🩺 Clinical Pearls: Initial vs Best Diagnostic Test (High-Yield Summary)

🔍 Why It Matters

• Initial test = first step to confirm suspicion or narrow differential (cost-effective, rapid).

• Best test = most accurate or definitive for diagnosis (often confirmatory, more invasive/expensive).

• Know both for shelf exams, Step 2 CK, and real-life triage decisions.

🫀 Cardiology

• Chest pain

  • Initial: ECG, troponins

  • Best: Cardiac catheterization (for ST-elevation MI)

• Suspected aortic dissection

  • Initial: Chest X-ray

  • Best: CT angiography (if stable) or TEE (if unstable)

• Heart failure

  • Initial: BNP or NT-proBNP, Chest X-ray

  • Best: Echocardiogram

• Valvular disease

  • Initial: Auscultation → Echocardiogram

  • Best: Transesophageal echocardiogram (TEE)

• Pericardial effusion

  • Initial: Chest X-ray

  • Best: Echocardiogram

• Rheumatic fever

  • Initial: Throat culture, ASO titer

  • Best: Jones criteria + echo for carditis

• Hypertrophic cardiomyopathy

  • Initial: ECG + Echocardiogram

  • Best: Cardiac MRI

🫁 Pulmonology

• Pulmonary embolism

  • Initial: D-dimer (low-risk), CT angio (high-risk)

  • Best: Pulmonary angiography (rarely used today)

• Suspected pneumonia

  • Initial: Chest X-ray

  • Best: Sputum culture + sensitivity

• COPD exacerbation

  • Initial: Chest X-ray, ABG

  • Best: Pulmonary function tests (PFTs) for diagnosis

• Tuberculosis

  • Initial: PPD or interferon-gamma release assay

  • Best: Sputum AFB culture (3x)

• Interstitial lung disease

  • Initial: Chest X-ray

  • Best: High-resolution CT

• Sleep apnea

  • Initial: Clinical history + STOP-BANG

  • Best: Polysomnography

• Cystic fibrosis

• Initial: Sweat chloride test

• Best: Genetic testing

🧠 Neurology

• First seizure

  • Initial: BMP (check electrolytes), glucose, tox screen

  • Best: MRI brain

• Stroke (acute)

  • Initial: Non-contrast head CT (r/o hemorrhage)

  • Best: Diffusion-weighted MRI

  1. Iron deficiency anemia

  • Initial: CBC + iron panel

  • Best: Bone marrow iron staining (rarely done)

  1. Thalassemia

  • Initial: CBC + smear

  • Best: Hemoglobin electrophoresis

  1. Lymphoma

  • Initial: Lymph node exam + imaging

  • Best: Excisional biopsy

  1. Hemophilia

  • Initial: Coagulation studies (PT/PTT)

  • Best: Factor VIII/IX assay

  1. Polycythemia vera

  • Initial: CBC + JAK2 mutation

  • Best: Bone marrow biopsy

🧬 Hematology/Oncology

• Suspected leukemia

  • Initial: CBC with smear

  • Best: Bone marrow biopsy

• Multiple myeloma

  • Initial: Serum protein electrophoresis (SPEP)

  • Best: Bone marrow biopsy

🧑‍⚕️ Infectious Disease

• HIV

  • Initial: Antigen/antibody test

  • Best: HIV viral load + CD4 count

• Syphilis

  • Initial: RPR or VDRL

  • Best: FTA-ABS (confirmatory)

• Hepatitis B

• Initial: HBsAg, anti-HBs

• Best: HBV DNA (viral load)

1. Hepatitis C

• Initial: HCV antibody

• Best: HCV RNA PCR

1. Sepsis

• Initial: Blood cultures + lactate

• Best: Source-specific imaging/cultures

1. Lyme disease

• Initial: ELISA

• Best: Western blot

1. Malaria

• Initial: Thick and thin blood smear

• Best: PCR (less used in acute settings)

🧠 Psychiatry

• New-onset psychosis

  • Initial: Urine drug screen

  • Best: Psychiatric evaluation after ruling out organic causes

🚨 Emergency Medicine

• Abdominal trauma

  • Initial: FAST ultrasound

  • Best: CT abdomen with contrast

• Suspected ectopic pregnancy

  • Initial: β-hCG + transvaginal ultrasound

  • Best: Diagnostic laparoscopy (if unstable or inconclusive)

🚻 GU / Reproductive

BPH

• Initial: DRE + PSA

• Best: Urodynamic studies (not routine)

1. Prostate cancer

• Initial: PSA + DRE

• Best: Transrectal ultrasound-guided biopsy

1. Testicular cancer

• Initial: Ultrasound

• Best: Orchiectomy + tumor markers (AFP, b-hCG, LDH)

1. Ovarian torsion

• Initial: Pelvic ultrasound with Doppler

• Best: Surgical exploration

1. Ovarian cancer

• Initial: Pelvic ultrasound

• Best: Exploratory laparoscopy + CA-125

🧑‍⚕️ GI / Hepatology

1. GERD

• Initial: Clinical diagnosis + response to PPIs

• Best: 24-hour pH monitoring

1. Peptic ulcer disease

• Initial: Upper endoscopy

• Best: Biopsy (rule out H. pylori or malignancy)

1. Celiac disease

• Initial: tTG-IgA antibodies

• Best: Duodenal biopsy

1. Pancreatitis

• Initial: Lipase

• Best: CT abdomen (if diagnosis unclear or complications suspected)

1. Gallstones

• Initial: RUQ ultrasound

• Best: ERCP (if obstruction suspected)

🩸 Rheumatology

1. SLE

• Initial: ANA

• Best: Anti-dsDNA + Anti-Smith antibodies

1. Rheumatoid arthritis

• Initial: RF + anti-CCP

• Best: MRI (for early joint erosion)

1. Ankylosing spondylitis

• Initial: X-ray sacroiliac joint

• Best: MRI sacroiliac joints

1. Gout

• Initial: Joint aspiration

• Best: Polarized light microscopy (urate crystals)

1. Vasculitis

• Initial: ESR, CRP, ANCA

• Best: Tissue biopsy

👶 Pediatrics / Neonatology

1. Developmental delay

• Initial: Hearing test, vision screen, lead level

• Best: Genetic microarray testing

1. Congenital hypothyroidism

• Initial: TSH/T4 (newborn screen)

• Best: Confirm with repeat TSH and thyroid scan

1. Intussusception

• Initial: Abdominal ultrasound

• Best: Air or contrast enema (diagnostic + therapeutic)

1. Pyloric stenosis

• Initial: Abdominal ultrasound

• Best: Same (no need for confirmatory)

1. Bronchiolitis

• Initial: Clinical diagnosis

• Best: Nasopharyngeal swab for RSV (if needed)

👁 Ophthalmology & ENT

1. Acute angle-closure glaucoma

• Initial: Tonometry

• Best: Gonioscopy

1. Macular degeneration

• Initial: Amsler grid test

• Best: Optical coherence tomography (OCT)

1. Chronic sinusitis

• Initial: Sinus X-ray

• Best: CT scan of sinuses

1. Otitis media

• Initial: Pneumatic otoscopy

• Best: Tympanocentesis (rarely needed)

1. Hearing loss

• Initial: Audiometry

• Best: Brainstem auditory evoked response (if sensorineural suspected in infants)

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Anticoagulants vs Antiplatelets vs Thrombolytics

Mechanisms, Use Cases & High-Yield Step 2 CK Exceptions Explained

🧪 1. Medication Classes Overview

⚙️ 2. Mechanism of Action Comparison

📚 3. Clinical Use Cases

📌 4. Key Step 2/CK + NBME Tips

• Anticoagulants = prevent new clots (do not break existing ones).

• Thrombolytics = used acutely to dissolve thrombi (e.g., ischemic stroke, STEMI without PCI).

• Antiplatelets = arterial clots (e.g., coronary, cerebral) — platelets matter more in high-flow systems.

• Anticoagulants = venous clots (DVT/PE) — coagulation cascade driven.

• Never combine anticoagulants + antiplatelets long term unless absolutely indicated (↑↑ bleeding risk).

• Thrombolytics are contraindicated in most cases of recent surgery, active bleeding, or hemorrhagic stroke history.

🧠 Mnemonic: "PAT-A"

💊 Drug Quick Sheet

🧠 Master Table with EXCEPTIONS and Nuance

🧩 NBME/Step-Style Exceptions

🧬 1. Atrial Fibrillation

• ✅ Use anticoagulants to prevent embolic stroke.

• ❌ Don’t use aspirin alone unless patient is at low CHA₂DS₂-VASc score (e.g., score = 0).

• ⚠️ Mechanical heart valve → must use warfarin (NOT DOACs like apixaban).

🩸 2. Post-MI

• ✅ Dual antiplatelet therapy (DAPT) (aspirin + clopidogrel/ticagrelor) after PCI.

• ❌ Avoid triple therapy (anticoagulant + 2 antiplatelets) unless compelling indication — increased bleeding risk.

• ⚠️ If patient is on warfarin for Afib + just got a stent, limit DAPT duration and monitor closely.

🧠 3. Ischemic Stroke

• ✅ Thrombolytics (tPA) if <4.5 hours, and patient meets criteria.

• ❌ Do NOT give tPA if:

  • BP >185/110

  • INR >1.7

  • Platelets <100k

  • Glucose <50 or >400

  • Stroke >1/3 of MCA territory on CT

🦵 4. DVT/PE

• ✅ Start with heparin, then bridge to warfarin or start DOAC directly.

• ❌ Avoid DOACs in severe renal failure (CrCl <30 mL/min) → use warfarin instead.

👶 5. Pregnancy

• ✅ Use LMWH (enoxaparin) or UFH (doesn’t cross placenta).

• ❌ Avoid warfarin → teratogenic, esp. in 1st trimester.

• ❌ Avoid DOACs → insufficient safety data in pregnancy.

💥 6. Massive PE with Hypotension

• ✅ Use thrombolytics (alteplase) if:

  • Patient is unstable (shock, hypotension)

• ❌ Do not delay lytics for CT angiogram if clinical signs of massive PE and patient crashing.

🛡️ Summary Chart: What's First-Line vs When to Avoid

⚠️ Bonus: Reversal Agents (Must-Know for Emergencies)

🫀 Cardio Question: Empiric Antibiotics in Prosthetic Valve IE

🫀 Cardio Question: Empiric Antibiotics in Prosthetic Valve IE

A 65-year-old man with a mechanical mitral valve presents with fevers, night sweats, and malaise. Blood cultures are pending. He had his valve placed 4 months ago. TEE reveals a vegetation on the prosthetic mitral valve.

Which of the following is the most appropriate empiric antibiotic regimen?

A) Vancomycin + Gentamicin
B) Vancomycin + Cefepime + Rifampin
C) Ampicillin + Ceftriaxone
D) Vancomycin + Piperacillin-Tazobactam
E) Linezolid + Ceftriaxone + Gentamicin

✅ B) Vancomycin + Cefepime + Rifampin

🧠 Here's Why:

This is early-onset prosthetic valve endocarditis (PVE) — occurring within 12 months of valve replacement.

💣 In early PVE, we worry about:

• Staph aureus (MSSA/MRSA)

• Staph epidermidis (coag-neg Staph)

• Gram-negatives (e.g. Pseudomonas)

• Fungal

• Resistant organisms from the OR

🔬 Empiric regimen must cover:

• MRSA → Vancomycin

• Gram-negative rods (including Pseudomonas) → Cefepime

• Biofilm on prosthetic material → Rifampin (excellent penetration + synergy)

💡 Key PVE Rules:

Why not the others?

• A) Vanc + gent = native valve, not broad enough for early PVE

• C) Amp + ceftriaxone = good for enterococcus, not prosthetic valve empiric tx

• D) Vanc + pip-tazo = OK for sepsis, not prosthetic valve IE (no rifampin)

• E) Linezolid = not first-line and doesn't replace vanc for IE

CABG vs PCI

🧠 CABG Indications:

✅ Left main coronary artery disease

50% stenosis of left main = automatic CABG

✅ Triple-vessel disease

70% stenosis in all three major vessels (RCA, LAD, LCx)
Especially with ↓ EF or diabetes

✅ 2-vessel disease involving proximal LAD + ↓ EF or diabetes

✅ Failed PCI or restenosis after PCI

✅ High SYNTAX score

Used in cardiology to assess lesion complexity (not tested heavily, but FYI)

🧠 PCI (Stenting) is preferred when:

✅ Single- or dual-vessel disease not involving left main
✅ Low SYNTAX score
✅ STEMI/NSTEMI with culprit lesion
✅ Unable to tolerate surgery (frail, comorbidities)

💡 USMLE Pro Tips:

• CABG is not used in acute STEMI unless anatomy requires it or PCI fails

• In patients with diabetes + multivessel disease, CABG improves long-term mortality more than PCI

• If you see "proximal LAD" or "left main" = think CABG

🫀 Cardio Question:

A 62-year-old man with type 2 diabetes, hypertension, and hyperlipidemia presents with exertional chest pain for the past 3 months. He reports the pain occurs after climbing one flight of stairs and resolves with rest. A stress echocardiogram shows reversible ischemia in the anterior and lateral walls. Cardiac catheterization shows:

• 80% stenosis of the proximal LAD

• 75% stenosis of the LCx

• 70% stenosis of the RCA

What is the best next step in management?

A) PCI with drug-eluting stents
B) CABG
C) Medical therapy alone
D) Repeat stress testing in 6 months
E) Implantable cardioverter-defibrillator (ICD)

Answer: B) CABG

🔍 Why?

This is a classic vignette for CABG over PCI:

✅ Triple-vessel disease
✅ Involves proximal LAD
✅ Patient has diabetes — big NBME keyword
✅ Reversible ischemia on stress testing

🔑 All of these stack the deck toward CABG, which improves long-term survival in diabetics with multivessel coronary disease far more than PCI.

🚫 Why not the other choices?

• A) PCI – not preferred in triple-vessel disease + diabetes

• C) Medical therapy – ischemia is too severe

• D) Repeat stress – not needed; cath already confirms diagnosis

• E) ICD – no indication; EF not mentioned, no arrhythmias or VT/VF