DrawingTacrolimus Trough Level

Q: Which one precaution should be taken while drawing blood for Tacrolimus (FK506) level?

Answer: Tacrolimus can leach into plastic catheters.

In the immediate transplant period, Tacrolimus prophylaxis is initiated via intravenous (IV) infusion. Tacrolimus can leach into plastic catheters, so the Central Venous Catheter (CVC) lumen used to measure serum levels should be separate from the lumen through which tacrolimus is infused; otherwise, serum levels are likely to be falsely elevated.

Tacrolimus should be converted to the oral route whenever the patient can utilize the enteral route. Tacrolimus is almost completely metabolized in the liver, so the half-life of nine hours can be longer in liver insufficiency. 

#transplant

#pharmacology

#laboratory-medicine

References:

1. Hacker C, Verbeek M, Schneider H, Steimer W. Falsely elevated cyclosporin and tacrolimus concentrations over prolonged periods of time due to reversible adsorption to central venous catheters. Clin Chim Acta. 2014 Jun 10;433:62-8. doi: 10.1016/j.cca.2014.02.031. Epub 2014 Mar 11. PMID: 24631133.

2. Han A, Jo AJ, Kwon H, Kim YH, Lee J, Huh KH, Lee KW, Park JB, Jang E, Park SC, Lee J, Lee J, Kim Y, Soliman M, Min S. Optimum tacrolimus trough levels for enhanced graft survival and safety in kidney transplantation: a retrospective multicenter real-world evidence study. Int J Surg. 2024 Oct 1;110(10):6711-6722. doi: 10.1097/JS9.0000000000001800. PMID: 38884261; PMCID: PMC11486932.

3. Yin S, Song T, Jiang Y, Li X, Fan Y, Lin T. Tacrolimus Trough Level at the First Month May Predict Renal Transplantation Outcomes Among Living Chinese Kidney Transplant Patients: A Propensity Score-Matched Analysis. Ther Drug Monit. 2019 Jun;41(3):308-316. doi: 10.1097/FTD.0000000000000593. PMID: 31083041; PMCID: PMC6553958.

Dig in pregnancy

Q: Digoxin is contraindicated in pregnancy?

A) Yes

B) No

Answer: B 

Digoxin is one of the unique medicines that is given to the mother for fetal cardiac indications. It crosses the placenta without causing fetal harm or teratogenicity. Moreover, it can be used in lactation for maternal cardiac indications.

It is mostly used to treat sustained fetal tachyarrhythmias, such as supraventricular tachycardia (SVT) and atrial flutter, and to prevent hydrops fetalis.

#ob-gyn

#pharmacology

#pediatrics

#cardiology

References:

1. Hauptman PJ, Kelly RA. Digitalis. Circulation 1999; 99:1265.

2. Wang C, Zhao L, Shao S, Yu H, Zhou S, Li Y, Zhu Q, Liu X, Duan H, Liu H, Hua Y, Zhou K. Transplacental digoxin treatment for fetal supraventricular arrhythmias: Insights from Chinese fetuses. Chin Med J (Engl). 2025 Jun 20;138(12):1499-1501. doi: 10.1097/CM9.0000000000003583. Epub 2025 Apr 9. PMID: 40204513; PMCID: PMC12180843.

3. Soyka LF. Digoxin: placental transfer, effects on the fetus, and therapeutic use in the newborn. Clin Perinatol. 1975 Mar;2(1):23-35. PMID: 1102216.

catamenial epilepsy

Q: Catamenial epilepsy occurs more frequently in which phase of the menstrual cycle?

A) early 

B) mid

C) late

Answer: C

Catamenial epilepsy can best be predicted by keeping a seizure diary. In a regular menstrual cycle, estrogen levels peak during mid-cycle (without conception) and drop just before the onset of menses. During this period, most seizure clusters are reported. Although a periovulatory seizure may occur. 

Standard treatment of seizures should be sufficient.

Use of Clobazam during the vulnerable phase of the menstrual cycle has shown some promise. 20 to 30 mg of Clobazam per day for 10 days during the high-risk phase of the menstrual cycle has been found to be effective. Intermittent lorazepam may also be used in the vulnerable period.

Some experts recommend the use of an adjunctive continuous estrogen-progestin contraceptive as hormonal prophylaxis for catamenial epilepsy, though evidence is weak for such practice. Other recommended treatments, but with very limited data, are acetazolamide, gonadotropin analogs, and neurosteroids (ganaxolone).

#neurology

#ob-gyn

References:

1. Herzog AG, Fowler KM, Sperling MR, et al. Variation of seizure frequency with ovulatory status of menstrual cycles. Epilepsia 2011; 52:1843.

2. Maguire MJ, Nevitt SJ. Treatments for seizures in catamenial (menstrual-related) epilepsy. Cochrane Database Syst Rev 2021; 9:CD013225.

3. Herzog AG, Fowler KM, Smithson SD, et al. Progesterone vs placebo therapy for women with epilepsy: A randomized clinical trial. Neurology 2012; 78:1959.

4. Feely M, Calvert R, Gibson J. Clobazam in catamenial epilepsy. A model for evaluating anticonvulsants. Lancet 1982; 2:71.

5. Ansell B, Clarke E. Acetazolamide in Treatment of Epilepsy. Br Med J 1956; 1:650.

6. Reddy DS. Neurosteroid replacement therapy for catamenial epilepsy, postpartum depression and neuroendocrine disorders in women. J Neuroendocrinol 2022; 34:e13028.

PP and Carbs

Q: A high-carbohydrate load is recommended in patients who present with hypokalemic Periodic paralysis (PP), including thyrotoxic PP.

A) True

B) False

Answer: B

PP attacks in hypokalemic thyrotoxic patients result from increased release of epinephrine or insulin, causing intracellular potassium shifts and low serum potassium levels. Known inciting events are:

• strenuous physical activity
• stress
• high-carbohydrate load (answer for above Q)
• cold exposure
• infection
• alcohol intake
• pulse corticosteroid therapy
• beta-2 adrenergic bronchodilator 
• menses 
• exogenous epinephrine or insulin
• acetazolamide
• thyroid supplements 

#electrolytes

References:

1. Hsieh MJ, Lyu RK, Chang WN, et al. Hypokalemic thyrotoxic periodic paralysis: clinical characteristics and predictors of recurrent paralytic attacks. Eur J Neurol 2008; 15:559.

2. Qing G, Zakaria WNA, Rom FZM, Nik WNFHW, Zulkeflee HA, Rahim SNA. Thyrotoxic Hypokalemic Periodic Paralysis: Pathophysiological Mechanisms. Endocrinol Metab (Seoul). 2025 Dec;40(6):821-829. doi: 10.3803/EnM.2025.2554. Epub 2025 Dec 11. PMID: 41376301; PMCID: PMC12765881.

3. Chang CC, Cheng CJ, Sung CC, et al. A 10-year analysis of thyrotoxic periodic paralysis in 135 patients: focus on symptomatology and precipitants. Eur J Endocrinol 2013; 169:529.

MH and gender

Q: Malignant Hyperthermia (MH) is disproportionally high in? - select one

A) males

B) females

Answer: A

The male-to-female ratio for MH is 2:1. The obvious explanation is the likely higher skeletal mass in males, though it does not fully account for the high prevalence in males. Moreover, children less than 19 years of age are more prone to develop MH.

#anesthesia

References:

1. Brady JE, Sun LS, Rosenberg H, Li G. Prevalence of malignant hyperthermia due to anesthesia in New York State, 2001-2005. Anesth Analg 2009; 109:1162.

2. Larach MG, Gronert GA, Allen GC, et al. Clinical presentation, treatment, and complications of malignant hyperthermia in North America from 1987 to 2006. Anesth Analg 2010; 110:498.

3. Rosenberg H, Davis M, James D, et al. Malignant hyperthermia. Orphanet J Rare Dis 2007; 2:21.

4. Rosenberg H, Pollock N, Schiemann A, Bulger T, Stowell K. Malignant hyperthermia: a review. Orphanet J Rare Dis. 2015 Aug 4;10:93. doi: 10.1186/s13023-015-0310-1. PMID: 26238698; PMCID: PMC4524368.

Metronidazole and disulfiram-like reactions.

Q: Metronidazole should be avoided with alcohol intake as it may cause disulfiram-like reactions.

A) True

B) False

Answer: B

Although it was once believed that metronidazole could cause disulfiram-like reactions with ETOH, this was based on a few weak reports. Evidence failed to prove any such association. The United States Centers for Disease Control and Prevention (CDC) Sexually Transmitted Infection Guidelines in 2021 removed abstaining from alcohol while taking metronidazole.

Metronidazole does not inhibit alcohol metabolism in the liver or increase blood acetaldehyde production, the basis for disulfiram-like reactions. It is suggested that metronidazole and ethanol both, independently, increase brain serotonin levels, potentially giving an impression of disulfiram-like reactions.

# pharmacology

References:

1. Visapää JP, Tillonen JS, Kaihovaara PS, Salaspuro MP. Lack of disulfiram-like reaction with metronidazole and ethanol. Ann Pharmacother 2002; 36:971.

2. Tillonen J, Väkeväinen S, Salaspuro V, et al. Metronidazole increases intracolonic but not peripheral blood acetaldehyde in chronic ethanol-treated rats. Alcohol Clin Exp Res 2000; 24:570.

3. Karamanakos PN, Panteli ES, Marselos M. Comment on 'Can Metronidazole Cause a Disulfiram-Like Reaction? A Case-Control Study Propensity Matched By Age, Sex and Ethanol. WMJ 2024; 123:3.

4. Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep 2021; 70:1.

5. Feldman R, Jaszczenski R. Can Metronidazole Cause a Disulfiram-Like Reaction? A Case-Control Study Propensity Matched by Age, Sex, and Ethanol Concentration. WMJ 2023; 122:171.

Acute HIV on PrEP

Q: What's the caveat of diagnosing HIV in patients who are using pre-exposure prophylaxis (PrEP) for HIV?

Answer: Unreliable clinical signs and routine HIV screening test

Patients who are on pre-exposure prophylaxis (PrEP) due to their lifestyle may not develop full-blown acute HIV symptoms on initial contraction, but may have mild symptoms called pauci-symptomatic acute HIV. Cardinal acute HIV symptoms such as fever and rash are usually absent, and there may be no pharyngitis or diarrhea. To make things more complicated, routine HIV screening with the antigen/antibody test may not be reliable. Diagnosis can be made by history, exposure, keeping a high clinical suspicion, and HIV RNA as the screening tool.

#ID

References:

1. Landovitz RJ, Delany-Moretlwe S, Fogel JM, et al. Features of HIV Infection in the Context of Long-Acting Cabotegravir Preexposure Prophylaxis. N Engl J Med 2024; 391:1253.

2. Moschese D, Lazzarin S, Colombo ML, Caruso F, Giacomelli A, Antinori S, Gori A. Breakthrough Acute HIV Infections among Pre-Exposure Prophylaxis Users with High Adherence: A Narrative Review. Viruses. 2024 Jun 12;16(6):951. doi: 10.3390/v16060951. PMID: 38932243; PMCID: PMC11209220.

3. Elliott T, Sanders EJ, Doherty M, Ndung'u T, Cohen M, Patel P, Cairns G, Rutstein SE, Ananworanich J, Brown C, Fidler S. Challenges of HIV diagnosis and management in the context of pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), test and start and acute HIV infection: a scoping review. J Int AIDS Soc. 2019 Dec;22(12):e25419. doi: 10.1002/jia2.25419. PMID: 31850686; PMCID: PMC6918508.

Calcium and Dengue Virus

Q: Dengue virus infection causes? - select one

A) hypercalcemia

B) hypocalcemia 

Answer: B

Most of the treatment for the Dengue virus during all three phases of the Dengue virus, i.e., early, critical, and recovery phase, is essentially supportive. One of the unique features of the Dengue virus is hypocalcemia, and its cause is still not well understood. That said, it is significant, as the level of hypocalcemia correlates with the severity of illness. Its clinical significance can be understood from the perspective that, in resource-limited countries where the dengue virus is common, and labs may not be readily available, calcium should be replaced empirically, correlating clinically with the level of shock.

Development of seizures or arrhythmia due to hypocalcemia predicts poor outcome and requires constant monitoring and replacement, particularly in the critical phase. IV calcium gluconate is preferred. Replacement of calcium also helps restore the coagulation defects, a cardinal feature of Dengue virus infection.

#ID

References;

1. Pourzangiabadi M, Najafi H, Fallah A, Goudarzi A, Pouladi I. Dengue virus: Etiology, epidemiology, pathobiology, and developments in diagnosis and control - A comprehensive review. Infect Genet Evol. 2025 Jan;127:105710. doi: 10.1016/j.meegid.2024.105710. Epub 2024 Dec 26. PMID: 39732271.

2. Shivanthan MC, Rajapakse S. Dengue and calcium. Int J Crit Illn Inj Sci 2014; 4:314.

3. Constantine GR, Rajapakse S, Ranasinghe P, et al. Hypocalcemia is associated with disease severity in patients with dengue. J Infect Dev Ctries 2014; 8:1205.

PAS

Q: 38 years old G5P2 female at 36 weeks of pregnancy is admitted to the ICU for high-risk delivery. She was found to have a placenta growing through the uterine wall and invading the urinary bladder. By definition, she has? - select one

A) Placenta accreta

B) Placenta increta 

C) Placenta percreta 

Answer: C

Although Placenta Accreta Spectrum (PAS) is an umbrella term for an abnormal trophoblast adherence to or into the myometrium, scar tissue, and sometimes to or beyond the serosa. At delivery, the placenta may not spontaneously separate, and iatrogenic removal may cause massive hemorrhage, which may require emergent hysterectomy. The highest risk factor for PAS is a placenta previa after a prior cesarean birth.

PAS has three grades:

• Placenta accreta  – Anchoring placental villi attach to the myometrium (rather than decidua)
• Placenta increta – Anchoring placental villi penetrate into the myometrium
• Placenta percreta – Anchoring placental villi penetrate through the myometrium to the uterine serosa or adjacent organ

#ob-gyn

References:

1. Jauniaux E, Ayres-de-Campos D, Langhoff-Roos J, et al. FIGO classification for the clinical diagnosis of placenta accreta spectrum disorders. Int J Gynaecol Obstet 2019; 146:20.

2. Society of Gynecologic Oncology; American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine; Cahill AG, Beigi R, Heine RP, Silver RM, Wax JR. Placenta Accreta Spectrum. Am J Obstet Gynecol. 2018 Dec;219(6):B2-B16. doi: 10.1016/j.ajog.2018.09.042. PMID: 30471891.

3. O'Connor D, Berndl A. Placenta percreta. CMAJ. 2018 Feb 12;190(6):E168. doi: 10.1503/cmaj.171411. PMID: 29440338; PMCID: PMC5809218.

iron concentration in high exercise training

Q: High-intensity athletic workout may cause iron deficiency due to loss of iron in sweat.

A) True

B) False

Answer: A

A liter of sweat causes 0.6 mg of Iron (Fe) loss! Iron deficiency may be seen in some high-intensity athletes. Other contributing factors for iron deficiency in athletics, besides loss in sweat, are:

• Reduced iron intake
• Occult GI blood loss
• Traumatic hemolysis

#hematology

References:

1. McMahon LF Jr, Ryan MJ, Larson D, Fisher RL. Occult gastrointestinal blood loss in marathon runners. Ann Intern Med 1984; 100:846.

2. Coates A, Mountjoy M, Burr J. Incidence of Iron Deficiency and Iron Deficient Anemia in Elite Runners and Triathletes. Clin J Sport Med 2017; 27:493.

3. DeRuisseau KC, Cheuvront SN, Haymes EM, Sharp RG. Sweat iron and zinc losses during prolonged exercise. Int J Sport Nutr Exerc Metab. 2002 Dec;12(4):428-37. doi: 10.1123/ijsnem.12.4.428. PMID: 12500986.

4. Saran T, Zawadka M, Chmiel S, Mazur A. Sweat iron concentration during 4-week exercise training. Ann Agric Environ Med. 2018 Sep 25;25(3):500-503. doi: 10.26444/aaem/78787. Epub 2017 Nov 15. PMID: 30260183.

CCB overdose

Q: Hemodialysis should be instituted as early as possible in a Calcium Channel Blocker (CCB) overdose.

A) True

B) False

Answer: B

CCBs are highly protein-bound, so extracorporeal removal via hemodialysis or Continuous Renal Replacement Therapy (CRRT) is usually not effective. Said that it may help in case acute kidney injury or severe acidosis ensues, it can be added as an adjuvant therapy. Extracorporeal membrane oxygenation (ECMO) should be considered early if standard-of-care therapies show no evidence of effectiveness. 

Major components of CCB overdose are:

• Atropine for symptomatic bradycardia
• Intravenous calcium
• Calcium infusion with close monitoring of ionized calcium.
• Glucagon 
• Vasopressors (norepinephrine is preferred)
• Insulin and glucose with monitoring of possible hypokalemia
• Methylene blue 
• High-dose cyanocobalamin

# toxicity

References:

1. Wong A, Hoffman RS, Walsh SJ, et al. Extracorporeal treatment for calcium channel blocker poisoning: systematic review and recommendations from the EXTRIP workgroup. Clin Toxicol (Phila) 2021; 59:361.

2. Slamowitz A, Sweberg T, Labgold K, Nickerson T. Extracorporeal Membrane Oxygenation for Calcium Channel Blocker Intoxication: A Multicenter Retrospective Registry Review. ASAIO J. 2025 Oct 31. doi: 10.1097/MAT.0000000000002593. Epub ahead of print. PMID: 41168146.

3. Saha BK, Bonnier A, Chong W. Rapid reversal of vasoplegia with methylene blue in calcium channel blocker poisoning. Afr J Emerg Med 2020; 10:284.

Hyperalbuminemia and calcium

Q: Hyperalbuminemia can cause hypercalcemia.

A) True

B) False

Answer: A

Although it is very well known that hypoalbuminemia can cause hypocalcemia and various formulae have been invented, it is less emphasized that the reverse is also true, meaning hyperalbuminemia can lead to hypercalcemia. The most common reason is extracellular volume depletion. Another well-recognized clinical scenario is the widespread use of high-protein powders among athletes and 'gym-goers', which may increase serum calcium. It occurs mostly when more than 2 g of protein per kg of body weight per day is consumed.

Said that many experts believe that, just as hypoalbuminemia and hypocalcemia are related and require correction, the same phenomenon applies to hyperalbuminemia and hypercalcemia. The best clinical practice should be to measure ionized calcium.

#electrolytes

References:

1. DENT CE. Some problems of hyperparathyroidism. Br Med J 1962; 2:1419.

2. Mutlu EA, Keshavarzian A, Mutlu GM. Hyperalbuminemia and elevated transaminases associated with high-protein diet. Scand J Gastroenterol 2006; 41:759.

On ESR

Q: Erythrocyte Sedimentation Rate (ESR) in patients with sickle cell disease is expected to be spuriously? - select one

A) high

B) low

Answer: B

As ESR gets affected by changes in red cell shape or number, including sickle cell disease, anisocytosis, spherocytosis, acanthocytosis, microcytosis, and polycythemia, it can be spuriously low, particularly in sickle cell disease. Other conditions which may result in falsely low ESR are:

• extremely high serum bile salt levels 
• CHF
• Hypofibrinogenemia 
• high-dose glucocorticoids
• high-dose salicylate therapy
• IL-6 inhibitors 
• biopsy-proven giant cell arteritis
• statins 
• nonsteroidal antiinflammatory drugs (NSAIDs) 
• light alcohol consumption 
• clotting of the blood sample 
• delay in testing of greater than two hours
• low room temperature
• Short ESR tube

One of the most paradoxical situations is having "declining ESR" during a "cytokine storm," when it is expected to rise. This is because low fibrinogen levels are characteristic of macrophage activation syndrome (MAS), also called acquired hemophagocytic lymphohistiocytosis, which causes consumptive coagulopathy, including fibrinogen degradation and decreased fibrinogen synthesis, both of which are main drivers of the ESR.

#hematology

#inflammatory-markers

References:

1.  Jurado RL. Why shouldn't we determine the erythrocyte sedimentation rate? Clin Infect Dis 2001; 33:548.

2. Lawrence C, Fabry ME. Erythrocyte sedimentation rate during steady state and painful crisis in sickle cell anemia. Am J Med 1986; 81:801.

3. Brigden ML. Clinical utility of the erythrocyte sedimentation rate. Am Fam Physician 1999; 60:1443.

Gaisböck Syndrome

Q: What is Gaisböck's syndrome?

Answer: A version of relative polycythemia.

 Gaisböck's syndrome is also called stress or spurious polycythemia, as it is classically described as erythrocytosis in tense/anxious patients. The components of the syndrome are:

• Anxiety
• Hypertension (HTN)
• No evidence of splenomegaly, and 
• Evidence of reduced plasma volume

Many of these patients are on a diuretic for HTN treatment, and are smokers to alleviate their anxiety. These factors contribute to the syndrome.

Many experts argue against the existence of this syndrome as a specific entity (see reference # 4)

#hematology

References:

1. Manal N, Rizvi M, Nugent K. Gaisbock Syndrome: A Review of Contemporary Studies, Pathogenesis, Complications, and Possible Treatment. Cardiol Rev. 2023 Sep-Oct 01;31(5):247-251. doi: 10.1097/CRD.0000000000000443. Epub 2022 Feb 7. PMID: 35148535.

2. LAWRENCE JH, BERLIN NI. Relative polycythemia; the polycythemia of stress. Yale J Biol Med 1952; 24:498.

3. Krishnamoorthy P, Gopalakrishnan A, Mittal V, Kalla A, Slipczuk L, Rangaswami J, Figueredo VM, Messerli FH. Gaisböck syndrome (polycythemia and hypertension) revisited: results from the national inpatient sample database. J Hypertens. 2018 Dec;36(12):2420-2424. doi: 10.1097/HJH.0000000000001805. PMID: 29847483.

4. Brown SM, Gilbert HS, Krauss S, Wasserman LR. Spurious (relative) polycythemia: a nonexistent disease. Am J Med 1971; 50:200.

DBP with age

Q: Overall, Diastolic Blood Pressure (DBP) tends to increase with age.

A) True

B) False

Answer: B

Various factors contribute to the decrease in diastolic pressure with age, particularly after age 55. The aorta starts to stiffen, reducing its elastic reservoir capacity. This causes more blood to be ejected with each stroke during systole, reducing the blood volume in the aorta at the onset of diastole. Overall, systemic vessels exhibit diminished elastic recoil, leading to a fall in diastolic pressure with age. This phenomenon is universal across the board, including normotensive and hypertensive patients.

#hemodynamics

References:

1. Franklin SS, Gustin W 4th, Wong ND, et al. Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study. Circulation 1997; 96:308.

2. Folkow B. Structure and function of the arteries in hypertension. Am Heart J 1987; 114:938.

RLS and BZRA

Case: A 74-year-old male with no major history, except for restless legs syndrome (RLS), is admitted to the ICU for community-acquired pneumonia. Patient is now recovering. The patient requested medicine for his insomnia in the ICU, and the resident prescribed zolpidem. Patient found to have hyperactive delirium in the early part of the next morning.

Discussion: As commonly said, restless legs syndrome and insomnia go hand in hand; most patients with RLS require some kind of pharmaceutical support for their insomnia. Precautions should be taken to prescribe selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), or antihistamines, as they can exacerbate RLS.

Particular care should be exercised in prescribing BZRAs (Benzodiazepine Receptor Agonists) such as zolpidem, as they increase the incidence of complex sleep-related behaviors.

Further readings/References:

1. Park YM, Shin HW. Zolpidem Induced Sleep-related Eating and Complex Behaviors in a Patient with Obstructive Sleep Apnea and Restless Legs Syndrome. Clin Psychopharmacol Neurosci. 2016 Aug 31;14(3):299-301. doi: 10.9758/cpn.2016.14.3.299. PMID: 27489385; PMCID: PMC4977817.

2. Mittal N, Mittal R, Gupta MC. Zolpidem for Insomnia: A Double-Edged Sword. A Systematic Literature Review on Zolpidem-Induced Complex Sleep Behaviors. Indian J Psychol Med. 2021 Sep;43(5):373-381. doi: 10.1177/0253717621992372. Epub 2021 Mar 9. PMID: 34584301; PMCID: PMC8450729.

3. Winkelman JW, Wipper B. Restless Legs Syndrome: A Review. JAMA. 2026 Feb 24;335(8):703-714. doi: 10.1001/jama.2025.23247. PMID: 41563785.

ART and CVS

Q: Antiretroviral therapy (ART) in HIV patients increases the risk of cardiovascular disease.

A) True

B) False

Answer: B

Although in the past it was believed and was partially true that abacavir and most protease inhibitors are associated with an increased risk of Myocardial Infarction (MI), overall, most antiretroviral therapy (ART) regimens do not increase the risk of MI. Instead, HIV infection itself accelerates atherosclerosis and the incidence of coronary artery disease (CAD). The rate of MI is higher in patients with HIV compared with patients without HIV who are matched for age and gender. 

Lower CD4 cell counts and higher HIV RNA levels have been found to be associated with increased MI risk.

#ID

#pharmacology

Reference:

Eyawo O, Brockman G, Goldsmith CH, et al. Risk of myocardial infarction among people living with HIV: an updated systematic review and meta-analysis. BMJ Open 2019; 9:e02587

Albumin and CIP

Q: Low serum albumin is a risk factor for Critical Illness Polyneuropathy (CIP).

A) True

B) False

Answer: A

CIP is commonly seen in patients who stay in the ICU for more than a week or two. Some of the known risk factors are:

• severe sepsis 
• severe systemic inflammatory response syndrome (SIRS)
• persistently elevated blood glucose
• low serum albumin 
• use of neuro-muscular blockade

Use of steroids is found to be more associated with Critical Illness Myopathy (CIM), though most patients in the ICU have a combined CIM and CIP.

#neurology

#icu-course

References:

1. Witt NJ, Zochodne DW, Bolton CF, et al. Peripheral nerve function in sepsis and multiple organ failure. Chest 1991; 99:176.

2. Zhou C, Wu L, Ni F, Ji W, Wu J, Zhang H. Critical illness polyneuropathy and myopathy: a systematic review. Neural Regen Res. 2014 Jan 1;9(1):101-10. doi: 10.4103/1673-5374.125337. PMID: 25206749; PMCID: PMC4146320.

3. Bednarík J, Vondracek P, Dusek L, Moravcova E, Cundrle I. Risk factors for critical illness polyneuromyopathy. J Neurol. 2005 Mar;252(3):343-51. doi: 10.1007/s00415-005-0654-x. Epub 2005 Mar 30. PMID: 15791390.

4. Atrash AK, de Vasconcellos K. Low albumin levels are associated with mortality in the critically ill: A retrospective observational study in a multidisciplinary intensive care unit. South Afr J Crit Care. 2020 Dec 1;36(2):10.7196/SAJCC.2020.v36i2.422. doi: 10.7196/SAJCC.2020.v36i2.422. PMID: 35493283; PMCID: PMC9045521.

Parovirus 19 fetal severe anemia

Q: A 24-year-old female with 22 weeks of pregnancy is admitted to the ICU with severe symptoms of Parvovirus 19, confirmed with a high IgM titer but a negative IgG titer. There is a severe fetal anemia, and thrombocytopenia is suspected. How should the blood transfusion be given? -select one

A) Slow Intravenous 

B) Intrauterine

C) Plasmapheresis

Answer: B

Usually, a fetus can handle mild to moderate anemia without any major intervention. Severe fetal anemia can lead to hydrops fetalis. Noninvasive methods to detect fetal anemia are:

• Doppler middle cerebral artery (MCA) peak systolic velocity (PSV), and 
• ductus venosus velocity  

Invasively, cord blood sampling can be performed via percutaneous umbilical venous sampling, but is reserved for suspected severe cases requiring intervention.

Interesting, blood transfusions in such situations are given directly via intrauterine. Intrauterine transfusion is possible only after 18 weeks of pregnancy due to the small vessel size prior to it.

The authors of this question highly encouraged students to review reference #4 below.

#Ob-gyn

References:

1. Fairley CK, Smoleniec JS, Caul OE, Miller E. Observational study of effect of intrauterine transfusions on outcome of fetal hydrops after parvovirus B19 infection. Lancet 1995; 346:1335.

2. Rodis JF, Borgida AF, Wilson M, et al. Management of parvovirus infection in pregnancy and outcomes of hydrops: a survey of members of the Society of Perinatal Obstetricians. Am J Obstet Gynecol 1998; 179:985.

3. von Kaisenberg CS, Jonat W. Fetal parvovirus B19 infection. Ultrasound Obstet Gynecol 2001; 18:280.

4. Devlieger R, Vergote S, Van den Eede E, Haenen K, Lewi L. Intrauterine transfusion: Best practices, techniques, and evolving trends. Best Pract Res Clin Obstet Gynaecol. 2026 Feb;104:102686. doi: 10.1016/j.bpobgyn.2025.102686. Epub 2025 Nov 20. PMID: 41289715.

NPPE - MOA

Case: 22 years old atheletic male went through a non-complicated appendectomy under general anesthesia. Patient became agitated on weaning sedation and started biting on the endotracheal tube (ETT). The patient was extubated, but on extubation developed severe pulmonary edema with desaturation. Patient recovered well with supplemental oxygen, non-invasive positive pressure ventilation (NIPPV), diuresis, and infusion of Dexmedetomidine, and was eventually extubated without complications. Why is post-extubation pulmonary edema called negative pressure pulmonary edema (NPPE)?

Answer: Post-extubation pulmonary edema is a common phenomenon in the PACU/ICU if a patient forcibly inhales against a closed glottis. This is also known as the Mueller or reverse Valsalva maneuver. This phenomenon occurs post-extubation due to laryngospasm, pharyngeal obstruction, or biting of the endotracheal tube during extubation. 

Conventional teaching holds that it occurs immediately, though this is not entirely true; a delayed NPPE has been reported up to 12 hours after extubation. People with obesity, short neck, obstructive sleep apnea, or acromegaly are at the highest risk, followed by young, healthy, athletic adults.

The correct term is negative pressure pulmonary edema, which refers to a non-cardiac form of pulmonary edema resulting from the development of negative interstitial pressure around the capillaries, drawing intravascular fluid into the interstitial space.

#procedure

#pulmonary

References:

1. Mulkey Z, Yarbrough S, Guerra D, et al. Postextubation pulmonary edema: a case series and review. Respir Med 2008; 102:1659.

2. Holmes JR, Hensinger RN, Wojtys EW. Postoperative pulmonary edema in young, athletic adults. Am J Sports Med 1991; 19:365.

3. Tsai PH, Wang JH, Huang SC, Lin YK, Lam CF. Characterizing post-extubation negative pressure pulmonary edema in the operating room-a retrospective matched case-control study. Perioper Med (Lond). 2018 Dec 6;7:28. doi: 10.1186/s13741-018-0107-6. PMID: 30534363; PMCID: PMC6282297.

PG

Q: A 43-year-old male with an established history of ulcerative colitis is admitted to the ICU with Lower GI bleed requiring transfusion. On physical exam, chronic ulceration was noted on the lower extremity and diagnosed as Pyoderma gangrenosum (PG). PG, as the name suggests, is an infectious process causing gangrene.

A) True

B) False

Answer: B

Pyoderma gangrenosum (PG) is a misnomer as it is neither an infectious nor a gangrenous condition! The probability of this misnomer arises from its striking, infectious-like appearance.

PG is a neutrophilic dermatosis that presents as an inflammatory, ulcerative skin disorder. The most common presentation of PG is an inflammatory papule or pustule that progresses to a painful ulcer with a violaceous, undermined border and a purulent base. It may also present with bullous, vegetative, peristomal, and extracutaneous lesions.

Clinical Significance: It has high association with an underlying systemic diseases like inflammatory bowel disease, hematologic disorders, and arthritis.

#dermatology

References:

1. Maverakis E, Marzano AV, Le ST, Callen JP, Brüggen MC, Guenova E, Dissemond J, Shinkai K, Langan SM. Pyoderma gangrenosum. Nat Rev Dis Primers. 2020 Oct 8;6(1):81. doi: 10.1038/s41572-020-0213-x. PMID: 33033263.

2. Łyko M, Ryguła A, Kowalski M, Karska J, Jankowska-Konsur A. The Pathophysiology and Treatment of Pyoderma Gangrenosum-Current Options and New Perspectives. Int J Mol Sci. 2024 Feb 19;25(4):2440. doi: 10.3390/ijms25042440. PMID: 38397117; PMCID: PMC10889749.

3. Moltrasio C, Romagnuolo M, Tavoletti G, Maronese CA, Marzano AV. Pyoderma gangrenosum: pathogenetic mechanisms and their implications for treatment. Semin Immunopathol. 2025 Oct 23;47(1):38. doi: 10.1007/s00281-025-01064-7. PMID: 41128863; PMCID: PMC12549756.

iNO and organ dysfunction

Q: Prolonged use of inhaled Nitric Oxide (iNO) is intended to cause more of? - select one

A) Kidney dysfunction

B) liver dysfunction

Answer: A

Prolonged use of iNO beyond 5-7 days may increase the risk of acute kidney injury (AKI). This inference is drawn primarily from trials of its use in patients with ARDS and after cardiac surgery. 

An interesting paradox is the finding that short-term use (24 hours post-surgery) of iNO in patients who require prolonged cardiopulmonary bypass may have a protective effect for AKI. This short-term benefit is due to the fact that, in prolonged bypass cases, increased hemolysis raises plasma levels of free oxyhemoglobin, which binds and depletes endogenous NO, leading to vasoconstriction, impaired tissue perfusion, and inflammation (reference #3).

#cardiovascular

#nephrology

References:

1. Ruan SY, Huang TM, Wu HY, et al. Inhaled nitric oxide therapy and risk of renal dysfunction: a systematic review and meta-analysis of randomized trials. Crit Care 2015; 19:137.

2. Gebistorf F, Karam O, Wetterslev J, Afshari A. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) in children and adults. Cochrane Database Syst Rev 2016; :CD002787.

3. Lei C, Berra L, Rezoagli E, et al. Nitric Oxide Decreases Acute Kidney Injury and Stage 3 Chronic Kidney Disease after Cardiac Surgery. Am J Respir Crit Care Med 2018; 198:1279.

The time-relationship of 'osmolal gap' and 'Anion gap' in toxic alcohols

Q: In Methanol and Ethylene Glycol toxicity, the time-relationship of 'osmolal gap' and 'Anion gap' is inversely proportional.

A) True

B) False

Answer: A

After ingestion of Methanol and Ethylene Glycol, the osmolal gap continues to drop as the alcohols are metabolized, while the anion gap rises. The following graph best describes the relationship.

#toxicity

References:

1. Kraut JA, Mullins ME. Toxic Alcohols. N Engl J Med. 2018 Jan 18;378(3):270-280. doi: 10.1056/NEJMra1615295. Erratum in: N Engl J Med. 2019 Jan 10;380(2):202. doi: 10.1056/NEJMx180046. PMID: 29342392.

2. Gallagher N, Edwards FJ. The Diagnosis and Management of Toxic Alcohol Poisoning in the Emergency Department: A Review Article. Adv J Emerg Med. 2019 May 22;3(3):e28. doi: 10.22114/ajem.v0i0.153. PMID: 31410405; PMCID: PMC6683589.

Clinical features of infective endocarditis

Q: A 52-year-old male with a history of End Stage Renal Disease (ESRD) is admitted to the ICU with suspected infective endocarditis (IE). On clinical exam found to have Janeway lesions. Janeway lesions are more common in? - select one

A) acute IE

B) subacute IE

Answer: A

Clinical exam in IE plays an important role. Three hallmark characteristic findings, though relatively uncommon, are highly suggestive of IE:

• Janeway lesions
• Osler nodes 
• Roth spots 

Janeway lesions are nontender erythematous macules on the palms and soles. Histologically, they are microabscesses with neutrophil infiltration of capillaries. Janeway lesions are more common in acute than subacute IE. 

In contrast, Osler nodes and Roth spots occur over a protracted time course of endocarditis. These two entities are sequelae of microthromboembolic occlusion, leading to localized immune-mediated vasculitis. Osler nodes, in contrast to Janeway lesions, are tender and subcutaneous (SQ) violaceous nodules mostly on the pads of the fingers and toes, and may also occur on the thenar and hypothenar eminences. Interestingly, tenderness begins a few days before the nodule appears. Roth spots are exudative, edematous, hemorrhagic lesions of the retina with pale centers.

#physical-exam

#ID

References:

1. Saccente M, Cobbs CG. Clinical approach to infective endocarditis. Cardiol Clin. 1996 Aug;14(3):351-62. doi: 10.1016/s0733-8651(05)70289-7. PMID: 8853130.

2. Loughrey PB, Armstrong D, Lockhart CJ. Classical eye signs in bacterial endocarditis. QJM 2015; 108:909.

3. Abdelgawad H, Azab S, Abdel-Hay MA, Almaghraby A. Clinical features and outcomes of infective endocarditis: a single-centre experience. Cardiovasc J Afr. 2023 May-Jun 23;34(2):82-88. doi: 10.5830/CVJA-2022-027. Epub 2022 Aug 3. PMID: 35924572; PMCID: PMC10512034.

extraocular muscles in CIM

Q: In Critical Illness Myopathy (CIM), the presence of extraocular muscle weakness is diagnostic.

A) True

B) False

Answer: B

CIM has a few characteristic features:

• Flaccid quadriparesis 
• Proximal muscles are affected more than distal muscles.
• Ventilatory failure
• Facial muscle weakness (may or may not present)
• Sparing of extraocular muscles (very rarely involved)
• Intact sensation*
• Intact deep tendon reflexes*

*feature of Critical Illness Polyneuropathy (CIP)

References:

1. Latronico N, Rasulo FA, Eikermann M, Piva S. Illness Weakness, Polyneuropathy and Myopathy: Diagnosis, treatment, and long-term outcomes. Crit Care. 2023 Nov 13;27(1):439. doi: 10.1186/s13054-023-04676-3. Erratum in: Crit Care. 2023 Nov 30;27(1):469. doi: 10.1186/s13054-023-04757-3. PMID: 37957759; PMCID: PMC10644573.

2. Hermans G, Van den Berghe G. Clinical review: intensive care unit acquired weakness. Crit Care. 2015 Aug 5;19(1):274. doi: 10.1186/s13054-015-0993-7. PMID: 26242743; PMCID: PMC4526175.

aortopulmonary angle

Q: On chest X-ray, the aortopulmonary angle can be found on? - select one

A) left side

B) right side

Answer: A

The aortopulmonary angle, also called the aortopulmonary space or window, is a space between the aortic arch and the left pulmonary artery. It contains the ligamentum arteriosum, the left recurrent laryngeal nerve, lymph nodes, and fatty tissue. The space is bounded anteriorly by the ascending aorta, posteriorly by the descending aorta, medially by the left main bronchus, and laterally by the mediastinal pleura.

Clinical Significance: The presence of water radiodensity in this space on radiography may indicate a lymphadenopathy or possible neoplasm.

#pulmonary

#radiology

References:

1. Dewey, Marc; Magid, Donna; Wheeler, Paul S.; Hamm, Bernd (2004). "Aortopulmonary Window or Angle on the Chest Radiograph?". American Journal of Roentgenology. 182 (4): 1085–1086. doi:10.2214/ajr.182.4.1821085. ISSN 0361-803X. PMID 15039195.

2. Heitzman E, Lane E, Hammack D, Rimmler L (1975). "Radiological evaluation of the aortic-pulmonic window". Radiology. 116 (3): 513–8. doi:10.1148/116.3.513. PMID 1153753.

Enteral free water in high ICP

Q: Patients with elevated Intra-Cranial Pressure (ICP) should not be fed enteral free water.

 A) True

B) False

 Answer: A 

Patients with elevated ICP should be kept euvolemic, rather normo- to hyperosmolar. Any hypotonic fluid administration, including enteral free water, should be avoided whenever possible. Isotonic fluids are usually utilized guided by close monitoring of labs. Serum osmolality is targeted to stay above 280 mOsm/L, between 295 and 305 mOsm/L. Colloids have no specific advantage. 

 Clinicians should be aware that hyponatremia is common in patients with elevated ICP, particularly in patients with subarachnoid hemorrhage SAH). Hypertonic saline in bolus, popularly known as 'salt bomb' can be used per clinical judgement.

 #neurology 

 References: 

 1. Schmoker JD, Shackford SR, Wald SL, Pietropaoli JA. An analysis of the relationship between fluid and sodium administration and intracranial pressure after head injury. J Trauma 1992; 33:476. 

 2. Tranmer BI, Iacobacci RI, Kindt GW. Effects of crystalloid and colloid infusions on intracranial pressure and computerized electroencephalographic data in dogs with vasogenic brain edema. Neurosurgery 1989; 25:173.

 3. SAFE Study Investigators, Australian and New Zealand Intensive Care Society Clinical Trials Group, Australian Red Cross Blood Service, et al. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med 2007; 357:874.

SCC

Q: Small cell carcinoma in the lungs is considered a neuroendocrine tumor.

A) True

B) False

Answer: A

Small cell carcinoma, large cell neuroendocrine carcinoma, typical carcinoid, and atypical carcinoid all fall under the category of neuroendocrine tumors and share features with carcinoid lesions arising at other body sites. 

Small cell carcinomas and large cell neuroendocrine carcinomas have aggressive courses and, pathologically, exhibit a higher mitotic rate, distinguishing them from pulmonary carcinoids.

#oncology

#pulmonary

References:

1. WHO Classification of Tumours Editorial Board. Thoracic Tumours. In: WHO Classification of Tumours, 5th ed, IARC Publications, 2021. Vol 5.

2. Orlandi R. Neuroendocrine neoplasms of the lung: The latest updates. World J Clin Oncol. 2025 May 24;16(5):106630. doi: 10.5306/wjco.v16.i5.106630. PMID: 40503410; PMCID: PMC12149839.

3. Rekhtman N. Lung neuroendocrine neoplasms: recent progress and persistent challenges. Mod Pathol. 2022 Jan;35(Suppl 1):36-50. doi: 10.1038/s41379-021-00943-2. Epub 2021 Oct 18. PMID: 34663914; PMCID: PMC8695375.

Midazolam as intranasal or buccal route

Q: What is the dose of Midazolam to give intranasally if no IV or IM route is available?

Answer: if its an emergency and no IV line is established or (let say) if no syringe is available even to give intramuscularly (IM), midazolam can be given intranasally using the injectable solution of 5 mg/mL as a metered spray of 0.1 mL containing 0.5 mg, three to five times per nostril, and can be repeated, to a total dose of 10 mg for adults.

It can also be given buccally as 0.2 mg/kg, or a total of 10 mg altogether, once in adults.

#neurology

#pharmacology

References:

1. McKee HR, Abou-Khalil B. Outpatient pharmacotherapy and modes of administration for acute repetitive and prolonged seizures. CNS Drugs 2015; 29:55.

2. Dittrich TD, Vock D, Fisch U, et al. Efficacy and Tolerability of Intranasal Midazolam Administration for Antiseizure Treatment in Adults: A Systematic Review. Neurocrit Care 2024; 41:632.

3. Kay L, Merkel N, von Blomberg A, Willems LM, Bauer S, Reif PS, Schubert-Bast S, Rosenow F, Strzelczyk A. Intranasal midazolam as first-line inhospital treatment for status epilepticus: a pharmaco-EEG cohort study. Ann Clin Transl Neurol. 2019 Dec;6(12):2413-2425. doi: 10.1002/acn3.50932. Epub 2019 Nov 4. PMID: 31682078; PMCID: PMC6917318.

4. Armijo JA, Herranz JL, Pena Pardo MA, Adín J. Midazolam intranasal y bucal en el tratamiento de las convulsiones agudas [Intranasal and buccal midazolam in the treatment of acute seizures]. Rev Neurol. 2004 Mar 1-15;38(5):458-68. Spanish. PMID: 15029526.

CIM

Q: The Critical Illness Myopathy (CIM) affects which group of muscles more? - select one

A) distal 

B) proximal 

Answer: B

CIM, although it causes flaccid quadriparesis, usually affects the proximal muscles more. It is also associated with facial muscle weakness.

A pure exclusive CIM can be distinguished from Critical Illness Polyneuropathy (CIP) by normal sensation and normal or attenuated deep tendon reflexes. Patients with exclusive CIM grimace to pain even when they are encephalopathic.

Unfortunately, most patients suffer from combined CIP and CIM.

#ICU-course

#neurology

References:

1. Lacomis D, Giuliani MJ, Van Cott A, Kramer DJ. Acute myopathy of intensive care: clinical, electromyographic, and pathological aspects. Ann Neurol 1996; 40:645.

2. Z'Graggen WJ, Tankisi H. Critical Illness Myopathy. J Clin Neurophysiol. 2020 May;37(3):200-204. doi: 10.1097/WNP.0000000000000652. PMID: 32358245.

3. Rodriguez B, Larsson L, Z'Graggen WJ. Critical Illness Myopathy: Diagnostic Approach and Resulting Therapeutic Implications. Curr Treat Options Neurol. 2022;24(4):173-182. doi: 10.1007/s11940-022-00714-7. Epub 2022 Mar 28. PMID: 35370393; PMCID: PMC8958813.

4. Friedrich O. Critical illness myopathy: what is happening? Curr Opin Clin Nutr Metab Care. 2006 Jul;9(4):403-9. doi: 10.1097/01.mco.0000232900.59168.a0. PMID: 16778569.

banana bag

Q: Utilizing "Banana bag" plays an integral part in the management of alcohol withdrawal as it contains thiamine.

A) True

B) False

Answer: B

Although in the United States, use of "banana bag" is almost an integral part of management in alcohol withdrawal, there is no evidence that it prevents or contributes much to preventing Wernicke's encephalopathy or Delirium Tremens (DTs). It is called a banana bag due to its yellow color and contains

• thiamine
• folate
• multivitamin (MVI)
• isotonic saline with 5% dextrose

It is true that thiamine (given first) and glucose should be administered to prevent or treat Wernicke encephalopathy in the early phase of management, but preparing or specifically requesting a banana bag is not supported by evidence! 

Electrolytes, vitamins, and volume should be administered as needed per clinical and laboratory values.

#toxicity

References:

1. Flannery AH, Adkins DA, Cook AM. Unpeeling the Evidence for the Banana Bag: Evidence-Based Recommendations for the Management of Alcohol-Associated Vitamin and Electrolyte Deficiencies in the ICU. Crit Care Med. 2016 Aug;44(8):1545-52. doi: 10.1097/CCM.0000000000001659. PMID: 27002274.

2. LoVecchio F. Multivitamin "banana bags" provide little value in emergency department patients. Ann Emerg Med. 2012 May;59(5):414-5. doi: 10.1016/j.annemergmed.2011.11.007. PMID: 22525531.

3. Wells C, Butcher R, McCormack S. Intravenous Multivitamin Therapy Use in Hospital or Outpatient Settings: A Review of Clinical Effectiveness and Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2020 Oct 15. Available from: https://www.ncbi.nlm.nih.gov/books/NBK567072/

Kt/V

Q: What is the target Kt/V in patients with peritoneal dialysis? - select one

A) ≥ 1.3/week

B) ≥ 1.7/week

Answer: B

The objective of this question is to introduce students to the concept of Kt/V in dialysis patients, which is used to indicate dialysis adequacy. The K, t, and V stand respectively for:

K – dialyzer clearance of urea

t – dialysis time

V – volume of distribution of urea*

Per the US National Kidney Foundation, in hemodialysis (HD), the target is ≥1.3^, and in peritoneal dialysis, the target is ≥1.7/week. Although there are various criticisms against its use, it remains a vital concept for clinicians to know.

Clinical significance: It correlates with survival.

There are online calculators available to determine Kt/V

*approximately equal to the patient's total body water

^ Per Centers for Medicare and Medicaid Services (CMS): the minimum required is ≥1.2 per session

References/further reading:

1. Churchill BM, Patri P. The Nitty-Gritties of Kt/Vurea Calculations in Hemodialysis and Peritoneal Dialysis. Indian J Nephrol. 2021 Mar-Apr;31(2):97-110. doi: 10.4103/ijn.IJN_245_19. Epub 2021 Apr 2. PMID: 34267430; PMCID: PMC8240937.

2. Gotch FA. Kt/V is the best dialysis dose parameter. Blood Purif. 2000;18(4):276-85. doi: 10.1159/000014449. PMID: 10965068.

3. Maliha G, Weinhandl ED, Reddy YNV. Deprescribing the Kt/V Target for Peritoneal Dialysis in the United States: The Path Toward Adopting International Standards for Dialysis Adequacy. J Am Soc Nephrol. 2023 May 1;34(5):751-754. doi: 10.1681/ASN.0000000000000101. Epub 2023 Feb 14. PMID: 36787755; PMCID: PMC10125636.