Journal Gems Flashcards
What is the role of Canagliflozin in patients with T2DM and CKD? (CREDENCE Trial)
Lowers rates of renal failure, and improves CV outcomes
What is the role of ARNIs in HFpEF?
NO ROLE
No CV / hospitalisation benefit shown in trials
What is the strongest risk factor for contrast-induced AKI?
Pre-existing CKD
What type of contrast agents should be used to minimise risk of contrast-induced AKI?
Low-osmolality and iso-osmolality agents
What is the current recommendation for prevention of contrast-induced AKI in those at risk?
IV isotonic saline pre and post large contrast loads for those at risk
Cease nephrotoxins if able
What is the current recommended approach for non-culprit lesions in patients undergoing PCI for STEMI?
- Primary PCI of the culprit lesion.
- Proceed with PCI of non-culprit lesions immediately after primary PCI in
- those with evidence of ongoing ischemia
- those in cardiogenic shock who do not significantly improve after PCI of the infarct-related artery - If stable after primary PCI but have non-culprit lesions that are potential causes of residual myocardial ischemia
- return to cath lab prior to discharge or within the first month after discharge to perform PCI of significant non-culprit lesions (as long as not planned for CABG/valve surgery)
- > Guided by FFR
In new onset symptomatic AF, what are the possible approaches to timing of cardioversion?
In patients presenting to the emergency department with recent-onset, symptomatic atrial fibrillation, waiting 48 hours was noninferior to early cardioversion in achieving a return to sinus rhythm at 4 weeks.
What are key options for management of HCM that is obstructive and resulted in HF?
Surgical septal myectomy
OR
Alcohol septal ablation
What interventional option is available for patients with secondary mitral regurgitation, who are still symptomatic despite optimal medical therapy?
Transcatheter mitral-valve repair (Mitra-Clip) -> shown to have lower rate of hospitalization for HF, and lower all-cause mortality within 24 months of follow-up than medical therapy alone (but significant device related complications)
What are the broad indications for catheter ablation in VT in a structurally normal heart?
In the absence of structural heart disease, catheter ablation is indicated if monomorphic ventricular tachycardia:
- causes symptoms
- or antiarrhythmic drugs are ineffective.
What is the role of Fractional Flow Reserve in angiography?
Fractional flow reserve (FFR) is the clinical standard for the invasive physiologic assessment of the hemodynamic significance of intermediate stenoses.
For intermediate stenoses where there is a question of whether revascularization should be carried out, and there are no prior useful noninvasive physiologic data to guide decision making, FFR should be measured before the decision to implant a stent.
What did ISAR-REACT 5 trial show with regards to optimal antiplatelet choice in ACS?
Rates of death, myocardial infarction, or stroke significantly lower in prasugrel group compared with ticagrelor. Bleeding rates were similar
What is the MOA of ezetimibe?
Ezetimibe blocks the Niemann–Pick C1-like 1 cholesterol transfer protein to inhibit intestinal and biliary cholesterol absorption, leading to an increase in the expression of hepatic LDL receptors
What is the role of ezetimibe in lipid management?
Ezetimibe is used in patients =
- who cannot tolerate statins
- who have severe primary hypercholesterolemia
- who have insufficient reduction in LDL cholesterol levels when taking the maximum tolerated statin dose
**Because no outcomes trial has shown benefit with ezetimibe when used in isolation, those who take ezetimibe because of statin intolerance should continue to take the maximum tolerated statin dose
Which groups of older men and women, aside from those with a diagnosis of osteoporosis, should be initiated on antiresorptive therapy for fracture prevention?
- Postmenopausal women with T-scores between -1.0 and -2.5 at high fracture risk as per FRAX.
- > A reasonable threshold to define high risk is a 10-year probability of hip fracture or combined major osteoporotic fracture of ≥3.0 or ≥20 percent, respectively.
- Men ≥50 years with T-scores between -1.0 and -2.5 who are at high risk for fracture as per FRAX tool
What did the EXTEND trial show with regards to time window for thrombolysis in stroke?
In ischaemic stroke, among patients selected via CT perfusion to have significant salvalgeable tissue in the ischaemic penumbra, thrombolysis between 4.5 and 9 hours post onset/time of waking had significant benefit in neurological outcomes
What novel combination of molecular targeted therapies has been shown to be efficacious as first line therapy in CLL among high-risk / older patients?
Ibrutinib (an inhibitor of Bruton’s tyrosine kinase) + venetoclax (inhibitor of B-cell
lymphoma 2 protein)
What is Voxelotor?
What is its potential role?
Voxelotor is an HbS polymerization inhibitor
Among those with sickle cell disease, voxelotor may significantly increase hemoglobin levels and reduce markers of hemolysis.
These findings are consistent with inhibition of HbS polymerization and indicate a disease-modifying potential.
What should generally be the first line anti-HTN agent in those with COPD?
Thiazides
How should glucocorticoid be replaced in an adrenal crisis?
Prompt administration of IV hydrocortisone, given as a 100-mg bolus, followed by 200 mg every 24 hours, administered as a continuous infusion or as frequent intravenous (or intramuscular) boluses (50 mg) every 6 hours
Subsequent doses tailored to the clinical response
Which antibiotic has been shown to be more effective than metronidazole in anaerobic lung infection?
Clindamycin
What treatment has been shown to be of benefit in emergently-intubated patients for reducing risk of aspiration pneumonia?
24 hours of antibiotic therapy
What is nintedanib?
What are the indications for nintedanib treatment?
Most common AE?
Nintedanib is an intracellular multi-kinase inhibitor
Uses: IPF, Systemic sclerosis-associated interstitial lung disease
AE -> diarrhoea
Which class of anti-HTN may have favourable effects on asthma?
CCBs -> possible favourable effects on smooth muscle contraction
What is the main concern with thiazide therapy for HTN and asthma?
Electrolyte disturbance -> hypokalaemia when taking significant doses of SABA also
What features on HRCT differentiate between NSIP and UIP?
Ground glass appearance -> NSIP
Honeycoming -> UIP
Which two medications have been shown to have benefit in IPF?
What benefits have been shown?
Nintedanib and pirfenidone
- slow the rate of FVC decline by approximately 50% over the course of 1 year
- some efficacy in reducing severe respiratory events, such as acute exacerbations, and hospitalization for respiratory events
- suggestion that these agents may reduce mortality
What effect has haloperidol or ziprasidone use been shown to have on duration of delirium in critically ill patients?
No effect on duration of delirium or coma
What is the role of prophylactic acid suppression in critically ill patients?
May have a role in high-risk patients, but should not be routinely given. Harms likely to outweigh benefits
What is the cornerstone of therapy in AERD, particularly after nasal polyp surgery?
Aspirin desensitisation, then daily aspirin therapy
What is the CFTR modulator treatment of choice in people with CF (over age of 12) with =
- F508del heterozygote / homozygote
- Gating variant without F508del
- Triple therapy -> Elexacaftor-tezacaftor-ivacaftor
2. Ivacaftor
What has been shown to be an effective option for patients with colorectal cancer with BRAF V600E mutation who have progressed on initial therapy?
BRAF + MEK + EGFR inhibitor
Encorafenib + binimetinib + cetuximab resulted in significantly longer overall survival and a higher response rate than standard therapy in patients with metastatic colorectal cancer with the BRAF V600E mutation
What has been shown to be the most frequent drug implicated in DILI?
Amoxycillin - clavulate
What biologics have been shown to be efficacious in UC?
Infliximab
Vedolizumab
NEW = Ustekinumab in refractory disease
Which non-invasive H.Pylori test is most sensitive and specific?
Which is cheapest?
Urease breath test is more accurate than stool antigen test
Stool antigen test is cheaper
What is the main treatment for intermediate stage HCC (multinodular or larger nodules)
Chemo-embolisation -> transarterial chemoembolization (TACE), which entails intra-arterial infusion of a cytotoxic agent, followed immediately by embolization of the vessels that feed the tumor
What is the new option now available for BRCA-mutated advanced pancreatic cancer?
Olaparib -> PARP inhibitor
Recommended as maintenance therapy for patients with advanced, BRCA or PALB2 germline-mutated pancreatic cancer who do not experience progression after at least 16 weeks of initial platinum-containing therapy
What is the general treatment for uncomplicated diverticulitis?
No need for routine antibiotics
Bowel rest may be required
Abx indicated for =
- immune compromise
- right-sided diverticulitis
- failure to improve after 72 hours of conservative treatment (ie no antibiotic therapy).
What should be routinely performed in patients 6-8 weeks post episode of diverticulitis?
Colonoscopy to rule out malignancy, unless has been performed in last year
Which benzodiazepines are the preferred choice for treating ETOH withdrawal in decompensated liver cirrhosis?
Lorazepam / oxazepam
Which agent for ETOH dependance can be used in decompensated liver disease?
Acamprosate -> reduces the neuronal hyperexcitability characteristic of alcohol withdrawal, possibly as NMDA receptor antagonist and a modulator of GABA type A receptor.
Reduces the symptoms of protracted alcohol withdrawal (eg anxiety, irritability, insomnia, craving). It has been shown to increase the time to first drink, prolong abstinence, and reduce the number of drinking days. Acamprosate combined with psychosocial treatment has been shown to significantly improve treatment outcomes when compared to psychosocial treatment alone.
What is the most common inherited syndrome causing CRC?
Lynch syndrome (Hereditary nonpolyposis colorectal cancer)
What type of therapy may be beneficial for advanced MSI-H (e.g. Lynch-associated) metastatic CRC that has progressed following conventional chemotherapy?
Immunotherapy with a checkpoint inhibitor that targets PD-1
Which checkpoint inhibitor more commonly causes hypophysitis, and which causes pirmary thyroid disease?
Hypophysitis occurs more frequently in patients taking CTLA-4 inhibitors
Primary thyroid dysfunction is seen more often with PD-1 inhibitors
How does lithium usually affect the thyroid?
Lithium use causes goiter and hypothyroidism by decreasing thyroid hormone release through the inhibition of colloid pinocytosis
Which autoimmune condition is alemtuzumab most associated with?
CD52 mab
Graves disease is very common
What are the differences between Type 1 and Type 2 amiodarone-induced thyrotoxicosis (pathology, clinical, management)?
Type 1 -> iodine-induced
Underlying predisposition present e.g. Toxic adenoma, Graves
Onset -> Quickly after commencement of amiodarone
Colour flow Doppler -> Normal vascularity (can be increased in Graves)
Mx -> Anti-thyroid therapy, can see response in 4 weeks
Type 2 - inflammatory
Destructive process
Onset -> Can occur after drug cessation
Colour flow Doppler -> Reduced / absent vascularity
Disproportionately elevated T4
Mx -> Steroid, can see response in 1-2 weeks
What effect does oral oestrogen have on thyroid function?
Increase in thyroxine-binding globulin, which leads to additional binding of T4, even in the presence of low free T4 levels
Patients on exogenous thyroid hormone -> will have an increased dose requirement
Patients with a functional thyroid -> endogenous thyroid hormone production will increase
What condition does biotin mimic on TFTs?
Primary Hyperthyroidism
What benefit has dapagliflozin been shown to have in heart failure?
DAPA-HF trial -> Compared with placebo, Dapa reduced all-cause mortality and the primary composite outcome (worsening HF or cardiovascular death)
Similar effects in patients with and without type 2 DM.
Known to reduce HF hospitalisations in DM
What is the classic triad of symptoms of phaeo?
Headaches, palpitations, and profuse sweating.
In Phaeo, what medications are typically given for pre-op optimisation and in what order?
Alpha-adrenergic blockade FIRST for BP, usually with phenoxybenzamine, titrated to target BP
Then β-adrenergic antagonist titrated to target average heart rate of 80 beats per minute
Alpha blockade must occur first, because with β-adrenergic blockade alone, severe hypertension or cardiopulmonary decompensation may occur as a result of unopposed α-adrenergic stimulation.
What is the mainstay of treatment for hypoparathyroidism?
High dose activated Vit D, and Calcium
Aiming to maintain Ca at lower end of normal range
What is primary hyperparathyroidism most commonly caused by?
It is most often caused by a single parathyroid adenoma
Who is surgery recommended for in primary hyperparathyroidism ? (6)
Surgery is recommended for
- patients younger than 50 years of age
- patients with clinically significant hypercalcemia
- osteoporosis or a fragility fracture
- renal calculi
- hypercalciuria
- impaired renal function
Which type of fractures are most commonly associated with steroid use?
Vertebral fractures are the most common fractures associated with glucocorticoids
What is the direct effect steroids have on the bone to lead to osteoporosis?
increases in expression of RANK ligand -> leads to increases in the number of bone-resorbing osteoclasts
At what duration / dose of steroid would you consider preventative treatment for bone health?
What is first line therapy?
In patients who will receive at least 7.5 mg prednis(ol)one per day for at least 3 months, and who have a baseline T-score lower than –1.5
Bisphosphonates
What is the main difference in outcome seen with adults vs adolescents having bariatric surgery?
Adolescents had remission of diabetes and hypertension more often than adults.
Adolescents and adults who underwent gastric bypass had marked weight loss that was similar in magnitude 5 years after surgery.
What is the favoured provocative test for diagnosing growth hormone deficiency?
Arginine-GHRH test in countries where GHRH is available
Otherwise -> macimorelin stimulation test (synthetic agonist of ghrelin)
What is the favoured approach re: surgery in metastatic RCC?
If feasible, in patients with metastatic disease at presentation who are candidates for immunotherapy, they should undergo debulking nephrectomy prior to treatment
What are the favoured 1st line immunotherapy options for advanced RCC?
Nivolumab + ipilimumab
Pembro + axitinib
Cabozantinib (if above are not available)
What are options for 1st line treatment of bacterial vaginosis?
Oral metro for 7 days
Topical metro for 5 days
Topical clindamycin for 7 days
What is the association between cannabis and schizophrenia?
Use of cannabis has the potential for worsening psychotic symptoms and increasing apathy
In addition, there is evidence that the use of cannabis is associated with an earlier onset of schizophrenia
What remains the standard of care for secondary prevention in cryptogenic stroke?
Aspirin (not anticoagulation)
What agent should those with NMO Spectrum Disorder who are AQP4 positive be treated with?
Eculizumab
Options for diagnosis of neurosyphilis?
CSF-VDRL
- specific but not sensitive
CSF FTA-ABS
- sensitive but not specific
What is the role of decolonisation of MRSA patients in the hospital setting?
For hospitalized patients with MRSA infection or MRSA colonization, recommend to initiate a decolonization regimen at the time of hospital discharge
Best studied regimen = 4% rinse-off chlorhexidine for daily bathing or showering, 0.12% chlorhexidine mouthwash twice daily, and 2% nasal mupirocin twice daily, all administered for five days twice per month for six months.
Recommended agents for treating glucocorticoid-induced osteoporosis?
- Bisphosphonates
2. Teriparatide
Who can nintedanib be used for, outside of the IPF population?
Systemic sclerosis - associated ILD, refractory to other measures
What is canakinumab?
What is the role of canakinumab in familial Mediterranean fever?
Anti–IL-1β monoclonal antibody
Has been shown to have benefit in patients with colchicine-resistant familial Mediterranean fever
What current treatment option is there for patients with Chronic spontaneous urticaria whose symptoms are refractory to antihistamines?
Omalizumab - IgE mab
What is the management of severe bleeding in ITP?
Platelet transfusion
Glucocorticoids
IVIG
What are the second line treatment options for refractory ITP?
Splenectomy
Rituximab
TPO agonists (only PBS approved if already had splenectomy or unable to have one)
What type of antibody are warm agglutinins usually?
IgG
What condition is warm AIHA associated with?
CLL
What is the 1st line Rx of warm AIHA?
What are 2nd line options?
Glucocorticoids
(some new data that steroids + ritux is better as 1st line)
2nd line:
Rituximab
Splenectomy
What are delayed haemolytic transfusion reactions in blood transfusion due to?
How can these be prevented?
Secondary (anamnestic) immune responses in patients immunised by previous transfusions, allogeneic stem-cell transplants, or pregnancy.
Extended antigen matching for transfusions
What are the key pathological features of antibody-mediated rejection in renal transplant?
Microvascular inflammation
Peri-tubular capillaritis
C4 deposition in vascular endothelium
What is the general Rx for antibody-mediated rejection in renal transplant?
IV methylpred + IVIG + Plasmapharesis
What is the most prevalent substance use disorder in later life?
Alcohol-use disorder
Which cytokine leads to increased hepcidin in inflammation?
Hepcidin synthesis increases predominantly but not exclusively because of interleukin-6
Most common arterial thrombosis event in APLS?
Stroke/TIA
APLS antibodies?
lupus anticoagulant
anticardiolipin antibodies
anti-β2GPI antibodies
Options for treatment of catastrophic APLS?
Anticoagulants
Glucocorticoids
IVIG
PLEX
*Rituximab if refractory
What defines catastrophic APLS?
Multiple (three or more) organ thromboses (with microthrombotic involvement of at least one organ) developing within 7 days in a patient with persistently positive test results for antiphospholipid antibodies.
Prevention of pregnancy complications in APLS: Mx in..
- Obstetric APLS?
- Thrombotic APLS? (previous non-obstetric thrombosis)
- Ab positive with no thrombosis hx?
- Low-dose aspirin and prophylactic heparin
- Low-dose aspirin and therapeutic-dose heparin, regardless of the pregnancy history.
- CONTROVERSIAL. NEJM suggests low-dose aspirin + prophylactic dose of low-molecular-weight heparin for at least 6 weeks post partum, but minimal data on this
What is the physiologic role of ADAMST13?
ADAMTS13 binds to von Willebrand factor -> leads to proteolysis of the ultralarge von Willebrand factor multimers into smaller molecules with less capacity to bind platelets.
In the absence of ADAMTS13, the ultralarge von Willebrand factor multimers persist, leading to spontaneous platelet adherence and aggregation
In cancer-related VTE, in which malignancies should DOACs certainly NOT be used?
GI malignancies
What is the preferred treatment for immune-mediated aplastic anaemia in young adults?
Bone marrow transplant
In HCT candidates who have aplastic anaemia, what is the treatment whilst awaiting a donor?
Immunosuppression with: - steroids - ATG - Cyclosporin PLUS eltrombopag should be added
What is durvalumab?
Role in Stage 3 unresectable NSCLC?
PD-L1 mab
Prolongs survival in Stage 3 unresectable NSCLC who have not progressed on chemoradiotx
How do PARP inhibitors work?
Why are they suited to BRCA-mutated cancers?
Poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors, such as olaparib, trap PARP on DNA at sites of single-strand breaks
- thereby prevents the repair of the single-strand breaks, and generates double-strand breaks that cannot be repaired accurately
This is particularly useful in tumours that have defects in homologous recombination repair, such as tumors with a mutation in BRCA1 or BRCA2.
The use of PARP inhibitors leads to an accumulation of DNA damage and tumour-cell death.
What are the common toxicities with CAR-T cell therapy?
On target effects ->
- B cell aplasia
- cytokine release syndrome
Neurotoxicity also common - mechanism unknown
How does Venetoclax work?
What is it used for?
Selectively inhibits the anti-apoptotic protein BCL-2
- restores apoptosis
AML and CLL
What are some poor molecular prognostic indicators for CLL? (4)
Chromosome 17p deletion
Mutated TP53
Chromosome 11q deletion
Unmutated IGHV
What type of drugs does urinary alkalisation enhance elimination of?
Weak acids e.g. aspirin
2 key differentiating features between anticholinergic and sympathomimetic toxidromes?
Urinary retention present in anticholinergic
Dry skin -> anticholinergic
Wet skin -> sympathomimetic
When is gastric lavage used for poisoning?
Potentially lethal ingestion within 1 hour
3 common medications that are amenable to dialysing off?
Lithium
Valproate
Salicylates
** needs to be intermittent rather than CRRT
What constitutes a toxic dose of paracetamol?
200mg/kg or 10g in 24 hours
What is the toxic metabolite of paracetamol in OD?
NAPQI
How is NAC thought to work in paracetamol OD?
Within what time frame of ingestion is NAC effective?
Common side effect?
Restores hepatic glutathione stores, lowering NAPQI build-up and subsequent hepatic injury.
Less than 8 hours from time 0
Anaphylactoid reaction -> give antihistamine and slow infusion
Quetiapine OD -> what inotrope is contraindicated?
Adrenaline -> due to alpha blocking effects of quetiapine, can cause paradoxical hypotension
Need to use norad
Which SSRIs are most QT prolonging, increase risk of Torsades? (2)
Citalopram / escitalopram
What is the antidote to TCA OD?
Sodium bicarb
What is flumazenil?
Benzo antidote
Risk of precipitating seizures
Only use in iatrogenic benzo OD
Within what time frame is activated charcoal used for paracetamol OD?
4 hours of ingestion
Who should get thrombophilia testing in DVT/PE?
Young patients with UNPROVOKED proximal DVT/PE
Also need age-appropriate cancer screening
How does heparin work?
Heparins act y binding to antithrombin
- Binding induces a conformational change in AT, which converts AT from a slow to a rapid inactivator of coagulation factors
i. e. enhances natural anticoagulant activity of AT
How does warfarin work?
Why is anticoagulant effect delayed?
Why is there a transient pro-coagulant effect?
Block the function an enzyme in liver, which leads to depletion of vitamin K. Vit K serves as a cofactor for gamma carboxylation of vitamin K-dependent coagulation factors (TV channels), so these factors cannot function properly.
Anticoagulant effect of VKAs is delayed until the previously synthesized, functional clotting factors are cleared from the circulation, as it does not effect existing ones. Factor II takes ~3 days to clear from system, long half life.
The initial prolongation of the PT is due primarily to depletion of factor VII, which has a short half-life (but this does not reflect actual anticoagulant effect yet)
VKAs also inhibit vitamin K-dependent gamma carboxylation of the anticoagulant factors protein S and protein C, thus transient procoagulant effect. Usually not clinically significant
topoi
s phase
vinca
m
taxanes
g2 / m
