Definition of Dyspnea

Q: As per American Thoracic Society (ATS), which of the following factor is NOT a part of definition of dyspnea? - select one

A) Anatomical

B) Environmental

C) Physiological

D) Psychological

E) Social

Answer: A

A consensus statement of the American Thoracic Society defines dyspnea as:

"Dyspnea is a term used to characterize a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity. The experience derives from interactions among multiple physiological, psychological, social, and environmental factors, and may induce secondary physiological and behavioral responses."

It's an important definition to understand the wide spectrum of dyspnea, describing cause and effect. The keywords are: - a "subjective experience", "qualitatively distinct sensations", "vary in intensity", various factors inducing "secondary physiological and behavioral responses."

#pulmonary

#psychology

# environmental-sciences

#social-sciences

Reference:

Parshall MB, Schwartzstein RM, Adams L, et al. An official American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med 2012; 185:435.

A succussion splash, Virchow's node and Sister Mary Joseph's node

Q: With the following three physical findings, what's the diagnosis, if proven otherwise?

• A succussion splash 
• A left Virchow's node
• Sister Mary Joseph's node

Answer: Metastatic gastric cancer

The objective of this question is to emphasize again the most vital art of the medicine - the physical exam.

A succussion splash is elicited by placing the stethoscope over the upper abdomen and rocking the patient back and forth at the hips. There may be a "splash" sound. It signifies Gastric Outlet Obstruction if positive after three hours of the meal. 

Virchow's node is a palpable supraclavicular lymph node, and Sister Mary Joseph's node is a palpable periumbilical lymph node.

* The author of this question highly recommends reading the case report in reference #4.

#oncology

#physical-exam

References:

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

2. Kobayashi T, Sato R, Kaneko N, Sato J, Kakugawa Y, Funayama Y. [Advanced Gastric Cancer with Virchow's Lymph Node Metastasis-A Long-Term Survival Case]. Gan To Kagaku Ryoho. 2024 Aug;51(8):821-823. Japanese. PMID: 39191712.

3. Whang TB, Wang L, Peng DH. Gastric carcinoma of the umbilicus: case report of Sister Mary Joseph nodule. Cutis. 2010 Feb;85(2):90-2. PMID: 20349683.

4. Fill S, Taran A, Schulz HU, Kahl S, Kalinski T, Smith B, Costa SD. Sister Mary Joseph's nodule as the first sign of pregnancy-associated gastric cancer: a case report. World J Gastroenterol. 2008 Feb 14;14(6):951-3. doi: 10.3748/wjg.14.951. PMID: 18240358; PMCID: PMC2687068.

Premedication in IV Fe infusion

Q: Premedication with diphenhydramine should be given before intravenous (IV) Iron (Fe) transfusion due to the risk of allergic reaction.

A) True

B) False

Answer: B

Surprisingly, and contrary to popular practice, Diphenhydramine before IV Fe infusion is strongly associated with an increased likelihood of an infusion reaction!

In regular IV Fe infusion, no premedication is required. The rules of thumb for premedication prior to IV Fe infusion are:

• history of asthma, 
• inflammatory arthritis,
• more than one drug allergy, or
• Clinician's suspicion of any other underlying disease which may trigger the reaction

Usually, premedication with IV 125 mg of methylprednisolone and an H2 blocker is recommended.

To note, patients with a history of inflammatory arthritis, a dose of IV methylprednisolone, 125 mg followed by 1 mg/kg prednisone per day orally for four days is recommended.

The best prevention against an IV Fe reaction is to infuse slowly and consult with pharmacy to find the formulation with the least risk of reaction. If a reaction occurs, only methylprednisolone is required without any H2 blocker.

#allergy

#elements

References:

1. Barton JC, Barton EH, Bertoli LF, et al. Intravenous iron dextran therapy in patients with iron deficiency and normal renal function who failed to respond to or did not tolerate oral iron supplementation. Am J Med 2000; 109:27.

2. Auerbach M, Chaudhry M, Goldman H, Ballard H. Value of methylprednisolone in prevention of the arthralgia-myalgia syndrome associated with the total dose infusion of iron dextran: a double blind randomized trial. J Lab Clin Med 1998; 131:257.

3. Gómez-Ramírez S, Shander A, Spahn DR, Auerbach M, Liumbruno GM, Vaglio S, Muñoz M. Prevention and management of acute reactions to intravenous iron in surgical patients. Blood Transfus. 2019 Mar;17(2):137-145. doi: 10.2450/2018.0156-18. Epub 2018 Oct 16. PMID: 30418128; PMCID: PMC6476739.

Fosphenytoin and phenytoin

Q: Which statement is true? - Select one

A) Fosphenytoin is the water-soluble prodrug of phenytoin

B) Fosphenytoin is the lipid-soluble prodrug of phenytoin

Answer: A

Fosphenytoin is a water-soluble prodrug that converts into phenytoin. It was created in the hope that it would act faster. It can also be given intramuscularly, which is an advantage when an IV line is not available. It can also be given three times faster, an advantage in status epilepticus scenarios.

Phenytoin carries various risks such as local irritation, tissue necrosis, and "purple glove syndrome", and if given faster, can cause cardiac arrhythmias. Fosphenytoin may negate those risks due to its water solubility.

#pharmacology

#neurology

References:

1. Madhiyazhagan M, Roshan R, Dhanapal SG, Joseph JV, Ganesan P, Mathew V, A Kundavaram PP. Comparison of Phenytoin and Fosphenytoin in Treatment of Active Seizures in the Emergency Department. Neurol India. 2023 May-Jun;71(3):447-452. doi: 10.4103/0028-3886.378665. PMID: 37322738.

2. Aaronson PM, Belgado BS, Spillane JP, Kunisaki TA. Evaluation of intramuscular fosphenytoin vs intravenous phenytoin loading in the ED. Am J Emerg Med. 2011 Nov;29(9):983-8. doi: 10.1016/j.ajem.2010.05.005. Epub 2010 Aug 3. PMID: 20685063.

3. DeToledo JC, Ramsay RE. Fosphenytoin and phenytoin in patients with status epilepticus: improved tolerability versus increased costs. Drug Saf. 2000 Jun;22(6):459-66. doi: 10.2165/00002018-200022060-00004. PMID: 10877039.

Clopidogrel & PPIs

Q: Which of the following Proton Pump Inhibitors (PPIs) is most likely to decrease the effect of clopidogrel? - select one

A) Lansoprazole

B) Omeprazole

C) Pantoprazole

D) Rabeprazole 

Answer: B

The interaction between clopidogrel and PPIs is overrated. Two ways to minimize this interaction are:

1. Avoid omeprazole, as clopidogrel and omeprazole share hepatic CYP2C19 metabolism. Other PPIs like pantoprazole, lansoprazole, and rabeprazole are less likely to interact. 

2. Taking clopidogrel and PPIs four or more hours apart.

#GI

#pharmacology

References:

1. Axelsson MAB, Parodi López N, Wikström Jonsson E, Wallerstedt SM. Efficacy and Safety of Clopidogrel With and Without a Proton Pump Inhibitor: A Systematic Review and Meta-Analysis. Basic Clin Pharmacol Toxicol. 2025 Aug;137(2):e70087. doi: 10.1111/bcpt.70087. PMID: 40685887; PMCID: PMC12277936.

2. Juurlink DN. Proton pump inhibitors and clopidogrel: putting the interaction in perspective. Circulation 2009; 120:2310.

HIV and OB transmission

Q: Antiretroviral use during pregnancy, at the time of delivery, and breastfeeding can eliminate the chances of HIV transmission by? - select one

A) about 50%

B) almost 100%

Answer: A

Over the years, antiretroviral therapy (ART) has become more of a preventive drug than a treatment. Interestingly and fortunately, use of ART during pregnancy, at the time of delivery, and breastfeeding can eliminate transmission almost 100%. 

The sad part is that the data up to 2024 showed that 1.4 million children under 15 years of age were living with HIV globally. And in resource-limited but high-burden countries, like Angola, Chad, and Nigeria, less than 50 percent of the pregnant or breastfeeding women living with HIV are receiving antiretroviral medicines.

#epidemiology

#ID

#Ob-gyn

References: 

1. Eke AC, Lockman S, Mofenson LM. Antiretroviral Treatment of HIV/AIDS During Pregnancy. JAMA. 2023 Apr 18;329(15):1308-1309. doi: 10.1001/jama.2023.5076. PMID: 37010862; PMCID: PMC10390091.

2. Short WR, Lowenthal ED, Momplaisir F, Powis KM, Scott RK, Yee LM, Miller ES, Mofenson LM. HIV and Pregnancy: Navigating Complex Decision Making and Preventing Perinatal Transmission. Curr HIV/AIDS Rep. 2025 Jun 7;22(1):36. doi: 10.1007/s11904-025-00745-0. PMID: 40481940; PMCID: PMC12145298.

3. Fleșeriu T, Meliț LE, Mărginean CO, Pop AV, Văsieșiu AM. Maternal HIV Infection and Antiretroviral Therapy in Pregnancy: Implications for Vertical Transmission, Fetal Safety, and Long-Term Infant Outcomes. Pathogens. 2025 Aug 19;14(8):818. doi: 10.3390/pathogens14080818. PMID: 40872328; PMCID: PMC12389244.

Sarcoid and IBD

Q: Sarcoidosis seems to have a greater tendency to exist with which of the following gastrointestinal immune/inflammatory disorders? - select one

A) Crohn disease

B) Ulcerative colitis

Answer: A

Bronchoalveolar lavage fluid lymphocytosis, elevated CD4/CD8 lymphocyte ratios, and nonnecrotizing granulomas in the lungs can be seen in both disorders, suggesting a possible common pathogenic mechanism between the two diseases. 

It is important to differentiate between coexistence of both disorders from pure intestinal sarcoidosis. Other manifestations of Crohn disease include pyoderma gangrenosum, rectal and perianal lesions, and enterocutaneous fistulas. Also, intestinal sarcoidosis usually involves only the mucosa, whereas Crohn disease can be transmural, with crypt inflammation, aphthae, and ulcers.

The concurrence of sarcoidosis and ulcerative colitis is rare.

#GI

References:

1. Mitchell DN, Rees RJ. Sarcoidosis and Crohn's disease. Proc R Soc Med 1971; 64:944.

2. D'Ercole C, Zullo A, Bragazzi MC, Campo SM. Sarcoidosis and coeliac disease: do not forget the association! Intern Emerg Med 2012; 7 Suppl 1:S25.

3. Mills K, Fatima S, Fas N. Crohn's Disease Diagnosed in a Man with Sarcoidosis: Coincidence or Correspondence? Case Rep Gastrointest Med. 2022 May 27;2022:5943468. doi: 10.1155/2022/5943468. PMID: 35669381; PMCID: PMC9166977.

Risk factors for CAPS

Q: In patients with antiphospholipid antibodies (aPL), which of the following carries the highest risk for Catastrophic antiphospholipid syndrome (CAPS)? - select one

A) Active systemic lupus erythematosus (SLE)

B) Cancer 

C) Infection

D) Pregnancy (or postpartum)

E) Surgery 

Answer: C

Contrary to conventional belief that estrogen use, pregnancy, postpartum, or active systemic lupus erythematosus (SLE) are the highest risk factors for CAPS, infection carries about 10 times more chances of bringing CAPS in patients with aPL or antiphospholipid syndrome (APS).

Above all, in its acute phase, infection (choice C) is the highest thrombotic risk. Another well-known reason for CAPS still stays valid, i.e., inadequate anticoagulation in a patient with known APS.

#rheumatology

References:

1. Cervera R, Rodríguez-Pintó I, Legault K, Erkan D. 16th International Congress on Antiphospholipid Antibodies Task Force Report on Catastrophic Antiphospholipid Syndrome. Lupus 2020; 29:1594.

2. Stammler R, Nguyen Y, Yelnik C, et al. Precipitating factors of catastrophic antiphospholipid syndrome: the role of anticoagulant treatment in a series of 112 patients. J Thromb Haemost 2023; 21:1258.

ECMO and HCPS

Q: Extracorporeal membrane oxygenation (ECMO) has shown no survival benefit in Hantavirus Cardiopulmonary Syndrome (HCPS) and should be considered only when death seems to be the probable outcome.

A) True

B) False

Answer: B

Early insertion of vascular sheaths and preemptive cannulation are associated with a higher survival rate, up to 65-80%, in HCPS. Mortality seems to increase once hemodynamic instability occurs later in the course.

Evidence showed that if a cardiac index remained below 2.5 L/minute/m2 despite volume, pressor, and inotropic support, ECMO should be pursued early in the course. 

Interestingly, ECMO in HCPS has been known to be beneficial for the last three decades (reference #1).

#hemodynamics

#ID

References:

1. Crowley MR, Katz RW, Kessler R, et al. Successful treatment of adults with severe Hantavirus pulmonary syndrome with extracorporeal membrane oxygenation. Crit Care Med 1998; 26:409.

2. Wernly JA, Dietl CA, Tabe CE, et al. Extracorporeal membrane oxygenation support improves survival of patients with Hantavirus cardiopulmonary syndrome refractory to medical treatment. Eur J Cardiothorac Surg 2011; 40:1334.

3. Yao H, McDonald EG. Extracorporeal membrane oxygenation for the treatment of severe refractory hantavirus cardiopulmonary syndrome. CMAJ 2016; 188:E528.

Hyperparathyroid crisis

Q: What are the three major causes of parathyroid crisis, also known as hypercalcemic crisis?

Answer: Parathyroid or hyperparathyroid crisis is clinically marked by severe abdominal pain, nausea, vomiting, peptic ulcer, pancreatitis, and, in particular, central nervous system dysfunction. 

The diagnosis relies on serum calcium concentration usually above 15 mg/dL and serum PTH 20 times the upper limit of normal. Concomitant bone disease and nephrolithiasis are usually present.

The three major causes are:

1. severe illness

2. volume depletion

3. infarction of a parathyroid adenoma

#endocrinology

References:

1. Ahmad S, Kuraganti G, Steenkamp D. Hypercalcemic crisis: a clinical review. Am J Med 2015; 128:239.

2. Muntaser A, Thelen A, Sehgal AR, McHenry CR. Hyperparathyroid crisis: Characteristics and outcomes. Am J Surg. 2023 Mar;225(3):477-480. doi: 10.1016/j.amjsurg.2022.10.028. Epub 2022 Oct 18. PMID: 36307336.

3. Bondeson AG, Bondeson L, Thompson NW. Clinicopathological peculiarities in parathyroid disease with hypercalcaemic crisis. Eur J Surg 1993; 159:613.

yellow fever vaccine and immunocompromised hosts

Q: A 52-year-old male recovering in the ICU after a heart-kidney transplant announces he will travel to South Africa to celebrate his successful outcome and freedom from dialysis. He asks the intensivist for advice, who advises against such travel as he may need to take the yellow fever vaccine. Why should the yellow fever vaccine ideally be avoided in immunocompromised hosts?

Answer: It contains a live attenuated viral strain 

Ideally, immunocompromised travelers due to any underlying disease process (such as asplenia or thymic dysfunction) or drugs (such as steroids) should avoid the yellow fever vaccine, or wait 4-12 weeks after stopping such drugs. It contains a live attenuated viral strain. Experts even advise omitting such travel to endemic areas and even accepting deportation instead of accepting the yellow fever vaccine if forced on arrival. If absolutely required, peak season should be avoided.

Some patients who are on TNF-alpha inhibitors, interleukin-1– and interleukin-6–blocking agents, immunosuppressive monoclonal antibodies targeting immune cells, alkylating drugs, and antimetabolites may not be aware of underlying risk. Similarly, patients with asplenia, renal failure, chronic liver disease, advanced HIV, diabetes, myasthenia gravis, thymoma, or prior thymectomy are at particular risk.

Fatal myeloencephalitis or yellow fever vaccine–associated viscerotropic disease may occur.

#ID

References:

1. Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014; 58:e44.

2. Cetron MS, Marfin AA, Julian KG, et al. Yellow fever vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2002. MMWR Recomm Rep 2002; 51:1.

3. Mileno M. Preparation of Immunocompromised Travelers. In: Travel Medicine, 1st ed, Keystone JS, Freedman DP, Nothdurft HD, Connor BA (Eds), Mosby, Edinburgh 2004. p.249.

4. Kengsakul K, Sathirapongsasuti K, Punyagupta S. Fatal myeloencephalitis following yellow fever vaccination in a case with HIV infection. J Med Assoc Thai 2002; 85:131.

VAS in COPD

Q: What does VAS stand for in the Rome criteria for COPD exacerbation?

Answer: Visual Analog Scale (VAS)

The Rome criteria for COPD is designed to simplify the classification of respiratory symptoms during exacerbations into mild, moderate, or severe. It consists of the following parameters:

1. Visual Analog Scale (VAS) at a scale of 0 to 10

2. Respiratory Rate (RR)

3. Heart Rate (HR)

4. Oxygen Saturation (SaO₂): Resting levels on room air or baseline oxygen

5. C-Reactive Protein (CRP) as a blood marker for systemic inflammation (mg/L)

Evaluation of arterial Blood Gases (ABG) has also been included if available.

Initially, it was designed for outpatient settings, but experts now believe it can also be used in inpatient settings. A couple of examples of the utility of this score are prescribing glucocorticoids for a moderate exacerbation of COPD or admission to the ICU for mechanical ventilation.

Full classification can be obtained via any search engine or AI portal.

#pulmonary

References:

1. Celli BR, Fabbri LM, Aaron SD, et al. An Updated Definition and Severity Classification of Chronic Obstructive Pulmonary Disease Exacerbations: The Rome Proposal. Am J Respir Crit Care Med 2021; 204:1251.

2. Cometa M, Ursitti A, Lombardo LP, Rana R, Gardani A, Contoli M, Papi A. Can the Rome classification of chronic obstructive pulmonary disease exacerbation severity be applied in the hospital setting? Respir Med. 2024 Feb;222:107509. doi: 10.1016/j.rmed.2023.107509. Epub 2023 Dec 24. PMID: 38145723.

3. Zeng J, Zhou C, Yi Q, Luo Y, Wei H, Ge H, Liu H, Zhang J, Li X, Pan P, Yi M, Cheng L, Liu L, Zhang J, Peng L, Pu J, Zhou H; MAGNET AECOPD Registry Investigators. Validation of the Rome Severity Classification of Chronic Obstructive Pulmonary Disease Exacerbation: A Multicenter Cohort Study. Int J Chron Obstruct Pulmon Dis. 2024 Jan 17;19:193-204. doi: 10.2147/COPD.S442382. PMID: 38249828; PMCID: PMC10800102.

extraintestinal site has the highest propensity for nntyphoidal Salmonella bacteremia

Q: Which of the following extraintestinal sites has the highest propensity for nontyphoidal Salmonella bacteremia? - select one

A) Heart valves

B) Endovascular  

C) Meninges 

D) Bone

E) Pancreas 

Answer: B

Nontyphoidal Salmonella bacteremia has a propensity to localize to atherosclerotic or pre-existing vascular disease in large vessels, particularly in older and immunosuppressed patients. 

The infrarenal aorta is the most frequent site of vascular infection. Other common sites include the thoracic aorta and other central arterial sites, characterized by fever (usually subacute), abdominal pain, and back pain, and are associated with relapsing or prolonged Salmonella bacteremia.

CNS infections are followed by endovascular infection, particularly in children. Other sites, as mentioned in the question above, are also possible but rare.

#ID

References:

1. Hsu RB, Lin FY. Risk factors for bacteraemia and endovascular infection due to non-typhoid salmonella: a reappraisal. QJM 2005; 98:821.

2. Benenson S, Raveh D, Schlesinger Y, et al. The risk of vascular infection in adult patients with nontyphi Salmonella bacteremia. Am J Med 2001; 110:60.

3. Chen SY, Weng TH, Tseng WP, et al. Value of blood culture time to positivity in identifying complicated nontyphoidal Salmonella bacteremia. Diagn Microbiol Infect Dis 2018; 91:210.

Delafloxacin

Q: Delafloxacin is a? - select one

A) tetracycline

B) fluoroquinolone

Answer: B

The objective of this question is to make students aware of one of the relatively unknown but potent antibiotics. Delafloxacin is a fluoroquinolone approved for the treatment of bacterial skin and soft tissue infections. 

It has broad-spectrum activity, including methicillin-resistant Staphylococcus aureus (MRSA) (though some resistance has already been reported), Pseudomonas aeruginosa, Enterobacteriaceae, and Clostridioides difficile.

#pharmacology

#ID

References:

1. Candel FJ, Peñuelas M. Delafloxacin: design, development and potential place in therapy. Drug Des Devel Ther 2017; 11:881.

2. Saravolatz LD, Stein GE. Delafloxacin: A New Anti-methicillin-resistant Staphylococcus aureus Fluoroquinolone. Clin Infect Dis 2019; 68:1058.

3. Iregui A, Khan Z, Malik S, et al. Emergence of Delafloxacin-Resistant Staphylococcus aureus in Brooklyn, New York. Clin Infect Dis 2020; 70:1758.

4. O'Riordan W, McManus A, Teras J, et al. A Comparison of the Efficacy and Safety of Intravenous Followed by Oral Delafloxacin With Vancomycin Plus Aztreonam for the Treatment of Acute Bacterial Skin and Skin Structure Infections: A Phase 3, Multinational, Double-Blind, Randomized Study. Clin Infect Dis 2018; 67:657.

DBS and Diathermy

Q: A 68-year-old male is recovering from community-acquired pneumonia (CAP) in the ICU. Patient has a Deep Brain Stimulator (DBS) implanted for his Parkinson's Disease. The patient's DBS is MRI-compatible and has had no issues in the past with his cardiac pacemaker. A physical therapist (PT) inquired with you about using diathermy for the patient to relieve his chronic muscle pain. Diathermy in a DBS patient can be used safely.

A) Yes

B) No

Answer: B

In the last few years, most DBSs have become MRI-compatible and can be safely inserted in patients with a cardiac pacemaker, though rechecking with the patient's home info packet is always needed prior to any such intervention.

Unfortunately, DBSs are incompatible with diathermy, which is frequently used during physical therapy sessions (and by chiropractors). Diathermy, as the name suggests, delivers heat to soft tissue using electrical energy. It increases blood circulation, decreases pain, and improves healing. Diathermy induces a radiofrequency current that may cause heating of the DBS electrodes and may cause life-threatening or disabling injury to the brain.

#procedures

References:

1. Capelle HH, Simpson RK Jr, Kronenbuerger M, et al. Long-term deep brain stimulation in elderly patients with cardiac pacemakers. J Neurosurg 2005; 102:53.

2. Nutt JG, Anderson VC, Peacock JH, et al. DBS and diathermy interaction induces severe CNS damage. Neurology 2001; 56:1384.

3. Boutet A, Chow CT, Narang K, Elias GJB, Neudorfer C, Germann J, Ranjan M, Loh A, Martin AJ, Kucharczyk W, Steele CJ, Hancu I, Rezai AR, Lozano AM. Improving Safety of MRI in Patients with Deep Brain Stimulation Devices. Radiology. 2020 Aug;296(2):250-262. doi: 10.1148/radiol.2020192291. Epub 2020 Jun 23. PMID: 32573388; PMCID: PMC7543718.

Body organ involved in IgAN besides kidney

Q: Which organ in the body may be related to IgA Nephropathy (IgN)? - select one

A) Adrenal gland

B) Brain

C) Cardia

D) Liver

E) Tonsils

Answer: E

Tonsillitis has been associated with hematuria and proteinuria in IgAN. Tonsils are considered a source of abnormal IgA that forms immune complexes and deposits in the glomeruli.

Although theoretically tonsillectomy can cure IgAN, there is limited evidence for this treatment; however, combining tonsillectomy with immunosuppressive therapy may be relatively more beneficial.

#nephrology

#immunology

References:

1. Hotta O, Miyazaki M, Furuta T, et al. Tonsillectomy and steroid pulse therapy significantly impact on clinical remission in patients with IgA nephropathy. Am J Kidney Dis 2001; 38:736.

2. Akagi H, Kosaka M, Hattori K, et al. Long-term results of tonsillectomy as a treatment for IgA nephropathy. Acta Otolaryngol Suppl 2004; :38.

3. Kochoyan ZS, Dobronravov VA. Tonsillectomy and immunosuppression improve outcomes in Caucasians with high-risk IgA nephropathy. Nephrol Dial Transplant 2026; 41:1284.

4. Rasche FM, Schwarz A, Keller F. Tonsillectomy does not prevent a progressive course in IgA nephropathy. Clin Nephrol 1999; 51:147.

Rapalogs and ACE-I-angioedema

Q: Post-transplant patients are at increased risk of ACE inhibitor-induced angioedema.

A) True

B) False

Answer: A

Post-transplant patients who take rapamycin (mTOR) inhibitors, commonly known as rapalogs such as sirolimus or everolimus, are at increased risk of Angiotensin-converting enzyme (ACE) inhibitor-induced angioedema when both are co-administered. Rapalogs reduce the metabolism of bradykinin. The effect appears to be dose-dependent for rapalog. 

Overall, all transplant patients are at increased risk of ACE inhibitor-induced angioedema because immunosuppressants decrease dipeptidyl peptidase 4 (DPP-4) levels, which is responsible for breaking down bradykinin, a key culprit in ACE inhibitor-related angioedema.

#toxicity

#pharmacology

#transplantation

References:

1. Duerr M, Glander P, Diekmann F, et al. Increased incidence of angioedema with ACE inhibitors in combination with mTOR inhibitors in kidney transplant recipients. Clin J Am Soc Nephrol 2010; 5:703.

2. Charmillon A, Deibener J, Kaminsky P, Louis G. Angioedema induced by angiotensin converting enzyme inhibitors, potentiated by m-TOR inhibitors: successful treatment with icatibant. Intensive Care Med 2014; 40:893.

3. Fuchs U, Zittermann A, Berthold HK, et al. Immunosuppressive therapy with everolimus can be associated with potentially life-threatening lingual angioedema. Transplantation 2005; 79:981.

4. Scott SI, Andersen MF, Aagaard L, Buchwald CV, Rasmussen ER. Dipeptidyl Peptidase-4 Inhibitor Induced Angioedema - An Overlooked Adverse Drug Reaction? Curr Diabetes Rev. 2018;14(4):327-333. doi: 10.2174/1573399813666170214113856. PMID: 28201967.

Paradoxes (and history) of LR

Q: Resuscitation with Lactated Ringer's (LR) may cause? - select one

A) Hypernatremia

B) Hyponatremia

Answer: B

Lactated Ringer's solution was accidentally invented in Dr. Ringer's laboratory in 1882 while his team was working on isolated frog hearts. De Ringer's laboratory assistant mistakenly used tap water instead of distilled water. It kept the heart beating longer than usual, and the team found that calcium in tap water (and other minerals) may be responsible. Also, they are safe and functional for tissues.

Over the years, with modifications, it is composed of

• Sodium (Na⁺): 130 mEq
• Chloride (Cl⁻): 109 mEq
• Potassium (K⁺): 4 mEq
• Calcium (Ca²⁺): 3 mEq
• Lactate: 28 mEq

Two Paradoxes of LR:

1. Though overall it is an isotonic solution, in terms of only Na, it is hyponatremic, as serum sodium isotonicity ranges from 135 to 145 mEq/L.

2. Although the PH of LR is 6.5, due to lactate in it, which converts to bicarbonate (HCO3), it causes metabolic alkalosis.

#electrolytes

#acid-base

References:

1. Sternbach G. Sydney Ringer: water supplied by the New River Water Company. J Emerg Med. 1988 Jan-Feb;6(1):71-4. doi: 10.1016/0736-4679(88)90254-5. PMID: 3283218.

2. Friedman JN; Canadian Paediatric Society, Acute Care Committee. Risk of acute hyponatremia in hospitalized children and youth receiving maintenance intravenous fluids. Paediatr Child Health. 2013 Feb;18(2):102-7. PMID: 24421667; PMCID: PMC3567908.

3. Park M, Sidebotham D. Metabolic alkalosis and mixed acid-base disturbance in anaesthesia and critical care. BJA Educ. 2023 Apr;23(4):128-135. doi: 10.1016/j.bjae.2023.01.002. Epub 2023 Feb 23. PMID: 36960435; PMCID: PMC10028421.

Pseudo-hypophosphatemia

Q: Intravenous (IV) mannitol may cause? - select one

A) pseudo-hypocalcemia 

B) pseudo-hypokalemia

C) pseudo-hypomagnesemia

D) pseudo-hyponatremia

E) pseudo-hypophosphatemia

Answer: E

The first step in the evaluation of pseudohypophosphatemia is to rule out spurious or pseudo-hypophosphatemia. Many well-known conditions and drugs may cause pseudohypophosphatemia either by the presence of paraproteins or by interference with the phosphate assay. Some of the causes are:

• multiple myeloma 
• other monoclonal gammopathies
• IV mannitol (usually in large or repeated doses)

#electrolytes

References:

1. Molinaris V, Bianchetti MG, Milani GP, et al. Interferences in the measurement of circulating phosphate: a literature review. Clin Chem Lab Med 2020; 58:1971.

2. Kerr S, Kindt J, Daram SR. Hypophosphatemia associated with paraproteinemia: a case report and review of the literature. WMJ 2007; 106:490.

3. Wen Wu L, Choi TS, Barbosa M, et al. PSEUDOHYPOPHOSPHATEMIA IN A PATIENT WITH MULTIPLE MYELOMA. AACE Clin Case Rep 2020; 6:e334.

4. Larner AJ. Pseudohyperphosphatemia. Clin Biochem. 1995 Aug;28(4):391-3. doi: 10.1016/0009-9120(95)00013-y. PMID: 8521592.

murmur of pulmonic stenosis

Q: The murmur of pulmonic stenosis can be best heard at? - select one

A) left upper sternal border

B) right upper sternal border

Answer: A

The murmur of pulmonic stenosis is a systolic ejection murmur and is best heard at the left upper sternal border. If the murmur varies with respiration, it is still considered mild. It radiates to the back, in the posterior lung fields. 

In severe cases, there is a prominent left parasternal lift, along with splitting of the second heart sound. As expected, there is a right-sided fourth heart sound over the left sternal border if pulmonic stenosis leads to right ventricular hypertrophy with diminished compliance. 

Cyanosis occurs only later in the most severe cases.

In Jugular Venous Pressure (JVP), there is a prominent "A" wave, but overall JVP remains in the normal range.

#cardiology

#physical-exam

References:

1. Marchini F, Meossi S, Passarini G, Campo G, Pavasini R. Pulmonary Valve Stenosis: From Diagnosis to Current Management Techniques and Future Prospects. Vasc Health Risk Manag. 2023 Jun 30;19:379-390. doi: 10.2147/VHRM.S380240. PMID: 37416511; PMCID: PMC10320808.

2. Heaton J, Horenstein MS, Kyriakopoulos C. Pulmonary Stenosis. 2024 Oct 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. PMID: 32809585.

3. Atiq M, Akhter S, Abdul Sattar S, Mohsin S, Aslam N. Murmur and Doppler alternans in critical pulmonary stenosis. Pediatr Cardiol. 2011 Oct;32(7):1004-7. doi: 10.1007/s00246-011-0033-6. Epub 2011 Jul 7. PMID: 21748495.

Treatment considerations in myasthenia gravis for the pregnant patient

Q: A 26-year-old female, first-time 30 weeks pregnant, and with a known history of Myasthenia Gravis (MG). pyridostigmine is preferred to be given? - select one

A) Intravenous (IV)

B) Oral

Answer: B

One of the first and mainstay treatments for MG is an acetylcholinesterase inhibitor such as pyridostigmine. Intravenous acetylcholinesterase inhibitors have the tendency to induce uterine contractions and are preferred to be given enterally, either by mouth or nasogastric tube. 

The other required precaution is a higher dose due to increased renal clearance, expanded maternal blood volume, delayed gastric emptying, and frequent emesis. The recommended way to increase the dose is to decrease the interval, or, if needed, to increase the dose and decrease the interval.

If the enteral route fails or labor ensues, IV administration is acceptable.

#ob-gyn

#neurology

References:

1. Norwood F, Dhanjal M, Hill M, et al. Myasthenia in pregnancy: best practice guidelines from a U.K. multispecialty working group. J Neurol Neurosurg Psychiatry 2014; 85:538.

2. Bansal R, Goyal MK, Modi M. Management of myasthenia gravis during pregnancy. Indian J Pharmacol. 2018 Nov-Dec;50(6):302-308. doi: 10.4103/ijp.IJP_452_17. PMID: 30783322; PMCID: PMC6364336.

3. Gilhus NE. Treatment considerations in myasthenia gravis for the pregnant patient. Expert Rev Neurother. 2023 Feb;23(2):169-177. doi: 10.1080/14737175.2023.2178302. Epub 2023 Feb 20. PMID: 36786092.

Katayama fever

Q: In acute schistosomiasis syndrome (Katayama fever), what should be given first?

A) Anthelminthic

B) Glucocorticoids

Answer: B

Acute schistosomiasis syndrome, popularly known as Katayama fever, is a highly inflammatory disease, and the first priority is to suppress inflammation via steroids.

Anthelmintic therapy, primarily praziquantel, is initiated once acute symptoms have fully resolved.

The idea behind this strategy is due to the following three facts;

1. Early treatment with praziquantel can be associated with recurrence of acute symptoms.
2. Glucocorticoids reduce plasma levels of praziquantel when given simultaneously
3. Praziquantel is effective only when given at least 8 weeks after exposure, once the infection is well established and the worms have fully matured

If the clinician decides to continue steroids with praziquantel due to fear of flare-up, it should be given two hours later due to the second reason given above.

#ID

#pharmacology

References:

1. Jauréguiberry S, Paris L, Caumes E. Acute schistosomiasis, a diagnostic and therapeutic challenge. Clin Microbiol Infect 2010; 16:225.

2. Ross AG, Vickers D, Olds GR, et al. Katayama syndrome. Lancet Infect Dis 2007; 7:218.

3. Jauréguiberry S, Paris L, Caumes E. Difficulties in the diagnosis and treatment of acute schistosomiasis. Clin Infect Dis 2009; 48:1163.

4. Neumayr AL, Tschirky B, Warren A, et al. Acute febrile respiratory reaction after praziquantel treatment during asymptomatic late form of acute schistosomiasis. J Travel Med 2012; 19:264.

TIPSS and HPS

Q: Transjugular intrahepatic portosystemic shunt (TIPSS) can cure Hepatopulmonary syndrome (HPS).

A) True

B) False

Answer: B

Transjugular intrahepatic portosystemic shunt (TIPSS) reduces the portal pressures. Previously, it has been advocated in HPS in several case reports, but recent evidence argues that it may worsen hepatic encephalopathy, may cause more pulmonary vasodilatation, shunting, and worsening of hypoxemia. It should be utilized as a last resort. 

#hepatology

#pulmonary

References:

1. Martinez-Palli G, Drake BB, Garcia-Pagan JC, et al. Effect of transjugular intrahepatic portosystemic shunt on pulmonary gas exchange in patients with portal hypertension and hepatopulmonary syndrome. World J Gastroenterol 2005; 11:6858.

2. Correa TL, Martins OC, Fernandes MV, et al. Effectiveness of Transjugular Intrahepatic Portosystemic Shunt Creation for the Treatment of Hepatopulmonary Syndrome. J Vasc Interv Radiol 2025; 36:1494.

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.