HPP - underlying electrolyte pathophysiology

Q: Patients with hypokalemic Periodic Paralysis (HPP) usually have? - select one

A) Calcium channel disorders 

B) Potassium channel disorders

C) Sodium channel disorders 

Answer: A

Although HPP is a potassium-related pathophysiology, as the name suggests, the most common underlying gene mutation is a calcium channel disorder, involving the gene that codes for the alpha-1 subunit of the dihydropyridine-sensitive calcium channel in skeletal muscle.

The mechanism by which the calcium channel defect leads to episodic potassium influx into cells is not fully understood. The proposed mechanism, along with a few others, is that a gene disorder causes a decreased calcium current density and slower rate of activation. 

There could also be a pathology involving insulin sensitivity or hyperthyroidism.

Some patients may also have sodium channel disorders with a mutation in the skeletal muscle sodium channel, SCN4A, but this is uncommon. It affects males and females equally, in contrast to calcium channel disorders, which affect mostly males.

Some patients may not have either of the above channel disorders but may have other potentially associated mutations.

#electrolytes

#musculoskeletal

References:

1. Ptácek LJ, Tawil R, Griggs RC, et al. Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. Cell 1994; 77:863.

2. Matthews E, Labrum R, Sweeney MG, et al. Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. Neurology 2009; 72:1544.

3. Ruff RL. Insulin acts in hypokalemic periodic paralysis by reducing inward rectifier K+ current. Neurology 1999; 53:1556.

4. Sternberg D, Maisonobe T, Jurkat-Rott K, et al. Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A. Brain 2001; 124:1091.

Diabetes and ACE-induced Angioedema

Q: Diabetes increases the risk of ACE inhibitor-induced angioedema.

A) True

B) False

Answer: B

Diabetes is found to have a protective effect in Angiotensin-converting enzyme (ACE) inhibitor-induced angioedema. The underlying mechanism is unknown, though it has been proposed that diabetes increases levels of the enzyme Dipeptidyl peptidase-4 (DPP-IV), which breaks down bradykinin. Bradykinin is considered to be the main culprit in inducing angioedema due to ACE inhibitors.

Some known risk factors for ACE inhibitor-induced angioedema are older age, Aspirin or NSAID use, female sex, Smoking, history of allergies, Coronary artery disease (CAD), and history of ACE inhibitor-induced cough.

#pharmacology

#endocrinology

References:

1. Miller DR, Oliveria SA, Berlowitz DR, et al. Angioedema incidence in US veterans initiating angiotensin-converting enzyme inhibitors. Hypertension 2008; 51:1624.

2. Byrd JB, Touzin K, Sile S, et al. Dipeptidyl peptidase IV in angiotensin-converting enzyme inhibitor associated angioedema. Hypertension 2008; 51:141.

3. Ali HA, Lomholt AF, Mahmoudpour SH, Hermanrud T, Bygum A, von Buchwald C, Jakobsen MA, Rasmussen ER. Genetic susceptibility to angiotensin-converting enzyme-inhibitor induced angioedema: A systematic review and evaluation of methodological approaches. PLoS One. 2019 Nov 11;14(11):e0224858. doi: 10.1371/journal.pone.0224858. Erratum in: PLoS One. 2019 Dec 19;14(12):e0227056. doi: 10.1371/journal.pone.0227056. PMID: 31710633; PMCID: PMC6844479.

SCAD

Q: Spontaneous coronary artery dissection (SCAD) is more common in young? - select one

A) males

B) females

Answer: B

SCAD is a nontraumatic, noniatrogenic separation of the coronary arterial wall. It is more common in young females. Among females ≤50 years old with acute coronary syndrome (ACS), SCAD accounts for about one-quarter of cases. Lately, it is increasingly seen in older and postmenopausal females. 

The underlying mechanism of nonatherosclerotic SCAD is not fully understood. It is basically an intimal tear and bleeding of vasa vasorum, with intramedial hemorrhage, creation of a false lumen filled with intramural hematoma.

An inflammatory component is also described with histological findings of eosinophilic infiltrates in the adventitia. Coronary artery tortuosity may also play a role.

Pregnancy, multiparity, and postpartum stress, with hormonal changes, are considered major risk factors.

#cardiology

#ob-gyn

References:

1. Tam LM, Naderi S, Chi G, et al. Sex Differences in Spontaneous Coronary Artery Dissection: A Report of the iSCAD Registry. J Am Heart Assoc 2026; 15:e042773.

2. Saw J, Aymong E, Sedlak T, et al. Spontaneous coronary artery dissection: association with predisposing arteriopathies and precipitating stressors and cardiovascular outcomes. Circ Cardiovasc Interv 2014; 7:645.

3. Alfonso F. Spontaneous coronary artery dissection: new insights from the tip of the iceberg? Circulation 2012; 126:667.

4. Vijayaraghavan R, Verma S, Gupta N, Saw J. Pregnancy-related spontaneous coronary artery dissection. Circulation 2014; 130:1915.

Diabetes and ICH

Q: Diabetes increases the risk of spontaneous intracerebral hemorrhage.

A) True

B) False

Answer: A

Due to inherent underlying pathology of vasculature in diabetes, the risk of spontaneous as well as related to anticoagulation ICH is higher in diabetes.

Unfortunately, anticoagulant-associated intraocular bleed is also higher in patients with diabetic retinopathy.

#hematology

#neurology

#endocrinology

References:

1. Huhtakangas J, Tetri S, Juvela S, et al. Effect of increased warfarin use on warfarin-related cerebral hemorrhage: a longitudinal population-based study. Stroke 2011; 42:2431.

2. Boulanger M, Poon MT, Wild SH, Al-Shahi Salman R. Association between diabetes mellitus and the occurrence and outcome of intracerebral hemorrhage. Neurology 2016; 87:870.

3. Nentwich MM, Ulbig MW. Diabetic retinopathy - ocular complications of diabetes mellitus. World J Diabetes. 2015 Apr 15;6(3):489-99. doi: 10.4239/wjd.v6.i3.489. PMID: 25897358; PMCID: PMC4398904.

"dying-back" degeneration of large distal axons

Q: The "dying-back" degeneration of large distal axons is characteristic of which chemical toxicity? 

Answer: Organophosphate (OP) 

Although most critical care medicine curricula emphasize acute management of OP poisoning, one vital and delayed aspect of OP often goes unnoticed. =

OPIDN (OP-induced delayed neuropathy) is characterized by a painful "stocking-glove" paresthesias followed by a symmetrical motor polyneuropathy with flaccid weakness of the lower extremities that ascends to involve the upper extremities, primarily affecting distal muscles; in severe neurotoxicity, proximal muscle groups may also be affected. Sensory disturbances are usually mild. 

It occurs one to three weeks after OP exposure (delayed). Usually transient, but in severe cases, an upper motor neuron syndrome with spasticity of the lower extremities usually causes permanent disability. Electromyograms and nerve conduction studies reveal decreased firing of motor conduction units, and histopathologic sections of peripheral nerves show Wallerian degeneration, commonly known as "dying-back" degeneration, of large distal axons. The underlying mechanism involves inhibition of neuropathy target esterase (NTE), which is found in the brain, peripheral nerves, and lymphocytes, and is basically responsible for the metabolism of various esters in the cytoplasm. 

Other reported long-term effects of OP toxicity are either transient or permanent decreased memory, abstraction, attention, and Parkinsonism. Severity may differ with different brands of OP pesticides. 

#toxicity 

#neurology 

 References: 

 1. Aygun D, Onar MK, Altintop BL. The clinical and electrophysiological features of a delayed polyneuropathy developing subsequently after acute organophosphate poisoning and it's correlation with the serum acetylcholinesterase. Electromyogr Clin Neurophysiol 2003; 43:421. 

 2. Johnson MK. Organophosphorus esters causing delayed neurotoxic effects: mechanism of action and structure activity studies. Arch Toxicol 1975; 34:259. 

 3. Arima H, Sobue K, So M, et al. Transient and reversible parkinsonism after acute organophosphate poisoning. J Toxicol Clin Toxicol 2003; 41:67.

PAs visualization via TEE

Q: Which Pulmonary artery (PA) is relatively harder to visualize in transesophageal echocardiography (TEE)? - select one

A) Left

B) Right

Answer: A

The best level to visualize PAs, including main, right, and (?) left, during TEE is the midesophageal ascending aorta short-axis view. Unfortunately, left PA is relatively hard to visualize due to its proximity to the left main bronchus.

#procedures

#pulmonary

References:

1. Pruszczyk P, Torbicki A, Kuch-Wocial A, Szulc M, Styczynski G, Bochowicz A, Kostrubiec M. Visualization of the central pulmonary arteries by biplane transesophageal echocardiography. Exp Clin Cardiol. 2001 Winter;6(4):206-10. PMID: 20428260; PMCID: PMC2859001.

2. Hausmann D, Daniel WG, Mügge A, Heublein B, Hamm M, Schäfers HJ, Haverich A. Imaging of pulmonary artery and vein anastomoses by transesophageal echocardiography after lung transplantation. Circulation. 1992 Nov;86(5 Suppl):II251-8. PMID: 1424008.

 

RTA-3

Q: What is TYPE-3 renal tubular acidosis (RTA)?

Answer: Mix of RTA-1 and RTA-2

Academic books describe in detail Type I, 2 and 4 RTAs, but RTA-3 is rarely mentioned.

The term RTA-3 is used when both proximal and distal acidification defects coexist. It is a failure to reabsorb bicarbonate and an inability to acidify urine properly, resulting in systemic metabolic acidosis. 

In the pediatric population, it is associated with growth hormone deficiency.

#nephrology

#acid-base

References:

1. Goswami RP, Mondal S, Karmakar PS, Ghosh A. Type 3 renal tubular acidosis. Indian J Nephrol. 2012 Nov;22(6):466-8. doi: 10.4103/0971-4065.106058. PMID: 23439805; PMCID: PMC3573491.

2. Reddy P. Clinical approach to renal tubular acidosis in adult patients. Int J Clin Pract. 2011 Mar;65(3):350-60. doi: 10.1111/j.1742-1241.2009.02311.x. PMID: 21314872.

3. Liew YP, Rogers TA, Garb JL, Allen HF, Reiter EO, Campfield TJ, Dharnidharka VR, Braden GL. Type 3 renal tubular acidosis associated with growth hormone deficiency. J Pediatr Endocrinol Metab. 2017 Oct 26;30(10):1047-1053. doi: 10.1515/jpem-2016-0460. PMID: 28888090.

protamine reaction - types

Q: What are the three types of Protamine reaction?

Answer: The term "types of protamine reaction" is kind of a misnomer. In fact, it is the severity level.

Type I is a mild, transient reaction usually caused by rapid infusion. It is histamine-mediated and causes manageable vasodilation and hypotension.

Type II is characterized by a true anaphylactic or anaphylactoid hypersensitivity reaction (probably IgE-mediated), with features such as hypotension, bronchoconstriction, and urticaria.

Type III is a catastrophic pulmonary vasoconstrictive reaction characterized by complement/IgG activation, leading to sudden pulmonary hypertension, right ventricular failure, and severe noncardiogenic pulmonary edema.

Risk factors for such reactions are 

• prior protamine exposure 
• NPH insulin use
• fish allergies, and 
• vasectomy 

Management is usually supportive with pressors, IVF, and, in severe cases, ECMO.

#allergy-immunology

#pharmacology

#hemodynamics

References:

1. Pannu BS, Sanghavi DK, Guru PK, Reddy DR, Iyer VN. Fatal right ventricular failure and pulmonary hypertension after protamine administration during cardiac transplantation. Indian J Crit Care Med. 2016 Mar;20(3):185-7. doi: 10.4103/0972-5229.178185. PMID: 27076733; PMCID: PMC4810899.

2. Porsche R, Brenner ZR. Allergy to protamine sulfate. Heart Lung. 1999 Nov-Dec;28(6):418-28. doi: 10.1016/s0147-9563(99)70031-2. PMID: 10580216.

3. Weiss ME, Adkinson NF Jr. Allergy to protamine. Clin Rev Allergy. 1991 Fall-Winter;9(3-4):339-55. doi: 10.1007/BF02802312. PMID: 1782626.

Octreotide and chylothorax

Q: How does octreotide help in the management of chylothorax?

Answer: By decreasing intestinal fat absorption

Chylothorax continues to remain a challenging situation for both traumatic, including post-surgical, as well as non-traumatic etiologies. Various dietary, surgical, and pharmacological interventions have been tried with varying degrees of success.

Somatostatin analogs such as octreotide and lanreotide are known to decrease intestinal fat absorption. A short course of subcutaneous (SQ) octreotide, 50 to 200 micrograms every 8 hours for 1 to 2 weeks, has been proposed by experts, with caution to discontinue after 2 weeks regardless of the response. 

Caution should be exercised to monitor for cutaneous flushing, nausea, diarrhea, sinus bradycardia, injection-site pain, and elevated liver function tests.

#Pulmonary

References:

1. Mincher L, Evans J, Jenner MW, Varney VA. The successful treatment of chylous effusions in malignant disease with octreotide. Clin Oncol (R Coll Radiol) 2005; 17:118.

2. Evans J, Clark MF, Mincher L, Varney VA. Chylous effusions complicating lymphoma: a serious event with octreotide as a treatment option. Hematol Oncol 2003; 21:77.

3. Kalomenidis I. Octreotide and chylothorax. Curr Opin Pulm Med. 2006 Jul;12(4):264-7. doi: 10.1097/01.mcp.0000230629.73139.26. PMID: 16825878.

ACE-I with diuretics in AA patients

Q: African American (AA) patients, with the addition of a low dose of a thiazide diuretic to an ACE inhibitor, get a similar response to a fall in blood pressure (BP) as comparable to White patients.

A) True

B) False

Answer: A

It is conventionally and, to some extent, rightly believed that AA patients don't respond to ACE (angiotensin-converting enzyme) inhibitors as well as white patients. This notion has led to improper management of hypertension in AA patients many times. Evidence shows that the addition of just a low dose of a thiazide diuretic to an ACE inhibitor can give a comparable fall in BP as in White patients. 

Mechanism of action: ACE inhibitors and diuretics have a synergistic effect: diuretic-induced hypovolemia increases renin release and subsequent angiotensin II production. This effect is prevented by converting enzyme inhibition, resulting in a marked reduction in BP. A similar mechanism applies to the synergistic enhancement observed with dietary sodium restriction and an ACE inhibitor.

Other effects of adding ACE inhibitors to diuretics are:

• prevention of hypokalemia, as reduced angiotensin II formation induced by the ACE inhibitor decreases aldosterone secretion. 
• prevention of  glucose intolerance, hyperlipidemia, and hyperuricemia (some of the diuretic-induced effects)

#hemodynamics

References:

1. Townsend RR, Holland OB. Combination of converting enzyme inhibitor with diuretic for the treatment of hypertension. Arch Intern Med 1990; 150:1175.

2. Pollare T, Lithell H, Berne C. A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension. N Engl J Med 1989; 321:868.

3. Borghi C, Soldati M, Bragagni A, Cicero AFG. Safety implications of combining ACE inhibitors with thiazides for the treatment of hypertensive patients. Expert Opin Drug Saf. 2020 Dec;19(12):1577-1583. doi: 10.1080/14740338.2020.1836151. PMID: 33047990.

SAAG in CHF

Q: One of the advantages of the serum-to-ascites albumin gradient (SAAG) in congestive heart failure (CHF) is that it can predict treatment efficacy.

A) True

B) False

Answer: A

SAAG can predict portal hypertension with 97 percent accuracy. It is easy to calculate by subtracting the ascitic fluid albumin value from the serum albumin value, which should be obtained the same day. 

• gradient ≥1.1 g/dL (≥11 g/L) predicts portal hypertension with 97 percent accuracy
• gradient <1.1 g/dL (<11 g/L) negates portal hypertension

Patients with CHF can narrow their gradient during diuresis, but patients with cirrhosis rarely do unless blood pressure or portal pressure decreases significantly. This is an added advantage of SAAG in establishing a differential diagnosis.

#hepatology

#GI

#cardiology

References:

1. Runyon BA, Montano AA, Akriviadis EA, et al. The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites. Ann Intern Med 1992; 117:215.

2. Hoefs JC. Serum protein concentration and portal pressure determine the ascitic fluid protein concentration in patients with chronic liver disease. J Lab Clin Med 1983; 102:260.

3. Goh ZNL, Teo RYL, Chung BK, Wong AC, Seak CJ. At the heart of the problem: congestive cardiac failure as a cause of ascites: A narrative review. Medicine (Baltimore). 2022 Aug 5;101(31):e29951. doi: 10.1097/MD.0000000000029951. PMID: 35945724; PMCID: PMC9351856.

DPP-4 with metformin

Q: Dipeptidyl peptidase 4 (DPP-4) inhibitors should not be combined with metformin to avoid the risk of severe hypoglycemia.

A) True

B) False

Answer: B

DPP-4 inhibitors, the most popular one in the USA is sitagliptin (trade name Januvia), have a low risk of hypoglycemia even when used as an add-on therapy with metformin. The risk of hypoglycemia is higher when combined with insulin or sulfonylureas, which are well-known to cause hypoglycemia by themselves. 

This characteristic of a lower rate of hypoglycemia is particularly useful in patients with chronic renal disease, including patients who require dialysis.

Similarly, good or bad, they have minimal effect on body weight.

#endocrinology

References:

1.  Nauck MA, Meininger G, Sheng D, et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab 2007; 9:194.

2. Gallwitz B, Rosenstock J, Rauch T, et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet 2012; 380:475.

3. Arjona Ferreira JC, Corry D, Mogensen CE, et al. Efficacy and safety of sitagliptin in patients with type 2 diabetes and ESRD receiving dialysis: a 54-week randomized trial. Am J Kidney Dis 2013; 61:579.

COVID-19, permissive hypercapnia,and permissive hypoxemia

Q: 72 years old male is admitted to the ICU with pneumonia and requires 12 L/min of oxygen flow. Respiratory culture from admission shows COVID-19. Targeting PaO2 ≥60 mmHg rather than ≥90 mmHg may result in more days alive without ventilatory support.

A) True

B) False

Answer: A

Permissive hypoxemia appears to have benefit in patients with COVID-19 who require mechanical ventilation. The HOT-COVID Randomized Clinical Trial, published in JAMA in 2024 at the tail end of the COVID-19 pandemic, went relatively unnoticed. It was a very strong trial with an average of 350 patients in each arm, showing that though there may not be a mortality benefit, patients receiving at least 10 L/minute of oxygen or mechanical ventilation, targeting PaO2 ≥60 mmHg, were associated with more days alive without ventilatory support compared with a target ≥90 mmHg.

The underlying mechanism of action may be due to the Bohr Effect, in which permissive hypercapnia, and thus concomitant permissive hypoxemia, may cause more O₂ to be released in metabolically active tissues.

#pulmonary

#ventilation

#ID

Reference:

1. Nielsen FM, Klitgaard TL, Siegemund M, et al. Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19: The HOT-COVID Randomized Clinical Trial. JAMA 2024; 331:1185.

Social factors in suicide

Q: Immigrants are at higher risk for suicide than the citizens of the host country.

A) True

B) False

Answer: B

Contrary to popular belief, immigrants are at less risk for suicide than the citizens of the native country. Though no single theory can explain this, the postulation is that immigrants in a new country still have hope of doing better after leaving the hopelessness of their home country behind. On the other hand, natives may feel more hopeless with the given system. 

Although the data came from a European country (reference #1), it appears applicable to other contexts. Other social protective factors against suicide are:

• Being married
• Pregnant 
• A parent
• Socially connected
• Financially independent
• Religious 

#psychiatry

References:

1. Brennecke G, Stoeber FS, Kettner M, et al. Suicide among immigrants in Germany. J Affect Disord 2020; 274:435.

2. Hung GC, Cheng CT, Jhong JR, et al. Risk and protective factors for suicide mortality among patients with alcohol dependence. J Clin Psychiatry 2015; 76:1687.

3. Miola A, Tondo L, Pinna M, et al. Suicidal risk and protective factors in major affective disorders: A prospective cohort study of 4307 participants. J Affect Disord 2023; 338:189.

4. Qin P, Mortensen PB. The impact of parental status on the risk of completed suicide. Arch Gen Psychiatry 2003; 60:797.

RDW, RDW-SD and RDW-CV

Q: What's the difference between RDW, RDW-SD and RDW-SC?

Answer: 

Red cell distribution width (RDW) signifies either microcytosis (low RDW) or macrocytosis (high RDW). The two major causes of microcytosis, probably accompanied by hypochromia, are thalassemia and iron deficiency.

RDW- Standard Deviation (RDW-SD) measures the actual variation in size of red blood cells. A high RDW-SD means cells vary significantly in size. RDW-SD is an actual, physical measurement of the cell volume distribution curve at a level 20% above the baseline of the histogram.

RDW — Coefficient of Variation (RDW-CV) is a calculation influenced by average red blood cell size. It is usually considered less precise than RDW-SD because it measures the histogram at the midpoint.

RDW-SD, RDW-CV, and Mean Corpuscular Volume (MCV) should be read together for better understanding. 

#hematology

#laboratory science

References:

1. Sarma PR. Red Cell Indices. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 152. Available from: https://www.ncbi.nlm.nih.gov/books/NBK260/

2. Salvagno GL, Sanchis-Gomar F, Picanza A, Lippi G. Red blood cell distribution width: A simple parameter with multiple clinical applications. Crit Rev Clin Lab Sci. 2015;52(2):86-105. doi: 10.3109/10408363.2014.992064. Epub 2014 Dec 23. PMID: 25535770.

3. Yang K, Sun B, Zhang S, Pan Y, Fang J. RDW-SD is Superior to RDW-CV in Reflecting Liver Fibrosis Stage in Patients with Chronic Hepatitis B. Infect Drug Resist. 2023 Oct 27;16:6881-6891. doi: 10.2147/IDR.S427047. PMID: 37920477; PMCID: PMC10619233.

Plasmapheresis during pregnancy

Q: A 32-year-old female, first-time, 26 weeks pregnant, with a known history of Myasthenia Gravis (MG), presented with severe myasthenia crisis requiring intubation. Plasmapheresis should not be performed during pregnancy.

 

A) True

B) False

Answer: B

Two major rescue therapies for myasthenic crisis are:

• Plasmapheresis 
• High-dose intravenous immune globulin

They are both safe in pregnancy.

#Ob-gyn

#neurology

References:

1. Varner M. Myasthenia gravis and pregnancy. Clin Obstet Gynecol 2013; 56:372.

2. Sanders DB, Wolfe GI, Benatar M, et al. International consensus guidance for management of myasthenia gravis: Executive summary. Neurology 2016; 87:419.

3. Watson WJ, Katz VL, Bowes WA Jr. Plasmapheresis during pregnancy. Obstet Gynecol 1990; 76:451.

SPS in hyperkalemia

Q: Sodium polystyrene sulfonate (SPS) or other cation-exchange resins should be utilized only in? - select one

A) acute hyperkalemia 

B) chronic hyperkalemia 

Answer: A

Sodium polystyrene sulfonate (SPS) or other cation-exchange resins are usually administered in combination with sorbitol to treat hyperkalemia. 

They were immensely popular in ICUs for the control of hyperkalemia, but evidence shows that they carry more harm than benefit, particularly causing potentially fatal intestinal necrosis and fluid overload as they exchange K for Na. 

Interestingly, some experts claim that the most effect comes from the laxative effect of added sorbitol. That's why SPS or other resins should be used only for short-term use and only in a semi-hyperkalemic emergency.

#electrolytes

References:

1. Hagan AE, Farrington CA, Wall GC, Belz MM. Sodium polystyrene sulfonate for the treatment of acute hyperkalemia: a retrospective study. Clin Nephrol. 2016 Jan;85(1):38-43. doi: 10.5414/CN108628. PMID: 26587776.

2. Rossignol P, Pitt B. Sodium polystyrene is unsafe and should not be prescribed for the treatment of hyperkalaemia: primum non nocere! Clin Kidney J. 2023 Apr 21;16(8):1221-1225. doi: 10.1093/ckj/sfad090. PMID: 37529653; PMCID: PMC10387396.

capsid inhibitor for HIV-1 treatment and prevention

Q: How do capsid inhibitors work in HIV?

Answer: They disrupt HIV capsid protein functions

Lenacapavir is the capsid inhibitor approved by the FDA in 2022. It has a unique mechanism of action that disrupts HIV capsid protein functions and impacts key protein-protein interactions necessary for viral entry and virion assembly.

It is very effective in patients with multidrug-resistant HIV, as well as in preventing HIV infection. It is administered in combination with an optimized background ART regimen. 

The beauty of this drug is that, after an initial induction regimen that includes an oral lenacapavir component, it is administered only every 6 months as a subcutaneous injection, thereby improving adherence, particularly in resource-limited countries.

#ID

#pharmacology

References:

1. Prather C, Lee A, Yen C. Lenacapavir: A first-in-class capsid inhibitor for the treatment of highly treatment-resistant HIV. Am J Health Syst Pharm. 2023 Dec 5;80(24):1774-1780. doi: 10.1093/ajhp/zxad223. PMID: 37767713.

2. Segal-Maurer S, DeJesus E, Stellbrink HJ, et al. Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection. N Engl J Med 2022; 386:1793.

3. De Clercq E, Zhang Y, Li G, Deng Y, Khouri R, Růžek D, Król E, Tan L. Lenacapavir: A capsid inhibitor for HIV-1 treatment and prevention. Biochem Pharmacol. 2025 Oct;240:117125. doi: 10.1016/j.bcp.2025.117125. Epub 2025 Jul 5. PMID: 40623458.

Brugada Syndrome in psychiatric disorder

Q: Which psychological condition is found to be associated with Brugada pattern ECGs? - Select one

A) Autism Spectrum Disorder  

B) Bipolar Disorder

C) Obsessive-Compulsive Disorders

D) Schizophrenia 

E) Social Anxiety

Answer: D

Brugada pattern ECGs are more significantly common in schizophrenia, and this association is without any significant impact of antipsychotic medications with sodium channel blocking activity.

Although the cause is not known, the same electrolyte channel dysfunction is suspected. It keeps the risk of sudden death in these patients high, an important element in the care of these patients, particularly when they are in hospitals and subject to various medications.

#psychiatry

#cardiology

References:

1. Blom MT, Cohen D, Seldenrijk A, et al. Brugada syndrome ECG is highly prevalent in schizophrenia. Circ Arrhythm Electrophysiol 2014; 7:384.

2. Rastogi A, Viani-Walsh D, Akbari S, Gall N, Gaughran F, Lally J. Pathogenesis and management of Brugada syndrome in schizophrenia: A scoping review. Gen Hosp Psychiatry. 2020 Nov-Dec;67:83-91. doi: 10.1016/j.genhosppsych.2020.09.003. Epub 2020 Oct 6. PMID: 33065406; PMCID: PMC7537626.

3. Treur JL, Thijssen AB, Smit DJA, Tadros R, Veeneman RR, Denys D, Vermeulen JM, Barc J, Bergstedt J, Pasman JA, Bezzina CR, Verweij KJH. Associations of schizophrenia with arrhythmic disorders and electrocardiogram traits: genetic exploration of population samples. Br J Psychiatry. 2025 Mar;226(3):153-161. doi: 10.1192/bjp.2024.165. Epub 2024 Nov 8. PMID: 39512114; PMCID: PMC7616879.

4. Sutterland AL, Blom MT, Ladee K, Lubbers JJM, Cohen D, de Haan L, Tan HL. Increased prevalence of ECG suspicious for Brugada Syndrome in recent onset schizophrenia spectrum disorders. Schizophr Res. 2019 Aug;210:59-65. doi: 10.1016/j.schres.2019.06.013. Epub 2019 Jun 24. PMID: 31248748.

AG in MM

Q: An anion gap (AG) in multiple myloma (MM) will be? - select one

A) high

B) low

Answer: B

Patients suspected of MM, typically with CRAB, i.e., hypercalcemia, renal insufficiency, anemia, and bone disease, would probably have a low anion gap. 

The two contributing factors to low AG are:

• Severe hypercalcemia acts as an unmeasured cation 
• A cationic IgG molecule

# electrolytes

#acid-base

References:

1. Mansoor S, Siddiqui I, Adil S, Nabi Kakepoto G, Fatmi Z, Ghani F. Anion gap among patients of multiple myeloma and normal individuals. Clin Biochem. 2007 Feb;40(3-4):226-9. doi: 10.1016/j.clinbiochem.2006.10.011. Epub 2006 Nov 1. PMID: 17156769.

2. Kraut JA, Madias NE. Serum anion gap: its uses and limitations in clinical medicine. Clin J Am Soc Nephrol 2007; 2:162.

3. De Troyer A, Stolarczyk A, De Beyl DZ, Stryckmans P. Value of anion-gap determination in multiple myeloma. N Engl J Med 1977; 296:858.

Aztreonam cross allergenicity

Q: Which cephalosporin allergy may also cause an allergy to aztreonam? - select one

A) Cefazolin 

B) Cefuroxime 

C) Ceftazidime 

D) Cefepime

E) Ceftaroline 

Answer: C

As a rule of thumb, there is no cross-allergenicity between aztreonam and other beta-lactam antibiotics, except ceftazidime. This cross-allergenicity between aztreonam and ceftazidime allergies is due to a shared side chain, called the R1 side chain.

#pharmacology

#ID

References:

Pérez Pimiento A, Gómez Martínez M, Mínguez Mena A, Trampal González A, de Paz Arranz S, Rodríguez Mosquera M. Aztreonam and ceftazidime: evidence of in vivo cross allergenicity. Allergy. 1998 Jun;53(6):624-5. doi: 10.1111/j.1398-9995.1998.tb03944.x. PMID: 9689350.

Gas explosion

Q: A gas explosion during a colonoscopy is a possibility.

A) True

B) False

Answer: A

A gas explosion during a colonoscopy is a rare but dreaded complication. Due to poor bowel prep, hydrogen or methane gas may be retained in the colonic lumen, and ignition from electrosurgical energy may cause a gas explosion. An alternative reason is the use of incompletely absorbable carbohydrate preparations, such as lactulose, mannitol, or sorbitol, which can serve as substrates for colonic bacteria, leading to fermentation and the production of high levels of combustible gases, including hydrogen and methane. 

One interesting case of a gas explosion is reported without the use of bowel preparation in a patient with colectomy for Gardner syndrome, who was found to have rectal polyps on proctoileoscopy. The polyps were treated with APC, which resulted in a gas explosion.

#procedures

#GI

References:

1. Manner H, Plum N, Pech O, et al. Colon explosion during argon plasma coagulation. Gastrointest Endosc 2008; 67:1123.

2. Tontini GE, Rimondi A, Pessarelli T, Ciprandi G, Kurihara H, Sorge A, Vecchi M. Clinical features and risk factors for colorectal gas explosion during digestive endoscopy and surgery: a systematic review. Surg Endosc. 2025 Jan;39(1):384-393. doi: 10.1007/s00464-024-11370-0. Epub 2024 Nov 15. PMID: 39548011; PMCID: PMC11666635.

3. Lin OS, Biehl T, Jiranek GC, Kozarek RA. Explosion from argon cautery during proctoileoscopy of a patient with a colectomy. Clin Gastroenterol Hepatol 2012; 10:1176.

4. Ladas SD, Karamanolis G, Ben-Soussan E. Colonic gas explosion during therapeutic colonoscopy with electrocautery. World J Gastroenterol. 2007 Oct 28;13(40):5295-8. doi: 10.3748/wjg.v13.i40.5295. PMID: 17879396; PMCID: PMC4171316.

Age's risk factor for acute renal transplant rejection

Q: Which of the following is at increased risk of acute kidney rejection post-transplant? - select one

A) older recipient and young donor

B) Younger recipient and older donor 

Answer: B

The following are the major risk factors for high immunologic risk of acute rejection.

• One or more human leukocyte antigen (HLA) mismatches
• Younger recipient and older donor age
• Presence of a donor-specific antibody (DSA)
• Blood group incompatibility
• Delayed onset of graft function
• Cold ischemia time greater than 24 hours
• Previous episode of rejection
• Receipt of a second or greater transplant
• Medication nonadherence

Younger patients' innate strong immunity may react vehemently to an older donor's organ.

#transplantation

#nephrology

References:

1. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009; 9 Suppl 3:S1.

Sweet syndrome

Q: All of the following are considered "classical" Sweet syndrome EXCEPT?

A) Drug-Induced

B) Infections associated

B) Inflammatory bowel disease associated

C) Pregnancy-associated

Answer: A

It is called Sweet syndrome after Dr. Robert Douglas Sweet, who first described it almost 60 years ago. Its medical terminology is 'acute febrile neutrophilic dermatosis'.  

It is an inflammatory disorder characterized by the abrupt appearance of painful, edematous, and erythematous papules, plaques, or nodules on the skin. Fever and leukocytosis frequently accompany the cutaneous lesions. Also, involvement of the eyes, musculoskeletal system, and internal organs may occur.

It is divided into three categories

1. Classical 
2. Malignancy-associated (common in AML)
3. Drug-induced (classically with Granulocyte-colony stimulating factor -G-CSF)

The majority of cases occur after the following three pathologies, and that's why called classical

• 1-3 weeks after upper respiratory tract and gastrointestinal infections (though it can also occur in other infections)
• In Crohn's disease and ulcerative colitis
• In Pregnancy 

Drug-induced sweet syndrome is not considered classical.

#dermatology

References:

1. SWEET RD. AN ACUTE FEBRILE NEUTROPHILIC DERMATOSIS. Br J Dermatol 1964; 76:349.

2. Cohen PR. Sweet's syndrome--a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis 2007; 2:34.

3. Ytting H, Vind I, Bang D, Munkholm P. Sweet's syndrome--an extraintestinal manifestation in inflammatory bowel disease. Digestion 2005; 72:195.

4. Satra K, Zalka A, Cohen PR, Grossman ME. Sweet's syndrome and pregnancy. J Am Acad Dermatol 1994; 30:297.

5. Raza S, Kirkland RS, Patel AA, Shortridge JR, Freter C. Insight into Sweet's syndrome and associated-malignancy: a review of the current literature. Int J Oncol. 2013 May;42(5):1516-22. doi: 10.3892/ijo.2013.1874. Epub 2013 Mar 28. PMID: 23546524.

rupture of pyogenic liver abscess

Q: Why does most hepatic abscess rupture not cause intraperitoneal dissemination?

Answer: Due to localization in adjacent spaces

The phenomenon of hepatic abscess rupture is rare because high-sensitivity early diagnostic modalities are now readily available. It is now mostly seen in highly remote resource-limited settings. The two most common risk factors for rupture are:

1. abscess diameter >6 cm

2. Coexisting cirrhosis

Fortunately, widespread intraperitoneal dissemination and contamination are rare, as most ruptures localize to the perihepatic, subphrenic, or pleural space.

#hepatology

References:

1. Jun CH, Yoon JH, Wi JW, et al. Risk factors and clinical outcomes for spontaneous rupture of pyogenic liver abscess. J Dig Dis 2015; 16:31.

2. Khim G, Em S, Mo S, Townell N. Liver abscess: diagnostic and management issues found in the low resource setting. Br Med Bull 2019; 132:45.

3. Singh A, Paruthy SB, Kuraria V, Dhawaria M, Khera D, M S H, Raju H, Madhuri SS, Saini Y, Kumar A. A Comprehensive Study on Ruptured Liver Abscess in a Tertiary Care Center. Cureus. 2024 Jul 14;16(7):e64526. doi: 10.7759/cureus.64526. PMID: 39139323; PMCID: PMC11321501.

Droxidopa as a pressor

Q: Droxidopa, after decarboxylation, worked as a which pressor or inotrope? - Select one

A) Dopamine

B) Dobutamine

C) Epinephrine

D) Norepinephrine

E) Vasopressin

Answer: D

Droxidopa has recently become widely used in ICUs to treat vasoplegia or persistent hypotension. Droxidopa is L-dihydroxyphenylserine, also known as (DOPS). It is an oral synthetic amino acid, identical to levodopa but with an added hydroxyl group. After oral administration, droxidopa is decarboxylated to norepinephrine, the naturally occurring sympathetic neurotransmitter. Patients with neurogenic orthostatic hypotension (nOH) retain the ability to convert droxidopa to norepinephrine, which helps in overcoming hypotension.

The starting dose is 100 mg three times daily, up to a total of 1800 mg in three divided doses.

One caveat are the patients with Parkinson disease who are on high doses of carbidopa (more than 200 mg/day) as carbidopa blocks the conversion of droxidopa to norepinephrine.

Side effects are supine hypertension, headache, and nausea. 

#hrmodynamics

#pharmacology

#neurology

References:

1. Biaggioni I, Arthur Hewitt L, Rowse GJ, Kaufmann H. Integrated analysis of droxidopa trials for neurogenic orthostatic hypotension. BMC Neurol 2017; 17:90.

2. Hauser RA, Hewitt LA, Isaacson S. Droxidopa in patients with neurogenic orthostatic hypotension associated with Parkinson's disease (NOH306A). J Parkinsons Dis 2014; 4:57.

3. Kaufmann H, Norcliffe-Kaufmann L, Palma JA. Droxidopa in neurogenic orthostatic hypotension. Expert Rev Cardiovasc Ther 2015; 13:875.

eventration of the diaphragm

Q: Complete eventration of the hemidiaphragm usually happens on? - select one

A) left 

B) right

Answer: A

Diaphragmatic eventration is defined as a thinning of a portion or all of the diaphragmatic muscle by fibroelastic tissue.

For a not completely understood reason:

• Partial eventration mostly happens on the right hemidiaphragm 
• Complete eventration mostly happens on the left hemidiaphragm

Bilateral involvement is rare.

Clinically, it may cause tachypnea, palpitations, chest pain, chronic cough, recurrent pneumonia, dyspepsia, GERD, and epigastric pain.

#pulmonary

#radiology

References:

1. Groth SS, Andrade RS. Diaphragmatic eventration. Thorac Surg Clin. 2009 Nov;19(4):511-9. doi: 10.1016/j.thorsurg.2009.08.003. PMID: 20112634.

2. Mouroux J, Venissac N, Leo F, et al. Surgical treatment of diaphragmatic eventration using video-assisted thoracic surgery: a prospective study. Ann Thorac Surg 2005; 79:308.

Urea and Na

Q: Oral Urea tablets can be used in the treatment of? - select one

A) Hypernatremia

B) Hyponatremia

Answer: B

Although not widely used because of other modalities for treating hyponatremia, oral urea is one option for lowering sodium concentration. It is particularly useful in patients who require long-term treatment with Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH). It is popularly known as 'poor man's Vaptan.' It has shown its efficacy in acute cases also, such as on Intracranial Pressure (ICP) in Patients With Acute Brain Injury and Hyponatremia (reference# 4)

Urea is available as oral packets in the USA and can also be given via a nasogastric tube (NGT). The mechanism of action is via increasing the excretion of electrolyte-free water. The usual maintenance dose is 15 to 30 g/day.

#electrolytes

References:

1. Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant 2014; 29 Suppl 2:i1.

2. Decaux G, Andres C, Gankam Kengne F, Soupart A. Treatment of euvolemic hyponatremia in the intensive care unit by urea. Crit Care 2010; 14:R184.

3. Soupart A, Coffernils M, Couturier B, et al. Efficacy and tolerance of urea compared with vaptans for long-term treatment of patients with SIADH. Clin J Am Soc Nephrol 2012; 7:742.

4. Annoni F, Fontana V, Brimioulle S, et al. Early Effects of Enteral Urea on Intracranial Pressure in Patients With Acute Brain Injury and Hyponatremia. J Neurosurg Anesthesiol 2016.

 

Clozapine and tobacco

Q: A 64-year-old male with only a past history of depression and smoking is admitted to the hospital for severe community-acquired pneumonia (CAP). His only home medication is clozapine. His dose for clozapine should be? - select one

A) decreased

B) increased

Answer: A

Clozapine has a complex relationship with smoking. Smokers require almost a twofold increase in dose. Once they are stable on a higher-than-usual dose, it needs to be tapered down when in a nonsmoking environment.

Another important aspect of chronic clozapine use is the risk of agranulocytosis and its strong anticholinergic, sedative, cardiac, and hypotensive properties, so any agents with these characteristics should be used with care. 

#pharmacology

#psychiatry

References:

1. Tsuda Y, Saruwatari J, Yasui-Furukori N. Meta-analysis: the effects of smoking on the disposition of two commonly used antipsychotic agents, olanzapine and clozapine. BMJ Open 2014; 4:e004216.

2. McEvoy JP, Freudenreich O, Wilson WH. Smoking and therapeutic response to clozapine in patients with schizophrenia. Biol Psychiatry. 1999 Jul 1;46(1):125-9. doi: 10.1016/s0006-3223(98)00377-1. PMID: 10394482.

3. Zeng L, Lv H, Li J, Xue R, Liu X, Zhou C, Yu H. Cigarette smoking, coffee consumption, alcohol intake, and clozapine metabolism: A Mendelian randomization study. Front Psychiatry. 2022 Sep 29;13:1002235. doi: 10.3389/fpsyt.2022.1002235. PMID: 36245885; PMCID: PMC9559606.

importance of paracentesis in SBP

Q: What's the importance of paracentesis in spontaneous bacterial peritonitis (SBP)?

Answer: Determination of mortality

As famously said for lungs: "the sun should never set on a parapneumonic effusion, " similarly, it is true for abdominal paracentesis in SBP, as mortality increases by 3.3 percent/hour of delay in performing a paracentesis in patients with SBP.

Overall, hospitalized patients with SBP who received delayed paracentesis (DP) had a 2.7-fold increased risk of mortality, adjusting for MELD score and renal dysfunction. Diagnostic paracentesis performed less than 12 hours from hospitalization in patients with cirrhosis and ascites has improved short-term survival.  

#procedures

References:

1. Kim JJ, Tsukamoto MM, Mathur AK, et al. Delayed paracentesis is associated with increased in-hospital mortality in patients with spontaneous bacterial peritonitis. Am J Gastroenterol 2014; 109:1436.

2. Sahn SA, Light RW. The sun should never set on a parapneumonic effusion. Chest. 1989 May;95(5):945-7. doi: 10.1378/chest.95.5.945. PMID: 2707086.

3. Harvey JJ, Prentice R, George J. Diagnostic and therapeutic abdominal paracentesis. Med J Aust. 2023 Jan 16;218(1):18-21. doi: 10.5694/mja2.51795. Epub 2022 Nov 30. PMID: 36450339; PMCID: PMC10099762.

BAT

Q: Which of the following has the highest likelihood ratio (LR) of Blunt Abdominal Trauma, popularly known as BAT? - select one

A) Abdominal distension 

B) Abdominal guarding

C) Hypotension  

D) Rebound tenderness 

E) Seatbelt sign

Answer: E

Of note, the most important pearl to remember during trauma evaluation of the abdomen is: "The absence of abdominal pain or tenderness does not rule out significant intra-abdominal injury."

A history and physical exam should be performed in detail. Interestingly, the seatbelt sign has the highest LR of probable underlying BAT. 

Seat Belt sign is followed by rebound tenderness, and in frequency down with hypotension, and abdominal distension. Abdominal guarding has the lowest LR in the above question for BAT.

Another important pearl to remember is that "the negative LR for the above signs, either alone or in combination, is low, which means that the absence of either sign does not exclude injury."

                                                     

Concomitant femur fracture can significantly distract the clinician from BAT, particularly in pedestrian trauma.

#trauma

References:

1. Nishijima DK, Simel DL, Wisner DH, Holmes JF. Does this adult patient have a blunt intra-abdominal injury? JAMA 2012; 307:1517.

2. Shreffler J, Smiley A, Schultz M, et al. Patients with Abrasion or Ecchymosis Seat Belt Sign Have High Risk for Abdominal Injury, but Initial Computed Tomography is 100% Sensitive. J Emerg Med 2020; 59:491.

3. Pourmand A, Terrebonne E, Shapovalov V, et al. Prevalence of intra-abdominal injury among patients with seatbelt signs, a systematic review and meta-analysis. Am J Emerg Med 2024; 76:199.

4. Agrawal A, Inamadar PI, Subrahmanyam BV. Seat belt sign and its significance. J Family Med Prim Care. 2013 Jul;2(3):288-90. doi: 10.4103/2249-4863.120769. PMID: 24479100; PMCID: PMC3902689.

cola colored urine

Q: What could be the underlying renal pathophysiology in cola or tea colored urine?

Answer: Possible glomerular bleeding

An astute physician can quickly differentiate glomerular and nonglomerular bleeding at first sight at the bedside.

Cola or tea-colored or dark brown urine may indicate glomerular bleeding, in which prolonged transit time through the nephron in an acidic urine environment can result in the formation of methemoglobin, giving the urine a smoky brown, tea, or cola color.

Obviously, this is a first glance bedside observation at the bedside. Urine can still appear red or pink in glomerular bleeding if urine is not acidic, or transit time is too fast, but by default, as a rule of thumb, in gross hematuria -

• nonglomerular bleeding appears red or pink, and
• glomerular bleeding appears dark brown (cola colored)

Other caveats are false colorations due to dye, food, drugs, or underlying non-renal pathophysiologies such as rhabdomyolysis or hyperbilirubinemia.

#nephrology

References:

1. Stark A, Kanduri SR, Ramanand A, Rosenbloom S, Varghese V, Chalmers DR, Velez SA, Gonzalez-Fuentes C, Wickman TJ, Mohamed M, Shueib A, Zarm A, Lukitsch I, Velasco-Gonzalez C, Seltzer JR, Velez JCQ. Glomerular Hematuria for the Diagnosis of Glomerulonephritis. Glomerular Dis. 2025 Apr 10;5(1):206-218. doi: 10.1159/000545051. PMID: 40406196; PMCID: PMC12097761.

2. Rose BD. Pathophysiology of Renal Disease, 2nd ed, McGraw-Hill, New York 1987. p.10.

3. Hamadah AM, Gharaibeh K, Mara KC, Thompson KA, Lieske JC, Said S, Nasr SH, Leung N. Urinalysis for the diagnosis of glomerulonephritis: role of dysmorphic red blood cells. Nephrol Dial Transplant. 2018 Aug 1;33(8):1397-1403. doi: 10.1093/ndt/gfx274. PMID: 29156008.