1. Stable angina - 3% risk per year of progression to MI/death
2. Treatment for angina:
- Decrease O2 demand: b-blockers, ca-channel blockers
- Increase O2 supply: nitrates
- Anticoagulate: aspirin, plavix in people s/p stent or who can't take aspirin
- Statin
- ACE/ARB in diabetics or people with HF
3. STEMI vs NSTEMI
STEMI = transmural ischemia or infarction
NSTEMI = subendomyocardial ischemia
4. Chest pain in the ER
- Around 15% of people with chest pain in the ER are having an MI
- New 1mm ST elevation: 80% prevalence of MI
- New ST depression/inversion: 20%
- No new changes in patient with known CAD: 4%
- No new changes in a patient without known CAD: 2%
5. Utility of physical exam findings for diagnosing MI {JAMA}

6. Cardiac enzymes
- Troponin and CKMB are both very sensitive and specific for MI. CKMB is not useful after 24 hours.
- Renal insufficiency can cause falsely elevated troponin, but even in people with high baseline troponin it should still rise and fall in acute MI
7. GERD vs MI
- Most helpful history: pain that is recurrent (>1/month), persists for several hours, awakens someone at night, provoked by recumbency, assoc with heartburn/regurg is much more likely to be GERD
- Symptoms that are NOT helpful for distinguishing the two (surprisingly): radiation to L arm, exacerbation with exercise, relief with nitroglycerin.
- Repeat: relief with nitroglycerin is useless in differentiating angina from GERD or other causes of chest pain
8. When to scope someone with GERD:
- Symptoms of complicated disease (dysphagia, extra-esophageal symptoms, bleeding, weight loss, chest pain of unclear etiology)
- Risk for Barett's (long standing reflux symptoms)
- Patients require long-term treatment
- Poor response to treatment
9. When to get pH monitoring:
- GERD sx + normal endoscopy
- Monitoring therapy in refractory cases
10. Surgery: 
- Limited role
- ONe study found a higher mortality of those treated with surgery at 11 years than those treated medically, #needed to harm = 8.3

1. Chest pain: pivotal questions for diagnosis: 
- acuity of onset
- pleuritic vs non-pleuritic
2. Differential: 
- Skin: zoster
- Breast: fibroadenoma, gynecomastia
- MSK: costochondritis, precordial catch syndrome, pec muscle strain, rib fracture, spine spondylosis (C4 to T6), myositis
- Esophagus: spasm, GERD, tear/rupture, cancer, medication-esophagitis (K-dur, tetracycline, bisphosphonates)
- GI: peptic ulcers, liver abscess (any abscess under diaphragm), pancreatitis, GB disease,
- Lung: PE, pneumonia (viral/bacterial infection of parenchyma or pleura), cancer (of pleura or parenchyma), pHTN, serositis of pleura
- Cardiac: MI, pericarditis, myocarditis
- Mediastinum: lymphoma, thymoma
- Aorta: AAA, dissection
- Psych
3. Stable angina with normal coronaries
- LVH
- Bad anemia
- Aortic stenosis (more O2 demand, increased diastolic filling pressure that compresses coronaries and compromises perfusion) (source)
- Tachycardia
- Heart failure (filling pressures)
4. Atypical presentations of stable angina
- Atypical triggers: cold weather, emotional stress, large meals
- Atypical symptoms: dyspnea, nausea/indigestion, pain elsewhere (jaw, neck, teeth, back, abdomen), palpitations, syncope, weakness/fatigue
- In women, they tend to describe the pain as more "burning" or "tender"
5. Risk factors for CAD
- Age > 55 (men), >65 (women)
- Chronic diseases (HTN, DM, etc), smoking, fam hx of CAD at <55 men and <65 women
- Bad lipids
- Hyperhomocysteinemia (causes endothelial damage)
- Elevated CRP
- Plasma fibrinogen
- Microalbuminemia
6. Likelihood of CAD
- Sx: substernal location, precipitated by exercise, relieved by rest
-0/3 sx = asymptomatic, 1/3 sx = nonanginal, 2/3 atypical angina, 3/3 typical angina

Overall prevalence of CAD at autopsy = asymptomatic 

7. Initial workup

- Lipids/A1c/glucose: tells you about risk factor diseases

- Hemoglobin/TSH: tells you alternate causes of angina 

- Resting EKG: look for current/past ischemia/infarction

- Cardiac enzymes

8. Stress test

- Purpose: diagnose CAD, determine whether they should get meds only, stent or CABG

- How it works: induce ischemia (exercise, dobutamine, adenosine, dipyridamole), detect ischemia (EKG, echo, nuclear imaging) 

- When not to get it: when you're so sure that they have CAD that you can go straight to cath, or they aren't a candidate for stent or CABG anyways 

9. When to get the more expensive imaging stress tests 

- Abnormal resting EKG

- High risk patients (where you need a high NPV to definitively rule it out) 

- Previous stent/cabg

10. When to go to the cath lab

- Stress test showing severe ischemia or ischemia at low stress

- Stress test with uncertain diagnosis

- Disabling symptoms despite treatment

- Clinical heart failure 

1. Febrile neutropenia
- Defined as T>38 for 1 hour or any T>38.3 + ANC <1500
- Mild neutropenia (ANC <1500)
- Moderate neutropenia (ANC <1000) - susceptibility to infection increases
- Severe (ANC <500) - lose ability to control endogenous flora, risk of death markedly increased
2. Management
- Mild: outpatient antibiotics
- Moderate/severe neutropenic fever: hospitalization with IV antibiotics
- If someone is really sick (ANC <100, shock vitals, invasive fungal infection, uncontrolled primary disease, pneumonia) consider adding G-CSF
3. Antibiotic choice 
- In chemotherapy patients: most common site of mucositis is GI tract, most frequently involved = GNR (pseudomonas), however more and more it's shifting to gram+ infections.
- Given this, recommend monotherapy with anti-psedudomonal b-lactam (zosyn, mero, cefepime)
- If there is evidence of pneumonia, sepsis, soft-tissue infection or line infection, shock vitals, severe mucositis, history of resistant staph/strep infections, recent fluroquinolone prophylaxis, add vanc
- If there is evidence of necrotizing mucositis, or abscess assoc with GI tract (periodontal, perirectal), intrabdominal or pelvic infection, typhlitis (necrotizing neutropenic colitis) or anaerobic bacteremia, add flagyl
- If neutropenic fever persists despite broad spectrum antibiotic therapy, add antifungals
4. Peripheral arterial disease. 
- PAD with intermittent claudication have 20% 5-year risk of nonfatal MI/stroke and 15-30% 5-year risk of death due to cardiovascular causes.
- PAD with critical limb ischemia have a 25% 1-year risk of cardiovascular death
- PAD with intermittent claudication - at 5 years, 70-80% will have stable symptoms, 10-20% progress to worsening claudication, 1-2% progress to critical limb ischemia with rest pain, nonhealing ulcers, and tissue gangrene that may lead to amputation.
5. Mortality and Cardiovascular Risk Across the Ankle-Arm Index Spectrum {Circulation}
Methods and Results— We examined total and cardiovascular mortality and cardiovascular events across the AAI spectrum among 5748 participants in the Cardiovascular Health Study (CHS). The mean age of the sample population was 73±6 years, and the sample included 3289 women (57%) and 883 blacks (15%). The median duration of follow-up was 11.1 (0.1 to 12) years for mortality and 9.6 (0.1 to 12.1) years for cardiovascular events. There were 2311 deaths (953 of which were cardiovascular) and 1491 cardiovascular events during follow-up. After adjustment for potential confounders, AAI measurements ≤0.60 (hazard ratio [HR] 1.82, 95% CI 1.42 to 2.32), 0.61 to 0.7 (HR 2.08, 95% CI 1.61 to 2.69), 0.71 to 0.8 (HR 1.80, 95% CI 1.44 to 2.26), 0.81 to 0.9 (HR 1.73 95% CI 1.43 to 2.11), 0.91 to 1.0 (HR 1.40, 95% CI 1.20 to 1.63), and >1.40 (HR 1.57, 95% CI 1.07 to 2.31) were associated with higher mortality risk from all causes compared with the referent group (AAI 1.11 to 1.20). The pattern was similar for cardiovascular mortality. For cardiovascular events, risk was higher at all AAI levels <1 but not for AAI levels >1.4 (HR 1.00, 95% CI 0.57 to 1.74). The association of a high AAI with mortality was stronger in men than in women and in younger than in older cohort members.
6. Stent vs tPA for MI
- Stents have better outcomes
- Door to balloon time (stent) goal <90 mins
- Door to needle time (tPA) goal <30 mins
7. Bacillary angiomatosis
- Typically caused by bartonella henselae and bartonella quntana
- Generally affects immunosuppressed patients (AIDS, liquid cancers, chemo, transplant)
- Systemic symptoms-- malaise, fever, weight loss, abdominal pain.
- Lesions (large, pedunculated exophytic papule with collarette of scale) appear on the skin and in the viscera, and are extremely prone to hemorrhage when biopsied
- Dx is with tissue biopsy -  microscopic ID of organisms and angiomatous histology
- Tx with antibiotics
8. Diarrhea in AIDS patients 
- CD4 < 180 - tend to have a more persistent course with parasitic infections.
- Oocysts on modified acid fast stain - cryptosporidum parum or isospora belli, however crypto is much more common
- MAI, usually assoc with lung infections in immunocompetent patients with chronic lung dx, can cause disseminated disease and invade intestinal epithelium in people who are very immune compromised and caused malabsorption.
- Spores in the stool- microsporidia organisms like enterocytozoon bieneusi and encephalitozoon intestinalis, very rare, can cause diarrhea in immunocompetent and severe/persistent diarrhea/malnutrition in immunocompromised.

9. Strep bovis

- S. gallolyticus (S. bovis type 1) is one of the 4 major species of group D strep and is associated with a significantly increased risk of colorectal cancer and endocarditis compared to S. Bovis type II. 

10. Drugs and toxins that cause liver injury

- Drugs that cause direct toxic effects (dose dependent, short latent periods: tylenol, carbon tetrachloride (CCl4), tetracycline, amanita phalloides

- Drugs that cause idiosyncratic reactions (not dose dependent, variable latent periods): isoniazid, chlorpromazine, halothane, antiretrovirals 

- Drugs that cause cholestatic liver damage: anabolic steroids, erythromycin, chlorpromazine, nitrofurantoin 

- Drugs that cause fatty liver: antiretrovirals, tetracycline, valproate 

- Drugs that cause hepatitis (histology: hepatic cell necrosis, panlobular mononuclear infiltration): isoniazid, halothane, phenytoin, alpha-methyldopa. 

- Drugs that cause fulminant liver failure: tylenol, CCl4, amanita

- Drugs that cause granulomatous liver injury: allopurinol, phenylbutazone. TB infection can also cause this. 

1. CAP
- Viruses that cause viral pneumonia - influenza A/B, para flu, adeno, rsv
- No recent exposure to serious organisms (no hospital stay within 90 days, not living in a nursing home, doesn't go to dialysis frequently) can treat as outpatient without coverage of hardcore gram negatives
- Low suspicion of resistance: can tx with z pack or doxy, if you suspect resistance can give respiratory quinolone or z pack plus cephalosporin
2. Inherited thrombophilias
- high risk mutations/deficincies : antithrombin, protein c and s deficiency, homozygous factor v or prothrombin
- low risk: heterozygous factor v
3. Anti phospholipid syndrome
- For diagnosis need both a vascular event or pregnancy morbidity and 2 positive anti phospholipid Ab tests at least 12 weeks apart
- Can occur alone or with other autoimmune disease (lupus)
4. When to screen for inherited thrombophilias: 
- first clot at age <50 without provoking factor
- family history
- recurrent clots
- unusual sites (i.e. mesentery)
5 Don't screen for inherited thrombophilias in the following
- Clots in the context of a reason (cancer, immobility, disease process known to cause clotting)
- Arterial clots, (inherited dx tend not to cause arterial clots)
- Upper limb clots (likely catheter releated) this is controversial.
6. When to anticoagulate people with inherited thrombophilias
- Asymptomatic/never had a clot: don't anticoagulate them (evidence grade 1c, unless they are going through a hyper coagulable period (surgery, pregnancy)
- History of one clot - treat as any other first clot : If provoked, 3 mos of anticoagulation, then stop. If unprovoked, give 3 mos anticoagulation, check bleeding risk, if bleed risk not high then treat forever, if bleeding risk high then stop at 3 months.
- If they clot multiple times, they've bought themselves a lifetime of coumadin.
7. What to anticoagulate with
- lovenox not tested in thrombophilia patients
- riviaroxaban/dabigatran not tested in thrombophilias
- recommend warfarin
8. Crich: (vs trach)
- Cricoid is the only complete tracheal ring; if you push the plastic against it, it's more likely to go down towards the trachea
- Lower risk of bleed as it avoids going through thyroid tissue
- Accessible in an emergency
- Its proximity to vocal cords leads to increased risk of subglottic stenosis, fibrosis over time. Should be converted to trach within 24-48 hours.
9. Trach (vs ETT)
- Usually for people who can't be off the ventilator
- People really shouldn't be on the ETT for longer than a week or so-- any longer and they should switch to trach
-  Shorter straw, less dead space
- Allow better suctioning
- More comfortable
- Decreased risk of subglottic stensois
- Allows speaking
- More secure
- These things all increase likelihood/ease of weaning vent
- If you see someone bleeding massively after they get a trach put it, they may have a tracheal-innominate fistula. If this happens, take out the trach, put your finger through the tracheostomy, and pull forward (as the vessel is usually anterior). Then put in an ETT tube with a cuff, inflate it, and go to the OR.
10. How to wean
- Weaning ETT/trial extubation: patient requires 3 things: adequate GCS to follow commands, strong cough, ability to control secretions. Deflate the cuff, see if you can hear air leak around it. If not, keep in the tube, if so, they can probably be extubated.
- Weaning trach: downsize the trach. Cap the trach to see how they do, then take it out.

1. Localization of ischemia: 
- ST elevation and q-waves are localizing. T-wave depression and ST depression are NOT localizing-- just because they are in leads of a certain distribution means nothing.
- Seeing reciprocal ST depressions in the opposite territory increases likelihood of MI, vs something like pericarditis which can have a similar clinical presentation and ST-elevation on EKG.
- Anterior: V1-V4 = LAD
- Lateral: I, aVL, V5, V6 = Lateral circumflex
- Inferior (meaning inferior part of septum): II, III, aVF = R coronary, lateral circumflex
- Posterior: see large R in V1, ST depression V1 and V2 = R coronary
2. Coronary anatomy 

- R acute marginal (labeled here as R marginal)- comes off RCA, supplies RV free wall. Thus if you clot off the RCA high enough, you will infarct out the RV as well as the posteroinferior part of the septum

- Posterior descending - comes off RCA in 80-90% of people. So inferior MIs are generally RCA infarcts. In the rest of the people, it comes off the circumflex from the LAD. 

- LAD - gives off septal branch that supplies the septum, and diagonal branches & obtuse marginals (labeled here as L marginals) that supply the lateral wall. 

3. When you see inverted T-waves, ST-elevations, and Q waves all at the same time on the same EKG- think resolving MI (~24 hours out). When the MI starts to resolve, T-waves start flipping back. 

4. If you suspect R side MI: 

- Put the leads on the R side of the chest, V1 in the center V6 on the lateral R. If you see ST elevation in V4, that is very characteristic of R MI. 

- Do NOT give nitroglycerin-- because the R side will be preload-dependent, if you give nitro (venodilator), blood will pool in the legs and you will have decreased preload and they will lose their pressure. 

- On the contrary, in L side MI, blood backs into the lungs as the L side fails, so venodilation will be good because it pulls blood out of the lungs. Probably still drops preload but in this case the cost-benefit is a little different. 

5. Things that mimic an MI: 

- Repolarization changes (benign early repolarization/BER) can cause ST elevation (usually concave up): common in young, healthy males. If your suspicion for MI is low, you can walk the patient. Changes in HR will often make the repolarization pattern change, often the ST elevation will disappear. If you have reason to suspect someone is actually having a STEMI, don't walk them. 

- Pericarditis: will see concomitant PR depression and ST elevation. ST elevation will often be diffuse, and there will be no reciprocal ST depressions. Also, PR elevation & ST depression in aVR are both very characteristic of pericarditis and are a rarely seen in MI or BER. 

- Dig toxicity: will cause rounded ST depression 

6. Electrolytes

- High K: peaked T, flattened P, eventually torsades 

- Low K: U-waves

- Hypercalcemia: short QT

- Hypocalcemia: long QT 

- Common causes of hypocalcemia: giant transfusions, as the citrate in the transfused blood chelates off all the Calcium. Watch out in MICU patients who get admitted for GI bleeds and get a lot of transfusions. Can also occur after parathyroidectomy. 

7. PE

- Most common EKG change? Sinus tach #trickquestion

- Can also see S1Q3T3: s-wave in I, Q wave in III, T wave inversion in III. 

8. Other EKG findings;: 

- Osborne wave: tiny peak after narrow QRS = hypothermia 

- Delta wave: WPW. Often accompanied by a short PR interval (the electrical signal bypasses) 

9. Pacemakers

- Looks like a LBB pattern, because they typically pace from RV apex

- Most modern pacemakers are dual chamber pacing and sensing; if they sense no P, they will give an atrial pace, await QRS; if they sense no QRS, they will give a ventricular pace. If they sense an intact P or QRS, they will allow the natural rhythm to occur. 

- Bi-ventricular pacemakers will have narrow-complex QRS because they are pacing bilaterally. 

10. Phosphate replenishing

- K-Phos: don't use if your K is >4.5 as it raises your K by around 0.2

- NaPhs: current national shortage. 

1. Hepatitis C 
- Peg-Interferon A + Ribavirin treatment led to undetectable HCV RNA level after treatment in 40% of  patients with genotype 1 infection and 75% of patients with genotype 2 or 3 infection.
- If they have genotype 1, trials have shown that boceprevir or telaprevir added to the above regimen can achieve higher remission rates (60s-70s) in genotype 1 patients; importantly, the people in those trials were all treatment-naive. It's unclear what the results would have been if it had been tried on people who had failed other regimens.
- Amazing Trial in NEJM found Daclatasvir plus Sofosbuvir could lead to viral remission rates of 98% in people with genotype 1 (both treatment naive and people who had failed other treatments), 92% in genotype 2 and 89% of genotype 3 patients. Of note, this study was non-blinded and did not have controls.
2. Lack of blinding/allocation concealment does not lead to biased results in studies with objectively measured outcomes. In studies with subjective outcomes, non-blinding does lead to exaggerations of effect outcomes. {BMJ} analysis of 146 meta-analyses containing 1346 randomized controlled trails.
3. Atrial enlargement 
- R atrial enlargement: large biphasic P with tall initial component on V1, Tall P "p pulmonale"  (>2.5 little boxes) in lead II
- L atrial enlargemnet: large biphasic P with wide terminal component on V2, Wide P "p mitrale" (>3 little boxes)
4. LVH 
- Ischemia can occur with increased demand (ie hypertrophy) and with decreased supply. Thus you can get an MI with patent coronaries if your hypertrophy is bad enough.
- Look for signs of ischemia in V5/V6
Some criteria:
- S of V1 + R of V5 or V6 >35 mm
- R in aVL > 11 mm
- R in 1 and S in 3 add to > 28 mm in men, > 20 mm in women.
5. Ischemia: 
- Can occur in the presence of a normal EKG - this happens most commonly with lateral wall MIs; treatment is still warranted if clinical suspicion is high enough. If an older guy with a history of multiple MIs and a medical history full of coronary equivalents comes stumbling into your ER, sweating, short of breath, telling you he has crushing substernal chest pain radiating down his left arm that feels just like his last MI, take him to the cath lab irrespective of what the EKG shows.
- Coronary angioplasty should happen as soon as possible. Door to balloon time should be <90 minutes, <60 minutes ideally. After around 18-24 hours, there is no benefit from intervention. If anything, the ischemic tissue is less elastic and more likely to be traumatized by the cath wires, leading to tamponade and perforation.
6. In ischemia, there is a predictable temporal progression of EKG findings: first you will see hyperacute T-waves:
- T-waves are tall, look like peaked T-waves, postulated to originate from localized hyperkalemia.

- This is a transient effect that occurs in the beginning and lasts only ~30 minutes, so most people coming in from outside of the hospital won't show up until after this period is over, so you won't see this pattern on EKG
7. In ischemia, next you will see Symmetrical T-wave inversions. 

- Asymmetric t-wave inversions are more characteristic of strain.

- Flat or minimal T-wave inversions may be a normal variant.

- Other causes of T-wave inversions: LVH, electrolyte disturbances, digoxin, head injury 

- Neurogenic T-waves: deep, symmetric T-wave inversions in all leads, can occur in acute stroke and SAH 

8. In ischemia, finally you will see ST segment depression 

- Straight and downsloping are more likely to reflect true ischemia, while upsloping ST-depression more likely to be due to repolarization variation 

9. EKG markers of myocardial injury: ST elevation

- ST elevation indicating STEMI is usually 3-5 mm high; ST elevations that are really high (like 10mm) are characteristic of vasospasm/prinzmetal's angina. 

- Earliest sign of infarction. 

- "Tombstone" shaped ST-elevation more common in acute MI, ventricular aneurysm 

- Scooping, concave-up ST elevation more likely reflective of a benign process like benign early repolarization (BER), pericarditis. Although can still be an acute MI 

(source)

10. EKG marker of infarction: Q-waves

- Must be at least 1mm wide or 1/3 height of the R wave to be considered pathological. 

1.Hemochromatosis arthritis presents clinically like RA but radiographically like OA
- Clinically: affects MCP, wrist, hip, knee (MCP and wrist are rarely affected in OA)
- Radiographically: osteophytes and join space narrowing (not seen with RA)
2. Inclusion body myositis
- ANA negative asymmetric inflammatory myositis in a middle aged man - think this
- affects distal and proximal muscles.
- usually symmetric but asymmetric in up to 15% of cases
- chronic and insidious course
- usually do not have extramuscular/systemic manifestations or symptoms.
- almost always ANA negative
3. Polymyositis
- Weakness of proximal muscles
- Acute or subacute course
- Frequently has extramuscular manifestations
- usually ANA+
4. Joint aspirate white count
<200 : normal
200-5000: gout
5,000-50,000: pseudo gout
>50,000: septic joint until proven otherwise, start broad spectrum antibiotics
5. Fluids in sickle cell patients

This quote below is from a “consult the expert column” in the Sickle Cell Newsletter for December 2008  http://listserv.emory.edu/cgi-bin/wa?A2=ind0812&L=sicklecell&T=0&P=70  (The Sickle Cell Information Center, PO Box 109, Grady Memorial Hospital, 80 Jesse Hill Jr Drive SE, Atlanta, GA 30303). 

“evidence comes from the 60, 70, and 80s…The principle is simple and based on the biochemistry of sickle hemoglobin polymerization and physiology. The rate of hemoglobin polymerization (sickling) is strongly dependent on the concentration of hemoglobin in the solution. This is exponential with the rate changing with the 25th to 35th power of the hemoglobin concentration. This means that sickling of intact sickle cells is very dependent on the concentration of hemoglobin within the red cell (MCHC)…..

         There are many other very important considerations. Almost all adults and most children with sickle cell anemia have renal tubular damage which prevents them from retaining free water. They cannot concentrate their urine so the loose large volumes of free water in the kidneys every day. The kidneys handle sodium normally and because of the anemia, they then to hold on to sodium they take in. When the patient becomes ill, they often decrease their intake of fluids and become free water dehydrated which greatly increases the sickling of their red cells and the potential for complications...sodium level will be 145 or higher when they come in crisis and 130 to 135 is ideal for reducing sickling without side effects.

             [a possible complication of normal saline?]  The third problem is the misconception about blood volume. Normal saline is used is a rehydrating solution because most dehydrated patients have reduced blood volume. Because of the chronic life-long anemia, the blood volume in sickle cell patients is normal or increased. This has been measured but the studies are old.  Administration of normal saline is potentially very dangerous in sickle cell patients during complications. Their plasma volume is increased, they have high cardiac demand from the anemia, and we are administering opiates that decrease cardiac output. Sodium will be retained and normal saline may precipitate heart failure.

             Very young children and individuals with Hb SC and Sbeta thalassemia may have less renal damage and be better able to retain water. Individuals with renal disease also may become hyponatremic with D5W. The best solutions for them are d5w ¼ normal or 1/3 normal saline.  I feel the best approach is to use one of the three and monitor the serum sodium, rather than to give a physiologically inappropriate replacement fluid (normal saline).

            There is no large clinical trial that directly addresses the issue.  The first reference is Guy et al In vitro and In vivo effect of hypotonic saline on the sickle phenomenon. Amer J Med Sci 266:267-277, 1973. It is also addressed indirectly in the article by Rosa et al in New Engl J Med 303:1138-1143, 1980. I don't think there will be further studies because people either believe the dogma and would consider it unimportant and unethical or such a small benefit off low cost so it is not important enough to spend the money required to test the hypothesis. There are recent attempts to capitalize on this effect by chronically decreasing the MCHC: chlotrimazole, Magnesium, and others. The studies on this are in process…"

    James Eckman, MD and Lewis Hsu, MD PhD

6. Coag negative staph

-Considered low virulence organisms
-Coagulase binds prothrombin and forms staphylothrombin, which is capable of cleaving fibrinogen to fibrin (just like thrmobin...) This fibrin coats the bacteria and makes them resistant to phagocytosis, which is why they are believed to be more virulent.
7. Staph hemolyticus: 
-Coag negative staph (CONS)
-More virulent than other CONS, perhaps because they make hemolysin (hemolysins are able to lyse RBCs to gain iron, often a rate-limiting nutrient for bacterial growth. An in vitro study of e.coli a-hemolysin from the early 1980s was shown to cripple leukocytes, significantly reducing phagocytosis and chemotaxis). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC347633/
-Can cause meningitis, cellulitis, prosthetic joint infections, bacteremia, and rarely, endocarditis (http://www.ncbi.nlm.nih.gov/pubmed?cmd=retrieve&list_uids=17141458&dopt=abstract).
-Known for their remarkable resistance patterns-- commonly R to methicillin, clindamycin, cephalosporins, macrolides, tetracyclines, sulfonamides, fluroquinolones, and even glycopeptide antibiotics (vanc, teicoplanin), which most staph bacteria are susceptible to.
-From a Japanese group that sequenced the entire genome: "A comparative analysis of the genomes of S.haemolyticus, S.aureus, and S.epidermidis elucidated differences in their biological and genetic characteristics and pathogenic potentials. We identified as many as 82 insertion sequences in the S.haemolyticus chromosome that probably mediated frequent genomic rearrangements, resulting in phenotypic diversification of the strain. Such rearrangements could have brought genomic plasticity to this species and contributed to its acquisition of antibiotic resistance." Takeuchi F et al, Whole-genome sequencing of staphylococcus haemolyticus uncovers the extreme plasticity of its genome and the evolution of human-colonizing staphylococcal species. J Bacteriol. 2005 Nov;187(21):7292-308.
 8. Interstitial lung disease DDx: 
- Idiopathic
- Sarcoid
- Pneumonitis (birdkeeper's lung, etc)
- Occupational: beryllium, coal dust,
- Rheum: mixed connective tissue disease!! (hence why people need regular PFTs after this diagnosis) scleroderma
9. Other facts about ILD: 
- Hear fine rales on exam "velco rales"
- Aspergillus balls can grow in the spaces left over after honeycombing
10. Basal Bolus insulin > sliding scale 
Umpierrez GE, et al Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes (RABBIT 2 trial). Diabetes Care. 2007 Sep;30(9):2181-6.
RESEARCH DESIGN AND METHODS:
We conducted a prospective, multicenter, randomized trial to compare the efficacy and safety of a basal-bolus insulin regimen with that of sliding-scale regular insulin (SSI) in patients with type 2 diabetes. A total of 130 insulin-naive patients were randomized to receive glargine and glulisine (n = 65) or a standard SSI protocol (n = 65). Glargine was given once daily and glulisine before meals at a starting dose of 0.4 units x kg(-1) x day(-1) for blood glucose 140-200 mg/dl or 0.5 units x kg(-1) x day(-1) for blood glucose 201-400 mg/dl. SSI was given four times per day for blood glucose >140 mg/dl.
RESULTS:
The mean admission blood glucose was 229 +/- 6 mg/dl and A1C 8.8 +/- 2%. A blood glucose target of <140 mg/dl was achieved in 66% of patients in the glargine and glulisine group and in 38% of those in the SSI group. The mean daily blood glucose between groups ranged from 23 to 58 mg/dl, with an overall blood glucose difference of 27 mg/dl (P < 0.01). Despite increasing insulin doses, 14% of patients treated with SSI remained with blood glucose >240 mg/dl. There were no differences in the rate of hypoglycemia or length of hospital stay.
CONCLUSIONS:
Treatment with insulin glargine and glulisine resulted in significant improvement in glycemic control compared with that achieved with the use of SSI alone. Our study indicates that a basal-bolus insulin regimen is preferred over SSI in the management of non-critically ill, hospitalized patients with type 2 diabetes.

1. Hypoammonemia

Path of ammonia - (associated illnesses)
- Ammonia made by gut enterocytes from glutamine or bacteria that metabolize nitrogen products like ingested protein, urea.
- Travel from portal vein to liver (portosystemic shunt)
- Metabolized in liver to urea (liver failure like Reyes, cirrhosis, inborn urea cycle disorders like citrullinemia or ornithine transcarbalymase deficiency)
- Urea is transported to kidneys and excreted (renal failure, distal renal tubular acidosis)
Other causes of hyperammonemia
- Organic acidemia/aciduria - disorders of amino acid metabolism (ie branched chain amino acids) leading to accumulation of organic acids in the blood and urine. Clinically manifest with high gap anion acidosis, ketoacidosis, pancytopenia (possibly these amino products inhibit hematological cell maturation) and hyperammonemia because coenzyme A derivatives accumulate and inhibit carbamyl phosphate synthase.
- Drugs- salicylates, antiepileptics (Depakote!!, carbamazepine, topamax), transexamic acid, some chemo agents (5-FU, rituximab)
- Pregnancy
2. Acute liver failure:
-Defined as INR >1.5 + any hepatic encephalopathy
-Fulminant: development of encephalopathy within 8 weeks of onset of hepatic sx
-Subfulminant: development after 8 but before 26 weeks.
3. DDx fulminant hepatic failure:
-Viral: Hepatidities, CMV, EBV, VZV, HSV, hemorrhagic fevers (ebola, marburg, lassa), adenovirus
-Drugs: Tylenol, hypersensitivity drug reactions, Isoniazid, weight-loss drugs (oxyelite pro)
-Toxins: Alcohol, Amanita, B.cereus toxin
-Vascular: Budd-Chiari, Ischemia of any cause, HELLP
-Metabolic: Wilsons, Reyes, Eclampsia, acute fatty liver of pregnancy, congenital enzymatic diseases (galactosemia, fructose intolerance, tyrosinemia)
-Miscellaneous: cancer (breast, small cell, lymphoma, myeloma, melanoma), autoimmune hepatitis
4. Transaminases & diagnosing liver disease 
<100: think hemochromatosis, chronic hep B/C, fatty liver
100-300: NASH, alcoholic hepatitis, autoimmune
>1000: toxins, acute hepatitis, autoimmune, ischemia
5. Figuring out timing of liver failure: 
- PT/INR half life of a few days, albumin has a half life of 21 days
- Albumin is low- are they malnourished or are they in liver failure? Look at factors, including factor VIII. It's not made in the liver, if its low you have malnutrition.
- Someone who appears well is more likely to have acute liver failure, someone with stigmata of cirrhosis (palmar erythema, spider veins, ascites)
6. Wilsons disease: 
-1:30,000-1:100,000
-Usually affects people aged 5-35, although can be older or younger; depends on penetrance.
-Children tend to present with more hepatic disease (jaundice, hepatosplenomegaly)
-Adults tend to present with more neuropsych disease (dysarthria, tremors, parkinsoninan sx, dementia)
-98% of people with neurological symptoms will have kayser-fleischer rings, however you need a slit-lamp exam as this is not always seen with a normal exam.
-In a study comparing wilsons disease to other causes of acute liver failure, the following were found to be most predictive of Wilsons: low Hb, low AST/ALT, very high urine copper, low serum ceruloplasmin (however this is an acute phase reactant)
-Labs: Alk phos is not that high-- it can be normal or sub-normal (Alk Phos/Tbili ratio <4), AST/ALT ratio >2
-Coombs-negative hemolytic anemia is also characteristic
-Thrombocytopenia from splenomegaly
7. Treatment for wilsons disease: 
-Fulminant Wilsons (defined as fulminant hepatic failure at first presentation, INR>2, hemolytic anemia or neuropsych symptoms): Transplant. You can try to bridge to transplant with plasma exchange or dialysis. Survival after transplant for wilsons is excellent- - 88% at 1 year, 80% at 5 years, kids do even better than adults.
-Decompensated Wilsons (defined as acute on chronic, no hemolytic anemia or neuropsych sx): may respond to chelation therapy
-Early Wilsons (few symptoms): chelation agents.
8. Chelation agents: 
-Trientine is now used as first-line by most hepatologists; it doesn't work quite as well as D-penicillamine but it has so many fewer side effects that it's preferred
-D-penicilliamine is second line despite its effectiveness because of its significant side effects- nephrotic syndrome & aplastic anemia (requiring regular CBC/BMP) and patients feel really bad
-Dimercaprol (not used anymore)
9. Transfusion strategies for acute upper gastrointestinal bleeding {RCT, NEJM, n=921}
Villanueva C et al, N Engl J Med. 2013 Jan 3;368(1):11-21.
METHODS:
We enrolled 921 patients with severe acute upper gastrointestinal bleeding and randomly assigned 461 of them to a restrictive strategy (transfusion when the hemoglobin level fell below 7 g per deciliter) and 460 to a liberal strategy (transfusion when the hemoglobin fell below 9 g per deciliter). Randomization was stratified according to the presence or absence of liver cirrhosis.
RESULTS:
A total of 225 patients assigned to the restrictive strategy (51%), as compared with 61 assigned to the liberal strategy (14%), did not receive transfusions (P<0.001) [corrected].The probability of survival at 6 weeks was higher in the restrictive-strategy group than in the liberal-strategy group (95% vs. 91%; hazard ratio for death with restrictive strategy, 0.55; 95% confidence interval [CI], 0.33 to 0.92; P=0.02). Further bleeding occurred in 10% of the patients in the restrictive-strategy group as compared with 16% of the patients in the liberal-strategy group (P=0.01), and adverse events occurred in 40% as compared with 48% (P=0.02). The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer (hazard ratio, 0.70; 95% CI, 0.26 to 1.25) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease (hazard ratio, 0.30; 95% CI, 0.11 to 0.85), but not in those with cirrhosis and Child-Pugh class C disease (hazard ratio, 1.04; 95% CI, 0.45 to 2.37). Within the first 5 days, the portal-pressure gradient increased significantly in patients assigned to the liberal strategy (P=0.03) but not in those assigned to the restrictive strategy.
CONCLUSIONS:
As compared with a liberal transfusion strategy, a restrictive strategy significantly improved outcomes in patients with acute upper gastrointestinal bleeding.
- Potentially due to increased portal pressure through varices with the blood transfusions/volume.
- Octreotide
10. Advice from rounds 
- B-blockers and surgery: if someone is on a b-blocker, they should definitely stay on it. There is some data that optimizing people to a HR of 60s to 70s may lead to better outcomes.
- Lovenox is better than heparin in people with cancer
- Sgarbossa's criteria: identifying ischemia in the context of LBBB.
- Most common cause of INR spikes: chronic CHF (2/2 liver congestion), diarrhea (loss of gut flora), those 2 are much more common than warfarin o/d's
- In bleeding peptic ulcers, people should be on a nexium drip for 72 hours and then BID PO dosing afterwards.

1. Potassium replenishment
- K-lor capsules are very large, for many people they sit at the LES and cause erosive esophagitis. Doxycycline does the same thing. If someone needs K, you're better off giving liquid K (although it tastes bad).
- 0.1 mEq K below = 20-40 mEq deficit. For a 1 mEq deficit, replenish with 40-60 mEq PO q4-6 or 10 mEq IV q1 hour if its urgent.
2. Syphillis
- in the CSF, the VDRL is specific but not sensitive (70% false negative), while FTA-ABS is sensitive. It's the opposite of the serum pattern. A negative csf VDRL does not rule out neurosyphillis!
- In the US, >50,000 cases diagnosed every year
- primary syphilis - 10-90 day incubation period, chancres
- secondary syphilis - weeks to months later, diffuse symmetric rash (although can take any form except vesicular) plus general malaise symptoms- fever, anorexia, etc. many people will have spirochetes in their csf at this point.
- latent syphilis
- late syphillis occurs 1-30 years after initial presentation will occur in 25-40% of people with untreated syphilis - cardiac (aortitis), Neuro (transient meningitis, cranial neuropathies ESP optic, facial, menigovascular - arteritis of vessels in subarachnoid space leading to thromboses)
- otosyphilis, oculosyphilis can occur too
- tabes dorsalis can present with lancing pain,
3. Fourniers gangrene
- 100% mortality with antibiotics alone, 40-80% mortality even with surgery
- "Localized infection adjacent to a portal of entry is the inciting event in the development of Fournier gangrene. Ultimately, an obliterative endarteritis develops, and the ensuing cutaneous and subcutaneous vascular necrosis leads to localized ischemia and further bacterial proliferation. Rates of fascial destruction as high as 2-3 cm/h have been described.... testicles usually spared because they have a separate blood supply (testicular arteries, from aorta)" (medscape)
4. Anti-Xa levels
- Lovenox levels are monitored with anti-Xa (all heparin-based a/c can be monitored with this); lovenox only needs monitoring in people who need dose adjustments, like people with ESRD
- Adjustment for renal function: increase the interval, rather than decrease the dose.
- Anti-Xa test: put antithrombin and factor Xa in a tube, add patients' serum; if there is a lot of lovenox in the serum, it will cleave all the factor Xa and there will be little remaining (this measured with chromophores that are cleaved upon enzymatic cleavage). This is then plotted on a concentration-activity curve to determine the amount of "anti-Xa" activity within the patient's serum
- Therapeutic anti-Xa levels: lovenox (0.5-1.2), unfractionated heparin (0.3-0.7)
- Prophylactic anti-Xa levels: lovenox (0.2-0.5), unfractionated heparin (0.1-0.4)
5. Low molecular weight heparins: 
- Lovenox comes in 80 mg pens
- Dalteparin does not accumulate even in people with renal failure
6. Antibiotics medley
- Keflex is good for wound infections, but it must be taken 3-4 times a day. Covers from MSSA to non-resistant GNR
- Augmentin has similar coverage, but is only BID. Better coverage of resistant GNR, coverage of anaerobes (no cephalosporins have any anaerobic coverage)
- Bactrim can cause a pseudo-type 4 RTA (decreased response to aldosterone, hyperkalemia) even at low doses. Especially relevant in ESRD patients.
- Many antibiotics affect warfarin metabolism in the liver - bactrim, cipro, macrolides (clarithro, erythro), flagyl! There are differences from what is seen in case reports (bad times) and what is seen when you co-administer warfarin and these antibiotics in healthy volunteers (not so bad!)
- "Some investigators advise that the hypothrombinemic response to warfarin can increase when acetaminophen is taken in a dosage of more than 2 g per day for longer than one week.3(pp7–8) Recent information suggests that the warfarin-acetaminophen interaction may be clinically significant at even lower dosages of the pain reliever. One case-control study identified acetaminophen as a cause of 30 percent of INR values greater than 6.0 in patients taking warfarin.4 This response occurred with as few as seven 325-mg tablets of acetaminophen. The proposed mechanism is a reduced capacity of cytochrome P450 enzymes caused by acetaminophen and resulting in decreased metabolism of warfarin." (from above article.... interesting)
7. Premature beats
- PAC: p-wave comes early, then the pacemaker resets. Comes from ectopic foci-- P wave morphology and PR interval are different. The PAC can be conducted normally or blocked through AV node.
- PVC: p-wave comes early, pacemaker resets. Wide QRS. Can be experienced as a "skipped heart beat", because the ventricles contract before they can adequately fill with blood.
- Atrial bigeminy: every normal sinus beat is followed by a PAC. Often due to mild irritation of atria: try stopping caffeine, checking electrolytes. Usually harmless
- Ventricular bigeminy: every normal sinus beat followed by PVC. The "true" heart rate will be half as fast as the measured heart rate-- because the PVC beats are not good beats, as the ventricles don't fill completely so the cardiac output is bad during those beats. Can occur in young healthy people and be fine-- they may be able to sit at an effective rate of 30 BPM. Can cause fatigue though, for decreased CO. If its severe enough you can treat this with ablation.
8. Escape rhythms/beats
- "escape" = higher levels of pacing have failed, now relying on downsteam pacemakers (junction, ventricular fascicles)
- Junctional escape rhythm: usually 40-60 bpm, narrow complex, may or may not have a p-wave (may conduct sightly retrograde and have an inverse form, may have no P wave.
- Ventricular escape rhythm: 20-40 bpm, wide complex, no p-wave for sure.
9. AV node blocks
- First degree: PR > 0.2 ms (one large box)
- Second degree type I wenckebach's: PRs lengthen than QRS drops; the ratio can be 1:2 - 1:10.
- Second degree type II: PRs same length, QRS randomly drops. vs PAC-- second degree blocks are sinus rhythms, so the P-P intervals are symmetric (ie not premature).
- Third degree: complete block. Frequently occurs after inferior wall MIs, as the RCA supplies the SA and AV node with blood. These people need a pacemaker, although the urgency varies; if they're healthy and compensating well, they might be able to stay on the floor and move to the OR at a leisurely pace to get the pacemaker (although should be within a day or so). If they're old and not able to compensate, they will need an ICU admission, an urgent temporary venous-catheter-placed-pacemaker and a trip to the OR as soon as feasible. Remember: in third degree block you are relying on ventricular escape rhythms, and those are really slow. An old person with lots of comorbidities may not be able to adequately perfuse at 20 bpm.
10. Bundle branch blocks:
- Most of the heart depolarizes R to L, but the septum depolarizes L to R
- RBBB: AV node to L fascicle is normal, and septum is able to depolarize normally. On the L lateral leads (V5, V6) you'll see a small Q (from the septal depolarization), a sharp R, and a widened S. On the right-side (V1, V2), you'll see a small R from the septal depolarization, a sharp S from the L ventricle depolarizing, and then a large R from the R side depolarizing (visible because the L ventricle is already done, so the direction of the vector will be very clearly towards the R) -- rabbit ears, rsR'. T wave inversions is normal.
- LBBB: AV node to R fascicle is normal, but septal depolarization and L side depolarization are both messed up. L lateral leads will see a widened R wave as the L ventricle depolarizing in a slow, inefficient way. R lateral leads will see a big widened S wave for the same reason-- L ventricle depolarizing.
- Hemi-blocks: Left bundle branch has anterior and posterior fascicle.
- L Anterior fascicular block is most common because it is supplied by the LAD. You get left axis deviation, Q1S3 (small Q in lead 1/avL, S wave in lead III), prolonged QRS
- L posterior fascicular block is less common because it has a dual blood supply- LAD and RCA. If you have ischemia of both, then you have bigger problems. Exact opposite EKG findings: R axis deviation, Q3S1, QRS prolonged.
- Combined blocks: L Anterior fascicular + RBBB because they are both supplied by LAD -- these have a high rate of progression to third degree AV block.

1. B12 deficiency
- Neuropsych signs (~33%, can occur w/ normal CBC): paresthesias, then ataxia with loss of vibration/position, then severe weakness, spasticity, clonus, paraplegia, incontinence, delirium/dementia.
- Homocysteine & MMA: they both need B12 to be converted to breakdown products, so they will increase in cases of B12 deficiency. Sensitivity of both tests are 85-95% sensitive. Homocysteine is less specific, can be elevated in vascular dx, some other processes.
- Anemia in ~75%, macrocytosis in ~80%. Normal CBC does NOT rule out B12 deficiency.
- B12 protien bound & released by acid digestion in stomach, binds IF in jejunum, absorbed in terminal ileum.
- Dietary deficiency rare bc 4 years of stores in liver.
- Old people who don't have stomach acid (atrophic gastritis, PPI, metformin) can have trouble absorbing B12.
- B12 level can be falsely low in folate deficiency, pregnancy, OCPs
- B12 deficiency: when to treat: when B12 is very low, when the B12 is borderline but either Homocysteine or MMA are low.
- Can treat with IM B12, or PO B12-- if you give huge doses, you can overcome even pernicious anemia.
2. Folate deficiency
- Drugs that interrupt the DHFR pathway: methotrexate, phenytoin, sulfasazlaine, alcohol
- People who need extra folate: chronic hemolytic anemia (like sickle cell), pregnancy, increased growth periods -- these people should always be taking folate
- Red cell folate reflects status over 3 months; sens/spec ~70%
3. Anemia of chronic disease
- Iron studies all slightly low, with high ferritin, low RPI
- Common causes: CKD, autoimmune dx, endocrinopathies, cancer, acute/chronic infection
- Cytokines change iron processing
- Hb <8 suggest additional cause
- Look for iron, B12, folate
- Should not be pancytopenic
4. TTP-HUS:
- fever, thrombocytopenia, hemolytic anemia, kidney injury, neuro sx
- w/u with smear, coags to r/o DIC
- tx with plasmapharesis to get off the anti-ADAMSTS13 antibodies
5. When someone walks in with AKI, consider the following first:
- Look at volume status => replenish volume
- Stop NSAIDs and other nephrotoxins
- Obstruction (older male, anticholinergics, urine problems) => bladder scan/straight cath => if the residual volume is high, get a renal u/s then relieve the obstruction
6. Prerenal (low FeNa)
- Dehydration, blood loss
- CHF/Cirrhosis
- NSAIDs
- Vascular - thrombi, severe b/l RAS
7. Intrarenal
- Glomerular: Nephritic syndrome (ie. red cell casts) , nephrotic
- Tubular: ATN from toxins (most common are contrast - muddy brown casts, and post-operative), prolonged hypotension
- Interstitial: 85% caused by meds: NSAIDs, antibiotics, diuretics (thiazides), anticonvulsants, PPIs, penicillins, cipro, 10% from infections (pyelo)
- Vascular
- TTP-HUS: vascular risk factors, DIC, TTP-HUS
8. Post-renal
- Prostate
- Stones
- Cancer obstructing all kidneys
- Neurogenic
- Once you relieve obstruction, there will be post-obstructive diuresis - keep up with IVF
9. Workup:
- Urine dipstick and microscopy
- Urine electrolytes
- Straight cath
10. FeNa/FeUrea 
- FeUrea more sensitive and specific than FeNa in people on diuretics, perhaps in everyone
- FeNa <1%, FeUrea <35% suggestive of pre-renal cause; higher suggest non-pre-renal cause.

1. Pancytopenia:
- primary process: aplastic anemia,
- secondary process:
- any infiltrative process
- sarcoid, lupus
- B12 deficiency (17% of people)
- acute alcohol
- overwhelming sepsis
- aplastic anemia
- hypersplenism
2. Anemia + thrombocytopenia:
- microangiopathic (TTP-HUS, DIC, HELLP)
- autoimmune
- hypersplenism
- HIV
3. Anemia alone
- RPI to differentiate between underproduction and overconsumption.
4. Hemolysis:
- Check coombs to diagnose autoimmune, look for schistocytes on smear to determine microangiopathic hemolysis
- Think of others: hereditary (sickle cell, g6pd) and acquired (hypersplenism, toxin, infection like malaria)
5. MCV
- not specific: cannot be used to rule out etiology.
- if its slightly elevated, reticulocytes are big, so many hemolytic anemias will cause slightly increased MCV
6. Iron deficiency anemia
- Causes PICA
- Can give trial of iron and measure H&H at 4-6 weeks, or measure retics in 7-10 days
- Iron sulfate - can cause nausea/constipation: to avoid, titrate up to 325 TID, take with food, try other forms of iron which are easier to digest but have lower bioavail so it will take longer.
- Blood loss is #1 cause (menstrual, GI)
- Inadequate intake (less bioavail from veggies than from meat, so vegetarians/vegans)
- Increased demand (pregnancy, rapid growth, epo use)
- Malabsorption (celiac, crohns, post-gastrectomy)
- Ferritin is the best test in patients without inflammation (in al patients, low ferritin rules IN iron deficiency, LR+51 for ferritin <15, LR+25 for ferritin <32).
- TIBC next best test, TIBC < 5% LR +10 for iron deficiency
7. Who needs a workup for iron deficiency anemia?
- All dudes
- Women over 50
- People at increased risk of colon cancer
- With malabsorption: 12% of patients with celiac dx present with iron deficiency
8. GI bleed:
- Even low dose aspirin can cause peptic ulcer dx
- GI AVMs can be easily missed on colonoscopy
- SBFT is not sensitive at all for GI bleed
- Video capsule is test of choice for looking @ small bowel, unless someone has a history of stricture.
9. Macrocytic anemia:
- Megaloblastic: B12, folate
- Non megaloblastic: alcohol, hypothyroid, liver disease
10. Microcytic anemia:
- Iron deficiency, thalassemia, sideroblastic anemia (defect in heme synthesis leads to accumulation of iron in mitochondria around nucleus of developing RBC instead of being incorporated into heme)

1. Viral causes of polyarticular arthritis
- Rubella (can get with vaccine administration), rash
- Hep B
- HIV
- Parvo (kids don't get the arthritis, just fever and rash - lacy macular lesion ie nonspecific viral exanthem)
2. DDx Monoarticular arthritis 
- Inflammatory: infectious, crystalline, trauma
- Infectious: septic joint (staph/GC), osteomyelitis, lyme
- Crystalline: gout, pseudogout/CPPT
- Non-inflammatory: osteoarthritis, trauma.
3. DDx Inflammatory polyarticular arthritis 
- Rheum: Lupus, Sarcoidosis, Rheumatoid arthritis/JRA, Seronegative spondyloarthropathies (Reactive arthritis/Reiters, Psoriatic, IBD, Ankylosing spondylitis), most of the other autoimmune diseases (Mixed connective tissue disease, dermatomyositis, sjogrens)
- Infectious (bacterial): bacterial endocarditis, lyme disease.
- Infectious (viral): rubella, hep B, HIV, parvo (adults)
- Post-infectious: enteric, urogenital, rheumatic fever.
4. Common causes of joint pain (non-OA) at...
- Neck: cervical radiculopathy, cervical sprain
- Shoulder: rotator cuff injury, impingement
- Elbow: olecranon bursitis, lateral epicondylitis (tennis elbow); overuse injury from extensor tendons... the tendon distal to the insertion is hypovascular and more prone to microtears from overuse. Likely the extensor carpi radialis brevis is implicated, among others. Medial epicondylitis is the same, but at the medial (all of the major wrist/finger flexors and arm pronators attach at one tendon on the ulna); more rare than lateral epicondylitis.

- Hand: carpel tunnel
- Hip: trochanteric bursitis (lateral), meralgia paresthetica (thigh)
- Knee: patellar tendonitis (pain directly on patellar tendon, often inferior), patellofemoral pain syndrome (pain under patella from friction), meniscal/ligamentous injuries
- Foot: achilles' tendonitis, plantar fasciitis
5. Metatarsalgia vs metatarsal stress fx
- Line up their toe with their foot, push in, that really hurts if they have a stress fx
- Tell them to take a week off, come back, if it still hurts then you'll xray-- gives time for metatarsalgia to resolve, also by then you'll actually see the fracture on x-ray
6. Acute, fluctuating confusion- delirum
- (Acute, non-fluctuating confusion - "acute confusional state" - look for another CNS insult: stroke, toxin, infection, hypoglycemia)
- To diagnose delirium, use confusion assessment method: AIDA
- Acute onset, fluctuating course
- Inattention (can't focus, easily distractible)
- Disorganized thinking (illogical, incoherent, rambling, rambling)
- Altered level of consciousness (lethargy, stupor, hypervigilant/climbing walls)
7. Workup of delirium
- H&P
- Basic labs
- CXR
- UA
- EKG
- Review meds
8. When to get further testing for delirium:
- EEG- delirium will show you diffuse slowing c/w toxic encephalopathy every time so there is usually no point. Only get this in someone with a hx of seizures. Non convulsive seizures are rare, usually at least they have eye deviation or something.
- LP- get it if they have a fever, delirium, and no source
- CT- get it if you have reason to believe there may be a subdural. Don't get it to "rule out stroke" if you can get a decent neuro exam; stroke almost always has focal neurological findings.
- Neuro consult
9.  Delirium is persistent-- it tends to go on for months, so if someone is ready for discharge and still delirious, keeping them more days will not help resolve the issue.
10. Preventing onset of delirium in hospitalized patients
- Let them sleep
- Reorientation (family members, make sure they have glasses/hearing aids/etc to prevent sensory deprivation)
- Early ambulation (i.e. get the nasal cannula, foley, IVs out)
- Keep them hydrated.

Nuclear imaging 

Few absolute contraindications for nuclear imaging: 

-renal fxn irrelevant, allergic reactions don't happen, metal OK 

-Pregnancy is a relative CI for all ionizing imaging modalities, absolute CI with I-131 as it crosses the placenta, irradiates fetal thyroid, causes cretinism 

Nuclear medicine: 

- Diagnostic (gamma rays) imaging - cardiac scan, bone scan, PET scan, (real GFR, RBC mass/volume, Schillings test), radioiodine, V/Q, HIDA, tagged RBC, tagged WBC, relative organ perfusion (how many counts are in R vs L kidney, etc), organ emptying-- GB/heart (EF)/stomach comparing counts within and outside. 

- Minor procedures: lymphoscintillagraphy (inject breast, watch tracer drain with the lymphatics; drops in eyes to see whether tear ducts are patent 

- Therapeutic: beta/alpha particles: medium dose I-131 (hyperthyroid), thyroid CA (high dose I-131), theraspheres (inject radioactive spheres into hepatic artery to get liver), radioactive seeds (bexxar, zevalin), painful bone mets (radium 223, strontium)

Bone scan: 

- Advantages: can scan whole body, great for blastic lesions, better for following evolution of bone mets over time (i.e. s/p chemo) because CT scans see the scarring/sclerosis of bone, which will stay the same even after chemo, but bone scan will see the osteoblastic activity which reflects the true act

- Disadvantages: not specific (also lights up osteo, fractures, DJD), takes hours, not sensitive for lytic lesions (renal cell CA) because can only see blastic/remodeling activity, marrow processes (MM) 

- Bone mets don't really go to bone-- they go to red marrow. When you're young, you have red marrow everywhere, but most of it is replaced by yellow marrow starting from the fingertips/toes out. Cancer goes to the red marrow first, then it goes to the adjacent bone-- once you have osteoblast activity, then and only then will the bone scan see it. 

- Kids: neuroblastoma will metastasize to the ends of the bones. 

1. Acute inflammatory monoarticular arthritis
- DDx: gout, pseudogout, septic joint, osteomyelitis, trauma (rarer: first episode of RA, reactive arthritis)
- Is an absolute indication for arthrocentesis, unless you're absolutely sure it's gout:
- Signs that point to gout:
>1 attack of acute arthritis (i.e. history of gout)
Maximal inflammation in <1 day ("thunderclap onset")
Monoarthritis
Joint erythema
1st MTP involvement ***
Unilateral MTP arthritis
Unilateral tarsal acute arthritis
Tophus
Asymmetric joint swelling
Hyperuricemia
Bone cysts without erosion on X-ray
Negative joint fluid culture
- 6 or more of the above criteria for diagnosing gout: Sens/Spec – 87%/96%, LR + 22, LR - 0.13
- 5 or more: Sens/Spec – 95%/89% LR + 8.6, LR - 0.005
2. Gout 
-Acute: colchicine (dose to the major side effect, which is diarrhea), prednisone PO or joint injection, NSAIDs
-Chronic: allopurinol, febuxistat (if they can't tolerate allopurinol bc of renal insufficiency), probenicid (if they are underexcreters)
-Also affects kidney (urate nephropathy ie CKD without any cause other than gout)
3. CPPD/Pseudogout
- Clinically resembles OA, treat it as if it was OA
- Pseudo RA
- Affects the knee
- Xray: linear calcifications within joint space.
- Due to hypercalcemia (occult hyperparathyroidism is most common cause)
- Treat with colchicine, NSAIDs, treat hyperparathyroid if they have it
4. Septic joint
- Either GC or Staph
- GC: triad of septic joint, tenosynovitis (87%), fever (50%), skin lesion (90%), positive blood cx (43%), because its a higher grade bacteremia than staph.
- Tenosynovitis: back of hands, tendons all inflamed, can't bend hands.
- Staph: less risk of all of the above sx. usually in people with a reason to get staph in their blood (IV drug use, recent surgery, port/dialysis cath, etc)
- Hand and such you can just give IV abx
- Big joints (hip) need to be washed out either in the OR or at bedside.
5. Lyme disease
- Nymph form of ixodes tick is the one that carries lyme disease (Nymphs are much tinier than adult ticks)
- Single dose 100 mg doxy prevents lyme. However the % of lyme-carrying, nymph, ixodes/deer ticks are so rare that it'd be egregious overtreating to prophylax everyone.
- Acute lyme tx: 21 days of doxy.
- If you don't treat lyme, the next things that you get are heart (heart block), brain (headache, meningitis), then 1-6 months out then you get joint pain (knee most common)
- Anything after acute phase you need IV ceftriaxone
- Can also get jarisch-herxheimer reaction as well with initiation of treatment... so warn your patients they may feel a lot worse before they feel better.
- Endemic areas: coastal mideast, northwest wisconsin, some in california
- Lyme rash hurts
6. RA
- Metatarsals, wrists
- In a younger person, lupus can cause similar symptoms
- Workup: ESR/CRP, RF, anti-CCP (specific), x-ray (erosive joint), rheumatoid nodules (over bony joints like knuckles and olecranon, LR +22)
- Tx: acutely, steroids and NSAIDs, once you get a diagnosis then 20mg/week of methotrexate and as much steroids as you need to control symptoms. After you fail that, then biologics (like remicade). Recent NEJM study showed that people who failed mtx randomized to remicade vs plaquenil, that many people did well on plaquenil.
- 20 mg one time a week. Then you wean by 2.5 mg every 2 months or so. Most people need at least ~12.5 mg.
7. Psoriatic arthritis
- Psoriasis, nail findings, DIP involvement, "sausage digits" - where whole finger is inflamed. Because you get enthasopathy (inflammation of tendon insertions) as well as arthritis.
- Even if people say they don't have psoriasis, look closely (umbilicus, genitals, etc) for hidden psoriasis.
- Arthritis mutilans, telescoping digits -- destruction of joint with tendon still pulling down, so fingers shorten.
8. Seronegative (ie ANA neg, RF neg) spondyloarthropathies (can affect spine) 
- Often cause asymmetric inflammation (one knee, one ankle), enthasopathy is common
- Chronic, polyarticular
- Psoriatic, Ankylosing spondylitis, reactive arthritis/reiter's, IBD
9. Lupus
- Hold on immune workup until you have 3+ clinical sx (i.e. malar/discoid rash, cardiac/pulmonary serositis, renal disease, arthritis) to avoid overdiagnosing and sending ANAs on everyone, b/c ANA is so nonspecific
10. Erythema nodosum
- Seronegative spondyloarthropathies (esp IBD), sarcoid
- Rheumatic fever (JONES criteria are major - migrating polyarthritis, peri/myo/endocarditis, subQ nodules, erythema nodosum, syndenham's chorea, minor criteria - fever, joint pain, PR prolongation, elevated ESR/CRP)

1. Cavernous sinus thrombosis 
-frontal/sinus pain
-waxing and waning
2. Migraines
POUNDing:
- Pulsatile
- Onset/duration 4-72 hours without treatment
- Unilateral
- Nausea
- Disabling - can't work through it
- classically: car sickness as a child
- neurological symptoms are from cerebral cortex and brainstem.
3. Treatment for migraines
- Abortive: NSAIDs (+/- antiemetics), Triptans (selctive sertotonin agonists)
- Corticosteroids are helpful to break a cluster of migraines (i.e. normally they come infrequently but they are getting them every day for a while and using abortive agents every day)
- Prophylactic: B-blockers, CCB, Topamax/neurontin/ARBs
4. GCA or temporal arteritis 
- older white female
- 15% of those with PMR have GCA
- 60% of those with GCA have PMR
- Jaw claudication - sens 34%, spec 92%
- Diplopia - sens 9%, spec 97% (unknown why this happens-- direct inflammation of CN III/IV/VI, vs ischemia to nerve or muscles)
- Headache & jaw claudication LR +8
- Scalp tenderness & jaw claudication LR +17
- Beading, enlargemnt, prominence of TA LR >4
- Temporal aretery tenderness, loss of pulse LR >2
- Abnormal ESR has sensitivity of 96%
- NSAIDs will alleviate sx, but will not treat underlying dx so don't send someone home on NSAIDs if your suspicion is high.
- Treatment is high-dose steroids
5. SDH
- Classic: AMS, somnolence, not commonly associated with headache
- Associated symptoms (% frequency)
- Falls 74%
- Progressive neuro deficit 70%
- Head trauma 37%
- Transient neuro deficit 21% (hence scan someone you think has a TIA before anticoagulation to r/o SDH)
- Seizure
6. Pseudotumor: headache in young women with visual changes.
7. Upper extremity injury: 
- 95% shoulder dislocations are anterior, 5% posterior, usually seizure or electrical shock
- Radial head fracture most common elbow fracture in adults
- FOOSH fractures:
4-10 y/o torus fracture (buckle fracture in radius)
11-16 : saltar harris II - through growth plate and metaphysis
17-40 scaphoid (risk for avascular necrosis in proximal pole
>40: colles (esp women distal radius fracture
8. IR procedures: 
- procedures with low risk of bleed, and if it bleeds, it is easily detected and controllable
dialysis access, ivc filter, centreal line removal, drainage catheter
- procedures with significant risk of bleed; bleeds are difficult to detect and to control (i.e. need way stricter coagulation parameters)
TIPS, renal bx, nephrostomy tube placement, RFA
9. General guidelines for coagulation parameters before starting IR: 
- Platelets > 50 PTT, INR <1.5
- heparin held for 3 hours
- aspirin held 5 days
- try to hold plavix
10. Contrast nephropathy 
>25% increase in Cr or abs cr increase of 0.5 mg/dL
Risk fx: pre-existing renal insufficiency (cr <60)
Diabetes
Hypovolemia
Typical CT 60-120 cc contrast
intensive procedures w lots of angios/cath can be as high as 200-300 cc contrast

1. Meniscal tears: 
-Chronic/Degenerative meniscal tear with or without OA (i.e. chronic injury)- surgery vs conservative management + sham surgery found no benefit for surgery.
-Acute traumatic meniscal tear-- go to surgery, evidence that surgery within 3 months leads to better outcomes
2. Shoulder pathology
-Painful arc test: LR +3.7 for rotator cuff disease
-External rotation lag gest LR+7.2, internal rotation lag test LR +5
Frozen shoulder
-occurs when people stop moving arm (i.e pain)
-pain near deltoid insertion (can't sleep on that side)
-Xrays normal
3. Baseline workup/initial management for newly diagnosed stable angina: 
-EKG
-Lipids
-BMP
-TSH
-CBC
-Sublingual nitroglycerin PRN (put one under tongue, feel fizz, if still have pain after 5 minutes, take another, if after 3 you still have pain go to ER)
-B-blocker if they are also hypertensive
-Aspirin (data shows that it helps in people with high CRPs
4. ER management of unstable angina: 
-DDx can't-miss: STEMI, Aortic dissection,
-O2, EKG, nitroglycerin, beta blocker, IV heparin (questionable whether you have to rule out dissection before giving heparin)
5. Stress tests
-EKG stress test: you look at EKG before and after stress, and you look for ischemic changes so if their baseline EKG is not normal, it won't really help. Sens & spec ~75%, good for low prettest probability, normal baseline ekg, low suspicion.
-Echos are very specific, because you have to have enough coronary disease to see a change in anterior wall motion
-Thallium is sensitive, but not specific (higher false postiive). At maximum level of exertion, inject with tracer, rest them to let the tracer redistribut to get a rest image.
6. CABG vs PCI 
- Low risk patients - (one or two vessel non complex dx) no difference in mortality between medical management only and stent. Stents have better symptom control, but lead to more procedures
- Moderate risk - (more complex multivessel dx but normal EF), PCI approximately equal to CABG, both are better than medical therapy, PCI leads to more procedures
- High risk- left main disease, 3 vessel dx or 2 vessel dx with proximal LAD involvement, low EF, CABG has better outcomes than PCI in diabetics, although stenting can have similar outcomes to surgery in selected patients.
7. CABG vs PCI: RCT Data from 1966 to 2006 {Ann Intern Med, 2007}

Ann Intern Med. 2007 Nov 20;147(10):703-16. Epub 2007 Oct 15.

Systematic review: the comparative effectiveness of percutaneous coronary interventions and coronary artery bypass graft surgery.

DATA SOURCES:

MEDLINE, EMBASE, and Cochrane databases (1966-2006); conference proceedings; and bibliographies of retrieved articles.

STUDY SELECTION:

Randomized, controlled trials (RCTs) reported in any language that compared clinical outcomes of PCI with those of CABG, and selected observational studies.

DATA EXTRACTION:

Information was extracted on study design, sample characteristics, interventions, and clinical outcomes.

DATA SYNTHESIS:

The authors identified 23 RCTs in which 5019 patients were randomly assigned to PCI and 4944 patients were randomly assigned to CABG. The difference in survival after PCI or CABG was less than 1% over 10 years of follow-up. Survival did not differ between PCI and CABG for patients with diabetes in the 6 trials that reported on this subgroup. Procedure-related strokes were more common after CABG than after PCI (1.2% vs. 0.6%; risk difference, 0.6%; P = 0.002). Angina relief was greater after CABG than after PCI, with risk differences ranging from 5% to 8% at 1 to 5 years (P < 0.001). The absolute rates of angina relief at 5 years were 79% after PCI and 84% after CABG. Repeated revascularization was more common after PCI than after CABG (risk difference, 24% at 1 year and 33% at 5 years; P < 0.001); the absolute rates at 5 years were 46.1% after balloon angioplasty, 40.1% after PCI with stents, and 9.8% after CABG. In the observational studies, the CABG-PCI hazard ratio for death favored PCI among patients with the least severe disease and CABG among those with the most severe disease.

LIMITATIONS:

The RCTs were conducted in leading centers in selected patients. The authors could not assess whether comparative outcomes vary according to clinical factors, such as extent of coronary disease, ejection fraction, or previous procedures. Only 1 small trial used drug-eluting stents.

CONCLUSION:

Compared with PCI, CABG was more effective in relieving angina and led to fewer repeated revascularizations but had a higher risk for procedural stroke. Survival to 10 years was similar for both procedures.

8. CABG vs PCI: RCT data from 2007 to 2013 {JAMA, 2013)

JAMA. 2013 Nov 20;310(19):2086-95. doi: 10.1001/jama.2013.281718.

Coronary artery bypass graft surgery vs percutaneous interventions in coronary revascularization: a systematic review.

FINDINGS:

Thirteen RCTs and 5 meta-analyses were included. CABG surgery should be recommended in patients with unprotected left main disease (ULMD, in which there is >50% left main coronary stenosis without protective bypass grafts), multivessel CAD, or LVD, if the severity of coronary disease is deemed to be complex (SYNTAX >22) due to lower cardiac events associated with CABG surgery. In cases in which coronary disease is less complex (SYNTAX ≤22) and/or the patient is a higher surgical risk, PCI should be considered. For patients with diabetes and multivessel CAD, CABG surgery should be recommended as standard therapy irrespective of the severity of coronary anatomy, given improved long-term survival and lower cardiac events (5-year MACCE, 18.7% for CABG surgery vs 26.6% for PCI; P = .005). Overall, the incidence of repeat revascularization is higher after PCI, whereas stroke is higher after CABG surgery. Current literature emphasizes the importance of a heart-team approach that should consider coronary anatomy, patient characteristics, and local expertise in revascularization options. Literature pertaining to revascularization options in LVD is scarce predominantly due to LVD being an exclusion factor in most studies.

CONCLUSIONS AND RELEVANCE:

Both CABG surgery and PCI are reasonable options for patients with advanced CAD. Patients with diabetes generally have better outcomes with CABG surgery than PCI. In cases of ULMD, multivessel CAD, or LVD, CABG surgery should be favored in patients with complex coronary lesions and anatomy and PCI in less complicated coronary disease or deemed a high surgical risk. A heart-team approach should evaluate coronary disease complexity, patient comorbidities, patient preferences, and local expertise.

9. CABG vs PCI in complex patients (left main/three vessel disease/diabetes): the SYNTAX trial {Eur J Cardiothoracic Surg, 2013}

Eur J Cardiothorac Surg. 2013 May;43(5):1006-13. doi: 10.1093/ejcts/ezt017. Epub 2013 Feb 14.

Treatment of complex coronary artery disease in patients with diabetes: 5-year results comparing outcomes of bypass surgery and percutaneous coronary intervention in the SYNTAX trial.

METHODS:

Patients (n = 1800) with LM and/or 3VD were randomized to receive either PCI with TAXUS Express paclitaxel-eluting stents or CABG. Five-year outcomes in subgroups with (n = 452) or without (n = 1348) diabetes were examined: major adverse cardiac or cerebrovascular events (MACCE), the composite safety end-point of all-cause death/stroke/myocardial infarction (MI) and individual MACCE components death, stroke, MI and repeat revascularization. Event rates were estimated with Kaplan-Meier analyses.

RESULTS:

In diabetic patients, 5-year rates were significantly higher for PCI vs CABG for MACCE (PCI: 46.5% vs CABG: 29.0%; P < 0.001) and repeat revascularization (PCI: 35.3% vs CABG: 14.6%; P < 0.001). There was no difference in the composite of all-cause death/stroke/MI (PCI: 23.9% vs CABG: 19.1%; P = 0.26) or individual components all-cause death (PCI: 19.5% vs CABG: 12.9%; P = 0.065), stroke (PCI: 3.0% vs CABG: 4.7%; P = 0.34) or MI (PCI: 9.0% vs CABG: 5.4%; P = 0.20). In non-diabetic patients, rates with PCI were also higher for MACCE (PCI: 34.1% vs CABG: 26.3%; P = 0.002) and repeat revascularization (PCI: 22.8% vs CABG: 13.4%; P < 0.001), but not for the composite end-point of all-cause death/stroke/MI (PCI: 19.8% vs CABG: 15.9%; P = 0.069). There were no differences in all-cause death (PCI: 12.0% vs CABG: 10.9%; P = 0.48) or stroke (PCI: 2.2% vs CABG: 3.5%; P = 0.15), but rates of MI (PCI: 9.9% vs CABG: 3.4%; P < 0.001) were significantly increased in the PCI arm in non-diabetic patients.

CONCLUSIONS:

In both diabetic and non-diabetic patients, PCI resulted in higher rates of MACCE and repeat revascularization at 5 years. Although PCI is a potential treatment option in patients with less-complex lesions, CABG should be the revascularization option of choice for patients with more-complex anatomic disease, especially with concurrent diabetes.
My conclusions:
-Diabetics: no difference in mortality, stroke, MI. Stents are ~50% likely to need repeat procedure at 5 years (50% vs 30%) 
-Non-diabetics: no difference in mortality, stroke. Stents have ~3x higher risk of MI (10% vs 3%). 
-Choose: A few extra trips to the cath lab VS thoracotomy/ICU stay. Which would you pick?

10. COURAGE trial: 

N Engl J Med. 2007 Apr 12;356(15):1503-16. Epub 2007 Mar 26.

Optimal medical therapy with or without PCI for stable coronary disease.

BACKGROUND:

In patients with stable coronary artery disease, it remains unclear whether an initial management strategy of percutaneous coronary intervention (PCI) with intensive pharmacologic therapy and lifestyle intervention (optimal medical therapy) is superior to optimal medical therapy alone in reducing the risk of cardiovascular events.

METHODS:

We conducted a randomized trial involving 2287 patients who had objective evidence of myocardial ischemia and significant coronary artery disease at 50 U.S. and Canadian centers. Between 1999 and 2004, we assigned 1149 patients to undergo PCI with optimal medical therapy (PCI group) and 1138 to receive optimal medical therapy alone (medical-therapy group). The primary outcome was death from any cause and nonfatal myocardial infarction during a follow-up period of 2.5 to 7.0 years (median, 4.6).

RESULTS:

There were 211 primary events in the PCI group and 202 events in the medical-therapy group. The 4.6-year cumulative primary-event rates were 19.0% in the PCI group and 18.5% in the medical-therapy group (hazard ratio for the PCI group, 1.05; 95% confidence interval [CI], 0.87 to 1.27; P=0.62). There were no significant differences between the PCI group and the medical-therapy group in the composite of death, myocardial infarction, and stroke (20.0% vs. 19.5%; hazard ratio, 1.05; 95% CI, 0.87 to 1.27; P=0.62); hospitalization for acute coronary syndrome (12.4% vs. 11.8%; hazard ratio, 1.07; 95% CI, 0.84 to 1.37; P=0.56); or myocardial infarction (13.2% vs. 12.3%; hazard ratio, 1.13; 95% CI, 0.89 to 1.43; P=0.33).

CONCLUSIONS:

As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy. (ClinicalTrials.gov number, NCT00007657 [ClinicalTrials.gov].).