Flashcards
Which of these agents will reverse anticoagulation with rivaroxaban for emergency surgery?
Prothrombinex
Idarucizumab
Phytomenadione
Andexanet Alfa
Correct answer
Andexanet Alfa
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Prothrombinex is not a reversal, rather it is factor supplementation, and does not affect the action of the Xa inhibitor
Idaracizumab is for dabigatran
https://www.nejm.org/doi/full/10.1056/NEJMoa1814051
A 35 year old woman presents with diplopia. She had gone to sleep at 2pm and awoken at 4pm with diplopia. She complains of seeing two images next to each other on a horizontal plane especially when looking to the right. Afternoon naps are not typical for her, she has been feeling increasingly fatigued in the past 2 weeks which she has attributed to work stress in her role as a medical records manager. She is alert and oriented. She is normotensive and afebrile. On examination ocular alignment is symmetric on primary gaze. On looking to the left, both eyes move smoothly. When looking to the right, the left eye fails to adduct past the midline and the right eye demonstrates horizontal nystagmus, and the patient complains that her diplopia increases. Pupils are equal and reactive to light. The rest of your examination, including careful neurological exam, is normal. Where is the lesion causing her symptoms?
Right medial longitudinal fasciculus
Right optic nerve
Left abducens nucleus
Left medial longitudinal fasciculus
Left medial longitudinal fasciculus
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This is a pretty classic description of internuclear ophthalmoplegia (which you will become very familiar with prior to your clinical exam).
A lesion in the medial longitudinal fasciculus causes this presentation. It is ipsilateral to the eye which fails to adduct properly. The most common lesions are demyelination and ischaemia, the former being more likely in this young woman.
3 months later the patient from the previous question returns to emergency complaining of painful vision loss in the right eye. This developed 48 hours ago and has not improved since developing acutely. The pain is worse on eye movement. She has noticed colours have become dimmer since the pain began. Visual acuity is 6/12 in the right eye and 6/6 in the left eye. Visual field exam reveals a central scotoma. Pupillary examination reveals a relative afferent pupillary defect on the right eye. Eye movements have improved significantly since your previous examination, however they are painful on horizontal movement. Fundoscopy shows a normal optic disc. What is the diagnosis?
Anterior ischaemic optic neuropathy
Eosinophilic granulomatosis with poly-angiitis
Acute closed angle glaucoma
Retrobulbar optic neuritis consistent with multiple sclerosis
Retrobulbar optic neuritis consistent with multiple sclerosis
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This woman has now presented with two clinically isolated events which are very typical of MS, and would be sufficient to make a diagnosis (although you would further evaluate with MRI to define the extent of disease).
Retrobulbar neuritis is the more common variant of optic neuritis (2/3 of cases) and the optic disc may not be visibly swollen on ophthalmoscopy at the time of the initial event. Optic papillitis (affecting the more anterior part of the optic nerve) will show disc swelling.
You have confirmed your diagnosis and are looking to start treatment with fingolimod. What would be a contraindication to this?
Second degree heart block
Renal impairment with creatinine clearance <60c.
Recent treatment for staph. aureus cellulitis of the leg.
Baseline hypotension.
Answer: Second degree heart block
Fingolimod is a sphingosine 1-phosphate receptor modulator, and a good oral option for treatment of moderately severe MS. It is associated with conduction block and the first dose is often given supervised for this reason.
Fingolimod is associated with hypertension, and BP should be controlled before starting.
A completely treated infection would not be a barrier.
The renal cut off point is ~30ml/min
A 40 year old man presents to genetics clinic with a strong family history of early onset Alzheimer’s dementia. Presymptomatic genetic testing is performed which revealed a pathogenic mutation in the PSEN1 gene. Which of the following is INCORRECT?
A. PSEN1 encodes for a subunit of gamma secretase enzyme
B. The mutation is usually a missense mutation with autosomal recessive transmission
C. PSEN1 mutations are more common than PSEN2 mutations
D. The mutation most likely increases the ratio of highly fibrillogenic amyloid beta 42 to amyloid beta 40
Answer: The mutation is usually a missense mutation with autosomal recessive transmission
Most cases of Alzheimer’s disease are not hereditary. However, there is a small subset of cases that have an earlier age of onset and have a strong genetic element.
These are generally autosomal DOMINANT and include mutations in the presenilin proteins (PSEN1, PSEN2) or the amyloid precursor protein (APP).
An important part of the disease process in Alzheimer’s disease is the accumulation of Amyloid beta (Aβ) protein. To form Aβ, APP must be cut by two enzymes, beta secretases and gamma secretase. Presenilin is the sub-component of gamma secretase that is responsible for the cutting of APP.
A 30 year old gentleman is seen in the first time in respiratory clinic for difficult to treat asthma. He has had recurrent exacerbations in the past year where he presented with shortness of breath, fever, and coughing up brown mucus plugs. A serum IgE is done which 1200 IU/ml. Which one of the following is the other obligate criteria for the diagnosis of his condition?
Positive aspergillus precipitating antibodies
HRCT demonstrating proximal cylindrical bronchiectasis that is upper lobe predominant
Elevated serum IgE against aspergillus fumigatus
Total eosinophil count > 0.5 x 10^9 cells/L
Answer: Elevated serum IgE against aspergillus fumigatus
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This is a question on the diagnostic criteria for ABPA. The two obligate criteria are an elevated serum IgE > 1000 IU/ml AND a test that demonstrates allergy to the aspergillus fumigatas. This can be a skin test or elevated IgE against the aspergillus. Other criteria (two of which must be present) include radiographic changes consistent with ABPA, eosinophil count > 0.5 x 10^9 cells/L and aspergillus precipitating antibodies
Which of the following causes of interstitial lung disease is typically upper lobe predominant?
Rheumatoid arthritis
Scleroderma
Asbestosis
Hypersensitivity pneumonitis
Answer: Hypersensitivity pneumonitis
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This is a question on memorising which pathologies cause upper versus lower lobe ILD. Generally upper lobe causes are due to inhalation of stuff with the exception of ankylosing spondylitis (remember upper lobes are more ventilated than lower lobes). Mnemonic is SCHART (sarcoidosis and silicosis, coal workers lung, hypersensitivity pneumonitis and histiocytosis, ank spond and ABPA, radiation, tuberculosis).
Lower lobe ILD is caused by problems in the blood (remember perfusion is more in lower lungs than upper lungs) with exception of asbestosis. Mnemonic is RASCO (RA, asbestosis, scleroderma, cryptogenic fibrosis alveolitis which is IPF, and others which include drugs)
Which of the following is NOT a feature of the antisynthetase syndrome?
Antisynthetase antibodies such as anti-Jo1
Muscle biopsy demonstrating endomysial lymphocytic infiltrate with rimmed vacuoles
Nonerosive inflammatory polyarthritis
Interstitial lung disease with HRCT demonstrating a NSIP pattern
Answer: Muscle biopsy demonstrating endomysial lymphocytic infiltrate with rimmed vacuoles
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Antisynthetase syndrome is seen in 30% of those with PM and DM. Patients present with constitutional symptoms. The syndrome is defined by presence of antibodies to aminoacyl-transfer (t) RNA synthetase enzymes (typically anti-Jo-1). Additional 2 of the following are needed: inflammatory myositis, ILD, or nonerosive inflammatory polyarthritis. Other features are Raynauds, mechanics hands, fever, weight loss.
A muscle biopsy demonstrating rimmed vacuoles is that of inclusion body myositis and is therefore incorrect
A 75 year old male with a history of hypertension, transient ischemic attacks, cataracts and benign prostate hypertrophy presents to hospital with a fall. His medications include a statin, ACEI, aspirin and Duodart (Dutasteride/tamsulosin). He provides a history of 12 weeks of progressive difficulty rising from standing, opening jars and associated impairment in performing ADLs. He also reports occassional difficulty with choking whilst drinking water. Upper limb examination reveals bilateral weakness of the wrist flexors and finger grip, opposition and extension with preserved proximal weakness with normal reflexes. Lower limb examination reveals bilateral moderate proximal predominant muscle weakness with sparing of distal power with mildly reduced reflexes bilaterally. He is unable to rise from standing. Speech examination doesn not reveal any overt abnormalities. CK is performed and is 2x upper limit of normal. EMG is performed and shows variable fibrillations and positive sharp waves with early recruitment. Which of the following antibodies is most likely to be present:
Anti-Signal recognition Peptide antibody (Anti-SRP antibody)
Anti-cytosolic 5’nucelotidase 1A antibody (Anti-cN1A antibody)
Anti-double stranded DNA
Anti- HMGCo-A Antibody
Answer: Anti-cytosolic 5’nucelotidase 1A antibody (Anti-cN1A antibody)
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Classical history provided of Inclusion body myositis- Dysphagia, Distal upper limb weakness with proximal lower limb weakness and potentially normal to low raised CK.
Anti-SRP and HMGCoA antibodies result in necrotising myositis with extremely high CK levels and result in upper limb proximal +/- distal weakness.
Differential in these cases would be motor neurone disease however EMG findings provided are consistent with myopathic changes (remember: EMG myopathy = early recruitment)
Which skin manifestation is not associated with IBD?
Pyoderma gangrenosum
Eczema
Erythema nodosum
Psoriasis
Answer: Eczema
In regards to the anti-resorptive medication Denosumab, which of the follow is INCORRECT?
A. The mechanism of action is a human monoclonal antibody that binds to RANK ligand and prevents RANK binding to inhibit osteoclast formation, function and survival.
B. It has a rapidly reversible effect leading to bone mineral density returning to baseline with a missed dose
C. It can cause hypocalcaemia especially in the setting of vitamin D deficiency
D. It increases mineralisation and reduced fracture risk at the hips but not the spine
Answer: It increases mineralisation and reduced fracture risk at the hips but not the spine
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The FREEDOM Trial NEJM 2009 - Denosumab shown to increase BMD in spine (by 18%) and decrease fracture risk (-68% spine, -40% hip, -20% other non-vertebral). All the other statements are correct (Binds to RANKL to inhibit osteoclasts, rapidly reversible effect and SE of hypocalcaemia).
In addition to a negative HLA-DQ2, absence of which of the following HLA alleles carries a negative predictive value of >99% for Coeliac disease?
A4
DQ8
B57
DR4
Answer: DQ8
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NPV of negative DQ2 and DQ8 is >99%, it has poor PPV (12%) for diagnosis as DQ2 and to a lesser extent DQ 8 are highly prevalent in the general population. Therefore a negative test virtually excludes the diagnosis.
What is the most common extra-colonic malignancy associated with Lynch syndrome?
Pancreatic cancer
Ovarian cancer
Endometrial cancer
Thyroid cancer
Answer: Endometrial Cancer
When interpreting pulmonary function tests, which of the following is true?
A significant bronchodilator response is an increase in FEV1 of >12% or >200mL
The forced vital capacity (FVC) is the maximal volume of air that can be inspired
The total lung capacity (TLC) is the volume in the lungs after a maximal inspiration, including residual volume
In restrictive lung disease, lung compliance increases
Answer: The total lung capacity (TLC) is the volume in the lungs after a maximal inspiration, including residual volume
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A significant bronchodilator response is >12% AND >200ml. FVC is the maximal volume of air that can be EXHALED. Lung compliance is REDUCED in restrictive lung disease.
The ventricles are completely depolarised during which portion of the ECG?
QT interval
QRS complex
PR interval
ST segment
Answer: QRS complex
A 35-year-old female presents with fever, malaise, a red indurated rash on her lower leg and marked painful swelling of both ankles. Her chest X-ray shows prominent hilar markings. What is the most likely diagnosis?
Systemic lupus erythematosus
Tuberculosis
Sarcoidosis
Lymphoma
Answer: Sarcoidosis
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Lofgren’s syndrome - erythema nodosum (the rash described), bilateral hilar lymphadenopathy, and polyarthralgia or polyarthritis
With regards to the haemoglobin-O2 dissociation curve, which of the following will cause a shift to the LEFT?
Decreased pH
Increased 2,3-DPG
Decreased CO2
Increased temperature
Answer: Decreased CO2
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Right shift - Hot, high (increase 2,3, DPG) and acidic (remembering CO2 is essentially an acid)
Oxygen dissociation shift to the right promotes lower O2 affinity and O2 supply to tissues as Hb will more easily offload O2
○ Right shift = hot, high (increased 2,3 DPG) and acidic (CO2 promotes acidity)
○ 2,3-DPG is produced in conditions of hypoxemia and tissue hypo perfusion
Left shift = increased Hb affinity for O2 and more uptake of O2
○ Opposite to right shift
○ Carbon monoxide and
methemoglobinaemia promote left shift
CO binds to Hb much more readily than O2
and effectively displaces O2 so can have
severe tissue hypoxia with normal pO2
When does the right coronary artery receive its coronary flow?
Diastole
At isovolumetric relaxation
Systole and diastole
Systole
Answer: Systole and diastole
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Although the majority of coronary blood flow occurs in diastole, the right coronary artery does have flow in both phases of the cardiac cycle. Flow never comes to zero in the right coronary artery, since the right ventricular pressure is less than the diastolic blood pressure.
What is the mechanism of action of sofosbuvir?
Disruption of virion assembly and release
Competition for HCV receptor binding
Interruption of viral protein production
Prevention of HCV RNA replication
Answer: Prevention of HCV RNA replication
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Nucleotide NS5B
-buvir: Sofosbuvir
Non-nucleoside NS5B
-buvir: dasabuvir
NS3/4 serine protease inhibitors
-previr: Grazoprevir, paritepravir
NS5A inhibitors
-avir Velpatasvir, ombaitasvir, daclatasvir
A 60-year-old man suddenly deteriorated following a myocardial infarction. A new systolic murmur is detected. Swan-Ganz catherisation is performed with the obtained pressures and oxygen saturations below. What is the most likely diagnosis?
Mixed venous oxygen saturation 65%
Right ventricular oxygen saturation 87%
Pulmonary artery pressure 60/25 mmHg
Pulmonary artery wedge capillary pressure 20mmHg
Options: Atrial septal defect Pulmonary embolism Ventricular septal defect Acute mitral regurgitation
Answer: Ventricular septal defect
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Ruptured intraventricular septum, causing a ventricular septal defect. A new systolic murmur following a myocardial infarction may be due to a ventricular septal defect or ruptured papillary muscle leading to mitral regurgitation. Distinction between these two possibilities may be very difficult on purely clinical grounds. Swan-Ganz catheterisation can be used to identify a ruptured intraventricular septum following a myocardial infarction. There is a raised pulmonary artery pressure, raised pulmonary capillary wedge pressure and an increase in oxygen saturation from right atrium (mixed venous) to right ventricle.
A 40 year old man is being investigated for dyspnoea, which has progressed over the last 18 months. He does not have a cough, wheeze or sputum. He is a lifelong non-smoker. He has lung function tests as below. Which of the following is the most likely cause of his dyspnoea?
PFTs: Pre-bronchodilator FEV1 98% predicted FVC 94% predicted FEV1/FVC 88% FEF25-27 (L/sec) 4.3
DLCO 47% predicted
Lung volumes TLC 80% Vital capacity 89% FVC 93% IC 66% RV 63%
Options: A. Chronic obstructive pulmonary disease B. Neuromuscular disorder C. Asthma D. Interstitial lung disease
Answer: Interstitial lung disease
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Spirometry is normal with high FEF25 75 and spirometric value consistent with a restrictive process. Gas transfer, uncorrected for haemoglobin, is severely reduced. Static lung volumes show a moderately reduced inspiratory capacity and residual volume but are otherwise normal. Overall, the results are consistent with intersitial lung disease
A 60 year old female is found to have a thyroid mass. She undergoes investigation with an elevated thyroglobulin and an FNA which is diagnostic of papillary thyroid cancer. She undergoes treatment with a total thyroidectomy with lymph node dissection and post operative TSH-Stimulated radioactive iodine remnant ablation. She is found to have metastatic disease which is resistant to radiotherapy and TSH suppression therapy. On genetic analysis of her tumour, she is found to have the most common genetic driver mutation associated with papillary thyroid cancer and is therefore commenced on vemurafenib. Which mutation is positive?
BRAF V600E
PPAR-gamma
RTK fusion (a fusion of RET and NTRK)
RAS
Answer: BRAF V600E
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BRAF V600E is the most common mutation associated with papillary thyroid cancer (positive in approximately 60% of cases). The hint for this is that Vemurafenib is a tyrosine kinase inhibitor against the BRAF V600E mutation (also used in treatment of BRAFV600E positive metastatic melanoma). Other less common mutation are RTK fusion (15%) and RAS (13%) - however Vemurafenib is not active against these driver mutations. PPAR-gamma is not a genetic driver mutation but the nuclear receptor can be expressed by papillary thyroid cancer leading to the occasional use of pioglitazone in treatment.
Which symptom is least likely to improve after a VP shunt insertion for normal pressure hydrocephalus?
Gait speed
Modified Rankin Scale scores
Moderate cognitive impairment
Urinary incontinence
Answer: Moderate cognitive impairment
Regarding hepcidin:
its expression decreases in response to high circulating and tissue levels of iron
it is synthesized primarily in the liver and kidneys
its transcription is increased in the state of iron deficiency
it binds to and induces degradation of ferroportin
Answer: it binds to and induces degradation of ferroportin
Which of the following is considered gluten free?
Rice
Barley
Oats
Beer
Answer: Rice
What is the mechanism of action of linaclotide?
Activates guanylate cyclase
Inactivates CFTR ion channel
Incretin (GLP-1) mimetic
Inhibits sodium/glucose transporter 2
Answer: Activates guanylate cyclase
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Linaclotide is used to treat chronic constipation of unknown cause and IBD-constipation subtype.
Based on the revised Ghent criteria, apart from the presence of aortic root aneurysm, what other feature is needed to sufficiently diagnose Marfan’s syndrome in the absence of family history?
A. Arm span >1.05 times the height
B. Long limbs and tall stature
C. Ectopia lentis
D. High arched palate
Answer: Ectopia Lentis
Criteria for Marfan’s syndrome WITHOUT family history:
- Aortic root dilatation (z-score >2) AND Ectopia Lentis
- Aortic root dilatation and FBN1 mutation
- Aortic root dilatation and systemic score ≥7 points
- Ectopia lentis and FBN1 mutation with any degree of aortic root dilatation
Criteria for Marfan’s WITH family history
- Ectopia lentis
- Systemic score ≥7 points
- Aortic root dilatation z-score ≥2 (>20yrs) or ≥3 (<20yrs old)
Marfan's systemic score: 3 points Wrist AND thumb sign 2 points pectus carinatum 2 points hindfoot derfomity 2 points spontaneous pneumothorax 2 points dural ectasia 2 points protucio acetabulae 1 point: pectus excavatum or chest asymmetry, plain flat foot, scoliosis, reduced elbow extension, 3 of 5 facial features, skin striae, severe myopia, mitral valve prolapse
Typical facial characteristics:
Dolichocephaly - disproportionately long and narrow head
Downward slanting palpebral fissures - down-slanting of the space between the eyelids
Enophthalmos - recession of the eyeball within the orbit
Retrognathia - condition in which either or both jaws recede with respect to the frontal plane of the forehead
Malar hypoplasia - underdeveloped cheekbones
