Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

FRACP Shuyu > NEJM editorial > Flashcards

NEJM editorial Flashcards

1
Q

hormone-receptor–positive, HER-2 negative metastatic breast cancer first line treatment

A

Post-menopausal women - 1st line:

  • CDK 4/6 inhibitor + aromatase inhibitor
  • fulvestrant and a CDK 4/6 inhibitor is an appropriate alternative

Pre-menopausal women - 1st line:

  • Ovarian suppression or ablation + ET + a targeted agent (e.g. CDK4/6 inhibitor)

Background info:

  • three agents (palbociclib, abemaciclib, and ribociclib, respectively all CDK4/6 inhibitors) significantly prolonged progression-free survival when administered in combination with endocrine therapy as first-line treatment in women with hormone-receptor–positive metastatic breast cancer. The MONALEESA-7 trial included pre-menopausal women showing positive results across the whole group. A premenopausal women in whom menopause is induced by ovarian suppression can be treated in the same way as a women with natural menopause PALOMA-2 (Palbociclib: Ongoing Trials in the Management of Breast Cancer–2), MONARCH-3, and MONALEESA-2 (Mammary Oncology Assessment of LEE011’s [Ribociclib’s] Efficacy and Safety–2)
  • Only approved for post-menopausal women on the PBS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

CDK4/6 inhibitors (3)

A

palbociclib, abemaciclib, and ribociclib

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what is the mechanism of prostate cancer progression after androgen deprivation therapy with castration

A

androgens produced by the tumour

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what drugs were developed to inhibit residual androgen stimulation of tumour tissue (in the case of castration-resistant prostate cancer)

A

abiraterone acetate and enzalutamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what other drug is administered with abiraterone

A

low dose corticosteroids (10mg prednisolone)

Background:

  • abiraterone leads to decreased cortisol production and increased build up of mineralcorticoids which causes hypokalaemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

MOA of abiraterone

A

inhibits the enzyme cytochrome P450 17A1 (CYP17A1), which is critical in the production of androgens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

MOA of enzalutamide

A

binds the androgen receptor and inhibits its nuclear translocation, DNA binding, and transcription of androgen-dependent genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

first line treatment in metastatic, hormone-sensitive prostate cancer

A
  1. ADT with either medical or surgical orchiectomy as a component of the initial treatment to suppress serum testosterone levels for all patients requiring systemic therapy
    1. Surgical orchiectomy - bilateral orchiectomy
    2. Medical orchiectomy - most commonly continuous treatment with a gonadotropin-releasing hormone (GnRH) agonist, which suppresses luteinizing hormone production and, therefore, the synthesis of testicular androgens
  2. For men with high-risk disseminated prostate cancer: ADT with either docetaxel or abiraterone rather than using ADT alone (choice of agent based on SE profile)
  3. Enzalutamide has also been shown to prolong survival free progression in an interim analysis when encoporated into a ADT regimen. However, it has a much higher cost than abiraterone

Enzalutamide or abiraterone w androgen-deprivation therapy https://www.nejm.org.acs.hcn.com.au/doi/full/10.1056/NEJMe1906363

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

management of castration resistant metastatic carcinoma of the prostate

A

Clinical pathological features of aggressive variant prostate cancer:

  • taxane + platinum based chemotherapy regimen

Assess for Lynch and BRCA genes

  • Consider pembro/PARP inhibitor

Consider combination of docetaxel, antiadrogens if not used before

enzalutamide or abiraterone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

pathogenesis of membranous nephropathy

A

IgG deposition in the subepithelial space of glomerular capillaries

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

membranous nephropathy with nephrotic range proteinuria treatment

A

currently cyclosporin or cyclophosphamide but MENTOR study showed superior efficacy of rituximab https://www.nejm.org.acs.hcn.com.au/doi/full/10.1056/NEJMe1906666

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

short-term effect of SGLT2 on eGFR

A

decreases eGFR due to vasoconstriction of the afferent arteriole due to increased sodium delivery to the distal renal tubule which is sensed by the juxtaglomerular apparatus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

effect of SGLT2 on renal outcomes

A

improves progression of kidney disease and death from renal or cardiovascular outcome this is because the SGLT2 inhibition causing decreased glomerular perfusion and intraglomerular pressure. The level of angiotensin II decreases and atrial natriuretic peptide too alongside w inflammation and an increase in intrarenal oxygenation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

most commonly genetic abnormality in CLL

A

deletion of chromosome arm 13q –> leads to loss of microRNAs mir-15a and mir-16-1, which act as inhibitors of BCL2 expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

venetoclax MOA

A

BCL2 inhibitor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

evidence for best agents in first line CLL

A

ibrutinib and venetoclax used in conjunction in the NEJM May 2019 paper to induce minimal residual disease remission in 60%. dual agent did not increase toxicity. ibrutinib was initiated first before venetoclax to reduce tumour burden to prevent TLS

Other options for 1st line therapy in symptomatic CLL:

  • Ibrutinib alone
  • Ibrutinib + ritux
  • Venetoclax + obinutuzumab (another anti-CD 20 humanized monoclonal antibody)
  • Venetoclax alone
    https: //www.nejm.org.acs.hcn.com.au/doi/full/10.1056/NEJMe1904362
17
Q

most commonly genetic abnormality in CLL

A

deletion of chromosome arm 13q –> leads to loss of microRNAs mir-15a and mir-16-1, which act as inhibitors of BCL2 expression

18
Q

major initial AE of venetoclax

A

TLS - need for graduated dosing

19
Q

first line in frail and elderly MM

A

Currently on UTD:

  • bortezimib + len + dex OR dara + len + dex
  • len + dex can be used in really frail patients

Background:

Lenalidomide and dexamethasone administered until disease progression resulted in superior progression-free and overall survival and had a more favorable safety profile than treatment with thalidomide plus melphalan and prednisone. The incorporation of daratumumab led to a substantially higher overall rate of response; an increased depth of response, including a significantly higher percentage of patients who were negative for minimal residual disease (at a threshold of 1 tumor cell per 105 white cells), as evaluated by next-generation sequencing; and significantly longer progression-free survival, with a higher percentage of patients having progression-free survival at 30 months (the primary end point) than lenalidomide and dexamethasone alone. However, the addition of dara leads to a higher incidence of neutropenia and infections, including pneumonia

20
Q

Daratumumab MOA

A

IgGκ monoclonal antibody that targets CD38 and exhibits pleiotropic antitumor activity. Causes cells expressing CD38 to apoptose via ADCC and complement activity.

21
Q

morphology of structural heart disease VT vs genetic VT

A

structural heart disease is usually monomorphic where as genetic causes are associated with channelopathies and usually polymorphic

22
Q

Timing of coronary angiogram in out of hospital cardiac arrests

A

Immediate for STEMI patients

Unclear for everyone else.

Background (n engl j med 380;15):

  • COACT trial showed no survival benefit in randomising to immediate coronary angio vs delayed
  • Subgroup analysis showed possible benefit in: patients >70 yr, history of coronary artery disease
23
Q

Anti-thrombotic therapy after PCI in atrial fibrillation patients

A

Still triple therapy with anticoagulant + aspirin + clopidogrel. NOACs appear superior to warfarin in patients who are eligible for it.

Aspirin has higher bleeding rates (mainly GI) but the study is not powered enough to see whether there is increased rate of coronary ischaemic events when aspirin is omitted.

It may be reasonable to have dual therapy (NOAC + clopidogrel) instead of triple therapy in patients with elective PCI with low angiographic and clinical risk.

Reference: NEJM editorial: Refining Antithrombotic Therapy for Atrial Fibrillation and Acute Coronary Syndromes or PCI

24
Q

TAVR vs surgical valve replacement in severe aortic stenosis

A

2 NEJM RCTs in 2019 (Mack et al, Popma et al) found that TAVR was non inferior and even superior than surgical aortic valve replacement.

Other considerations:

  • Patient <50 should have a mechanical valve unless there is a contraindication to anticoagulation
  • The trials were predominantly men and noone had bicuspid valves (which make up 50% of aortic stenosis cases)
25
Q

Most common mutation in hepatocellular carcinomas

A

Mutations in the TERT promoter (60% of cases); normally seen in the dysplastic nodule. Of note, TERT promoter is a recurrent insertion site for the HBV genome.

Reference:

n engl j med 380;15 nejm.org April 11, 2019

26
Q

Supply of benign vs malignant liver nodules

A

Benign nodules are supplied by the portal system where as malignant nodules are supplied by the hepatic artery

27
Q

HCC solitary nodule <2cm with preserved liver function

A

Ablation or resection

28
Q

HCC solitary nodule >2cm or 2-3 nodules all <3cm with preserved liver function treatment

A

Resection and if not feasible, transplant.

If not a transplant candidate, ablation

29
Q

Multinodular HCC with preserved liver function. 3 or more nodules or 2 or more nodules if 1 nodule >3cm.

No metastatic spread/macrovascular invasion.

Treatment?

A

Chemoembolization

30
Q

Metastatic HCC treatment with preserved liver function

A

Sorafenib or lenvatinib

31
Q

HCC criteria for liver transplantation

A

a single nodule ≤5 cm in diameter or up to three nodules, none larger than 3 cm in diameter

(The Milan criteria for liver transplantation)

32
Q

Strongest independent risk for contrast-assocaited acute kidney injury

A

severe chronic kidney disease

33
Q

what kind of contrast agent is recommended to prevent contrast associated AKI?

A

low-osmolality and iso-osmolality agents

34
Q

Pathophysiology of contrast induced AKI

A
  1. Nephrotoxicity
    1. Tubular damange
    2. Increased in viscosity of tubular fluids -> tubular obstruction
  2. Disturbance in renal blood flow
    1. Arteriolar vasoconstriction
    2. Increased in blood osmolality and viscosity -> microvascular thrombosis
35
Q

Ivacaftor

A

potentiator of residual CFTR function that has been approved for pa- tients with cystic fibrosis with gating and some splicing CFTR mutations

36
Q

Metastatic renal cell carcinoma management

A

In 2018, the combination of two immune checkpoint inhibitors, nivolumab and ipilimumab, were shown to have better efficacy than sunitinib.3 This combination, which was approved recently by the Food and Drug Administration and the European Medicines Agency, is the new standard of care, primarily in intermediate- and poor-risk patients.

In 2019 NEJM March 21st issue, the editorial discussed 2 new phase 3 trials that showed promising results for a PD-1 combined with axitinib and PD-L1 combined with axitinib

37
Q

What is the most common organism found in aspiration pneumonia?

A

Community acquired: Strep, staph

Hospital acquired: gram negatives

Anaerobes are more rare now

38
Q

Management of stage 1/2 HER-2 positive breast cancer who has residual disease found after surgery with previous neoadjuvant therapy

A

trastuzumab or Trastuzumab emtansine (T-DM1), an antibody–drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor

https://www.nejm.org.acs.hcn.com.au/doi/full/10.1056/NEJMoa1814017

39
Q

omadacycline

A

new tetracycline

not on PBS

FRACP Shuyu (65 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions