DM and DAPT

Q: Patients with diabetes mellitus may require ______________ dose of clopidogrel? (select one)

A) higher

B) lower

Answer: A

Patients with diabetes mellitus tend to have increased platelet activation, which means they may have a higher number of immature platelets circulating. This may affect the inhibitory effect of clopidogrel. Similar concerns can be applied to aspirin (ASA) in these platelets.

Patients with diabetes mellitus may require higher doses of ASA and clopidogrel. The other option is to use alternate agents.

#pharmacology

#cardiology

#endocrinology

References:

1. Gurbel PA, Bliden KP, Hiatt BL, O'Connor CM. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003; 107:2908. 

2. Mangiacapra F, Patti G, Peace A, et al. Comparison of platelet reactivity and periprocedural outcomes in patients with versus without diabetes mellitus and treated with clopidogrel and percutaneous coronary intervention. Am J Cardiol 2010; 106:619. 

3. Gurbel PA, Bliden KP, Butler K, et al. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation 2010; 121:1188.

Clubbing

Q: Clubbing is associated with all of the following EXCEPT? (select one)

A) bronchiectasis

B) idiopathic pulmonary fibrosis

C) lung cancer

D) COPD

Answer: D

Unfortunately, the art of detailed physical examination is dying. An astute clinician listens to heart and lung sounds and observes other related clinical features simultaneously. Patients with dyspnea may provide an important clue if clubbing is present on the hands.

Clubbing is found to be associated with bronchiectasis, idiopathic pulmonary fibrosis (IPF), lung cancer, and pediatric cyanotic heart disease. Interestingly, patients exclusively with asthma, COPD, or adult-onset hypoxemia usually do not develop clubbing.

#physical-exam

#pulmonary

Further reading:

1. Sarkar M, Mahesh DM, Madabhavi I. Digital clubbing. Lung India. 2012 Oct;29(4):354-62. doi: 10.4103/0970-2113.102824. PMID: 23243350; PMCID: PMC3519022.

2. Kanematsu T, Kitaichi M, Nishimura K, Nagai S, Izumi T. Clubbing of the fingers and smooth-muscle proliferation in fibrotic changes in the lung in patients with idiopathic pulmonary fibrosis. Chest. 1994 Feb;105(2):339-42. doi: 10.1378/chest.105.2.339. PMID: 8306725.

3. Sarkar M, Mahesh DM, Madabhavi I. Digital clubbing. Lung India. 2012 Oct;29(4):354-62. doi: 10.4103/0970-2113.102824. PMID: 23243350; PMCID: PMC3519022.

Distant murmurs

Q: Murmur heard over the back of the chest below or adjacent to the left scapula is most probably indicative of? (select one)

A) mitral regurgitation

B) mitral stenosis

C) aortic regurgitation

D) aortic stenosis

E) tricuspid regurgitation

F) tricuspid stenosis

Answer: A

One of the skills to acquire while listening to heart murmurs is to appreciate murmurs away from the heart. In this regard, two murmurs away from the heart can be a significant diagnosis.

• A systolic murmur of peripheral pulmonary stenosis can be audible over the anterior aspects of both lungs.
• A systolic murmur over the back of the chest below or adjacent to the left scapula can be appreciated as severe mitral regurgitation.

In this regard, it is interesting to know that in patients with End-Stage Renal Disease (ESRD), a continuous murmur in the apical region of the lung can be audible on the side of the arteriovenous fistula (AVF) created in the arm.

#cardiology

#physical-exam

#nephrology

References:

1. Moss AJ. Murmurs heard at a distance from the patient: report of an unusual case. J Pediatr. 1976 Nov;89(5):852-3. doi: 10.1016/s0022-3476(76)80826-8. PMID: 978338.

2. Alpert MA. Systolic Murmurs. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 26. Available from: https://www.ncbi.nlm.nih.gov/books/NBK345/

TRALI risk

Q: Which of the following organ transplant carries the higher risk of Transfusion Related Acute Lung Injury (TRALI)? (select one)

A) Liver 

B) Kidney

Answer: A

A whole list of risk factors has been identified for TRALI. Some of the major risk factors include (but are not limited to ) the following:

• Recent surgery (particularly cardiac)
• Cytokine treatment
• Massive blood transfusion
• Active infection (Sepsis/SIRS)
• Low levels of the anti-inflammatory cytokine interleukin-10 (IL-10) 
• High C-reactive protein (CRP) 
• Liver transplant surgery
• Chronic alcohol abuse
• Shock
• Higher peak airway pressure while being mechanically ventilated
• Current smoking
• Higher interleukin (IL)-8 levels
• Positive fluid balance
• Hematologic malignancy
• A high Acute Physiology and Chronic Health Evaluation II (APACHE II) score 
• Recipients of platelet or plasma-containing products
• Female gender

#hematology

References:

1. Toy P, Gajic O, Bacchetti P, et al. Transfusion-related acute lung injury: incidence and risk factors. Blood 2012; 119:1757.

2. Vlaar AP, Binnekade JM, Prins D, et al. Risk factors and outcome of transfusion-related acute lung injury in the critically ill: a nested case-control study. Crit Care Med 2010; 38:771.

3. Menis M, Anderson SA, Forshee RA, et al. Transfusion-related acute lung injury and potential risk factors among the inpatient US elderly as recorded in Medicare claims data, during 2007 through 2011. Transfusion 2014; 54:2182.

4. Toy P, Looney MR, Popovsky M, et al. Transfusion-related Acute Lung Injury: 36 Years of Progress (1985-2021). Ann Am Thorac Soc 2022; 19:705.

ILO

Q: 56 years old male who was "fast-tracked" for extubation after an uncomplicated cardiac bypass surgery developed acute upper respiratory distress. Lungs are clear to auscultation, but there is a wheezing at the upper laryngeal (throat) level. What could be the two major differential diagnoses?

Answer: laryngospasm and paradoxical vocal fold motion

The technical term for paradoxical vocal fold motion is Inducible laryngeal obstruction (ILO). It is very common after brief intubation for surgeries but can occur in patients intubated for longer periods. The other terms used are laryngeal dyskinesia, vocal cord dysfunction (VCD), and periodic laryngeal obstruction. It is different from laryngospasm. Similar pathology has been described after exercise, asthma exacerbation, neurologic injuries, and a few other instances. It is characterized by paradoxical vocal fold adduction during inspiration, expiration, or both.

Normally, the vocal folds abduct during inspiration and slightly adduct during expiration, coughing, and speech.

Prompt arrangements should be made for intubation in such instances, but ILO can be witnessed before applying neuromuscular blockade during laryngoscopy. Sometimes, the patient can be salvaged without intubation using inhaled broncho-dilating medications or helium-oxygen mixtures. It should not be delayed to wait for the response.

#procedures

#ENT

#pulmonary

References:

1. Arndt GA, Voth BR. Paradoxical vocal cord motion in the recovery room: a masquerader of pulmonary dysfunction. Can J Anaesth 1996; 43:1249.

2. Hammer G, Schwinn D, Wollman H. Postoperative complications due to paradoxical vocal cord motion. Anesthesiology 1987; 66:686.

3. Harbison J, Dodd J, McNicholas WT. Paradoxical vocal cord motion causing stridor after thyroidectomy. Thorax 2000; 55:533.

4. Larsen B, Caruso LJ, Villariet DB. Paradoxical vocal cord motion: an often misdiagnosed cause of postoperative stridor. J Clin Anesth 2004; 16:230.

Osborn wave

Q: J point elevation (Osborn wave) is pathognomonic of hypothermia.

A) True

B) False

Answer: B

J point elevation on EKG (Osborn wave) in hypothermia—found to be most prominent in leads V2 to V5—is overrated! Although it is usually roughly proportional to the degree of hypothermia, it is not pathognomonic for hypothermia. Similar EKG changes can be seen in subarachnoid hemorrhage (SAH), brain injury, patients with early repolarization, hypercalcemia, and Brugada syndrome. 

Also, it is not always present as it requires the ST segment to be unaltered.

#cardiology

References:

1. Graham CA, McNaughton GW, Wyatt JP. The electrocardiogram in hypothermia. Wilderness Environ Med 2001; 12:232.

2. Okada N, Matsuyama T, Morita S, Ehara N, Miyamae N, Okada Y, Jo T, Sumida Y, Watanabe M, Nozawa M, Tsuruoka A, Fujimoto Y, Okumura Y, Hamanaka K, Kitamura T, Nishiyama K, Ohta B. Osborn Wave Is Related to Ventricular Fibrillation and Tachycardia in Hypothermic Patients. Circ J. 2020 Feb 25;84(3):445-455. doi: 10.1253/circj.CJ-19-0856. Epub 2020 Jan 30. PMID: 31996488.

3. Patel A, Getsos JP, Moussa G, Damato AN. The Osborn wave of hypothermia in normothermic patients. Clin Cardiol. 1994 May;17(5):273-6. doi: 10.1002/clc.4960170511. PMID: 8004843.

Statin and uric acid level

Q: Which of the statins has a unique urate-lowering effect?

A) Atorvastatin 

B) Fluvastin 

C) Pravastatin

D) Rosuvastatin 

E) Simvastatin 

Answer: A

For patients who have gout and cardiovascular risk factors such as hypertension (HTN) and hypercholesterolemia (HCL), three drugs can be used as adjuvant treatment due to their unique uricosuric properties.

• Losartan
• Atorvastatin
• Fenofibrate

Losartan is the only angiotensin II receptor antagonist with a modest uricosuric effect when used up to a dose of 50 mg/day. Atorvastatin, in comparison to losartan, has a mild uricosuric effect but should be used in such patients. Fenofibrate works via increased uric acid renal clearance and can be considered.

#pharmacology

#rheumatology

References:

1. Würzner G, Gerster JC, Chiolero A, et al. Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia and gout. J Hypertens 2001; 19:1855.

2. Milionis HJ, Kakafika AI, Tsouli SG, et al. Effects of statin treatment on uric acid homeostasis in patients with primary hyperlipidemia. Am Heart J 2004; 148:635.

3. Feher MD, Hepburn AL, Hogarth MB, et al. Fenofibrate enhances urate reduction in men treated with allopurinol for hyperuricaemia and gout. Rheumatology (Oxford) 2003; 42:321.

Albumin and electrolytes

Q: Hypoalbuminemia may cause false negative? (select one)

A) hypokalemia

B) hypomagnesemia

Answer: B

One caveat to measuring magnesium in chronically malnourished patients is knowing their magnesium level via regular tests. About 30% of magnesium is bound to albumin and is inactive. 

Hypoalbuminemia may cause spuriously low magnesium levels. There is no formula to adjust total and ionized magnesium. The ionized (free) magnesium level should be ordered via direct measurement.

#electrolytes

References:

1. Kroll MH, Elin RJ. Relationships between magnesium and protein concentrations in serum. Clin Chem. 1985 Feb;31(2):244-6. PMID: 3967355.

2. Huijgen HJ, Soesan M, Sanders R, Mairuhu WM, Kesecioglu J, Sanders GT. Magnesium levels in critically ill patients. What should we measure? Am J Clin Pathol. 2000 Nov;114(5):688-95. doi: 10.1309/jr9y-pptx-ajtc-qdrd. PMID: 11068541.

3. Xu B, Sun J, Deng X, Huang X, Sun W, Xu Y, Xu M, Lu J, Bi Y. Low serum magnesium level is associated with microalbuminuria in chinese diabetic patients. Int J Endocrinol. 2013;2013:580685. doi: 10.1155/2013/580685. Epub 2013 Aug 26. PMID: 24065990; PMCID: PMC3770069.

Unique bactericidal action of metronidazole

Q: Unlike any other antibiotic, despite extensive global use over decades, resistance to metronidazole is almost unknown. What could be the explanation?

Answer: It seems like a miracle that, unlike any other antibiotic, despite extensive global use over decades, resistance to metronidazole is not known. The explanation lies in its mechanism of action (MOA). Metronidazole kills bacteria, particularly anaerobes, by producing free radicals inside the microbe cytoplasm. So far, microbes have failed to counter this action. This also explains the 'drug concentration proportional bactericidal effect' of metronidazole.

Metronidazole is a low molecular weight compound that easily diffuses across the microorganisms' cell membranes. Inside the microbe, metronidazole is reduced by the pyruvate:ferredoxin oxidoreductase (a system in obligate anaerobes). The reduction of metronidazole creates a concentration gradient that drives the uptake of more drugs and promotes the formation of intermediate compounds and free radicals that are toxic to the cell. It causes DNA strand breakage and fatal destabilization of the DNA helix. This process leads to the toxic-intermediate particles and inactive end products.

#pharmacology

#ID

References:

1. Edwards DI. Nitroimidazole drugs--action and resistance mechanisms. I. Mechanisms of action. J Antimicrob Chemother 1993; 31:9.

2. Edwards DI. Reduction of nitroimidazoles in vitro and DNA damage. Biochem Pharmacol 1986; 35:53.

3. Ralph ED, Kirby WM. Unique bactericidal action of metronidazole against Bacteroides fragilis and Clostridium perfringens. Antimicrob Agents Chemother 1975; 8:409.

SAH and associated symptoms

Q: Relatively, which of the following is more common in Subarachnoid hemorrhage (SAH)? - select one

A) loss of consciousness (LOC)

B) vomiting

C) neck pain or stiffness 

D) seizure

Answer: C

Conventionally, all academic books describe SAH classically as the 'worst headache of life.' It's very true! However, two-thirds of patients report neck pain or stiffness. Vomiting is also very common, but LOC is reported only by one in ten patients. Seizures are less common, but they are a poor prognostic sign if they occur. 

One important differential diagnosis is meningismus, which is more associated with lower back pain.

#neurology

References:

1. Perry JJ, Sivilotti MLA, Sutherland J, et al. Validation of the Ottawa Subarachnoid Hemorrhage Rule in patients with acute headache. CMAJ 2017; 189:E1379.

2. Claassen J, Park S. Spontaneous subarachnoid haemorrhage. Lancet 2022; 400:846.

3. Butzkueven H, Evans AH, Pitman A, et al. Onset seizures independently predict poor outcome after subarachnoid hemorrhage. Neurology 2000; 55:1315.

Understanding the difference between SRMD and PUD

We commonly use the terms Stress ulcer (Stress-Related Mucosal Disease = SRMD) and Peptic ulcer disease (PUD) interchangeably in the ICU while talking about "GI prophylaxis." But both are different conditions. Probably, what we are worried about in our "unit" patients is mostly SRMD.

SRMD is multiple superficial erosions occurring in the proximal gastric bulb involving superficial capillaries secondary to mucosal hypoperfusion, and perforations are rare.

PUD is a few deep erosions usually occurring in the duodenum involving one vessel secondary to other reasons (drugs, H.Pylori, hypersecretory states, etc.), and perforation is common.

#GI

References:

1. Bardou M, Quenot JP, Barkun A. Stress-related mucosal disease in the critically ill patient. Nat Rev Gastroenterol Hepatol. 2015 Feb;12(2):98-107. doi: 10.1038/nrgastro.2014.235. Epub 2015 Jan 6. PMID: 25560847.

2. Lanas A, Chan FKL. Peptic ulcer disease. Lancet. 2017 Aug 5;390(10094):613-624. doi: 10.1016/S0140-6736(16)32404-7. Epub 2017 Feb 25. PMID: 28242110.

Vitamin K

Q: Vitamin K1 is more effective than Vitamin K2.

A) True

B) False

Answer: B

There are two categories of Vitamin K.

Vitamin K1 is the most widely used form globally. It is a form produced by plants.

Vitamin K2 is mostly used in Japan. It is near human storage form as produced by bacteria and mitochondria. All other synthetic forms are also considered as Vitamin K2 for simplicity.

Both vitamin K1 and K2 are similarly effective in reversing coagulopathy.

#vitamins

References:

1. Nakagawa K, Hirota Y, Sawada N, et al. Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. Nature 2010; 468:117.

2. Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e44S.

3. Hifumi T, Takada H, Ogawa D, et al. Vitamin K2 for the reversal of warfarin-related coagulopathy. Am J Emerg Med 2015; 33:1108.e1.

Homan's sign

Case: 24 years old athletic male presented to the Emergency Room (ER) with severe acute pain in the right calf associated with unilateral leg edema and redness. Homans’ sign is positive. The presence of the Homans’ sign confirms Deep Vein Thrombosis (DVT) unless proven otherwise.

A) True

B) False

Answer: B

This question emphasizes that the widely used Homans sign, calf pain upon passive dorsiflexion of the foot, is not a 'very reliable' sign of DVT. It just suggests DVT. History, patient profile, lab, and imaging testing should be used to confirm the diagnosis.

Our patient is a young athlete who may have DVT due to possible steroid abuse, but most likely, he may have merely muscle strain, tear, or injury to the leg. Other differential diagnoses include cellulitis, lymphangitis or lymph obstruction, venous insufficiency, or popliteal (Baker's) cyst. It may be interesting to know that one-quarter of patients with unilateral calf pain, redness, swelling, and tenderness may not have any established diagnosis, which can be very frustrating for a clinician.

One of the physical exam techniques in such patients is to look for pain or firmness along the course of a vein. More than Homan's sign, a more reliable finding for DVT is a larger calf circumference in the affected leg.

Well's score is another way to calculate the risk factor for DVT. A negative D-Dimer can be an important test to rule out DVT.

#hematology

#physical-exam

References:

1. Hull R, Hirsh J, Sackett DL, et al. Clinical validity of a negative venogram in patients with clinically suspected venous thrombosis. Circulation 1981; 64:622.

2. Gorman WP, Davis KR, Donnelly R. ABC of arterial and venous disease. Swollen lower limb-1: general assessment and deep vein thrombosis. BMJ 2000; 320:1453.

3. Ambesh P, Obiagwu C, Shetty V. Homan's sign for deep vein thrombosis: A grain of salt? Indian Heart J. 2017 May-Jun;69(3):418-419. doi: 10.1016/j.ihj.2017.01.013. Epub 2017 Jan 23. PMID: 28648447; PMCID: PMC5485383.

4. Heick JD, Farris JW. Survey of methods used to determine if a patient has a deep vein thrombosis: An exploratory research report. Physiother Theory Pract. 2017 Sep;33(9):733-742. doi: 10.1080/09593985.2017.1345023. Epub 2017 Jul 17. PMID: 28715289.

Larva Currens

Q: What is Larva currens?

Answer: Larva currens is also called "running" larva of strongyloidiasis. It was first described almost seven decades ago. The most common entry site is via skin due to contaminated soil. Person-to-person transmission occurs due to fecal contamination, larvae-bearing fomites, and sexual contact. Donor-derived strongyloidiasis has been described in transplant recipients. Another major issue with transplant patients is the reactivation of remote infection in the form of hyperinfection/disseminated disease, also called accelerated autoinfection.

Larva currens is a dermatologic manifestation as raised, pink, pruritic, evanescent streaks along the lower trunk, thighs, and buttocks, resulting from migrating larvae through the subcutaneous tissues. It can be dramatic. As the larva moves, the progress can be approximately 1 cm in 5 minutes and 5 to 15 cm per hour. Larvae leave behind a thin red line that gradually fades to brown and disappears within 48 hours. It can be associated with urticaria, pruritus, angioedema, or rash.

Ivermectin is the treatment.

#ID

#dermatology

References:

1. ARTHUR RP, SHELLEY WB. Larva currens; a distinctive variant of cutaneous larva migrans due to Strongyloides stercoralis. AMA Arch Derm 1958; 78:186.

2. Zubrinich CM, Puy RM, O'Hehir RE, Hew M. Strongyloides infection as a reversible cause of chronic urticaria. J Asthma Allergy 2019; 12:67.

3. Tian Y, Monsel G, Paris L, Danis M, Caumes E. Larva Currens: Report of Seven Cases and Literature Review. Am J Trop Med Hyg. 2022 Dec 19;108(2):340-345. doi: 10.4269/ajtmh.21-0135. PMID: 36535252; PMCID: PMC9896332.

4. Puerta-Peña M, Calleja Algarra A. Larva Currens in Strongyloides Hyperinfection Syndrome. N Engl J Med. 2022 Apr 21;386(16):1559. doi: 10.1056/NEJMicm2115708. PMID: 35443110.

BB and K

Q: Beta Blockers (BB) tend to cause? (select one)

A) Hypokalemia 

B) Hyperkalemia

Answer: B

This question emphasizes the concept that catecholamines with beta-2 receptors, like epinephrine, promote the movement of extracellular potassium into the cells. Similarly, beta-adrenergic blockers impair potassium entry into the cells. Although total body potassium stays the same, high serum potassium levels lead to hyperkalemia (so it is not real hyperkalemia).

This effect is most pronounced with nonselective beta-blockers, such as propranolol or labetalol, and less with beta-1 selective, such as atenolol or metoprolol.

On an average, it increases potassium by about 0.5 meq/L . It is usually not significant, but it can become life-threatening in patients with underlying hypoaldosteronism, heart failure exacerbation, renal insufficiency, and a history of renal transplant.

#electrolytes

#pharmacology

References:

1. Reid JL, Whyte KF, Struthers AD. Epinephrine-induced hypokalemia: the role of beta adrenoceptors. Am J Cardiol 1986; 57:23F.

2. Nowicki M, Miszczak-Kuban J. Nonselective Beta-adrenergic blockade augments fasting hyperkalemia in hemodialysis patients. Nephron 2002; 91:222.

3. McCauley J, Murray J, Jordan M, et al. Labetalol-induced hyperkalemia in renal transplant recipients. Am J Nephrol 2002; 22:347.

Clonidine toxicity

Q: What does clonidine overdose tend to cause? (select one)

A) Miosis

B) Mydriasis

Answer: A

Clonidine is an alpha-2 adrenergic agonist. Its overdose causes a cluster of symptoms (toxidrome) as

• Depressed mental status
• Miosis
• Depressed respirations
• Bradycardia 
• Hypotension

Treatment is supportive, as clonidine can't be removed via dialysis.

#toxicity

#pharmacology

References:

1. Isbister GK, Heppell SP, Page CB, Ryan NM. Adult clonidine overdose: prolonged bradycardia and central nervous system depression, but not severe toxicity. Clin Toxicol (Phila). 2017 Mar;55(3):187-192. doi: 10.1080/15563650.2016.1277234. Epub 2017 Jan 20. PMID: 28107093.

2. Manzon L, Nappe TM, DelMaestro C, Maguire NJ. Clonidine Toxicity. 2023 Jun 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 29083752.

Myocardial Reperfusion Injury

Q: Reperfusion injury of the heart can be effectively controlled by performing 'endovascular cooling' before percutaneous coronary intervention (PCI).

A) True

B) False

Answer: B

This question aims to highlight the importance of reperfusion injury and the fact that no effective management was identified for it. Various treatment modalities have been tested, which include but are not limited to the following:

• Ischemic conditioning 
• Glycoprotein IIb/IIIa inhibitors 
• Adenosine
• Vasodilators such as nitric oxide (NO), and angiotensin converting enzyme (ACE)
• Ion channel modulation 
• Glucose-insulin-potassium solution
• Antineutrophil and anticomplement therapy 
• Antioxidant therapy
• Magnesium 
• Cyclosporine 
• Intravenous MTP-131
• Intravenous sodium nitrite 
• Losmapimod 
• Inhibitors of delta-protein kinase C 

Endovascular cooling on the concept of cardioplegia during cardiac bypass surgery is proposed before performing PCI. It was thought myocardial metabolism would decrease at lower temperatures and provide some cardioprotection. Studies fail to show any such benefits.

In summary, effective therapies remain elusive for reperfusion injury.

#cardiology

References:

1. He J, Liu D, Zhao L, Zhou D, Rong J, Zhang L, Xia Z. Myocardial ischemia/reperfusion injury: Mechanisms of injury and implications for management (Review). Exp Ther Med. 2022 Jun;23(6):430. doi: 10.3892/etm.2022.11357. Epub 2022 May 6. PMID: 35607376; PMCID: PMC9121204.

2. He J, Bellenger NG, Ludman AJ, Shore AC, Strain WD. Treatment of myocardial ischaemia-reperfusion injury in patients with ST-segment elevation myocardial infarction: promise, disappointment, and hope. Rev Cardiovasc Med. 2022 Jan 17;23(1):23. doi: 10.31083/j.rcm2301023. PMID: 35092215.

TLS and choice of fluid in initial phase

Q: Lactate Ringer's (LR) is the fluid of choice in initial resuscitation of Tumor Lysis Syndrome (TLS)? 

A) True

B) False

Answer: B

Ringer's Lactate, named after its inventor, is also known as Lactate Ringer or LR. It contains sodium, chloride, potassium, calcium, and lactate. Due to its more isotonic sodium content than normal saline (NS), it is now considered a primary fluid for resuscitation in the ICU. 

In TLS, LR may worsen hyperkalemia and hyperphosphatemia with calcium phosphate precipitation once the tumor breaks down. 

NS stays the fluid of choice, at least in the initial phase of TLS management.

#oncology

#electrolytes

References:

1. Coiffier B, Altman A, Pui CH, et al. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol 2008; 26:2767.

2. Mirrakhimov AE, Voore P, Khan M, Ali AM. Tumor lysis syndrome: A clinical review. World J Crit Care Med. 2015 May 4;4(2):130-8. doi: 10.5492/wjccm.v4.i2.130. PMID: 25938028; PMCID: PMC4411564.

3. McBride A, Trifilio S, Baxter N, Gregory TK, Howard SC. Managing Tumor Lysis Syndrome in the Era of Novel Cancer Therapies. J Adv Pract Oncol. 2017 Nov-Dec;8(7):705-720. Epub 2017 Nov 1. PMID: 30333933; PMCID: PMC6188097.

Decadron in meningitis

Q: Early intravenous (IV) administration of dexamethasone in bacterial meningitis particularly decreases the risk of? (select one)

A) hearing loss

B) vision loss

Answer: A

Administration of IV glucocorticoids has now become the standard of care in the early management of community-acquired bacterial meningitis. Dexamethasone is considered as the drug of choice. The dose is 10 mg administered 15 to 20 minutes prior or with the first dose of antibiotic every 6 hours for 96 hours. It has been found particularly useful in decreasing hearing loss in bacterial meningitis, which can be permanent. It also decreases other neurologic complications and overall mortality by decreasing cerebrospinal fluid (CSF) concentrations of cytokines, CSF inflammation, and cerebral edema.

#neurology

#ID

References:

1. Bhatt SM, Lauretano A, Cabellos C, et al. Progression of hearing loss in experimental pneumococcal meningitis: correlation with cerebrospinal fluid cytochemistry. J Infect Dis 1993; 167:675.

2. de Gans J, van de Beek D; European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002 Nov 14;347(20):1549-56. doi: 10.1056/NEJMoa021334. PMID: 12432041.

3. Gijwani D, Kumhar MR, Singh VB, Chadda VS, Soni PK, Nayak KC, Gupta BK. Dexamethasone therapy for bacterial meningitis in adults: a double blind placebo control study. Neurol India. 2002 Mar;50(1):63-7. PMID: 11960154.

Nitrates and platelets

Q: One of the caveats of using nitrates in angina is its prothrombotic characteristic.

A) True

B) False

Answer: B

One less-known positive contributing effect of Nitrates in coronary artery disease or any vasculopathy is its antithrombotic effect. 

The mechanism of action is probably via stimulation of platelet guanylate cyclase, which prevents fibrinogen binding to platelet IIb/IIIa receptors and, thus, platelet aggregation.

This effect is visible via both intravenous and transdermal nitroglycerin.

#pharmacology

#cardiology

#vascular

References:

1. Loscalzo J. Antiplatelet and antithrombotic effects of organic nitrates. Am J Cardiol 1992; 70:18B.

2. Lacoste LL, Théroux P, Lidón RM, et al. Antithrombotic properties of transdermal nitroglycerin in stable angina pectoris. Am J Cardiol 1994; 73:1058.

Listeriosis in pregnancy - treatment

Q: A 20-weeks pregnant patient is admitted to ICU with septic shock. Blood culture grew listeria. The patient is known to have had severe anaphylactic reactions to penicillin (PCN). What is the drug of choice in a pregnant penicillin-allergic patient with listeria bacteremia? (select one)

A) TMP-SMX

B) Clindamycin

C) Vancomycin

D) Ciprofloxacin

Answer: A

The first line of drugs in severe Listeriosis is ampicillin (or penicillin). Although few experts add gentamicin, it is not advisable due to its potential toxicity.

Trimethoprim/sulfamethoxazole (TMP-SMX), popularly known as Bactrim, is the drug of choice if a patient is PCN allergic. Unfortunately, Bactrim should be avoided in the first trimester and the last month of pregnancy. In the first trimester, Bactrim affects folic acid metabolism, and in the last month, it may cause kernicterus in the fetus. In those periods, meropenem can be used. Our patient is way out of those risk periods for Bactrim, so the answer is A.

Vancomycin has been proposed, but the failure rate is very high.

#ID

#ob-gyn

References:

1. Committee Opinion No. 614: Management of pregnant women with presumptive exposure to Listeria monocytogenes. Obstet Gynecol 2014; 124:1241.

2. Charlier C, Perrodeau É, Leclercq A, et al. Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study. Lancet Infect Dis 2017; 17:510.

3. Wang Z, Tao X, Liu S, Zhao Y, Yang X. An Update Review on Listeria Infection in Pregnancy. Infect Drug Resist. 2021 May 26;14:1967-1978. doi: 10.2147/IDR.S313675. PMID: 34079306; PMCID: PMC8165209.

abdominal exam

Q: In an abdominal examination, which is preferred to be performed first? (select one)

A) Palpation

B) Percussion 

Answer: B

In the abdominal examination, gentle percussion is preferred before palpation because patients with peritonitis may feel severe pain with even gentle palpation. Gentle percussion causes less pain, which makes further examination easier. Palpation, particularly rebound tenderness, can be agonizing for patients.

Muscular rigidity, aka "guarding," signifies local or diffuse peritonitis and is not a feature of pain originating from organs such as kidney stones or pancreatitis.

#physical-exam

References:

1. Fritz D, Weilitz PB. Abdominal Assessment. Home Healthc Now. 2016 Mar;34(3):151-5. doi: 10.1097/NHH.0000000000000364. PMID: 26925941.

2. Ferguson CM. Inspection, Auscultation, Palpation, and Percussion of the Abdomen. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 93. Available from: https://www.ncbi.nlm.nih.gov/books/NBK420/

3. Mealie CA, Ali R, Manthey DE. Abdominal Exam. 2022 Oct 10. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 29083767.

Supraclavicular Subclavian Vein Catheterization: A Forgotten Central Line

Advantages of the supraclavicular approach over infraclavicular technique include:

• a well-defined insertion landmark (the clavisternomastoid angle);
• a shorter distance from skin to vein;
• a larger target area;
• a straight path to superior vena cava; less proximity to lung; and
• fewer complications of pleural or arterial puncture.
• The supraclavicular approach less often necessitates CPR or tube thoracostomy interruption than the infraclavicular approach.
• A finder or seeker needle (21G and 3.5 cm length) can be used to locate vessel, which minimizes the risk of complications. A finder needle is used mostly when ultrasound is not available during insertion of the internal jugular vein, but it may also help locate the subclavian vein via a supraclavicular approach. The needle should be inserted 1 cm posterior to the sternocleidomastoid and 1 cm cephalad to the clavicle.

 

References:

1. Patrick SP, Tijunelis MA, Johnson S, Herbert ME. Supraclavicular subclavian vein catheterization: the forgotten central line. West J Emerg Med. 2009 May;10(2):110-4. PMID: 19561831; PMCID: PMC2691520.

2. Borisov B, Iliev S. Supraclavicular Approach to the Subclavian Vein - One Well Forgotten Technique with Impressive Results. Pol Przegl Chir. 2019 Jun 6;91(4):19-23. doi: 10.5604/01.3001.0013.2281. PMID: 31481642.

Beta receptors

Q: Activation of beta-3 receptors may reduce heart contractility.

A) True

B) False

Answer: A

Very seldom described, but there are three types of beta receptors:

Beta 1 is primarily in the heart muscle. Activation of these receptors results in tachycardia, increased contractility, increased atrioventricular (AV) conduction, and decreased AV node refractoriness.

Beta 2, although found in heart muscles, is more prominent in bronchial and peripheral vascular smooth muscle. Their activation results in vasodilation and bronchodilation.

Beta 3, which is not frequently described, is found in the heart as well as adipose tissues. Activation of these receptors may mediate catecholamine-induced thermogenesis and tend to reduce cardiac contractility.

#physiology

#cardiology

References:

1. Wachter SB, Gilbert EM. Beta-adrenergic receptors, from their discovery and characterization through their manipulation to beneficial clinical application. Cardiology. 2012;122(2):104-12. doi: 10.1159/000339271. Epub 2012 Jul 3. PMID: 22759389.

2. De Blasi A. Beta-adrenergic receptors: structure, function and regulation. Drugs Exp Clin Res. 1990;16(3):107-12. PMID: 1974837.

EVALI

Q: 24 years old male is admitted to ICU with severe respiratory distress. History corelates with starting E-cigarette one week ago. Presumed diagnosis of E-cigarette or vaping product use-associated lung injury (EVALI) is made. Which of the following is the most dominant feature of EVALI? (select one)

A) fever

B) tachycardia 

C) tachypnea 

D) hemoptysis 

Answer: B

EVALI patients generally present with many constitutional, respiratory, and gastrointestinal (GI) symptoms. EVALI is an umbrella term for various disease pathologies that occur in association with the use of E-Cigarettes or vaping. It includes acute eosinophilic pneumonia, diffuse alveolar hemorrhage, lipoid pneumonia, and respiratory-bronchiolitis interstitial lung disease. Interestingly, it is rarely an infectious process. The usual underlying culprit products are THC, vitamin E acetate, nicotine, CBD or other plant oils, medium-chain triglycerides, petroleum distillates, and terpenes.

Although patients may report subjective feelings of warmth, fever is present only in one-third of the patients. Tachycardia is extremely common. Only less than half have tachypnea, though all of them have some level of shortness of breath (SOB) and cough. Remember: Tachypnea and SOB are two different entities.  Pleuritic chest pain may be present. 

Hemoptysis is rare unless the underlying pathology is diffuse alveolar hemorrhage.

#toxicity

#pulmonary

References:

1. Layden JE, Ghinai I, Pray I, et al. Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Final Report. N Engl J Med 2020; 382:903.

2. Kalininskiy A, Bach CT, Nacca NE, Ginsberg G, Marraffa J, Navarette KA, McGraw MD, Croft DP. E-cigarette, or vaping, product use associated lung injury (EVALI): case series and diagnostic approach. Lancet Respir Med. 2019 Dec;7(12):1017-1026. doi: 10.1016/S2213-2600(19)30415-1. Epub 2019 Nov 8. PMID: 31711871.

3. Winnicka L, Shenoy MA. EVALI and the Pulmonary Toxicity of Electronic Cigarettes: A Review. J Gen Intern Med. 2020 Jul;35(7):2130-2135. doi: 10.1007/s11606-020-05813-2. Epub 2020 Apr 3. PMID: 32246394; PMCID: PMC7351931.

A case of skin exam

Q: Which disease comes to mind with the following characteristics of skin rash?

• associated with pharyngitis
• diffuse erythema that blanches with pressure
• sandpaper quality to the skin 
• usually starts in the groin and armpits 
• a strawberry tongue
• palms and soles are usually spared
• Pastia's lines

Answer: Scarlet fever 

The other common name for scarlet fever is scarlatina. It is a diffuse erythematous eruption that requires prior exposure to S. pyogenes. It is a delayed-type skin reactivity to pyrogenic/erythrogenic toxin, usually types A, B, or C).

It appears as numerous small (1 to 2 mm) papular elevations with all the qualities described in the question above. The rash expands quickly to the trunk, followed by the extremities, and ultimately desquamates.

The rash is most marked in the inguinal, axillary, antecubital, and abdominal skin folds and at pressure points. Pastia's lines are linear petechial characters in the antecubital fossae and axillary folds.

With so many tips given, this question aims to emphasize that the diagnosis of scarlet fever is made clinically. However, rapid strep testing and throat culture are required to establish the association.

#ID

#dermatology

#physical-exam

References:

1. Basetti S, Hodgson J, Rawson TM, Majeed A. Scarlet fever: a guide for general practitioners. London J Prim Care (Abingdon). 2017 Aug 11;9(5):77-79. doi: 10.1080/17571472.2017.1365677. PMID: 29081840; PMCID: PMC5649319.

2. Lau SK, Woo PC, Yuen KY. Toxic scarlet fever complicating cellulitis: early clinical diagnosis is crucial to prevent a fatal outcome. New Microbiol. 2004 Apr;27(2):203-6. PMID: 15164635.

3. Hurst JR, Brouwer S, Walker MJ, McCormick JK. Streptococcal superantigens and the return of scarlet fever. PLoS Pathog. 2021 Dec 30;17(12):e1010097. doi: 10.1371/journal.ppat.1010097. PMID: 34969060; PMCID: PMC8717983.

murmurs

Q: Which of the following is NOT considered a heart murmur configuration? (select one)

A) Harsh

B) Plateau 

C) Crescendo 

D) Decrescendo

E) Crescendo-decrescendo

Answer: A

The objective of this question is to make aware of the distinction between configurations, pitch, and intensity of heart murmurs.

Configurations are considered the description of the time course of the murmur. The four major configurations of heart murmurs are:

• Crescendo (increasing)
• Decrescendo (diminishing)
• Crescendo-decrescendo (increasing-decreasing)
• Plateau (unchanged in intensity)

Harsh, rumbling, scratchy, grunting, blowing, squeaky, vibratory, and musical is considered the pitch of the murmurs - can be described as a qualitative description.

The intensity of the murmur runs from Grades 1 to 6, depending on the faintness to the loudness of the murmur.

#cardiology

#physical-exam

References:

1. Ferasin L, Ferasin H, Cala A, Creelman N. Prevalence and Clinical Significance of Heart Murmurs Detected on Cardiac Auscultation in 856 Cats. Vet Sci. 2022 Oct 13;9(10):564. doi: 10.3390/vetsci9100564. PMID: 36288177; PMCID: PMC9611806.

2. Alpert MA. Systolic Murmurs. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 26. Available from: https://www.ncbi.nlm.nih.gov/books/NBK345/

3. Kumar D, Carvalho P, Antunes M, Paiva RP, Henriques J. Heart murmur classification with feature selection. Annu Int Conf IEEE Eng Med Biol Soc. 2010;2010:4566-9. doi: 10.1109/IEMBS.2010.5625940. PMID: 21095796.

Potassium and kidney stones

Q: 42 years old male is admitted to ICU with sepsis due to severe pyelonephritis. The patient has a chronic history of kidney stones. Patient potassium appears to be lower. Aggressive potassium repletion is ordered. Hyperkalemia increases the risk of nephrolithiasis?

A) True

B) False

Answer: B

Hyperkalemia (or a potassium level on the higher side of normal) decreases the risk of kidney stones. High potassium, particularly from an oral route, reduces urinary calcium excretion. It also increases urinary citrate excretion, thereby increasing urine's inhibitory properties. 

#electrolytes

#nephrology

References:

1. Domrongkitchaiporn S, Stitchantrakul W, Kochakarn W. Causes of hypocitraturia in recurrent calcium stone formers: focusing on urinary potassium excretion. Am J Kidney Dis 2006; 48:546.

2. Ferraro PM, Mandel EI, Curhan GC, et al. Dietary Protein and Potassium, Diet-Dependent Net Acid Load, and Risk of Incident Kidney Stones. Clin J Am Soc Nephrol 2016; 11:1834.

3. Lemann J Jr, Pleuss JA, Gray RW, Hoffmann RG. Potassium administration reduces and potassium deprivation increases urinary calcium excretion in healthy adults [corrected]. Kidney Int 1991; 39:973.

Exclusion criteria to be eligible for intravenous thrombolysis in acute ischemic stroke

Q: Which of the following is NOT an exclusion criterion to be eligible for intravenous thrombolysis in acute ischemic stroke? (select one)

A) Intracranial or intraspinal surgery within last 3 months

B) Symptoms suggestive of subarachnoid hemorrhage

C) Active internal bleeding

D) Large (≥10 mm), untreated, unruptured intracranial aneurysm

E) Persistent systolic blood pressure ≥185 mmHg

Answer: D

Exclusion criteria to be eligible for intravenous thrombolysis in acute ischemic stroke is usually divided into four headings:

• Patient history
• Clinical
• Hematologic
• Head CT

Patient history

• Ischemic stroke or severe head trauma in the previous three months
• Previous intracranial hemorrhage
• Intra-axial intracranial neoplasm
• Gastrointestinal malignancy
• Gastrointestinal hemorrhage in the previous 21 days
• Intracranial or intraspinal surgery within the prior three months

Clinical

• Symptoms suggestive of subarachnoid hemorrhage
• Persistent blood pressure elevation (systolic ≥185 mmHg or diastolic ≥110 mmHg)
• Active internal bleeding
• Presentation consistent with infective endocarditis
• Stroke is known or suspected to be associated with aortic arch dissection
• Acute bleeding diathesis, including but not limited to conditions defined under 'Hematologic'

Hematologic

• Platelet count <100,000/mm3
• Current anticoagulant use with an INR >1.7 or PT >15 seconds or aPTT >40 seconds
• Therapeutic doses of low molecular weight heparin received within 24 hours (eg, to treat VTE and ACS); this exclusion does not apply to prophylactic doses (eg, to prevent VTE)
• Current use (i.e., last dose within 48 hours in a patient with normal renal function) of a direct thrombin inhibitor or direct factor Xa inhibitor with evidence of anticoagulant effect by laboratory tests such as aPTT, INR, ECT, TT, or appropriate factor Xa activity assays

  

Head CT

• Evidence of hemorrhage
• Extensive regions of obvious hypodensity consistent with irreversible injury

  

Some conditions may be relative contraindications or warnings or need close monitoring, which includes

• Only minor and isolated neurologic signs or rapidly improving symptoms
• Serum glucose <50 mg/dL (<2.8 mmol/L)
• Serious trauma in the previous 14 days
• Major surgery in the previous 14 days
• History of gastrointestinal bleeding (remote) or genitourinary bleeding
• Seizure at the onset of stroke with postictal neurologic impairments
• Pregnancy
• Arterial puncture at a noncompressible site in the previous seven days
• Large (≥10 mm), untreated, unruptured intracranial aneurysm
• Untreated intracranial vascular malformation

  

There are additional warnings for treatment from 3 to 4.5 hours from symptom onset.

• Age >80 years
• Oral anticoagulant use, regardless of INR
• Severe stroke (NIHSS score >25)
• Combination of both previous ischemic stroke and diabetes mellitus

 

  

#neurology

  

  

References:

  

1. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359:1317.

2. Del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator. A science advisory from the American Heart Association/American Stroke Association. Stroke 2009; 40:2945.

3. Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force:, Levine SR, Khatri P, et al. Review, historical context, and clarifications of the NINDS rt-PA stroke trials exclusion criteria: Part 1: rapidly improving stroke symptoms. Stroke 2013; 44:2500.

4. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2016; 47:581.

5. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With 

Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2019; 50:e344.