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NEJM Jan2014-Sep2015 > Jul 2014 > Flashcards

Jul 2014 Flashcards

1
Q

True/False: for spinal stenosis, the addition of glucocorticoids to lidocaine confers significant short-term benefit compared to lidocaine alone.

A

False.

Minimal to no benefit.

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2
Q

APOC3 (apolipoprotein C3) gene mutation has what effect?

A

APOC3 mutations lead to reduction in non-fasting triglycerides levels and is associated with reduced incidence of ischaemic vascular disease, compared to noncarriers of APOC3 mutations.

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3
Q

Which HLA haplotypes are associated with increased risk of coeliac disease in the paediatric population?

A

HLA DR3-DQ2

HLA DR4-DQ8

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4
Q

With GCA/PMR, disease flares occur during tapering glucocorticoids. How should this be managed?

A

Flares often respond to 20% increase in glucocorticoid dose.

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5
Q

What proportion of patients with GCS will have involvement of the aorta and it’s major branches?

How should this concern be investigated?

A

25%

CTA/MRA

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6
Q

What opportunistic infection should be considered in a patient on long-term glucocorticoids for PMR/GCA.

A

PJP (pneumocytis jerovici pneumonia)

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7
Q

True/False: patients with GCA/PMR have a reduced lifespan.

A

False.

However, long-term glucocorticoids have yield morbidity from AEs.

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8
Q

For GCA/PMR which two immune response networks have been implicated?

A
  1. IL-12 / Th1 / IFN-gamma axis

2. IL6 / Th17 / IL-17 axis

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9
Q

What are the approximate sensitivities and specificities of CRP/ESR in the diagnosis of GCA/PMR?

What percentage of GCA/PMR cases have a normal CRP and ESR?

A 
Sensitivity = 85% (good)
Specificity = 30% (poor)

Only 4% (low)

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10
Q

True/False: in the management of GCA/PMR IL-6 levels are superior to CRP levels in guiding management.

A

False - no evidence for use of IL-6 levels

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11
Q

True/False: routine FDG PET-CT is useful in distinguishing vasculitic and non-vasculitic lesion in GCA/PMR.

A

False - no recommended for routine use.

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12
Q

In the diagnosis of temporal arteritis which of the following is a suitable alternative to temporal artery biopsy:

A. US
B. MRI

A

Neither - biopsies are most sensitive to even minor inflammatory changes.

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13
Q

Which glucocorticoid-sparing agents are used in the treatment of GCA/PMR?

A

None - no agents approved for use in GCA/PMR

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14
Q

Acquired acrodermatitis enteropathica is noted in a 54F with intractable rash refractory to steroid and antifungals with a previous history of bariatric bypass.

What is the treatment?

A

Cause = reduced zinc levels

Treatment of rash = replace zinc

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15
Q

Patient presents with typical HSV encephalitis with high pre-test probability and clinical suspicion. HSV PCR is however negative. Do you treat it?

A

Yes - re-test patient whilst commencing on empirical treatment.

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16
Q

True/False: in high risk vascular patients the addition of niacin-laropiprant to statin-bases LDL cholesterol lowering therapy significantly reduces major vascular event.

A

False.

No benefit and increases risk of many serious AEs (DM, GI, MSK, skin, infection, bleeding)

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17
Q

What is ibrutinib?

What are it’s currently approved indications?

A

Covalent inhibitor of Bruton’s tyrosine kinase

Indications:

  • Mantle cell lymphoma
  • CLL (chronic lymphocytic leukaemia) or SLL (small lymphocytic lymphoma)
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18
Q

What is ofatumumab?

Indications?

A

Monoclonal antibody to CD20.

Indications:

  • Haem: Refractory CLL/SLL, NHL (FL/DLBCL)
  • Other: RA, refractory MS
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19
Q

What are the AEs of ibrutinib?

A

nausea, diarrhoea, pyrexia, fatigue

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20
Q

In refractory CLL/SLL which is the preferred agent: ibrutinib or ofatumumab?

A

Ibrutinib with significantly improved progression-free survival, overall survival and response rate.

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21
Q

What is Lantreotide?

Indications?

Most common AE?

A

Somatostain analogue.

Indications: treats symtpoms related to hormone hypersecretion in neuroendocrine tumors.

Diarrhoea

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22
Q

How does Lantreotide modify the survival of patients with metastatic enteropancreatic neuroendocrine tumors of grade 1 or 2 compared to placebo.

A

Prolonged progression-free survival compared to placebo.

However - no change to QoL or overall survival

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23
Q

What is Raltegravir?

A

New class of antiretroviral HIV drug - integrase inhibitor

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24
Q

Describe in words the 6 step life-cycle of HIV.

Superimpose the potential therapeutic interventions.

A
  1. Binding (fusion/entry (CCR5) inhibitors)
  2. Reverse transcription (NRTIs and NNRTIs)
  3. Integration (integrase inhibitors)
  4. Transcription (transcriptor inhibitors)
  5. Translation
  6. Viral assembly and maturation (protease inhibitors)
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25
Q

NRTIs are first-line in anti-retroviral regimens for HIV therapy. Which of the following is preferred as the second-line therapy (i.e. in conjunction with NRTIs):
A. Protease inhibitor
B. Raltegravir (integrase inhibitor)
C. Either of the above

A

Protease inhibitor is the better than Raltegavir as the second-line agent.

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26
Q

True/False: virologic control in HIV is better with protease inhibitor monotherapy.

A

False.

NRTIs + protease inhibitors give better virologic control.

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27
Q

What is HAART in HIV therapy?

What type of HIV patient is HAART commenced?

A

HAART = Highly Active AntiRetroviral Therapy

Treat-naive patients are commenced on HAART.

ART (antiretroviral therapy) consists of 3 drugs:
BACKBONE (2x NRTIs) + 3rd ANCHOR (NNRTI or PI or INSTI)

NRTI = Nucleotide Reverse Transcriptase Inhibitor
NNRTI = Non-Nucleotide Reverse Trancriptase Inhibitor
PI = Protease Inhibitor
INSTI = INtegrase Strand Inhibitor
28
Q

Is HAART therapy available as a single pill?

A

Yes - 3 single pill options available.

Atripla (TDF-FTC and EFZ)
Complera (TDF-FTC and RPV)
Stribild (TDF-FTC and elvitegravir + cobicistat boost)

TDF = tenofovir (NRTI)
FTC = emtricitabine (NRTI)
EFZ = efavirenz (NNRTI)
RPV = rilpivirine (NNRTI)
29
Q

What needs to be tested prior to starting abacavir in a HIV patients?

A

HLA-B*5701 positive patients should NOT receive abacavir - patient may develop life-threatening hypersensitivity.

30
Q

True/False: HIV patients with renal impairment should avoid combination pills.

A

True

31
Q

In the treatment of HIV with integrase inhibitors, co-administration of which other medication may reduce the dose required?

A

Antacid

32
Q

Patient presents with diarrhoea, abdominal discomfort and facial flushing. Imaging reveals 2 hepatic lesions that upon biopsy reveal well-differentiated neuroendocrine tumour. Bloods reveal elevated chromogranin A and urine reveals high 5HIAA.

What is the initial treatment? Then later?

A

Initial treatment = octreotide

Later = everolimus

33
Q

What is blood chromogranin A and urinary 5HIAA useful for?

A

Diagnosis of carcinoid or neuroendocrine tumours.

34
Q

Which pathway is implicated in the formation of vascular lesion in antiphospholipid syndrome?

Which agent may be used to treat this? What is it’s MOA?

A

mTORC (mammalian Target Of Rapamycin Complex) pathway

Sirolimus (mTOR inhibitor) - inhibits IL-2 production and hence activation of T and B cells.

35
Q

True/False: bionic pancreas is NOT viable alternative to traditional insulin pumps in patients with Type 1 DM.

A

False.

Improved glycaemic control and less frequent hypoglycaemic episodes.

36
Q

Which interleukin is implicated in the pathogenesis of psoriasis?

Which drug is the the proof-of-concept therapy?

A

IL-17a

Secukinumab (IL-17a mAb) may be used in patients with mod-severe plaque psoriasis.

37
Q

What is etanercept?

A

TNF inhibitor

38
Q

How common is post-splenectomy sepsis?

A

50% (high)

39
Q

What vaccination are recommended in asplenic patients?

A 
Bacterial vaccinations (3): pneumococci, Hib, meningococci
Viral vaccinations (1): influenza
40
Q

Describe the duration of prophylactic antimicrobial therapy in adult asplenic patients:

  1. Post-splenectomy without complications
  2. After an episode post-splenectomy sepsis
A
  1. 1-2 years prophylaxis

2. Lifelong prophylaxis

41
Q

Why are vaccinations against encapsulated organisms important post-splenectomy?

A

Spleen is the most efficient organ at clearing IgG coated virulent encapsulated bacteria that are not opsonised by antibodies or complement.

42
Q

Name 3 organisms an asplenic patient may suffer a serious infection from (not the common ones that require vaccinations).

A

Capnocytophaga canimorsus or cynodegmi (gram negative)) - animal bite

Babesia (protozoan) - tick bite

Bordetella holmesii (gram negative rod)

43
Q

Influenza infection predisposes patients to bacterial pneumonia/sepsis from which 2 organisms?

A

S. pneumoniae

S. aureus

44
Q

What ‘new’ agent is useful in the rapid clearance of uncomplicated P. vivax or P. falciparum malaria?

A

KAE609 (Spiroindolone) - 30mg for 3 days.

45
Q

Artemisinin resistance to P-falciparum in South-East Asia is associated with which mutation?

A

mutations in keltch13 (kelch protein gene on chromosome 13)

46
Q

What is Enzalutamide?

Indication?

A

Androgen receptor inhibitor.

Metastatic prostate cancer:

  • prolongs survival in men with metastatic castration-resistant prostate cancer with progression despite chemotherapy.
  • decreased risk of radiographic progression and death and delayed initiation of chemotherapy.
47
Q

What 4 types of pathogens commonly cause brain abscesses?

A
  1. Bacteria
  2. Mycobacteria
  3. Fungi
  4. Parasites (protozoa and helminths)
48
Q

Which of the following is the most common clinical manifestation of a brain abscess:

  1. headache
  2. fever
  3. altered level of consciousness
A

headache.

49
Q

Give 4 predisposing factors for a brain abscess.

A
  1. HIV
  2. Immunotherapy
  3. Disruption of barriers (e.g. trauma, mastoiditis, dental caries, sinusitis)
50
Q

How does one differentiate a brain abscess from a cancer?

A

MRI combined with diffusion-weighted imaging (96% sensitivity and specificity)

51
Q

With a brain abscess, blood cultures and CSF identify the underlying pathogen in what % of cases?

A

25%

52
Q

In a HIV patient with suspected of toxoplasmosis without a tissue based diagnosis, what test can trigger empirical treatment?

What is the treatment?

A

Anti-toxoplasma IgG antibodies - if these are positive, then reasonable to start therapy.

Treatment of toxoplasmosis:
pyrimethamine + sulfasalazine

53
Q

True/False: it is routine in brain abscess management to directly administer antimicrobials into the abscess cavity.

A

False - NOT routine, not usually recommended.

54
Q

What size brain abscess required neurosurgical intervention?

A

2.5cm diameter.

55
Q

Which accurate but rarely employed test is employed to test for a suspected bacterial aetiology despite negative blood cultures?

A

PCR 16S rDNA sequencing

Expensive and technically more involved

56
Q

After organ transplantation what agents are used for prophylaxis agains the following organisms:

  • Bacteria
  • Nocardia / PJP
  • Fungal (esp. aspergillus)
A
  • Bacteria - ceftriaxone + metronidazole (for brain abscess)
  • Nocardia / PJP - Bactrim
  • Fungal (esp. aspergillus) - voriconazole
57
Q

What is the treatment for TB?

A

RIPE:

Rifampicin
Isoniazid
Pyrazinamide
Ethambutol

58
Q

What empirical antibiotic treatment is recommended in a patient post-neurosurgical procedure or sustained a skull fracture?

A
  1. Vancomycin
  2. 3rd/4th generation cephalosporin: ceftriaxone / cefepime
  3. metronidazole
59
Q

Patient has contraindications to the use of cephalosporins and metronidazole, what may be used?

A

merepenem

60
Q

True/False. In the treatment of brain abscess, the addition of glucocorticoids to antimicrobials is routine.

A

False.

Glucocorticoids may reduce passage of antimicrobials into the CNS. Reserved for use in patients with profound oedema leading to cerebral herniation.

61
Q

What type of scorpion toxin has medical use?

MOA?

A

Scorpion alpha-toxin

MOA - binds to voltage-gated sodium channels, leading to prolonged depolarisation and neuronal excitation.

62
Q

True/False: CNS effects are common scorpion envenomation as the scorpion toxins cross the blood-brain-barrier.

A

False.

CNS effects are uncommon.

63
Q

What is the possible effects scorpion envenomation (4)?

A

Cardiac e.g. injury, APO, shock.

Neuromuscular (PNS) e.g. muscle fasciculations/spasm

Renal impairment

Pancreatitis

64
Q

What is the treatment of scorpion envenomation?

A

Antivenom

CVS - prazocin and dobutamine

Neuromuscular - benzodiazepine

65
Q

A 47-year-old man presented with a 1-year history of progressive, repetitive, involuntary muscle twitching and cramps in his legs. He was having difficulty swallowing both solids and liquids, and he also noted excessive salivation and decreased volume of his voice. His medical history was otherwise unremarkable. Neurologic examination revealed mildly slurred speech, tongue atrophy and fasciculations, and weakness of the sternocleidomastoid muscle. Wasting of the intrinsic hand muscles, generalized hyperreflexia, and bilateral foot drop were also noted.

Diagnosis?

A

Amyotrophic lateral sclerosis (ALS) - causes death of UMN and LMN

66
Q

What are the 5 diseases referred to as ‘motor neuron disease’, describe the involvement of UMN +/- LMN.

A

UMN degeneration only:
Primary lateral sclerosis (PLS)
Pseudobulbar palsy (bulbar region only)

LMN degeneration only:
Progressive muscular atrophy (PMA)
Progressive bulbar palsy (PBP)

UMN + LMN:
Amytrophic lateral sclerosis (ALS)

67
Q

27M short man with blue sclera since birth, early fractures on history, mild mental retardation, ataxia, hearing loss and seizure disorder. Diagnosis?

A

Osteogenesis imperfecta - deficiency of type 1 collagen (gene deletion of COL1A1 or COL1A2)

NEJM Jan2014-Sep2015 (4 decks)

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