October - November 2020 Flashcards

Question

Ascites in cirrhosis: Na restriction vs fluid restriction?

Answer 1

Na restriction 2 gm/day Tip: Common misconception is fluid restriction

Answer 2

Pathology shows the presence of granulation tissue plugging airways, alveolar ducts, and alveoli. EWWW

Answer 3

Sulfur granules are an in vivo concretion of Actinomyces bacteria, calcium phosphate, and host material. Gram stain of Actinomyces infection shows intensely positive staining at the center with branching rods at the periphery

Answer 4

Hepatomegaly is the most common physical sign in patients with HCC, occurring in 50%–90% of the patients.

Answer 5

Gilbert: UDP glucuronosyltransferase deficiency - inability to conjugate unconjugated bili to conjugated - TIP: hence autoimmune hemolytic anemia is on the diff diagnosis - Criggler Najjar Type I/Type 2: same enzyme defect but more severe - Type I: U. Bili > 20 - present since birth and stays as compared to Gilbert - Type II: U. Bili < 20 Dubin Johnson: elevated CONjugated bili - TIP: hence obstructive jaundice is on the diff diag

Answer 6

Clinically, most patients with pemphigus vulgaris present after age 40, and the initial lesions are on mucosal surfaces, predominantly the oral mucosa. These lesions erode quickly to ulcers and are typically quite painful. They may be the only manifestation or precede the development of blistering skin lesions by several months

Answer 7

Acantholytic blister formation in the suprabasal layer of the epidermis with intradermal vesicle formation. Means junctions between the keratinocytes are lost. Basal keratinocytes remain attached to the epidermal basement membrane - hence a blister made from keratinocytes, hence easily broken blisters

Answer 8

Prednisone at a dose of 1 mg/kg daily

Answer 9

Autoimmune mediated blistering skin disorder in which IgG antibodies target desmoglein, the junction proteins between keratinocytes, causing blistering lesions that easily burst.

Answer 10

BAL - shows macrophages with PAF stain demonstrating a lot of protein and amorphous proteinacious material

Answer 11

Classically, the CT appearance is described as “crazy pavement” with ground-glass alveolar infiltrates in a perihilar distribution and intervening areas of normal lung

Answer 12

OCT 2020 Cochrane Systematic Review and Meta-analysis Studies: randomised controlled trials (RCTs) and controlled clinical trials (CCTs) - 6 studies, but only 2 could be evaluated Conclusion: Two of the six identified studies were relevant for current clinical settings. One showed no evidence of a benefit of retrievable filters in acute PE for the outcomes of PE, death, DVT and bleeding during the initial three months in people who can receive anticoagulation (moderate-certainty evidence). The other study did not show any benefit for prophylactic filter insertion in people who sustained multiple traumatic injuries, with respect to symptomatic PE, mortality, or lower extremity venous thrombosis (moderate-certainty evidence). We can draw no firm conclusions regarding filter efficacy in the prevention of PE from the remaining four RCTs identified in this review. Further trials are needed to assess vena caval filter effectiveness and safety, and clinical differences between various filter types Young T, Sriram KB Vena caval filters for the prevention of pulmonary embolism. Cochrane Database Syst Rev. 2020 Oct 8;10:CD006212. doi: 10.1002/14651858.CD006212.pub5.

Answer 13

"Controlled" refers to control group, hence in controlled studies, researchers are able to determine which subjects receive the intervention and which do not. Uncontrolled may mean there is NO control group. "Randomized" refers to randomization of the intervention

Answer 14

Studies: 19 studies (2 RCTs, 8 controlled NRSIs, 9 non-controlled NRSIs) with 38,160 participants, of whom 36,081 received convalescent plasma LOE: The overall certainty of evidence was low to very low, due to study limitations and results including both potential benefits and harms Conclusion: - We are uncertain whether convalescent plasma is beneficial for people admitted to hospital with COVID-19 - here was limited information regarding grade 3 and 4 AEs to determine the effect of convalescent plasma therapy on clinically relevant SAEs.

Answer 15

Neurologic manifestation at any time during disease course in 82.3% - 42.2% at symptom onset - 62.7% at hospital admission Neurologic manifestations included ``` myalgia in 44.8% headache in 37.7% encephalopathy in 31.8% dizziness in 29.7% dysgeusia in 15.9% anosmia in 11.4% syncope in 4.3% rhabdomyolysis in 3.5% orthostatic hypotension in 3.1% ischemic stroke in 1.4% ```

Answer 16

NEJM Sept 2020 messenger RNA vaccine encoding stabilized prefusion SARS-CoV-2 spike protein (mRNA-1273) reported to illicit neutralizing antibody response in all adults, but with high rate of mild-to-moderate adverse events Non controlled randomized trial 45 adults aged 18-55 years received mRNA-1273, 2 intramuscular injections given 28 days apart Conclusion: - High adverse rate: - > 30 % after first vaccination, dose dependent, that is, high the vaccine dose, more likely to get symptom - >50% after second - chills, HA, myalgias - ALL had seroconversion at 15 days with virus-neutralizing activity capable of reducing infectivity by ≥ 80% by day 43

Answer 17

- Occlusion in the LMCA - Proximal left anterior descending artery (LAD) occlusion - Severe triple-vessel disease (3VD) TIP: Almost all the indications for CABG

Answer 18

Tranexamic acid, a synthetic amino acid, is a competitive inhibitor of plasminogen activation, and at much higher concentrations, a noncompetitive inhibitor of plasmin (ie, actions similar to aminocaproic acid). Tranexamic acid is about 10 times more potent in vitro than aminocaproic acid TIP: Think of plasma (or lava) melting away clots

Answer 19

LANCET JUNE 2020 NO Study design: international, multicentre, randomised, placebo-controlled trial Participants: >16 yo, significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding - 5956 patients in the tranexamic acid group and 5981 patients Intervention: loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9% Results: Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82-1·18) Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. Lancet. 2020 Jun 20;395(10241):1927-1936. doi: 10.1016/S0140-6736(20)30848-5.

Answer 20

Primarily on T helper cells, although some inhibition of T suppressor

Answer 21

Solid organ transplant

Answer 22

End goal: T lymphocyte proliferation is reduced Both drugs bind with high affinity to a family of cytoplasmic proteins present in most cells: cyclophilins for cyclosporine and FK-binding proteins for tacrolimus. The drug-receptor complex specifically and competitively binds to and inhibits calcineurin, a calcium- and calmodulin-dependent phosphatase [1-4]. This process inhibits the translocation of a family of transcription factors (NF-AT), leading to reduced transcriptional activation of cytokine genes for interleukin (IL)-2, tumor necrosis factor (TNF)-alpha TIP: "Cyclo"philin bound by "cyclo"sporine; "FK Tacro"

Answer 23

Mobitz Type I: at the AV node (hence progressive prolongation of the PR interval) Mobitz Type II: His purkinje system

Answer 24

Mobitz Type II is more likely to be related to underlying structural heart abnormalities (e.g. infarction, fibrosis or necrosis)

Answer 25

Patients typically have an underlying LBBB OR bifascicular block, hence the 2nd degree AV block is produced by the intermittent failure of the remaining fascicle TIP: "Bilateral bundle branch block"

Answer 26

In around 75% of cases, the conduction block is located distal to the Bundle of His, producing broad QRS complexes. In the remaining 25% of cases, the conduction block is located within the His Bundle itself, producing narrow QRS complexes.

Answer 27

Intermittent non-conducted P waves WITHOUT progressive prolongation of the PR interval (compare this to Mobitz I). The PR interval in the conducted beats remains CONSTANT. The P waves ‘march through’ at a CONSTANT rate. The RR interval surrounding the dropped beat(s) is an exact multiple of the preceding RR interval (e.g. double the preceding RR interval for a single dropped beat, treble for two dropped beats, etc).

Answer 28

NEJM OCT 2020 No - Type: Randomized, Double Blind, Controlled Trial - Patients: COVID patients on supplemental O2; 243 patients; 141 (58%) were men, and 102 (42%) were women. Median age 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino - Design: 2:1, single dose, 8mg/kg of Tocilizumab (IL 6 blocker) - Outcome: death + preventing intubation - Results: The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P = 0.64) - Conclusion: Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Stone JH, Frigault MJ, Serling-Boyd NJ, et al. Efficacy of Tocilizumab in Patients Hospitalized with Covid-19. N Engl J Med. 2020 Oct 21. doi: 10.1056/NEJMoa2028836.

Answer 29

Oral soluble guanylate cyclase stimulator HFpEF Not effective in regards to improvement of physical limitation scores Armstrong PW, Lam CSP, Anstrom KJ, et al. Effect of Vericiguat vs Placebo on Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction: The VITALITY-HFpEF Randomized Clinical Trial. JAMA. 2020 Oct 20;324(15):1512-1521. doi: 10.1001/jama.2020.15922.

Answer 30

Type 1 HFE-related is a mutation in the HFE gene where patients are homozygous for the C282Y mutation

Answer 31

Caucasians have 6x higher risk compared to blacks

Answer 32

Virtually any organ Clinical tip: on differential diagnosis of "infiltrative" diseases affecting multiple organs

Answer 33

Transferrin saturation > 45% is diagnostic Ferritin > 300, but extremely high like > 4000 is highly suggestive

Answer 34

Yersinia Enterolitica Vibrio vulnificus

Answer 35

Tip: simply iron overload, RBC's are the source, hence remove the RBCs Phlebotomy weekly initially Goal: Iron sat < 50%, Ferritin 50-100

Answer 36

Splenic infarcts or hepatic infarcts can be indicative of mesenteric ischemia. TIP: Makes sense since the celiac artery and possibly the SMA feeds spleen/liver

Answer 37

A severe form of Leptospirosis that is characterized by - Pulmonary hemorrhage - Renal failure - Jaundice Hence, liver, renal and respiratory failure

Answer 38

- Gram negative aeriobic spirochete - Arab mouse with drills for hands - Penetrates non-intact skin - drills for hands penetrate skin -

Answer 39

Conjunctival erythema WITHOUT presence of an inflammatory exudate

Answer 40

Doxycycline TIP: Just like syphilis's second line treatment

Answer 41

Typical atrial flutter (90% of the cases), also called counterclockwise atrial flutter, is characterized by 1) POSITIVE waves in lead V1 2) NEGATIVE flutter waves in leads II, III, and aVF Tip: counter intuitive, because one would think "typical" is "clockwise", but its the reverse Clinical tip: the "teeth" or the "pointed" ends of the flutter waves indicate if they are positive or negative waves

Answer 42

Atypical atrial flutter, also called clockwise atrial flutter, is characterized by 1) NEGATIVE waves in inferior leads V1 2) POSITIVE flutter waves in leads II, III, and aVF Tip: counter intuitive, because one would think "typical" is "clockwise", but its the reverse Clinical tip: the "teeth" or the "pointed" ends of the flutter waves indicate if they are positive or negative waves

Answer 43

In typical atrial flutter, the reentrant wavefront travels up the interatrial septum and down the right atrial free wall anterior to the crista terminalis and traverses the cavotricuspid isthmus to complete the circuit in a counterclockwise direction in the right atrium

Answer 44

Simply different in the pathway of the circuit Left atrial flutter, double wave reentry atrial flutter (two reentrant wave fronts simultaneously circulating in the same reentrant circuit), lower loop and upper loop reentry right atrial flutter, and atrial flutter caused by reentry around a surgical incision160 have also been described

Answer 45

Atrial flutter often is initiated by AF. Atrial flutter occurs commonly in association with AF And hence, ANY disease state that is commonly associated with Afib, can easily cause Atrial Flutter such as chronic obstructive pulmonary disease, mitral or tricuspid valve disease, thyrotoxicosis, and postsurgical repair of certain congenital cardiac lesions (eg, atrial septal defect, the Mustard procedure, the Senning procedure, or the Fontan procedure), as well as enlargement of the atria for any reason, especially the right atrium.

Answer 46

Adenosine or vagal maneuvers to slow the AV node so that there will be longer time between every QRS and hence P or saw tooths can be seen more easily

Answer 47

Although the choice between rate and rhythm control is similar to that in AFib, there is bias toward rhythm control in atrial flutter as a result of the relative ease and HIGH success rate of catheter ablation, but also to the difficulty in many patients to achieve good rate control.

Answer 48

Valvular AF is defined as moderate-to-severe mitral stenosis or mechanical heart valves

Answer 49

There is agreement among guideline recommendations that women with a CHA2DS2-VASc score of ≥ 3 and men with a score of ≥ 2 are at an increased risk of stroke and should be given anticoagulant therapy based on the benefits greatly outweighing the bleeding risk.

Answer 50

Most will say consider AC American College of Chest Physicians (ACCP) - offer stroke prevention to patients with atrial fibrillation and ≥ 1 non-sex CHA2DS2-VASc stroke risk factor, such as males with CHA2DS2-VASc score ≥ 1 Strong recc, moderate evidence TIP: Almost ALL patients with Afib should be treated with AC

Answer 51

Catheter ablation is highly successful, typically 90% or greater, to eliminate the typical atrial flutter

Answer 52

Cochrane Review Sept 2020 TLDR: Sensitive, but no specific Our findings indicate that chest CT is sensitive but not specific for the diagnosis of COVID-19 in suspected patients, meaning that CT may not be capable of differentiating SARS-CoV-2 infection from other causes of respiratory illness. This low specificity could also be the result of the poor sensitivity of the reference standard (RT-PCR), as CT could potentially be more sensitive than RT-PCR in some cases. Salameh JP, Leeflang MM, Hooft L, et al. Thoracic imaging tests for the diagnosis of COVID-19. Cochrane Database Syst Rev. 2020 Sep 30;9:CD013639. doi: 10.1002/14651858.CD013639.pub2.

Answer 53

Treatment is not recommended for asymptomatic patients except for high-risk patients such as neonates and those with neutropenia or having urologic procedures

Answer 54

Fluconazole 200 mg orally daily for 14 days

Answer 55

Most commonly arises in catheterized, instrumented, or obstructed patients In inpatient settings: ``` diabetes indwelling catheter urinary tract obstruction recent surgery ICU patients ``` Patients receiving immunosuppressive therapy

Answer 56

Rarely, the presence of yeast in the urine is a sign of disseminated infection.

Answer 57

Expected R wave is NEGATIVE Why: aVR is positive, located in the right arm, and since the overall vector goes in a down and left direction, AWAY from aVR, then aVR shows a NEGATIVE R wave.

Answer 58

Poisoning with sodium-channel blocking drugs (e.g. TCAs) Dextrocardia Incorrect lead placement (left/right arm leads reversed) Commonly elevated in ventricular tachycardia (VT)

Answer 59

US Yes, EVEN if CT already obtained. It is because US characteristics are taken into account to determine risk of malignancy

Answer 60

ALL postmenopausal women with ovarian cyst regardless of the characteristics

Answer 61

NO It can be low in limited disease, and tends to be high in extensive disease. So it could rule out extensive disease, but not the presence of disease

Answer 62

Sept 2020 Meta-analysis and Systematic Review RIVAROXABAN - Seven comparative studies, comprising 2364 participants - VKA vs Rivaroxaban - Results: - [pooled unadjusted odds ratio (OR): 0.53, 95%CI: 0.43-0.65, P < 0.00001] - reduced risk of mild PTS (OR: 0.64, 95%CI: 0.50-0.82, P = 0.0005) - moderate PTS (OR: 0.64, 95%CI: 0.45-0.91, P = 0.01), - severe PTS (OR: 0.52, 95%CI: 0.33-0.82, P = 0.005). CONCLUSION: In comparison to VKAs, the use of rivaroxaban for DVT treatment has the potential to reduce PTS events. However, well-designed studies with larger sample sizes are needed to corroborate these findings. Li R, Yuan M, Cheng J, et al. Risk of post-thrombotic syndrome after deep vein thrombosis treated with rivaroxaban versus vitamin-K antagonists: A systematic review and meta-analysis. Thromb Res. 2020 Sep 17;196:340-348. doi: 10.1016/j.thromres.2020.09.014.

Answer 63

OCT 2020 JAMA - NO - Cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial - Intervention Tocilizumab at 1 and 3 days - 64 pts vs 63 pts, admitted on at leas 3 L NC, BUT not intubated OR in the ICU - Outcomes: progression score, death at 14 days, and need for MV Conclusion: TCZ did NOT reduce WHO-CPS scores lower than 5 at day 4 but MIGHT have reduced the risk of NIV, MV, or death by day 14. NO difference on day 28 mortality was found Hermine O, Mariette X, Tharaux PL, et al. Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia: A Randomized Clinical Trial. JAMA Intern Med. 2020 Oct 20. pii: 2772187. doi: 10.1001/jamainternmed.2020.6820.

Answer 64

About 50% of total calcium is ionized, and the rest is bound principally to albumin.

Answer 65

Every 1.0 g/dL of albumin below 4, add 0.8mg/dL to the Calcium

Answer 66

In acute myocardial infarction, ST elevations are CONVEX (big hill), and reciprocal depression is usually more prominent TIP: counter intuitive to what I would think. Con CAVE, makes me think of cave, that is, hill shaped. ConVEX, makes be think of the big V between the T wave and the QRS.

Answer 67

- Q waves - Concave (pericarditis) vs convex ST elevation (tombstone) - PR depression (compared to TP segment) - interesting: caused by atrial involvement - T wave inversion AFTER ST changes return to baseline is characteristic of pericarditis (TWI can occur in acute setting of AMI)

Answer 68

3 times more likely that a new diagnosis of brain tumor is metastatic

Answer 69

3x more likely metastatic If primary: - 30% glioma - 35% meningiomas - 10% vestibular schwannoma

Answer 70

Low grade glioma NOTE: Interesting!

Answer 71

Malignant brain tumors—whether primary or metastatic—typically enhance with gadolinium and may have central areas of necrosis; they are characteristically surrounded by edema of the neighboring white matter.

Answer 72

Nintedanib is an intracellular tyrosine kinase inhibitor that inhibits several growth factors including vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor. A recent trial demonstrated that use of this medication slowed the rate of decline in FVC and could potentially decrease mortality. Pirfenidone is an oral antifibrotic medication that has been demonstrated to decrease fibroblast proliferation and collagen synthesis. NOTE: both have antifibrotic qualities

Answer 73

Pulmonary function tests demonstrate restrictive ventilatory defect (low TLC, low RV, low VC) with a low DLCO.

Answer 74

Atypical findings that should cause one to consider an alternative diagnosis include the presence of ground-glass infiltrates, nodular opacities, an upper lobe predominance of disease, and prominent hilar or mediastinal lymphadenopathy Clinical: acute exacerbations of IPF will have GOO on imaging

Answer 75

The sulfonylureas are sulfa drugs! Phototoxicity: nonimmunologic reaction that can occur without a latency period after taking a drug. The response resembles a sunburn and occurs in sun-exposed areas. Like a sunburn, a phototoxic reaction can blister and desquamate Photoallergy: UV rays transform the drug into an unstable hapten capable of stimulating an immune response. This delayed hypersensitivity response is intensely pruritic. Sun-exposed skin appears lichenified and leathery. In rare cases (5%–10%), persistent hypersensitivity to light will persist even after the offending drug is discontinued, a condition known as persistent light reaction

Answer 76

The functional residual capacity of the lung refers to the volume of air that remains in the lung following a normal tidal respiration

Answer 77

Stage I and II (NO nodal involvement at all) - Stage I: Tumor < 2 cm WITHOUT extraparenchymal involvement - Stage II: Tumor > 2 cm WITHOUT extraparenchymal involvement Stage III - automatically once 1 LN has metastatic disease

Answer 78

Stage I and II (NO nodal involvement at all) - Stage I: Tumor < 2 cm WITHOUT extraparenchymal involvement - Stage II: Tumor > 2 cm WITHOUT extraparenchymal involvement Radiation therapy to preserve voice - NOT surgery

Answer 79

Normal BMI ranges between 20 and 25 kg/m2, and a patient is considered underweight with likely moderate malnutrition at a BMI of 18.5 kg/m2. Severe malnutrition is expected with a BMI of <16 kg/m2. In men, a BMI of <13 kg/m2 is lethal In women, the lethal BMI is <11 kg/m2

Answer 80

134,000 on any given night (2017)

Answer 81

Calcium (75 to 85%) > Uric acid > Cysteine > Struvite

Answer 82

ESRD Heart specific: PE, myo/pericarditis, hypotension, hypertension Lesson: It is important to remember that although cardiac troponin biomarkers (troponin I or T) are quite sensitive for myocardial infarction due to coronary occlusion, they lack somewhat in specificity.

Answer 83

QO2 = CO × [1.39 × hemoglobin × SaO2 + (0.003 × PaO2)] Delivery of O2 is dependent on the CO and the Oxygen content. Note that the PaO2 is negligible in regards to the content of O2

Answer 84

Anterior uveitis is the most common, occurring in 40% of patients with ankylosing spondylitis.

Answer 85

There is NO gold standard, not even endotraheal cultures (as this can be due to colonization) Usually, its the presence of a constellation of symptoms that point toward VAP: - New O2 requirement - Fever - Increased secretions - Leukopenia or leukocytosis

Answer 86

"Bismuth Quadruple therapy" - notice the QID for 14 days - Bismuth QID - PPI BID - Metronidazole QID - Tetracycline QID "Concomitant therapy" - not sure the meaning, but the tip is that each med is BID for 14 days - PPI BID - Clarithro BID - Amox 1gm BID - Metro 500 mg BID Tip: PPI and Metronidazole is the same for both regimens

Answer 87

Opioids reduce the sensitivity of the central respiratory drive center and often reduce the sensation of dyspnea. Clinical tip: Opioids are first line for dyspnea in end of life care

Answer 88

Because clinically meaningful aminotransferase elevations are so rare after statin use and do not differ in meta-analyses from the frequency of such laboratory abnormalities in placebo recipients, the National Lipid Association’s Safety Task Force concluded that liver test monitoring was not necessary in patients treated with statins and that statin therapy need not be discontinued in patients found to have asymptomatic isolated aminotransferase elevations during therapy

Answer 89

The most common manifestations of cryoglobulinemic vasculitis are cutaneous vasculitis, arthritis, peripheral neuropathy, and glomerulonephritis

Answer 90

RTA Type I

Answer 91

pH > 5.5 Basic because tubules unable to excrete H+ ions. In contrast with RTA Type II in which bicarb can't be reabsorbed, BUT DCT can still excrete H, hence pH < 5.5

Answer 92

COCHRANE REVIEW OCT 2020 Conclusion: There is a lack of high-certainty evidence for the effects of pentoxifylline compared to placebo, or other treatments, for IC. There is low-certainty evidence that pentoxifylline may improve PFWD and TWD compared to placebo, but no evidence of a benefit to ABI or QoL (moderate-certainty evidence). Broderick C, Forster R, Abdel-Hadi M, et al. Pentoxifylline for intermittent claudication. Cochrane Database Syst Rev. 2020 Oct 16;10:CD005262. doi: 10.1002/14651858.CD005262.pub4.

Answer 93

BMJ Oct 2020 PLACID Trial RCT Phase II Trial Patients: Indian; confirmed moderate covid-19 (partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2) ratio between 200 mm Hg and 300 mm Hg or a respiratory rate of more than 24/min with oxygen saturation 93% or less on room air Intervention: two doses of 200 mL convalescent plasma, transfused 24 hours apart NOTE: neutralizing ab NOT measured prior MAIN OUTCOME MEASURE: Composite of progression to severe disease (PaO2/FiO2 <100 mm Hg) or all cause mortality at 28 days post-enrolment. CONCLUSION: Convalescent plasma was not associated with a reduction in progression to severe covid-19 or all cause mortality Agarwal A, Mukherjee A, Kumar G, et al. Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial). BMJ. 2020 Oct 22;371:m3939. doi: 10.1136/bmj.m3939.

Answer 94

JAMA OCT 2020 Prospective, open label RCT - 1st for Tocilizumab Who: COVID-19 pneumonia documented by imaging, partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2/Fio2) ratio between 200 and 300 mm Hg, and an inflammatory phenotype defined by fever and elevated C-reactive protein. Patients: 60 vs 66 patients Intervention: Tocilizumab 8mg/kg (max 800) x 2 doses (12 hours apart) Outcome: composite outcome was defined as entry into the intensive care unit with invasive mechanical ventilation, death from all causes, or clinical aggravation documented by the finding of a Pao2/Fio2 ratio less than 150 mm Hg, whichever came first Results: Seventeen patients of 60 (28.3%) in the tocilizumab arm and 17 of 63 (27.0%) in the standard care group showed clinical worsening within 14 days since randomization (rate ratio, 1.05; 95% CI, 0.59-1.86) Conclusion: The trial was prematurely interrupted after an interim analysis for futility. Tocilizumab provided no benefit on disease progression was observed compared with standard care. Salvarani C, Dolci G, Massari M, et al. Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial. JAMA Intern Med. 2020 Oct 20. pii: 2772186. doi: 10.1001/jamainternmed.2020.6615.

Answer 95

MCA, PCA, ACA, Vertebrobasilar flow and ICA! ALL the arteries you'd be interested in and that a CTA or MR Angiography could evaluate TCD can detect acute MCA occlusions with high (> 90%) sensitivity, specificity, and positive and negative predictive values.40–43 TCD can also detect occlusion in the ICA siphon, vertebral, and basilar arteries with reasonable (70 to 90%) sensitivity and positive predictive value and excellent specificity and negative predictive value (> 90%

Answer 96

P1 – Midbrain stroke P2 – occipital and temporal lobe involvement

Answer 97

MCA stroke – spares the macula PCA stroke does NOT spare the macula since P2 segment perfuses the calcarine cortex

Answer 98

Acute onset of bilateral signs: - Bilateral ptosis - Pupillary asymmetry - Somnolence (few strokes cause somnolence) - Posturing - Myoclonic jerks that look like seizures

Answer 99

Review: PICA comes from the vertebral artery Lateral medulla AND inferior part of the cerebellum

Answer 100

Review: 4 parts of the vertebral artery - V1 and V4 and the most common part disposed to strokes - V1 and V4 atherothrombotic which can lead to thrombotic occlusion and extension OR embolism V2 and V3 dissection

Answer 101

Medial medullary: Vertebral artery (or branch of vertebral artery or lower basilar artery) Lateral medullary syndrome: any of the following 5 vessels - Vertebral - PICA - Superior, middle or inferior lateral medullary arteries

Answer 102

AKA Wallenberg’s Syndrome TIP: NO hemiparesis; Deficits are mainly from the neck above; brainstem heavy presentation ``` Horner syndrome Double vision Hoarseness Dysphagia Dysarthria Vertigo Numbness of ipsilateral face and CONTRA lateral limbs ``` Picmonic: - Horse with a horn like a unicorn; wearing glasses and crossed eyes, on a skate board, wearing a muzzle (dysarthria), half of face black and half of body black like a jester

Answer 103

Cerebellar edema leads to ICP and closure of the aqueduct of Sylvius and 4th ventricle leading to hydrocephalus NUS emergency! But easy fix if caught

Answer 104

PICMONIC Clinical tip: brainstem strokes can come from any variety of vessels that supply the brainstem, AKA any of the posterior cerebral circulation, hence vertebral, PICA, medullary arteries, basilar arteries and their branches, etc, but brainstem strokes tend to have the following presentation in common: - Vertigo - Dysarthria - Diplopia - Hyperacusis/Tinnitus - Ataxia - Coma - Word salad - Cranial nerve involvement Hence, lateral medullary syndrome, since it involves the vertebral artery, or PICA or medullary arteries, can have above findings on presentation

Answer 105

PONS Why: basilar artery first starts at the medullarpontine junction, spans the pons and ends at the midbrain pontine junction

Answer 106

EASY: - Bilateral long tract signs (motor/sensory), - cranial nerve involvement - cerebellar involvement Basilar artery supplies mostly the PONS, hence presentation of a basilar artery stroke should represent pontine ischemia Since basilar artery supplies the anterior part of the pons and that is where corticospinal tracts run through, the sx are bilateral and motor/sensory Ataxia due to cerebellar involvement TIP: Asymmetry but bilaterality of neurologic signs is the rule AKA one side is predominantly affected, but both sides are always affected to some extent

Answer 107

Since stroke is a clinical diagnosis, CT head is NOT needed for diagnosis. However, it aids in clarifying the diagnosis - looking for masqueraders and determining if the stroke is hemorrhagic. CT is helpful as part of treatment, as a hemorrhage would make TPA contraindicated Masqueraders: tumors, abscess, extraparenchymal hemorrhage

Answer 108

MRI scan shows extent and location of infarction in ALL areas of brain CT: does not show posterior fossa well; does not show infarct in the first 24-48 hours

Answer 109

CT Angiography is the GOLD standard WATCHOUT: gold might be X ray angiography

Answer 110

CT Angiography MR Angiography: Highly sensitive for extra and intracranial stenosis of LARGE vessels; Can also evaluate for dissections like CTA; However, overestimates the degree of stenosis in instances of higher grade stenosis compared to CTA. In acute stroke protocols, CTA is used. MRI, being time consuming, is used most often OUTSIDE the acute period.

Answer 111

AFTER the acute period given its limitations of availability and timing - Clearly defining the extent of tissue injury and discriminating old from new regions of infarction TIA patients as it allows identification of new infarction

Answer 112

In acute stroke, CT remains the main imaging modality given ease, availability, speed and efficacy - Non-contrast CT Head - Then, CT Angiography of head/neck to evaluate for stenosis All others are used in the post stroke period – MRI and Ultrasound Clinical tip: AHA/ASA - Suggest CT head OR MRI head first to eval for intracranial hemorrhage - Following the above, suggest either CTA OR MRA with DWI (with or without perfusion) to eval if patient candidate for thrombectomy TLDR: both CT and MRI are both kosher

Answer 113

CT Angiography OR MR Angiography does NOT imply perfusion. Perfusion is a technique that can be added to CT (SPECT) or MRI (perfusion) that reports relative cerebral blood flow and ultimately increases sensitivity of detecting ischemia

Answer 114

Cochrane OCT 2020 No to patients with active LDL lowering therapy - low certainty evidence Yes to patients NOT on active therapy Outcomes: CVD events, stroke, MI, all cause mortality 24 studies with 60,997 participants. 18 trials alirocumab and 6 to evolocumab. Alirocumab compared with placebo Alirocumab reduces CVD events, mortality, MI and stroke when compared to placebo all with high certainty evidence, but when compared to active treatments showed no difference in all outcomes with low certainty evidence Evolocumab reduces CVD events, not mortality, yes MI and stroke when compared to placebo all with high certainty evidence, but but when compared to active treatments showed no difference in all outcomes (stroke unable to measure) with low to very low certainty evidence TLDR: PSCK9 inhibitors are clearly beneficial for patients not actively being treated with LDL lowering therapy, but there is no evidence to demonstrate that would be helpful as additional therapy for people already on LDL lowering therapy Schmidt AF, Carter JL, Pearce LS, et al. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10:CD011748. doi: 10.1002/14651858.CD011748.pub3.

Answer 115

October 2020 Cochrane review 8 RCTs total with 811 patients total Conclusion: Interestingly, a lot of the treatments were associated with an increased risk of thromboembolic events - VKA vs NOAC - VKA with antiplatelet vs VKA alone - no placebo trials Bala MM, Celinska-Lowenhoff M, Szot W, et al. Antiplatelet and anticoagulant agents for secondary prevention of stroke and other thromboembolic events in people with antiphospholipid syndrome. Cochrane Database Syst Rev. 2020 Oct 12;10:CD012169. doi: 10.1002/14651858.CD012169.pub3

Answer 116

The dysfunctional tissue that surrounds the core of infarction in a stroke that is defined as “ischemic but reversible” Clinical tip: the acute treatment of stroke is focused on saving the penumbra

Answer 117

Worsens the brain injury, hence it is essential to control the hyperglycemia if present

Answer 118

Essential to prevent VTE as acute ISCHEMIC stroke patients have high morbidity from VTE. Hence, if no contraindication, start chemical ppx for VTE

Answer 119

Because cartilage is aneural, cartilage loss in a joint is not accompanied by pain. Thus, pain in OA likely arises from structures OUTSIDE the cartilage. Innervated structures in the joint include the synovium, ligaments, joint capsule, muscles, and subchondral bone.

Answer 120

If > 1000 WBC, likely inflammatory

Answer 121

Elderly Alcoholics Autistic children

Answer 122

Nintedanib is an intracellular tyrosine kinase inhibitor that inhibits several growth factors including vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor.

Answer 123

The most common form of familial amyloidosis is ATTRm in the updated nomenclature, caused by mutation of the abundant plasma protein transthyretin (TTR, also known as prealbumin) More than 100 TTR mutations are known, and most are associated with ATTR amyloidosis

Answer 124

ATTR amyloidosis warrants consideration in the differential diagnosis of African American patients who present with concentric cardiac hypertrophy and evidence of diastolic dysfunction, particularly in the absence of a history of hypertension

Answer 125

To provide a clinical and definitive diagnosis of endocarditis 2 Major 1 Major and 3 minor 5 Minor

Answer 126

1) Fever 2) Predisposing condition: IV drug user or heart condition 3) Vascular phenomenon: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions TIP: vascular means bleeding, clots or aneurysms 4) Immunologic phenomenon: glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor 5) Positive blood cultures

Answer 127

Major criteria: - Blood culture positive for IE - Evidence of endocardial involvement Blood culture positive for IE can be any of the following: - 1 blood culture for Coxiella burnetii, or positive Q fever serology (anti-phase 1 immunoglobulin G antibody titer > 1:800) - 2 separate blood cultures positive for typical organisms (Staphylococcus aureus, Enterococcus without primary focus, Streptococcus viridans, Streptococcus bovis, HACEK group) - Microorganism consistent with IE in ≥ 2 blood cultures drawn > 12 hours apart or on all of 3 blood cultures or most of ≥ 4 separate blood cultures, with first and last samples drawn ≥ 1 hour apart TIP: "1, 2, 3, 4 rule" - 1 coxiella or - 2 blood cultures consistent with typical organisms 12 hours apart or - 3 positive blood cultures or - most of 4 positive blood cultures (first and last cultures are 1 hour apart) Evidence of endocardial involvement: - Oscillating intracardiac mass on valve or support structure in path of regurgitant jets or on implanted material - Abscess - New partial dehiscence of prosthetic valve TIP: new or worsening murmur is NOT enough

Answer 128

Right ventricle bypass tract: - LBBB morphology (as seen in I and aVL) since impulse goes to RV via tract and then sweeps toward the LV just like LBBB - PR interval shorter (then PR interval in LV bypass tract) since SA node is VERY close to RV, the impulse travels from atria to RV faster than atria to LV tract - QRS is wider (than compared to LV bypass tract) because I imagine the atria impulse travels so quickly to the RV that depol starts from RV and sweeps over to the LV. If bypass tract was in the LV, impulse has time to go down the His Purkinje system and hence have a more narrow QRS

Answer 129

800 IU/day of Vit D3 for daily dietary intake 2000 IU/day of Vit D3 for Vit D def 50,000 IU of D2 (or D3) weekly for 8 weeks to achieve 25OH Vit D >30, then 2000 IU/day of Vit D3 for severe Vit D deficiency

Answer 130

Depletes eosinophils and inhibits mast cells

Answer 131

NEJM Oct 2020 RCT, Phase 2 Yes Patient: 43 patients vs 22 placebo Intervention: Lirentelimab, 4 monthly infusions Outcome: The primary end point was the change in gastrointestinal eosinophil count from baseline to 2 weeks after the final dose; Secondary end points were treatment response (>30% reduction in total symptom score and >75% reduction in gastrointestinal eosinophil count) and the change in total symptom score. Phase 2 trials – showed reduction of eosinophils compared to placebo and improved patient symptoms scores Dellon ES, Peterson KA, Murray JA, et al. Anti-Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis. N Engl J Med. 2020 Oct 22;383(17):1624-1634. doi: 10.1056/NEJMoa2012047.

Answer 132

Chest Oct 2020 Systematic Review - diffuse alveolar damage in 88% - pulmonary microthrombi in 57% - organizing fibrosis in 52% - superimposed pneumonia in 32% - pulmonary thrombosis in 15 - acute fibrinous and organizing pneumonia in 4% - end-stage fibrosis in 1%

Answer 133

CT or MRI "with perfusion"

Answer 134

0.9 mg/kg, 10% bolus, followed by remaining infusion over 60 minutes

Answer 135

Within 3 to 4.5 hours

Answer 136

The time of stroke onset is defined as the time the patient's symptoms were witnessed to begin or the time the patient was last normal. If awakens with stroke, onset is defined as when patient went to bed

Answer 137

- Mechanical thrombectomy | - Intra-arterial thrombolysis

Answer 138

MCA - M1 segment Internal carotid artery Explication: the larger the clot burden, the likelihood that systemic TPA will not be successful

Answer 139

Mechanical thrombectomy is FDA approved, but not intra-arterial thrombolysis, hence mechanical thrombectomy is preferred over intra-arterial thrombolysis

Answer 140

300mg x 1 on the first day, followed by 81 mg/day If received TPA: wait 24 hours following TPA to start ASA

Answer 141

- Recurrent ischemic stroke - Early mortality - Dependency/disability at discharge CAST TRIAL

Answer 142

No role - increases risk of brain hemorrhage

Answer 143

Blood glucose level Hypoglycemia can present with stroke-like symptoms

Answer 144

Intracranial internal carotid artery MCA PCA (infrequently ACA) TIP: I wonder if this is how UofL decided on TEE vs TTE. For example, if patient presented with lacunar stroke, likely more related to HTN, but still need to rule out embolism, hence TTE. If MCA stroke, TEE for more definitive eval of atria

Answer 145

Atrial fibrillation

Answer 146

Recent MI, especially affecting the anteroapical ventricular wall can predispose to clot formulation that leads to stroke.

Answer 147

Transcranial doppler with insonation of the MCA which shows bubbles immediately following the injection of agitate saline Especially when ECHO with bubble study fails to show a a right to left cardiac shunt

Answer 148

Thrombus formation on atherosclerotic plaques may embolize to intracranial arteries producing artery-to-artery embolic stroke TIP: unlike coronary arteries, it is less likely that local thrombosis with acute occlusion be the mechanism of stroke

Answer 149

Common carotid bifurcation Proximal internal carotid artery (part that comes soon after bifurcation) ``` Carotid siphon (portion within the cavernous sinus) TIP: makes sense since it is a cramped and tortuous space ```

Answer 150

Generally, the more stenotic the carotid artery, the more atherosclerosis there is, which increases the risk of thombosis and subsequent embolism. However, near occlusive disease is NOT associated with increased risk of stroke. TIP: so occlusive that there is no room for thrombosis to occur

Answer 151

Dissection of the ICA or vertebral arteries SAH

Answer 152

Trauma, usually a MVA or a sports injury, can cause carotid and vertebral artery dissections. Spinal manipulative therapy, such as osteopathic med maneuvers, care also associated

Answer 153

Lacunar comes from the word "lacune" which means lakes. Now called "small vessel strokes", what was previously called lacunar strokes was called this because of the autopsy findings. Small vessel strokes are strokes of the penetrating arteries caused by thrombotic OR lipohyalinotic occlusions TIP: stands out because it is one of the few strokes in which thrombotic occlusion is the main mechanism as opposed to embolism

Answer 154

- Pure motor hemiparesis: face, arm and leg almost ALWAYS involved - Cause: posterior limb of internal capsule or the pons - Pure sensory stroke - Cause: Ventral thalamus - Ataxic hemiparesis: AKA ataxia and hemiparesis of the same side of the body - Cause: Vental pons or internal capsule - Dysarthria and clumsy hand (AKA clumsy speech, clumsy hand syndrome): - Cause: Ventral pons or the genu of the internal capsule

Answer 155

Yes, though the main mechanism is from either atherothrombosis or lipohyalinotic occlusion, a larger vessel source may manifest itself as a small vessel stroke or infarction

Answer 156

Predilection for the EXTERNAL carotid artery - NOT internal

Answer 157

Both present with sudden, severe headache

Answer 158

Conventional X Ray angiography which would demonstrate changes in the vascular caliber thoughout the hemispheres that appears vasculitic, but is noninflammatory

Answer 159

Small vessel strokes (anterior temporal lobes)

Answer 160

``` Age DM Smoking HTN Cholesterol (low HDL, high LDL) ``` Clinical tips: - HTN is the most important factor - DM likely the most important modifiable factor to reduce stroke

Answer 161

Hypertension

Answer 162

Yes, even in patients WITHOUT elevated LDL or low HDL Clinical tip: SPARCL trial

Answer 163

Prevention of DM

Answer 164

1) Aspirin daily 81-325 mg daily 2) Aspirin + Dipyridamole ER 3) Clopidogrel 75 mg daily Clinical tip: ASA/Dipyridamole ER is effective as demonstrated by the ESPS II trial, but costs 100 monthly at Costco

Answer 165

Preventing platelet aggregation prevents the formation of atherothrombosis which can cause occlusive thrombosis or emboli

Answer 166

Aspirin, like other NSAIDs, are COX inhibitors ASA inhibits COX irreversibly by acetylating the COX enzyme This irreversibly inhibits (8 days) the formation of TXA2, thromboxane. Thromboxane normally causes both vasoconstriction and platelet aggregation No platelet aggregation, no atherothrombotic events

Answer 167

The effect on prostacyclin is transient

Answer 168

Following TIA, ASA/Clopidogrel can be used for 21 days and has shown a reduced risk of stroke within a 90 day window without increasing bleeding risk

Answer 169

25- 30% reduction in stroke risk Clinical tip: 25% reduction in all vascular events taken together

Answer 170

8-10% yearly Clinical tip: Hence the importance of taking secondary prevention like ASA!

Answer 171

SAME risk! Hence, in cryptogenic stroke, it is always a good idea to have ambulatory monitoring for 3-4 weeks for TIA or cryptogenic stroke

Answer 172

1) Prevents the uptake of adenosine by the endothelial cells. The accumulated adenosine acts as an inhibitor of aggregation. 2) Inhibits phosphodiesterase of the platelets which leads to accumulation of cAMP. cAMP also inhibits aggregation by potentiating the effects of NO and prostacyclin. A lot of cAMP outside platelets, a lot of adenosine outside the enthodelial cells => inhibits aggregation

Answer 173

Perform carotid endarterectomy (CEA) for patients with - symptomatic carotid stenosis - that's caused a TIA/ NON DISABLINGstroke within the last 6 months - caused by either ipsilateral severe (70%-99%) stenosis documented by noninvasive imaging or ipsilateral moderate (50%-69%) stenosis documented by catheter-based imaging - and a perioperative morbidity and mortality risk estimated to be < 6% NASCET

Answer 174

within 2 weeks of TIA/Stroke

Answer 175

Endarterectomy Carotid stenting is as effective as endarterectomy in preventing recurrent stroke in symptomatic carotid stenosis but associated with a higher risk of periprocedural stroke or death than endarterectomy. Combining procedural safety and long-term efficacy in preventing recurrent stroke favours endarterectomy. Stenting for asymptomatic carotid stenosis carries a small increase in the risk of periprocedural stroke or death compared with endarterectomy. COCHRANE REVIEW 2020

Answer 176

Symptomatic intracranial atherosclerosis - Stenting -> harmful (SAMMPRIS trial) - Anticoagulation -> harmful (WASID trial) Symptomatic carotid artery disease - Stenting and CEA -> beneficial

Answer 177

The consensus of the committee is that it would be safe to start statins after 48 hours. NICE Guidelines 2019

Answer 178

Following TIA, the combination of Clopidogrel and ASA for 21 days decreased risk of recurrent stroke within 90 days without increasing risk of bleeding TIP: Mulitple studies have shown that ASA/Clopidogrel combination for stroke prevention shows no benefit over ASA alone and only increases bleeds (CAPRIE, MATCH, CHARISMA trials)

Answer 179

Meta-analyses use either a fixed effect or a random effects statistical model. A fixed effect meta-analysis assumes all studies are estimating the same (fixed) treatment effect. This assumes all studies are estimating the same (common) treatment effect. In other words, there is no between study heterogeneity in the true treatment effect. Whereas a random effects meta-analysis allows for differences in the treatment effect from study to study. assumes the observed estimates of treatment effect can vary across studies because of real differences in the treatment effect in each study as well as sampling variability (chance).

Answer 180

COCHRANE REVIEW OCT 2020 TLDR: who knows; low evidence and high bias 27 studies, 1828 participants Shunts: total shunts, distal splenorenal shunts and TIPS Endoscopic therapy: sclerotherapy, banding High risk of bias Very low certainty of evidence ((i.e. the true effects of the results are likely to be substantially different from the results of estimated effects) Very low evidence CONCLUSIONS: Evidence on whether portosystemic shunts versus endoscopy interventions with or without medical treatment in people with cirrhosis and previous hypertensive portal bleeding have little or no effect on all-cause mortality is very uncertain. Evidence on whether portosystemic shunts may reduce bleeding and mortality due to bleeding while increasing hepatic encephalopathy is also very uncertain. We need properly conducted trials to assess effects of these interventions not only on assessed outcomes, but also on quality of life, costs, and length of hospital stay. Simonetti RG, Perricone G, Robbins HL, et al. Portosystemic shunts versus endoscopic intervention with or without medical treatment for prevention of rebleeding in people with cirrhosis. Cochrane Database Syst Rev. 2020 Oct 22;10:CD000553. doi: 10.1002/14651858.CD000553.pub3.

Answer 181

The so-called "classical 3-point MACE" is defined as a composite of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death

Answer 182

1) Hypoglycemia (as obtained by serum BG) 2) Symptoms consistent with hypoglycemia 3) Reversal of symptoms with resolution of BG Purpose: connect specific symptoms with episode of hypoglycemia

Answer 183

*** BG < 80, decreased insulin secretion BG of 70 is the lower limit of normal fasting glucose - Hence BG < 70 is considered hypoglycemia (my own logic) BG < 55 stop the 72 hour fast BG < 45 stop the 72 hour fasting test Normal fasting glucose is < 70 to 100 Normal post-prandial < 140

Answer 184

The brain, as its main source of energy is glucose and it has limited stores of glycogen (few minutes) and CANNOT synthesize its own glucose. Hence practically needs continuous supply of glucose. Reason why strokes present acutely

Answer 185

BG 70-110 mg/dL

Answer 186

8 hours The hepatic glycogen stores can maintain plasma glucose levels for about 8 hours. BUT it can be shorter if there is greater demand (illness/exercise) or stores have been depleted prior (pre-existing starvation)

Answer 187

Glucose making factories: liver and kidney - Via gluconeogenesis Glucose delivery centers: liver and kidney - Via glycogenolysis Glucose natural resources: Adipose and muscle - Via proteinolysis -> lactate, AA, glutamine, alanine - Via lipolysis -> Glycerol and FFA

Answer 188

Decreased secretion of insulin Which leads to glycogenolysis and gluconeogenesis, that is, liver and kidney release glycogen stores as well as make glucose with "spare parts"

Answer 189

First line: decreased insulin secretion - glycogenolysis and gluconeogenesis Second line: glucagon release - glycogenolysis and gluconeogenesis Third line: epinephrine release - glycogenolysis and gluconeogenesis - via the "sympathoadrenal" response; sympathetic system produces NE/cholinergic that leads to the neuroglycopenic and behavioral response; adrenal glands leads to Epinephrine

Answer 190

NO ROLE! When hypoglycemia is prolonged beyond 4 hours, cortisol and growth hormone are secreted. Growth hormone works 20% as powerful as Epinephrine to maintain glucose levels

Answer 191

BG < 80, insulin secretion is decreased TIP: Not even what we would considered "hypoglycemia". Remember, fasting BG is between 70-100, so BG <70 would be considered hypoglycemia

Answer 192

BG < 80: insulin secretion is decreased BG < 65 - triggers glucagon secretion - triggers Epinephrine secretion - triggers Cortisol/growth hormone secretion Clinical tip: these thresholds are dynamic. E.g. a diabetic with persistent hyperglycemia may experience sx at relative hypoglycemia (which may be technically in the normal range)

Answer 193

Clinical tip: these thresholds are dynamic. E.g. a diabetic with persistent hyperglycemia may experience sx at relative hypoglycemia (which may be technically in the normal range)

Answer 194

Hypoglycemia actually activates pro-inflammatory, pro-coagulant, pro-atherothrombotic responses in diabetic (type I and 2) and non-diabetic individuals which encourages platelet aggregation and reduce fibrinolysis.

Answer 195

Due to both hypoglycemia associated autonomic failure (HAAF, possibly reversible) and diabetic autonomic neuropathy (irrevesibile) HAAF: caused by iatrogenic or preceding hypoglycemia Diabetic autonomic neuropathy: actual pathology of the autonomic system and inability to produce a normal sympathetic response in the face of hypoglycemia Long standing Type I and II DM leads to failure of the Beta cell and subsequent insulin deficiency. In the face acute hypoglycemia, there is NO first line defense - no insulin means no decreased secretion of insulin. And patient likely on exogenous insulin. There is also NO second line of defense, as glucagon is secreted only when insulin is decreased, which can't occur if there is no insulin and patient receiving exogenous insulin.

Answer 196

Up to 10% of TIDM will die because of hypoglycemia!!! | 6-10%

Answer 197

Absolute numbers, there are more episodes hypoglycemia in TIIDM because there are simply more TIDM

Answer 198

Insulins, Sulfonyureas and Glinides TIP: easier to remember the few that cause hypoglycemia since the rest DO NOT!

Answer 199

The vast majority of risk factors leading to hypoglycemia in diabetes are identified on the basis of the premise that a relative or absolute insulin excess is the sole determinant of the risk 1) Insulin (or insulin secretagogue) doses are excessive, ill-timed or of the wrong type 2) Influx of exogenous glucose is reduced (e.g., during overnight fast, periods of temporary fasting, or after missed meals or snacks) 3) insulin-INDEPENDENT glucose use is inclrease (e.g., during exercise) 4) Sensitivity to insulin is increased (e.g. with improved glycemic control, in the middle of the night, late after exercise, or with increased fitness and weight loss) 5) Endogenous glucose production is decreased (e.g. after alcohol ingestion) 6) insulin clearance is reduced (e.g. in renal failure)

Answer 200

Long standing Type I and II DM leads to failure of the beta cell and subsequent insulin deficiency. In the face acute hypoglycemia, there is NO first line defense - no insulin means no decreased secretion of insulin. And patient likely on exogenous insulin. There is also NO second line of defense, as glucagon is secreted only when insulin is decreased, which can't occur if there is no insulin and patient receiving exogenous insulin. TLDR: absolute insulin def indicates that insulin levels will NOT decrease and glucagon levels will NOT increase as plasma glucose levels fall

Answer 201

Recent antecedent iatrogenic hypoglycemia

Answer 202

Iatrogenic hypoglycemia leads to an attenuated sympathoadrenal response. Hence, not much NE/Epi are being produced. This leads to less behavioral manifestations as these manifestations are dependent of NE/Epi

Answer 203

Avoidance of hypoglycemia, that is scaling back on insulin. This allows the sympathoadrenal response to be recalibrated

Answer 204

Decreases incidence of microvascular disease Has NO effect on macrovascular disease (e.g. myocardial infarction)

Answer 205

140-180 Clinical tip: - NICE SUGAR - ACCORD TRIAL - VADT TRIAL - ADVANCE TRIAL

Answer 206

SUPER INTERESTING! Alcohol blocks gluconeogenesis, NOT glycogenolysis Hence, the timing of hypoglycemia usually follows a several day binge, during which little food is ingested, and during which glycogen stores are depleted. Then when gluconeogenesis is required to respond to hypoglycemia, it is inhibited by alcohol.

Answer 207

Liver, renal and heart failure Liver failure: source of glucose production (gluconeo/glycogenolysis) Renal failure: source of gluconeogenesis, decreased clearance of insulin Heart failure: uncertain MOA

Answer 208

In sepsis, cytokines are being produced by macrophages in major organs such as liver, spleen and spleen which utilize glucose as source of energy. In sepsis, the glucose utilization surpasses the supply. Macrophages, during sepsis, use glucose to carry out their duties

Answer 209

In starvation, the brain utilizes alternative fuels such as ketones, lactate and pyruvate, so there is only a modest neuroendocrine and autonomic nervous system response My guess: maybe the body, having an alternative source of energy, doesn't respond as robustly to hypoglycemia

Answer 210

Cortisol deficiency is associated with impaired gluconeogenesis and low levels of gluconeogenic precursors; these associations suggest that substrate-limited gluconeogenesis, IN THE SETTING OF GLYCOGEN DEPLETION, is the cause of hypoglycemia

Answer 211

Mesenchymal or epithelial tumors such as hepatomas, adrenocortical carcinomas and carcinoids Most hypoglycemia is mediated by the over production of an unprocessed insulin like growth factor II ("big IGF II") that does not complex normal with circulating binding proteins and thus more readily gains access to target tissues

Answer 212

- High IGF II to IGF I ratio - Free IGF II - High pro IGF II

Answer 213

2 broad categories: 1) Relative or absolute excess of insulin 2) Hormone related causes of hypoglycemia: A) Excess hormones e.g - insulin I) Primary B cell disorder - which can be a primary B cell tumor - or functional B cell disorder such as B cell hypertrophy/plasia (nesidioblastosis) II) Antibody to insulin or to the insulin receptor - Autoimmune hypoglycemia III) B cell secretagogue IV) Ectopic insulin secretion - IGF II B) Hormone deficiency e.g. GH and Cortisol deficiency Tip: obviously an overlap exists

Answer 214

1) Primary B cell disorder - which can be a primary B cell tumor - or functional B cell disorder such as B cell hypertrophy/plasia (nesidioblastosis) 2) Antibody to insulin or to the insulin receptor - Autoimmune hypoglycemia 3) B cell secretagogue 4) Ectopic insulin secretion

Answer 215

Benign in 90% of the cases!

Answer 216

Failure of insulin secretion to fall to very low levels despite the presence of hypoglycemia

Answer 217

The alveolar-arterial oxygen (A-a O2) difference can be helpful in distinguishing hypoventilation (elevated partial pressure of carbon dioxide [PCO2]) as a cause of hypoxemia. The A-a O2 difference on room air should be less than 15 mmHg in a young adult and typically increases slightly with age. The A-a O2 difference cannot easily be interpreted when the fraction of inspired oxygen (FiO2) is greater than 0.21. The A-a O2 difference elevated: ventilation-perfusion (V/Q) mismatch, shunt, or diffusion defect Normal A-a O2 difference normal: hypoventilation

Answer 218

PAO2 – PaO2 PAO2 = PiO2 – PaCO2/0.8 PiO2 = 0.21 x (760 – 47) – sea level PiO2 = 150mmHg PAO2 = 150 – PaCO2/0.8 PAO2 – PaO2 = (150 – PaCO2/0.8) – PaO2 Normal: difference < 15 (for young adult and increases as one ages) KEY: must be FiO2 of 21%

Answer 219

Palmar erythema Gynecomastia Testicular atrophy

Answer 220

MRI with T2 and Flair

Answer 221

TLDR: T1 good for fat and subacute hemorrhage TLDR: Flair and T2 are related; FLAIR is a subset of T2 TLDR: T2O, hence, higher intensity with substances that have water like CSF and edema (metastatic brain disease)

Answer 222

Magnetic resonance imaging (MRI) is generated from the interaction between the hydrogen protons in biologic tissues, the magnetic field, and the radiofrequency (Rf) of waves generated by the coil placed next to the body part of interest. The Rf pulses transiently excite the protons of the body with a subsequent return to the equilibrium energy state, a process known as relaxation. During relaxation, the protons release Rf energy creating an echo that is then transformed via Fourier analysis to generate the MRI. The two relaxation rates that influence the signal intensity of the image are T1 and T2. T1 refers to the time in milliseconds that it takes for 63% of protons to return to their baseline state. T2 relaxation is the time for 63% of protons to become dephased due to interactions among nearby protons. The intensity of the signal is also influenced by the interval between Rf pulses (TR) and the time between the Rf pulse and the signal reception (TE). T1-weighted images are produced by keeping both TR and TE relatively short, whereas T2-weighted images require long TR and TE times. Fat and subacute hemorrhage have relatively short TR and TE times and thus appear more bright on T1-weighted images. Conversely, structures with more water such as CSF or edema have long T1 and T2 relaxation times, resulting in higher signal intensity on T2-weighted images. T2 images are also more sensitive for detecting demyelination, infarction, and chronic hemorrhage. Fluid-attenuated inversion recovery (FLAIR) is a type of T2-weighted image that suppresses the high-intensity signal of CSF. As a result, images created by the FLAIR technique are more sensitive to detecting water-containing lesions or edema than the standard spin images

Answer 223

This is typical of individuals with α-thalassemia trait. α-Thalassemia trait results when there is a defect in two of the α-globin genes (-α/-α or --/αα) Overall, the production of the α-globin is adequate to yield a normal hemoglobin and not result in excessive hemolysis. However, microcytosis and hypochromia are seen. Hematocrit is normal or only minimally reduced while RBC count may be increased. In addition, to microcytosis and hypochromia, the characteristic finding on peripheral smear is the target cell

Answer 224

α-Thalassemias are most common in individuals of African, Asian, Middle Eastern, or Mediterranean descent.

Answer 225

Heath care workers! - CLINICAL TIP: the patient being a healthcare worker is NOT necessarily good. Gut instinct to trust and be relieved that patient is a healthcare worker should be tempered knowing that healthcare workers are the very patients who have factitious disorder Patients with diabetes Relatives of patients with diabetes History of factitious disorder

Answer 226

Hours or even DAYS TIP: Don't rule it out so quickly when hypoglycemia lasts for days

Answer 227

Via glycogenolysis Clinical tip: hence, in patient's with depleted glycogen stores, such as alcoholics, glucagon will have little to no effect

Answer 228

1 mg IM dose of glucagon (adult dose)

Answer 229

Inborn errors of metabolism

Answer 230

Fructose is absorbed by facilitated diffusion and there is a limited capacity. When capacity is reached, there is malabsorption Review: Facilitated diffusion is the PASSIVE movement of molecules across the cell membrane via the aid of a membrane protein (carrier protein or channel protein)

Answer 231

Lactose is a Disaccharide, which must be split. Retained disaccharides cause an osmotic retention of fluid in the intestine and bacteria ferment it into gases

Answer 232

Further characterizing watery diarrhea: secretory vs osmotic

Answer 233

290 mOsm/kg − 2 × (stool Na + stool K) Gap > 75, means there is a lot of unmeasured non-electrolyte is contributing to the fecal osmolality hence, osmotic diarrhea Gap < 50, secretory diarrhea

Answer 234

Opioid Loperamide which as a mu receptor acts specifically on the intestines and has low abuse potential

Answer 235

Bile acid resins such as cholestyramine, colestipol and colesevelam. Though effective in (BAM), bile acid malabsorption, there is a constipating effect

Answer 236

DM can lead to "diabetic diarrhea" Clonidine, alpha 2 adrenergic agonist, can stimulate absorption and and slow transit. In DM there is a LOSS of noradrenergic innervation int he gut

Answer 237

Antibiotics to selectively target bacterial strains causing SIBO syndrome if possible - Rifaximin, with usual dose 1,200 mg/day or 1,600 mg/day for 7-10 days as one treatment course or as cyclic therapy, has the largest experience base - other options include tetracycline, neomycin, norfloxacin, amoxicillin/clavulanate, erythromycin

Answer 238

Heart infections: endocarditis Blood infections: bacteremia from catheter or hepatobiliary GI infections: complication of intestinal, pelvis or biliary tract surgery, cholangitis, peritonititis GU infections: UTIs most commonly from catheter or instrumentation CNS infections: meningitis, but in the setting NUS or head trauma Skin infecions: surgical wounds, especially GI, and decubitus ulcers; diabetic foot infections

Answer 239

Heart: endocarditis Blood: bacteremia from catheter or hepatobiliary GI: complication of intestinal, pelvis or biliary tract surgery, cholangitis GU: UTIs most commonly from catheter or instrumentation NOTE: bacteremia from enterococcal UTI is uncommon Intraabdominal: peritonitis, intraabdominal infection, pelvic infection (tends to be mixed with other flora) CNS: meningitis (in the setting of neurosurgery) Skin/Soft tissue: surgical wounds (especially GI), decubitus ulcers

Answer 240

10-14 days SANFORD

Answer 241

Typically signifies advanced stage cancer and usually indicates that death will likely occur within an average of four to seven months UTD 11/11/2020

Answer 242

Pleural abrasion or pleurectomy

Answer 243

Observation Therapeutic thoracentesis Chest catheter drainage only Chest catheter drainage with chemical pleurodesis (eg, talc slurry) Thoracoscopy with talc insufflation Long-term indwelling pleural catheter Long-term indwelling pleural catheter with talc instillation Pleural abrasion or pleurectomy Pleuroperitoneal shunt Chemotherapy Radiotherapy

Answer 244

Observation Therapeutic thoracentesis Chest catheter drainage only Chest catheter drainage with chemical pleurodesis (eg, talc slurry) Thoracoscopy with talc insufflation Long-term indwelling pleural catheter Long-term indwelling pleural catheter with talc instillation Pleural abrasion or pleurectomy Pleuroperitoneal shunt Chemotherapy Radiotherapy

Answer 245

Concern exists that prolonged observation of these effusions without drainage results in a nonexpandable lung that may complicate palliative benefit from later drainage, AKA lung entrapment

Answer 246

Therapeutic thoracentesis is the first-line treatment for symptomatic MPE and is typically performed using a needle/catheter under ultrasound guidance.

Answer 247

The normally rapid renal clearance of serum FLCs is reduced in the presence of renal insufficiency (eg, creatinine clearance <60 mL/min). As a result, serum FLC concentrations rise as the glomerular filtration rate falls, and may be 20 to 30 times normal in end-stage renal failure

Answer 248

Refer to SIS Guideline 2017 Hepatic abscess is a type of intra-abdominal abscess Hence empiric treatment depends on the category of patient - Low risk community acquired IAI - High risk community acquired IAI - Health care-associated IAI

Answer 249

Immediately TIP: osteomyelitis is one of the only, if not the only, infection in which antibiotics are held until cultures are obtained and organism identified

Answer 250

CT with oral contrast

Answer 251

Coliforms (Enterobacteriaceae, especially E. coli) and anaerobes (especially B. fragilis) Organism found in at least 30% of the cases - E. Coli - Bacterioides - Clostridium species - Streptococcus specis

Answer 252

An aerobic organism or aerobe is an organism that can survive and grow in an oxygenated environment. In contrast, an anaerobic organism (anaerobe) is any organism that does not require oxygen for growth Facultative anaerobes can grow with or without oxygen because they can metabolise energy aerobically or anaerobically. They use dissolved oxygen (DO) or oxygen obtained from food materials such as sulfate or nitrate ions, or some can respire through glycolysis. The bacteria can live under aerobic, anoxic, or anaerobic conditions.

Answer 253

Obligate anaerobes are organism which can only live in environments which lack oxygen. Unlike the majority of organisms in the world, these organisms are poisoned by oxygen. Obligate anaerobes are typically bacteria, and live in a variety of places naturally.

Answer 254

Antibiotics used for empiric treatment of community acquired intra-abdominal infection should be active against: Enteric gram-negative aerobic and facultative bacilli and enteric gram-positive streptococci

Answer 255

Low risk vs high risk Community acquired vs “health care-associated intraabdominal infection”

Answer 256

“Health care–associated infection” includes “community onset” and “hospital-onset.” Community-onset health care–associated infection includes cases involving patients with at least 1 of the following health care risk factors: (1) presence of an invasive device at time of admission (2) history of MRSA infection or colonization (3) history of surgery, hospitalization, dialysis, or residence in a long-term care facility in the 12 months preceding the culture date. 4) Hospital-onset infection includes cases involving patients with positive culture results from a normally sterile site obtained 48 h after hospital admission. Clinical tip: "Health care associated" is commonly caused by more resistant flora IDSA 2010

Answer 257

A clinical trial in which the investigator conceives the research, develops the protocol, and serves as sponsor investigator As opposed to an industry initiated trial

Answer 258

JAMA OCT 2020 RCT Objective: To compare the risk of overcorrection in rapid infusion bolus (RIB) and slow continuous infusion (SCI) with hypertonic saline in patients with symptomatic hyponatremia. Design, Setting, and Participants: This prospective, investigator-initiated, multicenter, open-label, randomized clinical trial - 178 patients - Na < 125 Interventions: RIB or SCI of hypertonic saline( 3%, for 24 to 48 hours) Main Outcome: The primary outcome was overcorrection at any given period, defined as increase in the sNa level by greater than 12 or 18 mmol/L within 24 or 48 hours, respectively. Results: mean Na concentrations, 118.2 - RIB group (n = 87) vs SCI group (n = 91). - Overcorrection 15 of 87 (17.2%) and 22 of 91 (24.2%) patients in the RIB and SCI groups, respectively (absolute risk difference, -6.9% [95% CI, -18.8% to 4.9%]; P = .26). - The RIB group showed lower incidence of relowering treatment than the SCI group (36 of 87 [41.4%] vs 52 of 91 [57.1%] patients, respectively; absolute risk difference, -15.8% [95% CI, -30.3% to -1.3%]; P = .04; number needed to treat, 6.3). - Groups did not differ in terms of efficacy in increasing sNa concentrations nor improving symptoms - RIB, when compared with SCI, showed better efficacy in achieving target correction rate within 1 hour P = .02 Conclusions and Relevance: This randomized clinical trial found that both RIB and SIC therapies of hypertonic saline for treating hyponatremia were effective and safe, with no difference in the overcorrection risk. However, RIB had a lower incidence of therapeutic relowering treatment and tended to have a better efficacy in achieving sNa within 1 hour than SCI. RIB could be suggested as the preferred treatment of symptomatic hyponatremia, which is consistent with the current consensus guidelines. Baek SH, Jo YH, Ahn S, et al. Risk of Overcorrection in Rapid Intermittent Bolus vs Slow Continuous Infusion Therapies of Hypertonic Saline for Patients With Symptomatic Hyponatremia: The SALSA Randomized Clinical Trial. JAMA Intern Med. 2020 Oct 26. pii: 2772353. doi: 10.1001/jamainternmed.2020.5519.

Answer 259

RCT, open-label Small study in Iran: 39 patients vs 39 pateints Bromhexine TID Outcome: ICU admissions, Intubations and deaths Results: - There was a significant reduction in ICU admissions (2 out of 39 vs. 11 out of 39, P = 0.006) - intubation (1 out of 39 vs. 9 out of 39, P = 0.007) - death (0 vs. 5, P = 0.027) in the bromhexine treated group compared to the standard group. Conclusion: Bromhexine, in a small study, showed decreased, ICU admissions, intubations and deaths in COVID patients Background: bromhexine (international) is a known mucolytic Ansarin K, Tolouian R, Ardalan M, et al. Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: A randomized clinical trial. Bioimpacts. 2020;10(4):209-215. doi: 10.34172/bi.2020.27. Epub 2020 Jul 19.

Answer 260

Bamlanivimab As of Nov 2020 Efficacy based on BLAZE-1 clinical trial

Answer 261

Bamlanivimab is a recombinant neutralizing human IgG1k monoclonal antibody that binds to spike protein of SARS-CoV-2 virus, which prevents SARS-CoV-2 from attaching to human ACE2 receptors Efficacy based on BLAZE-1 clinical trial

Answer 262

Dosing: 700 mg single IV infusion over ≥ 60 minutes give bamlanivimab as soon as possible after positive test result and within 10 days of symptom onset monitor patients during infusion and observe for ≥ 1 hour after infusion Efficacy based on BLAZE-1 clinical trial

Answer 263

Mild-to-moderate COVID-19 in adults and children ≥ 12 years old weighing ≥ 40 kg who are at HIGH RISK of progressing to severe COVID-19 and/or hospitalization Bamlanivimab is associated with poor clinical outcomes when given to hospitalized patients with COVID-19 who require high flow oxygen or mechanical ventilation Not authorized for use in patients who are hospitalized, require oxygen therapy, or are on pre-existing chronic oxygen therapy requiring increase in baseline oxygen flow rate Efficacy based on BLAZE-1 clinical trial

Answer 264

Based on nonclinical outcome in prespecified interim analysis of randomized trial Patients: - 467 adults (median age 45 years, 54% women) - mild (76%) or moderate COVID-19 - not hospitalized - ≥ 1 risk factor for severe disease Intervention: single infusion of bamlanivimab 700 mg vs. 2,800 mg, vs. 7,000 mg vs. placebo Results: follow-up 29 days Note: decrease in log viral load of 3.81 corresponds to elimination of > 99.97% of viral RNA - mean decrease in log viral load at 11 days - 3.67 with 700 mg (not significant vs. placebo) - 4 with 2,800 mg (p = 0.02 vs. placebo) - 3.38 with 7,000 mg (not significant vs. placebo) - 3.47 with placebo Hospitalization at 29 days in 1.6% vs. 6.3% (no p value reported) !!!

Answer 265

Ticagrelor and ASA

Answer 266

PLATO trial Tip: most of the guideline recc for Ticagrelor is really from 1 major RCT, the Plato Trial

Answer 267

Intermediate-acting insulins, such as neutral protamine Hagedorn is known as NPH or lente (means slow in spanish!) insulin - delayed onset of action ranging between 2 to 4 hours - approximately 6 to 7 hours to reach peak concentration - duration of action: up to 20 hours Clinical tip: This leads to a distinct peak and trough effect, and therefore, when used as basal insulin, 2 or MORE injections are often required each day to minimize the daily excursions of insulin levels

Answer 268

NPH is treated like a long acting, and hence, it's use is for basal insulin coverage So, just like any typical basal bolus regimen, NPH acts as the basal and rapid acting acts as the meal time and correctional Ex: - Basal: NPH 30 U BID - Meal time: 3U lispro TID w/ meals - Correctional: SSI with lispro Ex: - Basal: Lantus 40 nightly - Meal time: 3U lispro TID w/ meals - Correctional: SSI with lispro BOTH are functional basal bolus regimens

Answer 269

NPH can be administered alone, simply NPH OR It can be administered in what is called "premixed conventional insulin". Ex: 70/30 Humulin/Novolin means (70% NPH, 30% regular) - The regular insulin can be either Humulin or Novolin - they both are regular insulin

Answer 270

The first group is called "conventional premixed human insulins" and the 2nd group is called "Insulin analogue mixes". The conventional premixed human insulins are a mixture of NPH and Regular insulin The insulin analogue mixes are a mixture of intermediate acting (ex: insulin lispro protamine) and rapid acting insulin (ex: lispro) Pharmacokinetically, the analogues have a faster onset and peak, but BOTH groups have the same duration of action Conventional premixed human insulins have an onset of action of approximately 0.5 to 2 hours, usually plateau at 3 to 6 hours, and last up to 24 hours. Insulin analogue mixes have an onset of action of approximately 15 minutes,reach a peak biological action at 1 to 4 hours, and last up to 24 hours (24)

Answer 271

LIN is regular Linhs are regular people LOG is rapid Think of log rolling down a hill

Answer 272

Deep vein thrombosis and/or pulmonary embolism treatment: NO dosage adjustment is recommended by the manufacturer for any degree of reduced kidney function. For Nonvalvular Atrial Fibrillation: If Cr <1.5: no dose adjustment - UNLESS >80 yo AND weight < 60kg: 2.5mg BID If Cr > 1.5 AND one of the following - >80 yo - <60kg Then adjust to 2.5mg BID Otherwise, no adjustment

Answer 273

Bence Jones proteins is the other name to refer to Free Light Chains, that is, the kappa or lamda light chains that are NOT attached to heavy chains, hence they are FREE

Answer 274

16 % patients with Multiple Myeloma produce only Bence Jones proteins, that is, only FLC Hence the SPEP and Serum Immunofixation may be negative, but the FLC would catch the multiple myeloma

Answer 275

Monoclonal plasma cells ≥10% in the bone marrow and by negative results on serum and urine electrophoresis and immunofixation studies.

Answer 276

Increase level of kappa and lambda Conflicting results in regards to the ratio per studies Clinical tip: Kappa/lamda ratio > 3 is too abnormal for renal insufficiency alone

Answer 277

Kappa/lambda ratios >3.0 are unlikely to be due to renal insufficiency alone

Answer 278

The serum tests may obviate the initial need for urine protein studies in the initial evaluation for monoclonal gammopathies when serum FLC analysis is performed along with serum protein electrophoresis and serum immunoelectrophoresis [43]. If a monoclonal protein is found, electrophoresis and immunofixation of an aliquot from a 24-hour urine collection should then be performed.

Answer 279

Low risk vs high risk Community acquired vs “health care-associated intraabdominal infection”

Answer 280

High Risk APACHE II score > 10 Or 2 of the following: - Advanced age (‡ 70 y) - Malignancy - Significant cardiovascular compromise, liver disease or cirrhosis or renal disease - Diffuse, generalized peritonitis - Hypoalbuminemia - Extent of infection/adequacy of initial source control - Elevated MPI score - Delayed initial source control - Inability to achieve adequate source control - Microbiologic characteristics - Suspected infection with resistant pathogens

Answer 281

Infection developing greater than 48 h after initial source control. Hospitalized for greater than 48 h during current admission or within the previous 90 d. Residence in a skilled nursing or other long-term care facility within the previous 30 d. Home infusion therapy, home wound care, or dialysis within the preceding 30 d. Use of broad-spectrum antimicrobial therapy for 5 d or more during the preceding 90 d. TIP: all the risk characteristics that help define "health care-associated" are simply places that are healthcare associated and whether the patient has been exposed between 30 to 90 days

Answer 282

Cefotaxime PLUS Metro (Grade 1-A). Cetriaxone PLUS Metro (Grade 1-A). Cipro PLUS Metro (Beta lactam allergy) Monotherapies: - Ertapenem - Moxifloxacin (Beta lactam allergy)

Answer 283

Critically ill patients, such as ICU patients

Answer 284

Piperacillin-tazobactam MONO (Grade 2-A) Doripenem MONO (Grade 2-A) Imipenem-cilastatin MONO (Grade 2-A) Meropenem MONO (Grade 2-A) Cefepime PLUS Metro (Grade 2-A) Ceftazidime PLUS Metro (Grade 2-B). TIP: notice that that “high risk” patients can get dual or monotherapy TIP: notice that the dual therapies have different cephalosporins compared to "low risk" empiric therapy

Answer 285

TIP: Same as high risk community acquired intra-abdominal infection Use the broader-spectrum agents recommended for higher-risk patients with CA-IAI for initial empiric therapy of patients with HA-IAI.

Answer 286

TIP: depends on source control 1 day if small bowel perforation but operated within 12 hours, gastroduodenal perf operated on within 24 hours 4 days in source control 5-7 days without definitive source control 7 days if secondary bacteremia

Answer 287

Enterobacteriaceae is the group (or family) and Enterobacter species is the species

Answer 288

E. Coli Klebsiella Shigella Salmonella Proteus Citrobacter Enterobacter

Answer 289

“Enteric organisms” are gram negative organisms part of the normal intestinal flora and can include gram positive organisms too Under the Enteric organisms are “groups” or “families” such as Enterobacteriaceae, Vibrionaceae, Pseudomaceae and Bacterioidaceae Enterobacter or E. Coli are “species” under the groups, and in this case, Enterobacteriaceae

Answer 290

In addition to the enteric flora (gram negative aerobic/facultative and anaerobic organisms) Incidence of other Enterobacteriaceae, such as Enterobacter spp., as well as lactose-negative gram-negative bacilli, such as P. aeruginosa and Acinetobacter spp., have increased. Gram positive micro-organisms, particularly Enterococcus spp., Staphylococci, both coagulase-negative species and Staphylococcus aureus are also identified more frequently in patients with HA-IAI

Answer 291

Systematic Review JAMA Nov 2020 Objective: To update the evidence on screening and treatment of hypertension in childhood and adolescence for the US Preventive Services Task Force. Study selection: English only, RCT, cohort and meta-analysis Results - 43 studies, N>12,400 - 13 RCTs and 1 Meta-analysis showing reduction of BP with ACEi and ARB, but NOT with CCB, BB or Mineralocorticorticoid blocker - No studies looking at adult outcomes - 20 observational studies showing association of childhood HTN with adult - No conclusion in regards to accuracy of BP measurements in office setting Gartlehner G, Vander Schaaf EB, Orr C, et al. Screening for Hypertension in Children and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2020 Nov 10;324(18):1884-1895. doi: 10.1001/jama.2020.11119.

Answer 292

RCT Nov 2020 CIRCULATION POPular CABG Trial Type: investigator-initiated, randomized, double-blind, placebo-controlled, multicenter trial Patients: - 500 patients: 220 vs 223, 1:1 - Male, 70 years of age, 30% for ACS Outcome: SVG occlusion at 1 year by CT Angiography -Secondary: 1-year SVG failure, which was a composite of SVG occlusion, SVG revascularization, myocardial infarction in myocardial territory supplied by a SVG, or sudden death. Results: - SVG occlusion rate in the ticagrelor group was 10.5% (51 of 484 SVGs) versus 9.1% in the placebo group (43 of 470 SVGs), odds ratio, 1.29 [95% CI, 0.73-2.30]; P=0.38. - SVG failure occurred in 35 (14.2%) patients in the ticagrelor group versus 29 (11.6%) patients in the placebo group (odds ratio, 1.22 [95% CI, 0.72-2.05]). Conclusion: NO, addition of ticagrelor to standard aspirin did not reduce SVG occlusion at 1 year after CABG Willemsen LM, Janssen PWA, Peper J, et al. Effect of Adding Ticagrelor to Standard Aspirin on Saphenous Vein Graft Patency in Patients Undergoing Coronary Artery Bypass Grafting (POPular CABG): A Randomized, Double-Blind, Placebo-Controlled Trial. Circulation. 2020 Nov 10;142(19):1799-1807. doi: 10.1161/CIRCULATIONAHA.120.050749. Epub 2020 Aug 31.

Answer 293

“Persistently positive blood cultures” defined as follows: 1) at least 2 positive cultures of blood samples drawn >12 h apart 2) or all 3 3) or a majority of ≥4 separate cultures of blood (with first and last sample drawn at least 1 h apart) TIP: "2,3,4" Rule

Answer 294

At least 3 sets of blood cultures obtained from different venipuncture sites should be obtained, with the first and last samples drawn at least 1 hour apart (Class I; Level of Evidence A). Clinical tip: the modified Duke criteria makes more sense – the Major Criteria Blood culture positive for IE Typical microorganisms consistent with IE from 2 separate blood cultures: Viridans streptococci, Streptococcus bovis, HACEK group, Staphylococcus aureus; or community-acquired enterococci in the absence of a primary focus, OR Microorganisms consistent with IE from persistently positive blood cultures defined as follows: at least 2 positive cultures of blood samples drawn >12 h apart or all 3 or a majority of ≥4 separate cultures of blood (with first and last sample drawn at least 1 h apart) OR Single positive blood culture for Coxiella burnetii or anti–phase 1 IgG antibody titer ≥1:800 IDSA 2015

Answer 295

Blood culture positive for IE Typical microorganisms consistent with IE from 2 separate blood cultures: Viridans streptococci, Streptococcus bovis, HACEK group, Staphylococcus aureus; or community-acquired enterococci in the absence of a primary focus, OR Microorganisms consistent with IE from persistently positive blood cultures defined as follows: at least 2 positive cultures of blood samples drawn >12 h apart or all 3 or a majority of ≥4 separate cultures of blood (with first and last sample drawn at least 1 h apart) OR Single positive blood culture for Coxiella burnetii or anti–phase 1 IgG antibody titer ≥1:800

Answer 296

Domain Phylum Class Order Family Genus Species DPCOFGS Dirty People Carry Old, Festering, Gross Sicknesses

Answer 297

Gram positive cocci, diplococci, short chains or long chains TIP: one cocci, then 2, then 3, then 4

Answer 298

Facultative, anaerobic, gram positive bacteria found in the colon Hydrolyze esculin in the presence of 40% bile salts Grows/lives at high salt concentration (6.5%) and high temperatures (46 degrees) Non-hemolytic

Answer 299

Vast majority of enterococcus can hydrolyze PYR – pyrrolidonyl-beta-naphthylamide

Answer 300

Enterococcus Faecalis Enterococcus Faecium TIP: 18 species of enterococcus total

Answer 301

Normal inhabitants of the LARGE bowel, but it only makes up <1% of the organisms

Answer 302

Most antibiotics used normally don’t target enterococcus, rather, target the gram negative organisms and anaerobes of the gut. Since enterococcus only makes up <1% of the colonic bacteria, exposure to antibiotics wipe out other colonic bacteria, allowing enterococcus to move into the open niche

Answer 303

They go hand in hand, the former is part of the pathogenesis of the latter. Those colonized are the ones who get disease

Answer 304

1) ”Enterococcal secreted factors” are factors released outside of the bacterial cell wall. The main ones are hemolysin/cytolysin/serine protease which destroy cells/tissue 2) ”Enterococcal surface compounds” that are adhesins. Important one is “aggregation substance of Enterococcus faecalis”. 3) ”Stress protein GLS24” which yields resistance to bile salts

Answer 305

#2 organism recovered from hospital acquired infections after Staph (MSSA/MRSA) Faecalis is much more common historically, but now both are just as even

Answer 306

E. Faecalis susceptible to ampicillin and vanc E. Faecium 90% resistant to ampicillin and 80% resistant to vancomycin

Answer 307

Colonization

Answer 308

US/Asia > Europe > Latin America

Answer 309

No However, chronic prostatitis can lead to recurrent enterococcal bacteremia

Answer 310

Gastrointestinal, hepatobiliary, intra-abdominal abscess, pelvic Intravascular source Less commonly, UTI, wound infections and bone infections

Answer 311

In hospital acquired endocarditis, it is the second most common cause!

Answer 312

Heart failure and hence valve replacement may be needed

Answer 313

Defined as the lack of killing at concentrations 32 times higher than the MIC

Answer 314

No, always dual therapy for synergistic effect

Answer 315

2 different mechanisms of action: -The Beta lactam or glycopeptide is a cell wall active agent that creates a way for the aminoglycoside to enter for better penetration

Answer 316

Aminopenecillins (ampicillin/amoxicillin)/Ureidopenecillins (piperacillin/tazobactam) > Penicillin G and Imipenem

Answer 317

``` LineZOLID TediZOLID TelaVANCIN OritaVANCIN DaptoMYCIN FosfoMYCIN Quiniprisin/Dalfopristin Tigelcycline ``` Clinical tip: Though active, not all the antibiotics are FDA approved or beneficial in all clinical scenarios

Answer 318

Enterococcus species are resistant to ALL cephalosporins

Answer 319

Enterococcus faecium The penicillin binding protein of the species is called PBP5 which has a LOW affinity for the ampicillin so the bacteria can continue to grow cell wall in the presence of aminopenicillin

Answer 320

Like beta lactams, it is a cell wall agent. It works in the step prior to that of beta lactams It targets and binds to D-ala D-ala of the peptidoglycan of the cell wall and prevents transpeptidylation

Answer 321

D-ala D-ala is replaced with D-lactate or D-serine, hence changing the very target of vancomycin Secondary MOA of resistence is that enterococcus can produce substances that literally destroy the D-ala D-ala

Answer 322

Gentamicin and Streptomycin

Answer 323

Naltrexone is an opioid antagonist that can be administered orally or as a monthly injection. It is thought to act by decreasing activity in the dopamine-rich ventral tegmental area of the brainstem and subsequently decreasing the pleasurable feelings associated with alcohol consumption.

Answer 324

Acamprosate inhibits NMDA receptors, decreasing symptoms of prolonged alcohol withdrawal.

Answer 325

Disulfiram is an aldehyde dehydrogenase inhibitor that has been used for many years in the treatment of alcoholism The primary mechanism by which it acts is to create negative effects of vomiting and autonomic nervous system hyperactivity when alcohol is consumed concurrently with use of the medication. Because it inhibits an enzyme that is part of the normal metabolism of alcohol, it allows the buildup of acetaldehyde, which creates these unpleasant symptoms. As a result of the autonomic side effects, it is contraindicated in individuals with hypertension, a history of stroke, heart disease, or diabetes mellitus

Answer 326

An ultrasound examination of the liver is an excellent screening tool. The two characteristic vascular abnormalities are hypervascularity of the tumor mass (neovascularization or abnormal tumor-feeding arterial vessels) and thrombosis by tumor invasion of otherwise normal portal veins.

Answer 327

Clostridium septicum is seen often in conjunction with GI tumors.

Answer 328

Probably because of its ubiquity and ability to stick to foreign surfaces, S epidermidis is the most common cause of infections of CNS shunts as well as an important cause of infections on artificial heart valves and orthopedic prostheses

Answer 329

Testosterone to estrogen ratio Pathologic gyecomastia occurs when there is a decrease in the testosterone to estrogen ratio: 1) Decreased testosterone production 2) Increased Estrogen production - E production: HCG stimulating Leydig cells to produce E, Carney syndrome, Peutz Jegher or Sertoli cell tumor - Increased conversion of androgens to estrogens: Hyperthyroid, adrenal tumors - Decreased clearance: liver disease

Answer 330

A variety of drugs, including diethylstilbestrol, heroin, digitalis, spironolactone, cimetidine, isoniazid, and tricyclic antidepressants, also can cause gynecomastia.

Answer 331

Mild statin-induced myopathy is noninflammatory and usually resolves with discontinuation of therapy. In rare patients, however, muscle weakness continues to progress even after the statin is withdrawn; in these cases, a diagnostic muscle biopsy is indicated and search for antibodies to 3-hydroxy-3 methylglutarylcoenzyme A reductase (HMGCR) is suggested The latter has persistent elevation of CK after discontinuation

Answer 332

Antisynthetase Syndrome Myositis + Lung disease

Answer 333

Patients with Graves disease produce thyroid-stimulating immunoglobulins. They subsequently produce higher levels of T4 compared with the normal population. As a result, many patients with Graves disease are mildly iodine deficient, and T4 production is somewhat limited by the availability of iodine. Exposure to iodinated contrast thus reverses iodine deficiency and may precipitate worsening hyperthyroidism by replenishing the iodine supply. Additionally, the reversal of mild iodine deficiency may make iodine-125 therapy for Graves disease less successful because thyroid iodine uptake is lessened in the iodine-replete state.

Answer 334

NOV 2020 NEJM RCT The primary outcome was the patient's clinical status 30 days after the intervention, as measured on a six-point ordinal scale ranging from total recovery to death. Results: At day 30 day, no significant difference was noted between the convalescent plasma group and the placebo group in the distribution of clinical outcomes according to the ordinal scale (odds ratio, 0.83 (95% confidence interval [CI], 0.52 to 1.35; P = 0.46). Overall mortality was 10.96% in the convalescent plasma group and 11.43% in the placebo group, for a risk difference of -0.46 percentage points (95% CI, -7.8 to 6.8). CONCLUSIONS: No significant differences were observed in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo. Simonovich VA, Burgos Pratx LD, Scibona P, et al. A Randomized Trial of Convalescent Plasma in Covid-19 Severe Pneumonia. N Engl J Med. 2020 Nov 24. doi: 10.1056/NEJMoa2031304

Answer 335

Fusarium species

Answer 336

Voriconazole + Liposomal Amphotericin

Answer 337

Affected organs may include ``` Skin sinuses lungs joints retina liver spleen kidneys ```

Answer 338

Blood malignancy and stem cell transplant

Answer 339

Fusarium filaments were hyaline, septate and 3- to 8-mcm in diameter, typically branching at acute or right angles Tip: Blue bananas hanging off of a stalk at acute and right angles

October - November 2020 Flashcards

(373 cards)