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Preclerkship > Host defence & neoplasia > Flashcards

Host defence & neoplasia Flashcards

1
Q

Epstein Barr Virus predisposes to what cancer(s), esp in immunodeficient patients?

A

Non-Hodgkin Lymphoma

Hodgkin Lymphoma

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2
Q

Increased cancer risk in HIV/AIDS is likely due to what? Evidence?

A

immunosuppression, immunologic stimulation, oncogenic infections

Immunodeficiency (because similar to transplant pts, reduced in cART treatment)
HIV doesn’t incorporate into specific genome locations, HIV DNA/proteins not in most malignant cells
However doesn’t seem to be correlated to CD4+ count (more related to chronic antigenic stimulation, inflammation, cytokines; also more oncogenic virus infections)

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3
Q

Leading cause of death of HIV pts in developed countries

A

Cancer

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4
Q

AIDS-defining cancers?

A

Kaposi’s sarcoma, aggressive B-cell NH lymphoma, invasive cervical cancer

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5
Q

Name 5 non-AIDS defining cancers that are common HIV-associated cancers

A 
Lung
Anal
Oropharyngeal
Hepatocellular
Hodgkin's lymphoma
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6
Q

What are some oncogenic viruses that may have particularly high incidence in AIDS pts

A

KSHV (HHV8), HPV, HBV = sexually-transmitted

HBV/HCV spread by needle-sharing

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7
Q

Kaposi sarcoma is what type of tumor? Caused by what?

A

Malignant spindle cell tumor

Human Herpesvirus 8 (Kaposi sarcoma-associated herpesvirus, KSHV)

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8
Q

Where are lesions in Kaposi sarcoma?

A

Cutaneous/oral plaques

can also involve internal organs: GI tract, lymph nodes, lungs, bones

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9
Q

KSHV mainly transmitted via

A

Saliva

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10
Q

What do Kaposi Sarcoma lesions look like?

A

Changes over time
Papular –> plaques/nodules that can coalesce or ulcerate
Light brown/pink –> darker violet; do not blanch
Most commonly lesions on trunk, extremities, face; oral lesions on hard palate

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11
Q 
HHV 1 = 
HHV 2 = 
HHV 3 = 
HHV 4 = 
HHV 5 = 
HHV 8 =
A 
HSV1
HSV2
Varicella-zoster virus
Epstein-Barr virus
Human cytomegalovirus
Kaposi's sarcoma-associated herpesvirus
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12
Q

HSV-1 & -2 both cause oral, ocular, and genital infection, but which more common for which

A

1 –> oral/eye

2 –> genital

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13
Q

Herpes keratitis

A

Corneal infection (HSV-1)

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14
Q

First HSV-1 oral infection is usually ____ whereas recurrences are usually ____

A 
Herpetic gingivostomatitis (oral mucosa/gingiva)
Herpes labialis
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15
Q

Neonatal HSV is usually which? Results?

A

HSV-2 (transmitted via vaginal secretions)

Mucocutaneous vesicles/CNA involvement –> major morbidity/mortality

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16
Q

What severe conditions can herpes lead to in HIV patients?

A

Esophagitis, colitis, perianal ulcers
Pneumonia
Encephalitis, meningitis

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17
Q

How is herpes zoster distinct from HSV on clinical exam?

A

Herpes zoster rarely recurs
More severe pain
larger lesions groups, distribution along dermatome, usually not crossing the midline

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18
Q

Culture/PCR/antigen detection tests should be done for HSV infections in which populations?

A

Neonates
Immunocompromised
Pregnant
CNS/severe disease

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19
Q

Clusters of vesicles/ulcers on an erythematous base on genitals is most likely

A

HSV (probably -2)

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20
Q

What is the mechanism of action of acyclovir? Why is it generally considered to be a “clean” drug?

A 
Chain termination (no 3' OH), dGTP analogue
Prodrug is inactive, only activated in virally infected cells (viral kinase)
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21
Q

Name 3 oral medicals that can be used for HSV, VSV, EBV

A

Acyclovir (oral or IV)
Famciclovir (prodrug of penciclovir, more bioavailable than acyclovir orally)
Valacyclovir (prodrug of acyclovir, more bioavailable orally)

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22
Q

Treatment for keratoconjunctivitis caused by HSV?

A

Trifluridine (+optho consult)

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23
Q

Treatment for keratoconjunctivitis caused by HSV?

A

Trifluridine (+optho consult)

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24
Q

Treatment for neonates, immunosuppressed pts, or CNS spread of HSV?

A

IV acyclovir

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25
Q

Chicken pox is caused by what?

A

Varicella-zoster virus (HHV-3)

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26
Q

When is varicella contagious? Route of transmission?

A

From 48 hours before lesions appear until final lesions crusted
Extremely contagious via mucosal spread (droplet/airborne) + direct contact

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27
Q

Can vaccinated children develop varicella?

A

Yes, “breakthrough” varicella

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28
Q

Prodrome of varicella starts how long after exposure? New lesions continue to appear for how long?

A

1-3 weeks

New lesions for ~5 days, most crusted by 6th day

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29
Q

In what populations might oral treatment be necessary for varicella? IV?

A

Oral (valacyclovir, famciclovir, acyclovir): 12+ yo, eczema, chronic lung disease, pregnancy (TORCH!)
IV: immunocompromised children & adults, severe infection in pregnant women

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30
Q

What should a high-risk individual exposed to varicella receive?

A

VariZIG (postexposure prophylaxis) ASAP!

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31
Q

How is varicella prevented?

A

LAVV (live attenuated varicella vaccine)

  • contraindicated if acutely ill, immunocompromised, pregnancy
  • high-dose version to prevent Herpes zoster, although recombinant vaccine preferred for that noe
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32
Q

What is herpes zoster? (pathophys)

AKA shingles

A

Reactivation of VSV from posterior dorsal root ganglion –> inflames sensory root ganglia, skin of associated dermatome
(sometimes posterior/ant grey matter horns, meninges, dorsal/ventral roots)

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33
Q

What is the first sign of herpes zoster? How long does it take the rash to appear?

A

Dysesthesis/stabbing pain usually along dermatome
Followed in 2-3 days by rash (crops of vesicles on erythematous base), unilateral, not crossing midline, lesions form for 3-5 days

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34
Q

Recurrence of herpes zoster is rare, but ___ is more common

A

Postherpetic neuralgia (can last indefinitely and be debilitating)

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35
Q

Treatment of postherpetic neuralgia

A

Pregabalin (Lyrica), gabapentin, TCAs, topical lidocaine/capsaicin, botox

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36
Q

Oral antivirals for herpes zoster should be started when?

A

(Acyclovir, famciclovir, valacyclovir)
Most effective when started during prodrome, less effective if started >72 hrs after lesions appear (sooner = better!)
*IV in severely immunocompromised pts

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37
Q

In what populations is the recombinant zoster vaccine recommended?

A

Immunocompetent adults 50+ (regardless of whether they’ve had the virus or not)
Immunocompromised adults considered on case-by-case basis (CANNOT have LAZV)

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38
Q

Which 2 shingles vaccines are available in Canada? Which is recommended for whom?

A

Zostavax II = Live Attenuated Zoster Vaccine, LAZV, 1 dose
Shingrix = Recombinant Zoster Vaccine, RZV, 2 doses
RZV recommended for ages 50+ even if you received LZV before!! LZV in immunoCOMPETENT people only if RZV not available

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39
Q

Epstein Barr Virus infects what cells?

A

B lymphocytes (remains for life w/ intermittent asymptomatic shedding, >90% of adults seropositive)

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40
Q

Incubation of infectious mononucleosis

A

1-2 months

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41
Q

Triad of symptoms in mono?

A

Fever + pharyngitis + adenopathy

+fatigue which is worst in first 2-3 wks but can last months

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42
Q

___ occurs in 50% of patients with mono

___ in 95% of pts

A

Splenomegaly in 50%

Temporarily elevated liver enzymes

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43
Q

2 differentials considered in pt presenting with EBV-like symptoms

A

R/o HIV

Test for strep, though presence of strep DOES NOT EXCLUDE MONO

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44
Q

What is seen on CBC of pt with EBV?

A

High numbers of morphologically atypical WBCs (heterogenous, diff than leukemia)

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45
Q

Serologic testing for EBV

A

Monospot: heterophilic ABs (*FNs possible if tested too early)
Specific EBV Abs (IgM for primary infection, some IgGs persist for lyfe)

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46
Q

Pts with mono should avoid ___ for at least a month. Why?

A

Heavy lifting/contact sports

Splenomegaly (risk of rupture)

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47
Q

What meds can be used for EBV?

A

Antivirals not recommended

steroids only for complications

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48
Q

What oncologic emergency is most common after chemo is started for hematological malignancy?

A

Tumor lysis syndrome

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49
Q

TLS pathophys

A

Rapid destruction of tumor cells –> release of intracellular components (K, PO4^3-, uric acid) –> AKI, renal failure

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50
Q

Summarize the electrolyte imbalances in TLS?

A

PUKE Calcium
Phosphate, Uric acid (nucleotides), K are Elevated
Calcium decreased (binds phosphate)

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51
Q

Consequences of electrolyte imbalances in TLS?

A

PO4 –> low Ca –> crystals obstruct renal tubules (AKI); hypocalcemia –> tetany, muscle cramps, seizures
Hyperkalemia –> arrhythmia, nausea/vomiting, diarrhea, seizures, sudden cardiac death
Nucleic acids –> hyperuricemia –> urate nephropathy (crystals in kidney stroma) –> AKI

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52
Q

Management of TLS

A

Fluid therapy (K-free!)
RRT may be required
Uric acid reduction (allopurinol prophylaxis, prevents synth; rasburicase breaks down for treatment or high-risk prophylaxis)
Oral phosphate binders, may require some Ca, glucose/insulin for hyperkalemia

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53
Q

Oncologic emergency most common in acute leukemia (AML > ALL)

A

Leukostasis: blasts increase blood viscosity –> microvascular obstruction –> tissue hypoxemia/infarction (–> end-organ damage; resp, ophtho, neuro, etc)

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54
Q

Treatment of leukostasis

A

Inductive chemo, leukapheresis, hydroxyurea

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55
Q

Back pain in a cancer patient is ___ until proven otherwise

Usually caused by?

A

SC compression!

Metastasis to bone (e.g. prostate, breast, lung cancers)

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56
Q

Urgent diagnostics for possible SC compression in cancer patient

A

Urgent MRI w/ contrast

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57
Q

Treatment of SC compression?

A

Palliative (symptom management)
Steroids even if don’t have MRI (treat edema encroaching upon SC)
Surgery + radiotherapy (unless not surgical candidate)

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58
Q

Some things that may make someone with SC compression not a surgical candidate and just XRT instead?

A

Multiple lesions spaced out
Life expectancy <3 months
ECOC 3-4 (poor performance status)
Extensive extraaxial metastases

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59
Q

___ in SC compression means surgery is advisable if possible

A

Spinal instability (caused by 2/3 of the anterior, middle, and posterior spinal columns compromised)

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60
Q

Brain mets come from what primary cancers? Are they more common than primary brain cancers?

A

10x more common than primary (better periph treatments making it more common)
30% lung/breast cancer, 70% melanoma

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61
Q

Median survival of SC compression oncology pt

A

3 mo

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62
Q

Prognosis of brain metastasis

A

1-2 mo w/out treatment

1.5 years w/ treatment

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63
Q

Default treatment for brain mets

A

Dexamethasone for symptomatic relief

```
Stereotactic Radiosurgery
if very large mass or causing mass effect then do Sx
~~~

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64
Q

WBRT vs SRS

A

Whole brain radiotherapy = standard dose

Stereotactic radiosurgery = higher dose, smaller area; may work even in radiation-resistant tumors

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65
Q

Treatment of bone metastasis

A

NSAIDS, steroids, narcotics
Bisphophonates
Local XRT (reduces cell counts though because usually met is in axial skeleton where most BM is)
Brachytherapy
Kyphoplasty to restore height after fractures

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66
Q

Oncologic emergency most commonly caused by non small cell lung cancer?

A

SVCO

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67
Q

Presentation of pt w/ SVCO?

A

DYSPNEA (airway compression = main emergency!)
Swelling of face/arms
R chest mass

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68
Q

Diagnosis of SVCO?

A

CXR & CT will show mass

Tissue biopsy to confirm to stage tumor

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69
Q

Treatment of SVCO?

A

Often palliative, occasionally not
Chemo, XRT
Stent = most rapid palliation
Steroids for symptoms

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70
Q

Diagnostic criteria for febrile neutropenia

A

Neutrophils <1.5 x 10^9 (esp if <0.5)

Fever >38 (2x, 1 hr apart) or >38.3 x1

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71
Q

FN infections are typically __ or ___

A

Bacteria or fingi

Esp Gram + bacteria (indwelling catheters/PICC lines)

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72
Q

How do you decide if a pt w/ febrile neutropenia should be managed inpatient or outpatient?

A

Inpatient IV ABs unless

  • low risk (no medical comorbidities, clinically stable, anticipated neutropenia <7 days)
  • pt easy to contact and close to hospital w/ transportation
  • able to tolerate oral meds
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73
Q

Antibiotics for FN:

A

Inpatient IV: any of pip/taz, carbapenem, ceftazidime, cefepime; + vanco if skin/soft tissue infection, catheter-associated, pneumonia, hemodynamic instability, MRSA…
Outpatient oral: ciprofloxacin + amoxicillin-clavuanate

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74
Q

What do you do if FN persists after 4-7 days of treatment?

A

Add broad-spectrum fungal coverage

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75
Q

In all cases of fever + neutropenia consider ____ and ____ immediately

A

Sepsis (full workup)

Treat w/ antibiotics immediately even if non-infectious cause postulated

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76
Q

2 strategies to PREVENT febrile neutropenia during chemo?

A

1) Antibiotic prophylaxis (hematological malignancies)

2) Recombinant granulocyte-colony stimulating factor (rG-CSF) - no mortality benefit

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77
Q

Symptoms of hypercalcemia of malignancy

A

Stones (nephrolithiasis)
Bones (fractures/pain)
Groans (abdominal gramps, nausea, ileus, constipation)
Thrones (polyuria/dehydration)
Psychiatric overtones (lethargy, depression, psychosis, stupor/coma)

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78
Q

What correction has to be done when measuring Ca?

A

Albumin (decrease of 10 –> increase Ca by 0.2)

*most advanced cancer pts are hypoalbuminemic

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79
Q

Treatments for hypercalcemia of malignancy?

A

IV normal saline +/- furosemide (forced diuresis)
Bisphosphonates (pamidronate, zoledronate)
Dialysis if severe
2nd line: glucocorticoids, calcitonin

80
Q

Define primary, secondary, and tertiary prevention

A 
Primary = before disease occurs
Secondary = early detection of disease (subclinical) = screening
Tertiary = treating established disease to reduce severity/sequelae
81
Q

Cancer screening programs in Ontario (4)

A

Breast
Lung
Colon
Cervical

82
Q

The vast majority of women who have an abnormal mammogram…

A

Do NOT have breast cancer (0.5% of total screened women have BC, but 8% screen positive)

83
Q

Average- and high-risk Ontario Breast Screening Program guidelines?

A

Average: 50-74yo, mammography every 2 years

High-risk: from 30-69 get annual mammogram + breast MRI (or U/S if MRI not appropriate)

84
Q

What makes someone “high risk” for breast cancer

A

Known gene mutation (BRCA1/2, TP53, etc)
First degree relative has known mutation & pt has received genetic counselling and refuses testing
>25% lifetime risk based on family Hx (genetics clinic assessment)
Radiation therapy to chest for other cancer <30yo, 8+ years ago

85
Q

Possible next steps after abnormal mammogram

A

More mammography, U/S, MRI, biopsies

86
Q

Ontario Lung Cancer Screening includes who?

A

55-74 yo

Smoked cigarettes daily for cumulative 20+ years

87
Q

Lung cancer screening test =

A

low-dose CT scan

88
Q

Cervical cancer screening guidelines

A

Pap every 3 years from ages 25-70 (if 3 neg in past decade at 70)

89
Q

Women who are not sexually active by the age of initiation [should/should not] delay cervical cancer screening until sexually active.

A

Should!

90
Q

Should you have a pap during pregnancy?

A

Yes if it’s due at that time

91
Q

Women who are immunocompromised should receive ___ screening for cervical cancer

A

Annual

92
Q

ColonCancerCheck Ontario average risk definition + screening

A

50-74yo, no 1st degree relative w/ CC
No PMHx of pre-cancerous colorectal polyps requiring surveillance or IBD

Fecal immunochemical test (FIT) every 2 years (if abnormal, colonoscopy within 8 wks)
OR sigmoidoscopy every 10 yrs

93
Q

ColonCancerCheck Ontario HIGH risk definition + screening

A

FmHx colon cancer in 1st-degree relative(s)

Colonoscopies starting 50yo or 10 years before relative’s age of diagnosis
every 5 yrs of relative diagnosed before 60, otherwise every 10 yrs

94
Q

ColonCancerCheck Ontario doesn’t screen who?

A

People @ high risk w/ hereditary colorectal cancer syndromes (FAP, Lynch syndrome)
These people must be managed by geneticist/gastro

95
Q

Is FIT more or less sensitive for colon cancer screening than FOBT?

A

FIT

96
Q

3 lung risks caused by asbestos exposure

A

asbestosis, lung cancer, and mesothelioma (which can be of the pleura as well as the peritoneum)

97
Q

Characteristics that point twd a potential hereditary cancer disorder
(4 for individual + fam characteristics)

A

Multiple primary tumors (same/diff/paired organs)
Young age at diagnosis (<50)
Rare histology
Sex not usually expected for that cancer

Fam characteristics:
- 1st degree relatives w/ same/related tumor or suspicious signs, family members w/ tumors belonging to known familial syndrome, rare cancers

98
Q

HER2 is an ____ related to ___ cancer but it’s NOT ____

A

Oncogene
Breast cancer
NOT hereditary (acquired)

99
Q

Define HBOC syndrome

A

Hereditary Breast & Ovarian Cancer Syndrome
Autosomal dominant
Behind up to 10% of BECAUSE
Mutations in one of several genes, half the time it’s BRCA1 or BRCA2 (tumor suppressors)

100
Q

HBOC increases the risk of what cancers? (5)

A 
Breast!!
Ovarian!!
Prostate
Fallopian tube
Pancreatic
101
Q

Define Lynch syndrome

A

Hereditary nonpolyposis colon cancer syndrome
Familial cancer syndrome caused by autosomal dominant mutation in DNA MMR
–> adenomas –> can rapidly progress to CRC
Also predisposes to endometrial, gastric, ovarian cancer

102
Q

Define Li-Fraumeni syndrome

A

autosomal dominant mutation of p53 tumor suppressor
(one abnormal copy inherited, 2nd hit –> multiple malignancies at early age; breast, osteosarcoma, leukemia/lymphoma, brain tumors, adrenocortical carcinoma)
BLAST53: Breast/Brain, Leukemia/Lymphoma, Adrenocortical carcinoma, Sarcoma, Tp53

103
Q

Familial adenomatous polyposis (mutation, symptoms, treatment)

A

Autosomal dominant mutations in APC tumor suppressor gene (25% spontaneous, 75% have family Hx)
Polyposis appears in teens/20s –> const/diarrhea, blood in stool, abdo pain
100% risk of CRC by 45yo! Can get prophylactic proctocolectomy + ileoanal anastomosis

104
Q

Why do people with FAP need upper endoscopies as well?

A

Increased risk of gastric/duodenal cancers

105
Q

Highly aggressive B cell lymphoma associated with EBV

AIDS-defining cancer

A

Burkitt lymphoma

106
Q

Specific type of pneumonia which is an AIDS-defining illness, the most common opp infection in HIV patients, and the most common cause of death in AIDS.
What is unusual about treatment?

A 
Pneumocystis jirovecii
(fungus but doesn't respond to antifungals, need AB treatment)
107
Q

3 steps to reduce maternal-infant HIV transmission

A

1) ARVT in mother
2) C-section
3) Treat bebe

108
Q

How do HIV virions leave the cell?

A

Budding (enveloped virus)

109
Q

What has to bind in order for HIV to attach/penetrate host cell

A

HIV Env = gp41 + gp120
gp120 binds CD4 on host cell –> conformation changes –> diff part of gp120 binds coreceptor(s) (CCR5 and/or CXCR4 depending on strain)

110
Q

HIV effects on humoral immunity

A

B cell hyperplasia –> lymphadenopathy

Hyperglobulinemia for previously-encountered Ags

111
Q

HIV-2 restricted almost completely to…

A

West Africa

112
Q

What is anemia of chronic disease?

A

normocytic –> microcytic anemia

Inflammatory cytokines upregulate hepcidin –> more storage, less absorption (binds/downregulates ferroportin)

113
Q

Most sensitive/specific test for HIV in first few weeks of infection?

A

Plasma HIV RNA

114
Q

Recommended diagnostic test for HIV?

A

Combined antigen/antibody immunoassay

(antigen = p24 = core viral protein, detectable before Abs during “window period”

115
Q

CD4 count = ?

Normal = ?

A

WBC x %lymphocytes x %CD4

Normal = 750 +/- 250 /ul (500-1000)

116
Q

3 stages of HIV based on CD4 count

A

Stage 1 = 500+
Stage 2 = 200-499
Stage 3 <200

117
Q

What does the CD4/CD8 ratio tell us in HIV?

A

Measure of immune dysfunction

Normally >1, decreases in AIDS (CD4 destruction and/or CD8 proliferation)

118
Q

What is IRIS?

A

Immune reconstitution inflammatory syndrome = clinical deterioration as CD4 rises because of IS responding to subclinical opp infections
Paradoxical: infection previously diagnosed
Masked IRIS: opportunistic infection previously unknown

119
Q

Common med regimes for ART

A

3 NRTIs OR 2 NRTIs + 1 NNRTS OR 1 PI OR 1 INI

120
Q

Name 3 NRTIs

A

Abacavir
Zidovudine
Lamivudine

121
Q

Name the 4 stages of the HIV life cycle at which meds can intervene, and which meds

A

Attachment & penetration (CCR5-antagonists, fusion inhibitors)
Reverse transcription (NRTIs, NtRTIs, NNRTIs)
Integration (INIs)
Post-translational modifications (protease inhibitors)

122
Q

HIV resistance to meds comes from mutations in which gene?

A

Pol gene (encodes RT/integrase/protease)

123
Q

Which ART is given to pregnant HIV+ women during labour and orally to neonate after birth?

A

Zidovudine

124
Q

Common PrEP med combo?

A

TDF/FTC = tenofovir (NtRTI) + emtricitabine (NRTIs)

125
Q

How long to continue prep after exposure?

A

1 month (if exposure won’t repeat again)

126
Q

PEP should contain __ ARTs and be started within ___ hrs and continued for ___

A

3+
72 hrs (MAX, sooner is much better!!!)
28 days

127
Q

TH1 cells are more involved in the ___ immune response, where TH2 cells are more involved in ____ immunity

A 
TH1 = cellular; more involved in autoimmunity
TH2 = humoral; more involved in allergies
128
Q

Name 4 SMALL cutaneous lesions (<0.5 cm) & their large counterparts

A

Macule vs Patch (flat)
Papule vs nodule (raised, solid) or plaque (superficially raised)
Vesicle/pustule (clear vs pus) vs Bulla

129
Q

Superficial dilated BV =

A

telangectasia

130
Q

Purpura are ___ lesions that ___ under presure

A

Red-purple

Do not blanch

131
Q

Adenocarcinoma forms from ___ cells

A

Glandular epithelial cells

132
Q

Viruses contribute to ___ of all cancers

A

20%

133
Q

The majority of primary immunodeficiencies involve defective ___ immunity. 2 examples?

A

Humoral immunity
Selective IgA deficiency
Common variable immunodeficiency (CVID)

134
Q

Labs show what in CVID?

A

Decreased levels of all Igs and plasma cells

Normal B/T cells on flow cytometry

135
Q

5 categories of primary immunodeficiencies

A 
Humoral
Cellular
Combined
Phagocytic 
Complement
136
Q

CVID usually diagnosed when? Heritability?

A 
20-40yo
Usually sporadic (no FMHx)
137
Q

Name 3 combined immunodeficiencies

A

SCID
Wiskott-Aldrich syndrome
Hyper-IgM syndrome

138
Q

Define SCID. Prognosis if untreated?

A

Severe combined immunodeficiency

Multiple mutations –> defective B&T cells –> death in 1 year if untreated

139
Q

Genetics of Wiskott-Aldrich syndrome?

A

Mutation in WASp gene (X-linked recessive)
WASp is important in cytoskeleton (platelets, T cells, NK cells, phagocytes)
Small mutation –> thrombocytopenia, large –> WAS

140
Q

Ig levels in WAS

A

low IgG/IgM, high IgE/IgA

141
Q

WAS AKA?

A

Eczema-thrombocytopenia-immunodeficiency syndrome

Triad = eczema + purpura + recurrent OIs

142
Q

Hyper-IgM syndrome bloodwork?

A

High IgM, low IgG/IgA/IgE (class-switching defect, impaired interaction b/w B&T cells, usually CD40 ligant)

143
Q

Consequences of complement protein primary immunodeficiency? (2 pathways)

A

Defective opsonization/phagocytosis/lysis –> recurrent infection
Reduced clearance of Ag-Ab complexes –> autoimmunity, SLE, glomerulonephritis

144
Q

Immune deficiency that presents <6mo old is likely to be a ___ defect

A

T-cell (maternal Abs until 6-9 mo)

145
Q

T-cell IDs: Cervical lymph nodes/adenoids/tonsillar tissues ____ despite recurrent infections

A

Small or absent

146
Q

Aplastic anemia =

A

Pancytopenia due to BM deficiency

147
Q

Screening for SCID

A
  • SCID screening is performed using the same blood samples that are collected for routine newborn screening.
  • NSO uses a DNA test (real-time polymerase chain reaction) to measure T-cell receptor excision circles (TRECs), which are small pieces of DNA made during the maturation of the T-cells of the immune system. Newborns with SCID lack or have low TRECs.
148
Q

Which Igs cross placenta? Breast milk?

A

IgG crosses placenta

IgA secreted into breast milk

149
Q

Define adjuvant & neo-adjuvant chemo

A

Neo –> shrinks tumors to optimize surg/XRT

Adjuvant –> after surg/XRT

150
Q

Scales used to describe pt functioning when choosing chemo (or when describing outcomes in trial)

A

Karnofsky for adults

Lansky for children

151
Q

What category of chemo drugs causes single-strand breaks and/or crosslinking of DNA
Incld mitrogen mustards, nitrosoureas, alkyl sulfonates,
Cyclophosphamide

A

Alkylating agents

152
Q

Chemo category of drugs that imitate building blocks of DNA. 2 examples?

A

Anti-metabolites:
Methotrexate
6-mercaptopurine (purine anlogue)

153
Q

Plant alkloid chemos, including vinca alkaloids and taxanes work how? examples?

A

Disrupt microtubules (mitotic spindle, cytoskeleton, etc)
Vinca alkaloids: vincristine, vinblastine (prevent MT assembly)
Taxanes: Paclitaxel (taxol) prevents MT disassembly

154
Q

What ABs can be used for chemo? What do they do?

A

Intercalating DNA or oxidation/forming free rads
Anthracyclines (e.g. doxorubicin)
Actinomycin
Bleomycin

155
Q

What class of chemo interferes w/ enzymes maintaining DNA topology

A

Topoisomerase I & II inhibitors

156
Q

4 examples of targeted chemo therapies

A

Anti-angiogenesis (Bevacizumab targets VEGF)
Tyrosine kinase inhibitors (Imatinib - bcr-abl)
Receptor mediated apoptosis (Rituximab, CD20)
Immune therapy (pembrolizumab, PD-L1)

157
Q

Drugs ending in -ib are…

A

Small molecule inhibitors

158
Q

Max tolerated chemo dose usually defined by

A

BM suppression (RBCs/anemia, WBCs/infections, platelets/bleeding)

159
Q

BM counts start falling ____ after chemo, hit nadir around ____

A

3-5 days, nadir around 7-10 days

160
Q

Chemo can cause nausea/vomiting and ___

N/V happens when? ___ when?

A

Mucositis worst 5-7 days after chemo

Nausea acute within 24 hours, delayed >1 week slater

161
Q

radioactive isotopes put near/inside tumor =

A

brachytherapy

162
Q

Carcinoma before and after permeating the basement membrane?

A

Carcinoma in situ

Invasive carcinoma

163
Q

Most carcinomas metastasize via…

A

Lymphatic spread

164
Q

Define organ tropism in the context of cancer

A

Tendency for certain cancers to spread to particular organs

target organ usually the first capillary bed encountered by disseminated cells

165
Q

name 3 common sites for cancer metastasis

A

Liver, Bone, Brain

166
Q

what 3 cancers metastasize to the liver?

A

Colon, Stomach, Pancreas

Cancers Spread Progressively to the liver

167
Q

Specific grading systems for breast/prostate cancer

A

Nottingham/Gleason

168
Q

AJCC grading system for nonhematological malignancies: define lowest and highest

A 
G1 = low-grade = well-differentiated
G4 = high-grade = undifferentiated/anaplastic
169
Q

Is tumor staging or grading better for prognostic value?

A

Staging is a better indicator!! (higher stage is worse than higher grade)

170
Q

in TNM staging, each letter has ____ prognostic value. ___ & ___ are the most important for prognosis

A

Independent

N&M most important

171
Q

Staging:
T =
N =
M =

A 
T = extent of primary tumor (Tis = in situ, 1-4 where 4 = infiltration of neighbouring organs)
N = regional lymph node involvement (N0-3)
M = distant metastases (0-1, x = unknown)
172
Q

What are the 3 non small cell lung cancers? Which is most common in women/nonsmokers? Which is central?

A

Lung adenocarcinoma, lung squamous cell carcinoma, large cell carcinoma
Squamous = “sentral”
adenocarcinoma most common in women/nonsmokers; better prognosis

173
Q

Lung cancer most commonly metastasizes where?

A 
BLAB
Bone
Liver
Adrenals
Brain
174
Q

Steps after incidentally finding solidary pulmonary nodule on CXR?

A
  1. Compare with previous imaging if available (if stable 2-3yrs, no f/u reqd)
  2. Chest CT, assess malignancy risk
  3. High risk –> surgical excision; intermediate –> PET or biopsy, serial CT scans, or reassurance depending on size
175
Q

Is upper or lower/middle lobe location of a pulmonary nodule higher cancer risk?

A

Upper lobe = higher risk

176
Q

AJCC staging
0 =
I-III =
IV =

A 
0 = carcinoma in situ
I-III = spread to nearby tissues
IV = distant metastasis
177
Q

Lynch syndrome involves mutation of a protein involved in ____.
AKA _____
Predisposes to ____

A

DNA repair
Hereditary non-polyposis colorectal cancer (HNPCC)
Colorectal cancer
(There is also an increased risk of developing other types of cancers, such as endometrial (uterine), stomach, breast, ovarian, small bowel (intestinal), pancreatic, prostate, urinary tract, liver, kidney, and bile duct cancers.)

178
Q

Prostate cancer is most commonly a _____ expressing ____ in the ____ zone

A

Adenocarcinoma
Expressing PSA
Peripheral zone (posterior lobe)

179
Q

The ___ zone is the main area felt against the rectum on DRE

A

Peripheral

180
Q

Common metastasis sites for prostate cancer

A

Lung
Liver
Bone

181
Q

Utility of DRE for screening for prostate cancer

A

NOT effective
Low sensitivity even in symptomatic pts
High specificity if irregular/nodular & painless

182
Q

How would BPH feel on prostate exam?

A

Homogenous, rubbery, nontender

183
Q

How would prostatitis feel on prostate exam?

A

Painful/swollen

184
Q

___ of abnormal PSAs are actually due to cancer

A

25%

Can be high due to BPH, UTI, prostatitis, trauma, manipulation of prostate gland

185
Q

APC (gene) stands for what? Mutated in what disease?

A

Adenomatous polyposis coli gene

mutated in FAP

186
Q

Name 3 genes that when mutated can lead to polyps/colorectal cancer

A

APC
p-53
K-RAS (oncogene)

187
Q

Colon cancer patterns in ascending vs descending colon

A

Ascending: grows BEYOND mucosa (no obstruction)
Descending: lumen narrowing (napkin-ring constriction)

188
Q

Apple-core sign is seen where?

A

Descending colon cancer

Barium enema x-ray

189
Q

AB prophylaxis for post-op infections

A

start before incision (within 1 hour, 2 hrs for vancomycin/fluoroquinones), continue postoperatively for <24 hrs (48 for cardiothoracic surgery)

190
Q

__ is used most often for surgical prophylaxis in patients with no history of beta-lactam allergy, no history of MRSA infection, and no surgical sites in which the most probable organisms that are not covered by cefazolin alone (e.g., appendectomy, colorectal).

If MRSA risk, ___ may be used

A

Cefazolin (1st-gen cephalosporin)

Vancomycin

191
Q

Define sepsis & septic shock according to the 3rd international consensus definition

A

Sepsis = dysregulated response to infection –> tissue/organ damage + organ dysfunction
Septic shock = above + need vasopressors for MAP >65 & persistent lactic acidosis despite fluid resuscitation

192
Q

4 SIRS criteria for systemic inflammatory response syndrome? How many do you need?

A

2 + suspected infection

Temp (>38 or <36), HR >90, RR >20, WBC high/low or high bands

193
Q

What is the SOFA score?

A

Sequential Organ Failure Assessment score

Calculate after 24 hrs in ICU then every 48 hrs to predict MORTALITY (not diagnostic)

194
Q

Most common etiology of sepsis

A

Pneumonia

195
Q

Hour 1 bundle for sepsis/septic shock

A

1) Blood cultures
2) Serum lactate
3) IV crystalloids (30 mg/kg)
4) Vasopressors
5) Broad-spectrum ABs (as soon as cultures drawn)

196
Q

What vasopressors are used in shock?

A

1st line = norepinephrine
2nd = +vasopressin OR +continuous IV epinephrine
3rd = and/or dopamine, dobutamine
+corticosteroids if refractory or adrenal insufficiency

197
Q

Common empiric AB regime for sepsis in pt w/ unknown risk factors

A

Vancomycin
+ one of the following:
- broad-spectrum carbapenem
- extended-range penicillin/B-lactamase inhibitor (Pip/taz, ticarcillin/clavulanate)
- 3rd or 4th gen cephalosporine (cefepime, ceftriaxone, etc.)

Preclerkship (25 decks)

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