"steal" phenomenon of inhaled nitric oxide (iNO)

"steal" phenomenon of inhaled nitric oxide (iNO)

iNO is frequently used as a rescue therapy in patients with no underlying pulmonary hypertension but who develop severe pneumonia or acute respiratory distress syndrome (ARDS). Although evidence is weak regarding any mortality benefits, it certainly provides breathing space for a clinician to provide more proven modalities like extracorporeal membrane oxygenation (ECMO). This benefit of iNO has been utilized frequently by clinicians during the COVID-19 pandemic.

iNO improves oxygenation by a phenomenon known as "steal" phenomenon. Contrary to popular belief, iNO has a relatively small effect on ventilation-perfusion (V/Q) mismatch by vasodilating the pulmonary vascular bed. The larger improvement in hypoxemia comes from the "steal" phenomenon in lung parenchyma by decreasing the intra-pulmonary shunt in areas less perfused. This also explains the immediate improvement in hypoxemia while patients are prone, particularly when obese. iNO and prone position, when combined, can have a highly synergistic effect.

#pulmonary 

#ARDS

Reference:

1. Mizutani T, Layon AJ. Clinical applications of nitric oxide. Chest 1996; 110:506.

2. De Wet CJ, Affleck DG, Jacobsohn E, et al. Inhaled prostacyclin is safe, effective, and affordable in patients with pulmonary hypertension, right heart dysfunction, and refractory hypoxemia after cardiothoracic surgery. J Thorac Cardiovasc Surg 2004; 127:1058.

3. Rossaint R, Falke KJ, López F, et al. Inhaled nitric oxide for the adult respiratory distress syndrome. N Engl J Med 1993; 328:399.

Esmolol duration of action

Q: Esmolol duration of action can last up to? (select one)

A)  9 minutes

B) 30 minutes

Answer: B

This question aims to highlight the difference between half-life and duration of action. Although Esmolol gets rapidly metabolized by blood esterases with a short half-life of about 8-9 minutes, its effect can last up to 30 minutes. The popular belief of esmolol getting out of the system very quickly may not always be true!

#cardiology

#pharmacology

Reference:

Ehud Grossman, Franz H. Messerli, Chapter 63 - Hypertensive Urgencies and Emergencies, Comprehensive Hypertension, Mosby, 2007, Pages 761-774, ISBN 9780323039611, https://doi.org/10.1016/B978-0-323-03961-1.50066-0. 

blood donation from COVID-19 patient

Q; What's the US Food and Drug Administration (FDA) recommendation regarding blood donation from COVID-19 patient?

Answer: FDA does not recommend testing donated blood for the COVID-19 virus. There is no documented case of COVID-19 transmission via blood donation so far. A COVID-19 person is OK to donate blood if

- symptomatic but the illness resolved more than 10 days prior to blood donation

- asymptomatic but a positive test for the virus (antigen, nucleic acid) was more than 10 days prior

Similarly, a person with suspected COVID like symptoms or close-contact with an individual with SARS-CoV-2 infection should not donate blood for 10 days.

#transfusion-medicine

#COVID-19

References:

1. https://www.aabb.org/regulatory-and-advocacy/regulatory-affairs/infectious-diseases/coronavirus (Accessed on January 07, 2023).

2. FDA Updated Information for Blood Establishments Regarding the COVID-19 Pandemic and Blood Donation https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/updated-information-blood-establishments-regarding-covid-19-pandemic-and-blood-donation (Accessed on January 07, 2023)

Predictor of successful transplant in PAH

Q: Which of the following lab can be used as a predictor of the success of organ transplant in pulmonary arterial hypertension (PAH) patients?

A) bilirubin

B) troponin

Answer: A

Bilateral lung or heart-lung transplantation is required for a patient with pulmonary hypertension if any of the following is suspected.

• World Health Organization (WHO) functional class III or IV during escalating therapy
• Rapidly progressive disease (before or on therapy)
• Use of parenteral prostanoid therapy regardless of functional class symptoms
• Known or suspected pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis

Elevated bilirubin is found to be correlated with postoperative mortality. Also, the likelihood of successful transplantation is poor if bilirubin does not come down post-transplantation.

#transplantation

#pulmonary

References:

1. Weill D, Benden C, Corris PA, et al. A consensus document for the selection of lung transplant candidates: 2014--an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2015; 34:1.

2. Keogh AM, Mayer E, Benza RL, et al. Interventional and surgical modalities of treatment in pulmonary hypertension. J Am Coll Cardiol 2009; 54:S67.

3. Russo MJ, Davies RR, Hong KN, Iribarne A, Kawut S, Bacchetta M, D'Ovidio F, Arcasoy S, Sonett JR. Who is the high-risk recipient? Predicting mortality after lung transplantation using pretransplant risk factors. J Thorac Cardiovasc Surg. 2009 Nov;138(5):1234-1238.e1. doi: 10.1016/j.jtcvs.2009.07.036. PMID: 19837222; PMCID: PMC3073984.

dark urine and rhabdomyolysis

Q: The diagnosis of rhabdomyolysis requires dark-colored urine? 

A) Yes

B) No

Answer: B

Clinically rhabdomyolysis is a diagnosis consisting of a triad of myalgias, muscle weakness, and colored urine. The classic triad is present in less than 10 percent of the patients and requires laboratory evidence of elevated CK. Also, dark-colored urine is present in less than 10 percent of patients and requires urinalysis to confirm myoglobinuria.

Another less appreciated symptom of rhabdomyolysis is muscle swelling from edema, which may become apparent after fluid resuscitation.

#musculoskeletal

#nephrology

References:

1. Huerta-Alardín AL, Varon J, Marik PE. Bench-to-bedside review: Rhabdomyolysis -- an overview for clinicians. Crit Care 2005; 9:158.

2. Stahl K, Rastelli E, Schoser B. A systematic review on the definition of rhabdomyolysis. J Neurol 2020; 267:877.

3. Cervellin G, Comelli I, Benatti M, et al. Non-traumatic rhabdomyolysis: Background, laboratory features, and acute clinical management. Clin Biochem 2017; 50:656.

4. Nance JR, Mammen AL. Diagnostic evaluation of rhabdomyolysis. Muscle Nerve 2015; 51:793.

Cardiac amyloidosis

Q: Cardiac amyloidosis usually presents with? (select one)

A) right-sided heart failure

B) left-sided heart failure

Answer: A

Cardiac amyloidosis usually cause restrictive cardiomyopathy with mostly right ventricular failure (RVF). Symptoms are typical of RVF i.e., dyspnea, leg edema, elevated jugular venous pressure (JVP), liver congestion, and ascites. Angina is not common. Is symptoms of syncope are present, attention should be paid to evaluate atrioventricular blocks.

#cardiology

References:

1. Cuddy SAM, Dorbala S, Falk RH. Complexities and Pitfalls in Cardiac Amyloidosis. Circulation 2020; 142:409.

2. Bhogal S, Ladia V, Sitwala P, Cook E, Bajaj K, Ramu V, Lavie CJ, Paul TK. Cardiac Amyloidosis: An Updated Review With Emphasis on Diagnosis and Future Directions. Curr Probl Cardiol. 2018 Jan;43(1):10-34. doi: 10.1016/j.cpcardiol.2017.04.003. Epub 2017 Apr 13. PMID: 29173805.

3. Ash S, Shorer E, Ramgobin D, Vo M, Gibbons J, Golamari R, Jain R, Jain R. Cardiac amyloidosis-A review of current literature for the practicing physician. Clin Cardiol. 2021 Mar;44(3):322-331. doi: 10.1002/clc.23572. Epub 2021 Feb 17. PMID: 33595871; PMCID: PMC7943900.

North-South syndrome

Q: What is North-south syndrome in peripheral Veno-arterial (VA) ECMO?

Answer: When patients are cannulated peripherally, i.e., the Femoral vein and Femoral artery, the upper part of the body may turn hypoxic. (see picture). This upper body hypoxia occurs when the heart ejects against the blood delivered retrogradely in the aorta through the femoral artery cannula. This creates a water shade area where the two blood streams meet in the middle. Blood delivered through an ECMO cannula is very oxygenated. Still, blood from the heart may not be well oxygenated, mainly when the lungs are not doing well and are flooded with pulmonary edema. This is called North-South or Harlequin syndrome, as a patient may have a Harlequin-like appearance.

A few measures which help to resolve this are 

• Optimize the vent and other maneuvers in the lung 

• Using Esmolol drip to decrease hyperdynamic of the left ventricle 

• Applying a splitting Y connector to the arterial arm of the ECMO and delivering good-oxygenated blood into the venous and pulmonary circulation. 

In other words, VA ECMO has now become VAV ECMO. 

#hemodynamic

References:

1. Lindholm JA. Cannulation for veno-venous extracorporeal membrane oxygenation. J Thorac Dis. 2018 Mar;10(Suppl 5):S606-S612. doi: 10.21037/jtd.2018.03.101. PMID: 29732177; PMCID: PMC5911563. 

2. Prashant Rao, Zain Khalpey, Richard Smith, Daniel Burkhoff and Robb D. Kociol Venoarterial Extracorporeal Membrane Oxygenation for Cardiogenic Shock and Cardiac Arrest Cardinal Considerations for Initiation and Management Originally published, 18 Sep 2018,  https://doi.org/10.1161/CIRCHEARTFAILURE.118.004905 Circulation: Heart Failure. 2018;11:e004905

mumps meningitis

Q: Aseptic meningitis due to mumps is more common in males?

A) True

B) False

Answer: A

Aseptic meningitis is mumps' most common neurologic complication and was first reported more than six decades ago. For reasons not fully understood, it is three times more common in males. It can also cause orchitis and, in a few cases, sterility, particularly in non-vaccinated patients. 

Although aseptic meningitis is usually benign, it can occur before, during, or after mumps parotitis. To make diagnosis difficult, half of the cases related to mump parotitis, meningitis may occur without the symptoms of parotitis.

#ID

#neurology

References:

1. RUSSELL RR, DONALD JC. The neurological complications of mumps. Br Med J 1958; 2:27.

2. Johnstone JA, Ross CA, Dunn M. Meningitis and encephalitis associated with mumps infection. A 10-year survey. Arch Dis Child 1972; 47:647.

3. Rhie K, Park HK, Kim YS, Yeom JS, Park JS, Seo JH, Park ES, Lim JY, Park CH, Woo HO, Youn HS. Factors associated with mumps meningitis and the possible impact of vaccination. Korean J Pediatr. 2016 Jan;59(1):24-9. doi: 10.3345/kjp.2016.59.1.24. Epub 2016 Jan 22. PMID: 26893600; PMCID: PMC4753196.

AG with K

Q: If potassium is added/counted in Anion gap (AG) formula, the anion gap will? (select one)

A) decrease

B) increase

Answer: B

The objective of this question is to highlight the fact that each laboratory has its own value of normal AG, depending on the method they use. Labs which use ion-selective electrodes usually have lower range of AG, somewhere at 6±3 mEq/L. This is due to the fact that ion-selective electrodes counts higher serum chloride concentrations leading to lower value of AG.

Many labs now routinely use potassium in AG calculation with the formula: (Na + K) - (Cl + HCO3). This increases the AG on average by 4 mEq/L.

#acid-base

#electrolytes

References:

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

2. Jurado RL, del Rio C, Nassar G, et al. Low anion gap. South Med J 1998; 91:624.

3. Paulson WD, Roberts WL, Lurie AA, et al. Wide variation in serum anion gap measurements by chemistry analyzers. Am J Clin Pathol 1998; 110:735.

4. Pratumvinit B, Lam L, Kongruttanachok N, et al. Anion gap reference intervals show instrument dependence and weak correlation with albumin levels. Clin Chim Acta 2020; 500:172.

abnormalities of taste and smell

Q: 32 years old patient admitted to ICU with COVID infection complained of loss of taste and smell. What are the five abnormalities of taste and four abnormalities of smell?

Answer: The medical terminologies for normal taste and smell functions are normogeusia and normosmia, respectively.

There are five dysfunctions of taste:

1. Hypogeusia – Diminished taste function to one or more specific tastants

2. Ageusia – Absent taste function

3. Dysgeusia – Altered (sweet, sour, salty, bitter, or metallic) perception of taste in response to a tastant stimulus

4. Aliageusia – Taste disturbance in which a typically pleasant-tasting food or drink tastes unpleasant

5. Phantogeusia – Unpleasant taste due to a gustatory hallucination (in the absence of any stimulus)

There are four dysfunctions of smell (olfaction)

1. Hyposmia – Diminished smell function (also sometimes referred to as microsmia)

2. Anosmia – Absent smell function

3. Parosmia – Abhorrent odor perception. This is described in two categories. A) with an odorant stimulus (troposmia or smell distortion), or B) without an odorant stimulus (phantosmia)

4. Dysosmia – A general term describing distortion of smell sensations

#neurology

Reference:

Denis Lafreniere - Taste and olfactory disorders in adults: Evaluation and management - © 2023 UpToDate - Link: https://www.uptodate.com/contents/taste-and-olfactory-disorders-in-adults-evaluation-and-management (last accessed January 20, 2023)

pentad of TTP

Q: The classic "pentad" of Thrombotic thrombocytopenic purpura (TTP) is now considered obsolete?

A) True

B) False

Answer: A

Classically TTP is known for its "pentad," i.e.,

• microangiopathic hemolytic anemia (MAHA) 
• thrombocytopenia
• fever
• acute kidney injury
• severe neurologic findings

This pentad is preset only in less than 5 percent of the patients. TTP is a progressive disease. Since diagnosis and management are now readily done and available, classic pentad is rarely seen and considered obsolete in this age and time. Management with plasma exchange has been considered a game-changer in this regard.

#hematology

References:

1. Page EE, Kremer Hovinga JA, Terrell DR, et al. Thrombotic thrombocytopenic purpura: diagnostic criteria, clinical features, and long-term outcomes from 1995 through 2015. Blood Adv 2017; 1:590.

2. Amorosi EL, Ultmann JE. Thrombotic thrombocytopenic purpura: Report of 16 cases and review of the literature. Medicine (Baltimore) 1966; 45:139.

Nitrofurantoin induced pulmonary edema

Q: 23 years old female is admitted to ICU with acute pulmonary edema after 24 hours of initiating nitrofurantoin. Which two points speak against the diagnosis of "Nitrofurantoin induced pulmonary edema"?

Answer: Four decades ago, nitrofurantoin was considered the mainstay of treatment for cystitis amongst women. The rise of quinolones resulted in the disappearance of nitrofurantoin from clinical practice. Since the antibacterial resistance is rising for quinolone, the is a reemergence of interest in nitrofurantoin. This led to an increase in the cases of nitrofurantoin toxicity, particularly pulmonary edema. It can occur acutely as well as in patients who are prescribed chronic therapy.

The patient's age and the symptoms' timeline are the two things that speak against the diagnosis of nitrofurantoin-induced edema. Nitrofurantoin-induced pulmonary edema is more common in patients above 65, particularly in chronic users. It takes about 8-9 days for symptoms to emerge in acute cases.

Treatment is the discontinuation of the drug. Steroids may or may not be helpful.

#pharmacology

#toxicity

#ID

References:

1. Holmberg L, Boman G. Pulmonary reactions to nitrofurantoin. 447 cases reported to the Swedish Adverse Drug Reaction Committee 1966-1976. Eur J Respir Dis 1981; 62:180.

2. Santos JM, Batech M, Pelter MA, Deamer RL. Evaluation of the Risk of Nitrofurantoin Lung Injury and Its Efficacy in Diminished Kidney Function in Older Adults in a Large Integrated Healthcare System: A Matched Cohort Study. J Am Geriatr Soc 2016; 64:798.

3. Kabbara WK, Kordahi MC. Nitrofurantoin-induced pulmonary toxicity: A case report and review of the literature. J Infect Public Health 2015; 8:309.

Obesity and cancer

Q: Obesity is associated with __________ cancer outcomes? (select one)

A) improved

B) worse

Answer: B

Knowing it may be easy to predict poor outcomes in obese patients who develop cancer, this question aims to direct clinicians to their role in this poor outcome. Although not entirely explained but one of the major reasons for poor outcomes in obese patients with cancer is the underdosing of chemotherapeutic agents by clinicians. Most anti-neoplastic drugs, except for a few, need to be dosed as per actual body weight. The capping of doses of cytotoxic chemotherapy agents leads to poor outcomes in these patients. 

Unfortunately, obese have higher cancer incidence rates, and this under-dosing increases cancer-related mortality.

#oncology

Reference:

Reeves GK, Pirie K, Beral V, et al. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. BMJ 2007; 335:1134.

Severe Malaria

Q: Which of the following is responsible for 90 percent of severe malaria cases? (select one)

A) Plasmodium falciparum 

B) Plasmodium vivax 

C) Plasmodium knowlesi

Answer: A

The objective of this question is to highlight the fact that it is important to establish the diagnosis of "severe malaria" as, without intervention, death can occur within 24 hours. Severe malaria is defined as one or more of the following criteria occurring in the presence of malaria infection and in the absence of an identified alternative cause:

• Impaired consciousness
• Prostration
• Convulsions
• Acidosis
• Hypoglycemia
• Severe anemia
• Renal impairment
• Jaundice
• Pulmonary edema
• Significant bleeding
• Shock
• Hyperparasitemia

(Readers are advised to refer to other sources as each of the above criteria has further detailed sub-specifications)

90 percent of cases of severe malaria are attributable to P. falciparum.

#ID

References:

1. World Health Organization. Guidelines for malaria. WHO: Geneva 2022. Available at: https://apps.who.int/iris/handle/10665/351995 (Last accessed on January 10, 2023).

2. Severe malaria. Trop Med Int Health 2014; Suppl 1:7.

3. https://www.cdc.gov/malaria/about/disease.html.(Last accessed on January 10, 2023)

4. World Health Organization World Malaria Report 2017. http://apps.who.int/iris/bitstream/handle/10665/259492/9789241565523-eng.pdf;jsessionid=7CE964134B0D083EA92FBB9F1F9D4775?sequence=1 (Last accessed on January 10, 2023).

Runyon's criteria

Q: Which of the following is not part of Runyon's criteria to diagnose secondary bacterial peritonitis? (select one)

A) Total protein >1 g/dL

B) Glucose <50 mg/dL

C) LDH >the upper limit of normal for serum

D) Absolute neutrophil count (ANC) >10,000 per microliter

  

Answer: D

  

Proposed laboratory criteria for diagnosis of secondary bacterial peritonitis, also known as Runyon's criteria, include at least two of the following ascetic fluid:

• Total protein >1 g/dL (10 g/L)
• Glucose <50 mg/dL (2.8 mmol/L)
• LDH >the upper limit of normal for serum

Cultures showing a polymicrobial infection or a Gram stain demonstrating large numbers of different bacterial forms suggest gut perforation.

Although the specificity of the criteria is about 96%, sensitivity is only 67%.

  

Two other lab findings that may make the suspicion stronger but not part of the criteria are ascetic fluid carcinoembryonic antigen (CEA) level and alkaline phosphatase levels, which suggest gut perforation. 

  

  

#GI

#ID

  

  

References:

  

1. Akriviadis EA, Runyon BA. Utility of an algorithm in differentiating spontaneous from secondary bacterial peritonitis. Gastroenterology 1990; 98:127.

  

2. Soriano G, Castellote J, Alvarez C, et al. Secondary bacterial peritonitis in cirrhosis: a retrospective study of clinical and analytical characteristics, diagnosis and management. J Hepatol 2010; 52:39.

3. Runyon BA, Hoefs JC. Ascitic fluid analysis in the differentiation of spontaneous bacterial peritonitis from gastrointestinal tract perforation into ascitic fluid. Hepatology 1984; 4:447.

  

4. Wu SS, Lin OS, Chen YY, et al. Ascitic fluid carcinoembryonic antigen and alkaline phosphatase levels for the differentiation of primary from secondary bacterial peritonitis with intestinal perforation. J Hepatol 2001; 34:215.

Miosis in opioid toxicity

Q: Normal pupillary exam excludes opioid toxicity, and the examiner should look for other causes of decreased mental status?

A) True

B) False

Answer: B

Patients with opioid toxicity do not necessarily need to have constricted pupils (miosis). This can be due to various other reasons. Patients may have simultaneously ingested other medications that are prone to cause pupillary dilatation (mydriasis), such as meperidine and/or sympathomimetics or anticholinergics. In fact, patients can even have larger or dilated pupils.

Studies have shown that decreased respiratory rate is the best predictor of opioid toxicity out of all the vital signs.

#toxicology

#neurology

#pharmacology

References:

1. Ghoneim MM, Dhanaraj J, Choi WW. Comparison of four opioid analgesics as supplements to nitrous oxide anesthesia. Anesth Analg 1984; 63:405.

2. Hoffman JR, Schriger DL, Luo JS. The empiric use of naloxone in patients with altered mental status: a reappraisal. Ann Emerg Med 1991; 20:246.

Lactate vs BD in trauma

Q: Which is a better predictor of mortality in normotensive elderly blunt trauma patients? (select one)

A) Lactate 

B) Base Deficit

Answer: A

Lactate and base deficit (BD) remain favorites amongst intensivists as a guide to gauge the level of acidosis. At least one study shows that in elderly blunt trauma patients with normal blood pressure, underlying high lactate is a better predictor of mortality. If lactate level is severely elevated (level more than 4 mmol/L), the odds of dying are four times higher than BD!

Editors' note: It's an interesting study for trauma patients and highly recommended to browse.

#trauma

Reference:

Callaway DW, Shapiro NI, Donnino MW, Baker C, Rosen CL. Serum lactate and base deficit as predictors of mortality in normotensive elderly blunt trauma patients. J Trauma. 2009 Apr;66(4):1040-4. doi: 10.1097/TA.0b013e3181895e9e. PMID: 19359912. Link: https://pubmed.ncbi.nlm.nih.gov/19359912/

Ca 125

Q: CA 125 is a specific biomarker for ovarian cancer?

A) True

B) False

Answer: B

Although CA 125 is well-known as a biomarker for ovarian cancer but can be misleading as there are many other non-gynecological and non-oncological diseases where it can be elevated. Although the list is long, below are the conditions commonly encountered in ICUs

• Ascites
• Appendicular abscess
• Cirrhosis and other liver disease
• Colitis
• Cystic fibrosis
• Diverticulitis
• CHF
• MI
• Pancreatitis
• Pericardial disease
• Pleural effusion
• Pneumonia
• Pulmonary embolism
• Recent surgery
• Renal insufficiency
• Sarcoidosis
• Systemic lupus erythematosus
• Tuberculosis peritonitis
• Urinary tract infection 
• Pelvic inflammatory disease (PID)

#ob-gyn

References:

1. Buamah P. Benign conditions associated with raised serum CA-125 concentration. J Surg Oncol 2000; 75:264.

2. Miralles C, Orea M, Espana P, et. al. Cancer antigen 125 associated with multiple benign and malignant pathologies. Ann Surg Oncol 2003; 10:150.

3.Moss EL, Hollingworth J, Reynolds TM. The role of CA125 in clinical practice. J Clin Pathol 2005; 58:308.

PONV score

Q: Which group of patients is more prone to have postoperative nausea and vomiting (PONV)? (select one)

A) smokers

B) nonsmokers

Answer: B

A few of the risk factors for postoperative nausea and vomiting are

• female gender
• nonsmoker
• postoperative opioid administration
• history of motion sickness

There is a validated simplified risk score to evaluate adults preoperatively to predict PONV and treat it pre-emptively. The score of 0, 1, 2, 3, and 4 correspond with the risk of PONV of 10, 20, 40, 60, and 80 percent, respectively.

#GI

#anesthesia

Reference:

Apfel CC, Läärä E, Koivuranta M, et al. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology 1999; 91:693.

Plasma Exchange in Multiple Sclerosis

Q: Give at least three indications of plasma exchange (PLEX) in acute exacerbation of multiple sclerosis (MS)?

Answer: PLEX is not the first line treatment for acute exacerbation of MS, but it can be very vital in the following situations

• Partial or no response to treatment with high-dose glucocorticoids 
• Large, tumefactive lesions 
• Severe deficits, i.e., hemiplegia, paraplegia, quadriplegia, coma, aphasia, or severe cognitive dysfunction
• Optic neuritis with severe visual impairment.

A neurologist should be consulted to decide on the frequency and monitoring of PLEX. 

#neurology

References:

1. Arrambide G, Iacobaeus E, Amato MP, et al. Aggressive multiple sclerosis (2): Treatment. Mult Scler 2020; :1352458520924595.

2. Bevan C, Gelfand JM. Therapeutic management of severe relapses in multiple sclerosis. Curr Treat Options Neurol 2015; 17:345.

3. Cortese I, Chaudhry V, So YT, et al. Evidence-based guideline update: Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2011; 76:294.

4. Ehler J, Koball S, Sauer M, et al. Response to Therapeutic Plasma Exchange as a Rescue Treatment in Clinically Isolated Syndromes and Acute Worsening of Multiple Sclerosis: A Retrospective Analysis of 90 Patients. PLoS One 2015; 10:e0134583.

A note on glucocorticoid and arrhythmias connection

A note on glucocorticoid and arrhythmias connection 

A less recognized risk in patients on chronic glucocorticoid is cardiac arrhythmias, particularly atrial fibrillation and flutter. Also, in few cases sudden cardiac death is also reported. Interestingly, risk is higher in new users and long-term users but not for former users. 

This risk is irrespective and independent of any underlying pulmonary or cardiac disease. This risk is higher with the use of diuretics as probable underlying cause is hypokalemia.

#cardiology

#pharmacology

References:

1. van der Hooft CS, Heeringa J, Brusselle GG, et al. Corticosteroids and the risk of atrial fibrillation. Arch Intern Med 2006; 166:1016.

2. Christiansen CF, Christensen S, Mehnert F, et al. Glucocorticoid use and risk of atrial fibrillation or flutter: a population-based, case-control study. Arch Intern Med 2009; 169:1677.

3. White KP, Driscoll MS, Rothe MJ, Grant-Kels JM. Severe adverse cardiovascular effects of pulse steroid therapy: is continuous cardiac monitoring necessary? J Am Acad Dermatol 1994; 30:768.

Types of AF

Q: What are the cutoff days to establish between paroxysmal and persistent Atrial fibrillation (AF)? (select one)

A) 3 days

B) 7 days

C) 10 days

D) 14 days

Answer: B

As per 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society guidelines on AF management, specific terminologies have been established for different forms of AF depending on time length:

- Paroxysmal - AF that terminates spontaneously or with intervention within seven days of onset. Episodes may recur with variable frequency.

- Persistent - AF that fails to self-terminate within seven days. 

- Long-standing persistent - if AF lasted for more than a year.

- Permanent AF – whenever a patient and his physician agree to just pursue a rhythm control strategy

AF may switch/change between different categories. 

#cardiology

Reference:

January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation 2014; 130:e199.

Rx for Salmonella intestinal infection above the age of 50

Q: All males above the age of 50 should be treated with antibiotics for Salmonella intestinal infection regardless of the severity of the disease?

A) Yes

B) No

Answer: A

In salmonella infection of the gut, younger and older patients as well as patients who are in immunocompromised status such as HIV, past transplantation, to those who are on chronic steroid therapy should be treated pre-emptively with antibiotics, regardless of disease severity. Older patients, in particular with cardiac, valvular, endovascular, or joint diseases, are at high risk. This prompts antibiotic treatment in all patients over the age of 50. 

Beyonf age 50, almost 10% of patients with Salmonella intestinal infection develop arteritis as this organism has a high affinity for atherosclerotic endothelium.

#ID

References:

1.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.

2. Cohen PS, O'Brien TF, Schoenbaum SC, Medeiros AA. The risk of endothelial infection in adults with salmonella bacteremia. Ann Intern Med 1978; 89:931.

PH - Types and classes

Q: 34 years old female with a known history of pulmonary Arterial Hypertension (PAH), group 1, is admitted to ICU with severe shortness of breath. Medical Record shows that she is classified as class 1V of functional classification. What is the difference between types and functional groups of pulmonary hypertension (PH)?

Answer: Patients with pulmonary hypertension are classified into two classifications.

1. They are classified among 5 types depending on the etiology.

2. They are classified among 4 classes depending on their functional capacity.

Types depending on etiology: Clinical classification of pulmonary hypertension per 6th World Symposium on Pulmonary Hypertension.

1 Pulmonary Arterial Hypertension (PAH)

2 PH due to left heart disease

3 PH due to lung disease and/or hypoxia

4 PH due to pulmonary artery obstructions

5 PH with unclear and/or multifactorial mechanisms 

These groups have further subclassifications depending on further underlying etiologies. Classification under types is extremely vital as managements are different for different groups.

Classes depending on functional capacity: World Health Organization's (WHO) functional classification for pulmonary hypertension divides patients into 4 classes.

I PH without resulting limitations of physical activity

II PH resulting in slight limitation of physical activity

III PH resulting in marked limitation of physical activity

IV PH resulting in an inability to carry on any physical activity without symptoms

#pulmonary

References:

1. European Respiratory Journal 53 (1) 1801913; DOI: 10.1183/13993003.01913-2018. Published 24 January 2019.

2. Rich S. Primary pulmonary hypertension: executive summary. Evian, France. World Health Organization, 1998.

drug-associated bullous pemphigoid

Q: Medications implicated in drug-associated bullous pemphigoid are described under all of the following EXCEPT?

A) Absolute association

B) Likely association

C) Probable association

D) Uncertain association

Answer: A

Although bullous pemphigoid is an autoimmune cutaneous blistering disease, many drugs are implicated in its manifestation due to cross-reactivity. It is characterized by autoantibody deposition at the epithelial basement membrane zone. It mostly affects patients over the age of 60. Clinically it causes generalized, pruritic, urticarial plaques and tense, subepithelial blisters.

Unfortunately, the mainstay of treatment is either topical or systemic corticosteroids. Doxycycline also counts as the first line of treatment. Contrary to popular belief, immunomodulatory therapies are used not as an adjuvant treatment but mostly to minimize the side effects of chronic steroid treatment. However, evidence suggests it may have some direct effect.

Drugs are classified as likely associated when recurrence or exacerbation with rechallenge supports an association with medication (choice B).

A probable or temporal relationship exists when the initiation of the drug or spontaneous resolution on cessation of the drug justifies the association in younger patients (choice C). 

But if such an association occurs in older patients, it is an uncertain association (choice D) since bullous pemphigoid is described as a disease f older patients.

#dermatology

#pharmacology

Reference:

Verheyden MJ, Bilgic A, Murrell DF. A Systematic Review of Drug-Induced Pemphigoid. Acta Derm Venereol 2020; 100:adv00224. Copyright © 2020 Acta Dermato-Venereologica. 

AUB-POCES

Q: AUB-POCES index includes all of the following EXCEPT?

A) history of heart disease

B) age ≥75 years

C) anemia with hemoglobin <8 mg/dL

D) vascular surgery

E) emergency surgery

                             

                             

Answer: C

                             

AUB-POCES index stands for American University of Beirut-Pre-Operative Cardiovascular Evaluation Study. It is a prospectively derived and validated preoperative cardiovascular risk index (CVRI) for patients undergoing noncardiac surgery. It became popular due to its ease to use. 

It has six components of risk which are identified by multivariate logistic regression analysis in the derivation cohort.

                             

1. history of heart disease

2. heart symptoms of angina or dyspnea

3. age ≥75 years

4. vascular surgery

5. emergency surgery.

The sixth component is anemia. Interestingly anemia level is set pretty high at <12 mg/dL 

The level of risk correlates well and steadily rises as the number of predictors rise.

AUB-POCES index is also known as AUB-HAS2 index.

#surgical-critical-care

#cardiology

References:

1. Dakik HA, Chehab O, Eldirani M, et al. A New Index for Pre-Operative Cardiovascular Evaluation. J Am Coll Cardiol 2019; 73:3067.

2. Dakik HA, Sbaity E, Msheik A, et al. AUB-HAS2 Cardiovascular Risk Index: Performance in Surgical Subpopulations and Comparison to the Revised Cardiac Risk Index. J Am Heart Assoc 2020; 9:e016228.

first-line therapy for status epilepticus

Q: Which of the following is considered first-line therapy for status epilepticus? (select one)

A) Clonazepam 

B) Lorazepam

C) Both clonazepam and lorazepam

Answer: C

Clonazepam is as good as lorazepam as first-line therapy for status epilepticus. In fact, there is weak evidence that clonazepam may be slightly superior. Unfortunately, Intravenous (IV) clonazepam is unavailable in the USA.

#neurology

References: 

1. Alvarez V, Lee JW, Drislane FW, et al. Practice variability and efficacy of clonazepam, lorazepam, and midazolam in status epilepticus: A multicenter comparison. Epilepsia 2015; 56:1275.

2. Shorvon S, Baulac M, Cross H, et al. The drug treatment of status epilepticus in Europe: consensus document from a workshop at the first London Colloquium on Status Epilepticus. Epilepsia 2008; 49:1277.

Interactions between warfarin and fluoroquinolones

Case: 34 years old female with history of recurrent DVT, now on chronic Coumadin therapy, presented with black tarry stool and probable GI bleed. There was no change in her usual coumadin dose of 5 mg/day, on which she had a therapeutic INR of 2.5 for the last 2 years. Today her INR is 7.8. One week ago, she had a bout of severe UTI (urinary tract infection) and was started on antibiotics by her primary care physician. Which antibiotic seems to be the probable culprit? 

 

Answer: Quinolone (Ciprofloxacin/levofloxacin) - Coumadin interaction 

 Coumadin-Quinolone is among the top ten drug-drug interactions. The exact mechanism for the warfarin-quinolone drug interaction is unknown. The reduction of intestinal flora responsible for vitamin K production by antibiotics is the most probable cause. Also, decreased metabolism and clearance of warfarin are described. Quinolone can notoriously increase the effects of warfarin, with potential for life-threatening bleeding. The best approach is to avoid quinolone in Coumadin-dependent patients, but if required, INR should be monitored daily during co-administration of warfarin with quinolone. 

 #pharmacology 

 Reference: 

 Carroll DN, Carroll DG. Interactions between warfarin and three commonly prescribed fluoroquinolones. Ann Pharmacother. 2008 May;42(5):680-5. doi: 10.1345/aph.1K605. Epub 2008 Apr 15. PMID: 18413687.

Hepatitis and HCC

Q: Which type of hepatitis can directly cause hepatocellular carcinoma (HCC) - without causing cirrhosis first? (select one)

A) Hepatitis A

B) Hepatitis B

C) Hepatitis C

Answer: B

Chronic hepatitis B is unique because it can directly cause HCC bypassing the cirrhosis stage. Although any underlying hepatic disease can cause HCC, patients with chronic hepatitis B & C, nonalcoholic steatohepatitis (NASH), and hemochromatosis are more prone to develop HCC.

As expected vaccine against Hepatitis B is found to have a protective effect against HCC. Other protective factors are statin, ASA, NSAIDs, metformin, coffee, and active lifestyle.

#hepatology

References:

1. Rizzo GEM, Cabibbo G, Craxì A. Hepatitis B Virus-Associated Hepatocellular Carcinoma. Viruses. 2022 May 7;14(5):986. doi: 10.3390/v14050986. PMID: 35632728; PMCID: PMC9146458.

2. Kanwal F, Khaderi S, Singal AG, Marrero JA, Loo N, Asrani SK, Amos CI, Thrift AP, Gu X, Luster M, Al-Sarraj A, Ning J, El-Serag HB. Risk factors for HCC in contemporary cohorts of patients with cirrhosis. Hepatology. 2022 Mar 1:10.1002/hep.32434. doi: 10.1002/hep.32434. Epub ahead of print. PMID: 35229329; PMCID: PMC9433461.

3. Bravi F, Tavani A, Bosetti C, et al. Coffee and the risk of hepatocellular carcinoma and chronic liver disease: a systematic review and meta-analysis of prospective studies. Eur J Cancer Prev 2017; 26:368.