Fecal microbiota transplantation for treatment of Clostridioides difficile infection

Q: Serial Fecal Microbiota Transplant (FMT) for treatment of Clostridioides difficile infection is more effective than a single administration.

A) True

B) False

Answer: A

At least two (or more)  sequential administrations of FMT are recommended to have optimum results for the treatment of Clostridioides difficile infection. FMT can be used with either fresh or frozen samples. With sequential FMT, the improvement of the symptoms can be up to 90 percent, though a single treatment may result in only 50 percent improvement.

One of the remarkable features of FMT in the treatment of Clostridioides difficile infection is its ability to maintain efficacy for many months or even a couple of years.

Said that FMT is not recommended for patients who have inflammatory bowel disease (IBD) and develop Clostridioides difficile infection. It may flare up the IBD.

#GI

#ID

References:

1. Lee CH, Steiner T, Petrof EO, et al. Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial. JAMA 2016; 315:142.

2. Mamo Y, Woodworth MH, Wang T, et al. Durability and Long-term Clinical Outcomes of Fecal Microbiota Transplant Treatment in Patients With Recurrent Clostridium difficile Infection. Clin Infect Dis 2018; 66:1705.

3. De Leon LM, Watson JB, Kelly CR. Transient flare of ulcerative colitis after fecal microbiota transplantation for recurrent Clostridium difficile infection. Clin Gastroenterol Hepatol 2013; 11:1036.

4. Fischer M, Kao D, Kelly C, et al. Fecal Microbiota Transplantation is Safe and Efficacious for Recurrent or Refractory Clostridium difficile Infection in Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis 2016; 22:2402.

Effects of giardiasis

Q: Effects of giardiasis may last for 10 years despite effective treatment.

A) True

B) false

Answer: A

Not fully explained but the follow up studies have demonstrated that symptoms and effect of giardiasis in previously infected individuals may last for a decade. The most common lingering symptoms are irritable bowel syndrome (IBS) and chronic fatigue. These patients report relatively a lower Quality of Life (QoL).

#GI

#ID

References:

1. Hanevik K, Wensaas KA, Rortveit G, et al. Irritable bowel syndrome and chronic fatigue 6 years after giardia infection: a controlled prospective cohort study. Clin Infect Dis 2014; 59:1394.

2. Litleskare S, Rortveit G, Eide GE, et al. Quality of life and its association with irritable bowel syndrome and fatigue ten years after giardiasis. Neurogastroenterol Motil 2019; 31:e13559.

3. Nakao JH, Collier SA, Gargano JW. Giardiasis and Subsequent Irritable Bowel Syndrome: A Longitudinal Cohort Study Using Health Insurance Data. J Infect Dis 2017; 215:798.

The Alice in Wonderland syndrome

Q: In which type of toxicity do patients develop "Alice in Wonderland-like" syndrome?

Answer: Anticholinergic intoxication 

Anticholinergic toxicity is common, particularly with over-the-counter and commonly prescribed medications such as antihistamines, tricyclic antidepressants, sleep aids (doxylamine), cold syrups, scopolamine patches, and mydriatic & cycloplegic eye drops.

The usual side effects are tachycardia, constipation, anxiety, agitation, dysarthria, confusion, disorientation, visual hallucinations, bizarre behavior, delirium, psychosis, paranoia, coma, and seizures.

A few famous terms described are

• "Red as a beet" (peripheral) due to cutaneous vasodilation 
• "Dry as a bone" as Sweat glands are innervated by muscarinic receptors
• "Hot as a hare" - hyperthermia is common
• "Blind as a bat" due to ineffective ocular accommodation
• "Mad as a hatter" - CNS symptoms as described above
• "Full as a flask"  due to urinary retention

Hallucinations are often described as "Alice in Wonderland-like" or "Lilliputian type," in which people appear to become larger and smaller to a patient. Patients may appear to grab invisible objects from the air.

#toxicity

References:

1. Lanska DJ, Lanska JR. The Alice-in-Wonderland Syndrome. Front Neurol Neurosci. 2018;42:142-150. doi: 10.1159/000475722. Epub 2017 Nov 17. PMID: 29151098.

2. Mantingh MR. Het 'Alice in Wonderland'-syndroom [The Alice in Wonderland syndrome]. Ned Tijdschr Geneeskd. 2014;158:A7225. Dutch. PMID: 24666533.

3. Broderick ED, Metheny H, Crosby B. Anticholinergic Toxicity. 2023 Apr 30. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 30521219.

EGPA diagnosis

Q: Which of the following is NOT  a part of the diagnostic criteria for eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss) per the American College of Rheumatology (ACR)? (select one)

A) Asthma 

B) Greater than 10 percent eosinophils on the differential leukocyte count

C) Migratory or transient pulmonary opacities detected radiographically

D) Paranasal sinus abnormality

E) Tender subcutaneous nodules on the extensor surfaces of the arm and legs

Answer: E

There are two well-known criteria for EGPA. The ACR and the Lanham criteria. Said that experts believe that in light of new advances and literature, there is a need to propose, modify or update new criteria.

The Lanham criteria was proposed in 1984, has three components and all three need to be met to establish the diagnosis of EGPA

• asthma
• peak peripheral blood eosinophilia over 1500 cells/microL, and 
• systemic vasculitis involving two or more extra-pulmonary organs

The ACR criteria was first proposed in 1990 and has six components. The presence of four or more of these criteria had a sensitivity of 85 percent and a specificity of 99.7 percent

• Asthma (a history of wheezing or the finding of diffuse high-pitched wheezes on expiration)
• Greater than 10 percent eosinophils on the differential leukocyte count
• Mononeuropathy (including multiplex) or polyneuropathy
• Migratory or transient pulmonary opacities detected radiographically
• Paranasal sinus abnormality
• Biopsy containing a blood vessel showing the accumulation of eosinophils in extravascular areas 

However, the tender subcutaneous nodules on the extensor surfaces of the arm, particularly the elbows, hands, and legs (choice E) are frequently found in these patients but are not a part of the criteria.

#rheumatology

References:

1. Lanham JG, Elkon KB, Pusey CD, Hughes GR. Systemic vasculitis with asthma and eosinophilia: a clinical approach to the Churg-Strauss syndrome. Medicine (Baltimore) 1984; 63:65.

2. Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990; 33:1094.

3. Cottin V, Bel E, Bottero P, et al. Revisiting the systemic vasculitis in eosinophilic granulomatosis with polyangiitis (Churg-Strauss): A study of 157 patients by the Groupe d'Etudes et de Recherche sur les Maladies Orphelines Pulmonaires and the European Respiratory Society Taskforce on eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Autoimmun Rev 2017; 16:1.

drug interaction

Case: A 62-year-old male with a past medical history of diabetes mellitus, hyperlipidemia, atrial fibrillation, hypertension, and mild renal insufficiency - presented to the ER with severe weakness, anuria, and renal failure. The patient reported extremely dark urine for a few days before presentation. The patient was discharged 5 weeks ago from the hospital with Aspirin, Coumadin, Lopressor, Amiodarone, and simvastatin. ED laboratory workup showed creatine kinase (CK) in the 80,000 U/L range. BUN 65 mg/dL, creatinine 4.6 mg/dL. Liver function tests (LFT) are also moderately elevated. Which drug interactions can be the reason for this life-threatening Rhabdomyolysis?

Answer: Simvastatin-Amiodarone Interaction

Simvastatin is metabolized primarily by CYP3A4, and amiodarone is a recognized inhibitor of this enzyme. This drug interaction may cause severe, life-threatening Rhabdomyolysis. The risk is higher in patients, particularly with simvastatin doses greater than 20 mg daily.

#pharmacology

References:

1. Marot A, Morelle J, Chouinard VA, Jadoul M, Lambert M, Demoulin N. Concomitant use of simvastatin and amiodarone resulting in severe rhabdomyolysis: a case report and review of the literature. Acta Clin Belg. 2011 Mar-Apr;66(2):134-6. doi: 10.2143/ACB.66.2.20625533. PMID: 21630612.

2. Ricaurte B, Guirguis A, Taylor HC, Zabriskie D. Simvastatin-amiodarone interaction resulting in rhabdomyolysis, azotemia, and possible hepatotoxicity. Ann Pharmacother. 2006 Apr;40(4):753-7. doi: 10.1345/aph.1G462. Epub 2006 Mar 14. PMID: 16537817.

3. Borders-Hemphill V. Concurrent use of statins and amiodarone. Consult Pharm. 2009 May;24(5):372-9. doi: 10.4140/tcp.n.2009.372. PMID: 19555146.

Pulmonary Artery Diastolic-Pulmonary Wedge Pressure Gradient

Q: What is the clinical significance of Pulmonary Artery Diastolic-Pulmonary Wedge Pressure Gradient (PADP - PAOP)?

Answer: Once the PADP - PAOP gradient starts to exceed 6 mm Hg or more, the patient has shown to have a much poorer prognosis, particularly in septic patients. The probable explanation is pulmonary venous vasoconstriction induced by endotoxemia in sepsis or postcapillary leukocyte aggregation in the development of ARDS.

At least one study suggests that although an initial PAD-PWP gradient in patients with sepsis is associated with high mortality, a much more sensitive indicator is to follow the trend. There was a 91% mortality in patients with persisting or increasing gradients.

#hemodynamic

References:

1. Pulmonary hypertension in sepsis: Measurement by the pulmonary arterial Diastolic-pulmonary wedge pressure gradient and the influence of passive and active factors. Chest 1978; 73:583-91

2. Significance of the pulmonary artery diastolic-pulmonary wedge pressure gradient in sepsis. Crit Care Med 1982; 10:658-61

3. Pulmonary artery diastolic and wedge pressure relationships in critically and injured patients. Arch Surg 1988; 123:933-6

4. Increased Pulmonary Venous Resistance Contributes to Increased Pulmonary Artery Diastolic-Pulmonary Wedge Pressure Gradient in Acute Respiratory Distress Syndrome - Anesthesiology: Volume 102(3) March 2005 pp 574-580 

Theophylline induced seizure

Q: Paramedics have been called at home by the family for a 32-year-old asthmatic patient who is suspected to have Theophylline toxicity. Para-medics intubated the patient and administrated repeated doses of Lorazepam in the ambulance. In the ER patient is still noted to have bouts of seizure. Keppra was administrated without any effect. What should be the next drug of choice in this probable Theophylline-induced seizure?

A) Phenytoin

B) Phosphenytoin

C) Carbamazepine

D) Phenobarbital

Answer: D

The objective of this question is to emphasize that Phenytoin is usually not effective in Theophylline-induced seizure. Lorazepam or Diazepam (benzodiazepines) are the first line of drugs. If the seizure continues, phenobarbital is indicated. One of the other advantages of Phenobarbital is that it enhances the hepatic metabolism of theophylline.

In case of phenobarbital failure, general anesthesia is indicated. Hemodialysis should be strongly considered along with treatment for the seizure.

#neurology

#toxicity

References:

1. Journey JD, Bentley TP. Theophylline Toxicity. [Updated 2023 Jun 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532962/

2. Gitomer JJ, Khan AM, Ferris ME. Treatment of severe theophylline toxicity with hemodialysis in a preterm neonate. Pediatr Nephrol. 2001 Oct;16(10):784-6. doi: 10.1007/s004670100650. PMID: 11605782.

HVPG

Q: Hepatic venous pressure gradient (HVPG) is calculated by subtracting hepatic vein pressure from? (select one)

A) Central venous pressure (CVP)

B) Right atrial (RA) pressure

C) Pulmonary Artery Occlusion Pressure (PAOP)

D) Inferior vena caval (IVC) pressure 

Answer: D

HVPG is a gradient of pressures between the portal vein and the inferior vena cava (IVC). 

Clinical significance: It is a reliable quantification of the degree of portal hypertension. Once it goes above 5 mmHg, the risk of portal hypertension progressively varies goes up - like once HVPG is ≥12 mmHg, the risk for variceal bleeding and the development of ascites is almost universal.

How to measure: WHVP is usually measured in an interventional radiology suite. A balloon-tipped catheter is introduced via the right jugular (R-IJ) vein under ultrasound (like a central line or swan-ganz catheter) and advanced through the right atrium into the IVC and the right hepatic vein. Fluoroscopic guidance is required. If R0IJ is not available, femoral or antecubital veins can be used. The catheter is maintained in the hepatic vein 2 to 4 cm from its takeoff from IVC. The hepatic vein is occluded by inflating the balloon. An operator may introduce a little contrast to confirm occlusion (no reflux) or wash-out.

In contrast to Pulmonary Artery Occlusion/wedge pressure, the pressure may take up to 60 seconds to record a reliable HVPG. Experts can simultaneously calculate free hepatic venous pressure (FHVP) and wedged hepatic venous pressure (WHVP). This further pressure management details pre-sinusoidal, sinusoidal, and post-sinusoidal sites of resistance to portal blood flow.

#procedures

#hepatology

References:

1. Berzigotti A, Seijo S, Reverter E, Bosch J. Assessing portal hypertension in liver diseases. Expert Rev Gastroenterol Hepatol 2013; 7:141.

2. Groszmann RJ, Wongcharatrawee S. The hepatic venous pressure gradient: anything worth doing should be done right. Hepatology 2004; 39:280.

3. Leung JC, Loong TC, Pang J, et al. Invasive and non-invasive assessment of portal hypertension. Hepatol Int 2018; 12:44.

MAID

Q: All of the following drugs are part of the protocol recommended by the American Clinicians Academy on Medical Aid in Dying (ACAMAID) for patients who qualify for Medical Aid in Dying (MAID), EXCEPT? (select one)

A) Diazepam 

B) Digoxin 

C) Morphine 

D) Amitriptyline

E) Succinylcholine 

Answer: E

MAID is a very restrictive legal process and is available in very few states in the United States. Once all the legal requirements are fulfilled, a patient can be eligible for help. American Clinicians Academy on Medical Aid in Dying (ACAMAID) recommends a combination of drugs abbreviated as DDMAPh.

• Diazepam 1 g
• Digoxin 100 mg
• Amitriptyline 8 g
• Morphine 15 g
• Phenobarbital 5 g

It may surprise many that the intravenous (IV) route in MAID is not part of the protocol. All medications must be sourced as powder, not crushed tablets. Crushing of tablets is discouraged as they may contain a large amount of filler material. Specific pharmacies provide a compounded powder. If powder can be administrated orally, the rectal route should be considered.

Said all of the above, only certified and legible physicians should take care of such patients - again - once all legal, moral, and ethical requirements are satisfied.

#palliative-care

References:

1. American Clinicians Academy on Medical Aid in Dying. Instructions for mixing aid-in-dying medications. https://www.acamaid.org/mixinginstructions/.

2. Data on Rectal Self-Administration of Aid-in-Dying Medications. American Clinicians Academy on Medical Aid in Dying. Available at: https://www.acamaid.org/rectaldata/ 

3. American Clinicians Academy on Medical Aid in Dying. Available at: https://www.acamaid.org/pharmacologyinfoupdates/ 

(Above sites last accessed on January 21, 2024).

Endophthalmitis

Q: What are the two types of Endophthalmitis?

Answer: Endophthalmitis as the name suggests means infection within the eye.

It is broadly divided into two types:

• Endogenous
• Exogenous 

Endogenous endophthalmitis occurs due to bacterial or fungal seeding of the eye via the bloodstream. This is because the choroid is highly vascular and is usually seeded first. Infection progresses from the "back of the eye to the front" (posterior to anterior.)

Exogenous endophthalmitis occurs when an infection gets introduced from the outside. The most common reasons are eye surgery, trauma, and extension of fungal infection of the cornea ("fungal keratitis" / "keratomycosis"). It is also called aqueous endophthalmitis, as many times the vitreous chamber is not involved. 

Though this distinction sounds simple but carries significance in management.

#ID

#opthalmology

References:

1. Vaziri K, Schwartz SG, Kishor K, Flynn HW Jr. Endophthalmitis: state of the art. Clin Ophthalmol. 2015 Jan 8;9:95-108. doi: 10.2147/OPTH.S76406. PMID: 25609911; PMCID: PMC4293922.

2. Lemley CA, Han DP. Endophthalmitis: a review of current evaluation and management. Retina. 2007 Jul-Aug;27(6):662-80. doi: 10.1097/IAE.0b013e3180323f96. Erratum in: Retina. 2007 Sep;27(7):table of contents. Dosage error in article text. PMID: 17621174.

3. Xie CA, Singh J, Tyagi M, Androudi S, Dave VP, Arora A, Gupta V, Agrawal R, Mi H, Sen A. Endogenous Endophthalmitis - A Major Review. Ocul Immunol Inflamm. 2023 Sep;31(7):1362-1385. doi: 10.1080/09273948.2022.2126863. Epub 2022 Oct 28. PMID: 36306406.

Metoprolol and Labetalol.

Q: What is the equivalency ratio of Metoprolol and Labetalol?

Answer: 1:2 

Metoprolol and Labetalol are the two most widely used B-blockers in ICUs. 50 mg of Metoprolol is equivalent to 100 mg of Labetalol.

Metoprolol is a selective beta-blocker. Labetalol is an alpha-1 and non-selective b1 blocker. Due to its alpha-1 blocking effect, it reduces the SVR without reducing total peripheral blood flow.

Beta-blockers are lipophilic and so have a tendency to diffuse into adipose tissues. This may lead to restricted tissue distribution in obese patients. Obese patients may require higher doses. 

Labetalol is unique in the sense that its oral and intravenous (IV) forms have different alpha and beta effects. the ratio of the beta-alpha blocker effect is

• 3:1 after oral 
• 7:1 after IV 

#pharmacology

#cardiology

References:

1. Frishman WH, Michelson EL, Johnson BF, Poland MP. Multiclinic comparison of labetalol to metoprolol in treatment of mild to moderate systemic hypertension. Am J Med. 1983 Oct 17;75(4A):54-67. doi: 10.1016/0002-9343(83)90137-7. PMID: 6356900.

2. https://www.drugs.com/compare/labetalol-vs-metoprolol (last accessed January 10, 2024)

3. MacCarthy EP, Bloomfield SS. Labetalol: a review of its pharmacology, pharmacokinetics, clinical uses and adverse effects. Pharmacotherapy. 1983 Jul-Aug;3(4):193-219. doi: 10.1002/j.1875-9114.1983.tb03252.x. PMID: 6310529.

WE and gender paradox

Q: Females are more prone to develop Wernicke encephalopathy (WE)?

A) True

B) False

Answer: A

It is interesting that though epidemiologically the ratio of men to women for WE is way higher, but if the ratio for alcohol dependence is taken into consideration the female-to-male ratio for WE is higher.

Although various reasons have been proposed for this paradox such as the female gender is more prone to anorexia nervosa, hyperemesis of pregnancy, or malnutrition worldwide - still it is not fully explained.

#neurology

References:

1. Victor M, Adams RA, Collins GH. The Wernicke-Korsakoff syndrome and related disorders due to alcoholism and malnutrition, FA Davis, Philadelphia 1989.

2. Harper C. The incidence of Wernicke's encephalopathy in Australia--a neuropathological study of 131 cases. J Neurol Neurosurg Psychiatry 1983; 46:593.

Mumps contagion source

Q: 28 years old internal medical intern while rotating ICU during January month developed 'Mumps' like symptoms. His newborn 12-week-old infant had similar symptoms about 2 weeks ago. He believes he may have contracted mumps from his newborn child. His suspicion must be right as the child has not received vaccination yet and the timeline fits the clinical scenario?

A) Yes

B) No

Answer: B

Mumps is very unlikely to develop in infants less than one year of age because they are protected via maternal antibodies. It is recommended that children get two doses of MMR vaccine, starting with the first dose at 12 through 15 months of age, and the second dose at 4 through 6 years of age.

Mumps typically occurs from the late winter to early spring, though outbreaks can occur any time of the year. Symptoms of Mumps are usually self-limited in an immunocompetent individual, although it is highly infectious. It is transmitted by respiratory droplets, direct contact, or fomites. It should be remembered that the highest rate of infectivity is present immediately preceding the onset of parotitis. Other usual symptoms are fever, headache, myalgia, fatigue, and anorexia.

#ID

#peds

References:

1. Hviid A, Rubin S, Mühlemann K. Mumps. Lancet 2008; 371:932.

2. Sato H, Albrecht P, Reynolds DW, Stagno S, Ennis FA. Transfer of measles, mumps, and rubella antibodies from mother to infant. Its effect on measles, mumps, and rubella immunization. Am J Dis Child. 1979 Dec;133(12):1240-3. doi: 10.1001/archpedi.1979.02130120032005. PMID: 229727.

3. Muthiah N, Galagoda G, Handunnetti S, Peiris S, Pathirana S. Dynamics of maternally transferred antibodies against measles, mumps, and rubella in infants in Sri Lanka. Int J Infect Dis. 2021 Jun;107:129-134. doi: 10.1016/j.ijid.2021.04.002. Epub 2021 Apr 22. PMID: 33895406.

GI stress ulcer in ICU

Q: Which of the gastrointestinal (GI) stress ulcers tend to bleed more in the ICU? (select one)

A) developed early on ICU admission

B) developed late in ICU course

Answer: B

The most common site for GI stress ulcerations in ICU is the fundus and body of the stomach, though they can develop in the antrum, duodenum, or distal esophagus. Most of the GI stress ulcerations developed in the ICU are shallow and may ooze from the superficial capillary beds. Though under-appreciated, ulcerations develop within hours of major trauma or severe sickness. Early ulcerations are usually gastric.

Stress ulcerations that develop late after a few days of ICU admission tend to be deeper and intestinal in the antrum and duodenum.

Various mechanisms lead to these ulcerations. Hypovolemia, shock, sepsis, or trauma leads to poor gut perfusion. There may be an excessive gastrin stimulation of parietal cells in patients with head trauma. Also, there may be an increased concentration of refluxed bile salts or uremic toxins, which may disturb the barrier of the glycoprotein mucous layer in the stomach.

#GI

References:

1. Stollman N, Metz DC. Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients. J Crit Care. 2005 Mar;20(1):35-45. doi: 10.1016/j.jcrc.2004.10.003. PMID: 16015515.

2. Buendgens L, Koch A, Tacke F. Prevention of stress-related ulcer bleeding at the intensive care unit: Risks and benefits of stress ulcer prophylaxis. World J Crit Care Med. 2016 Feb 4;5(1):57-64. doi: 10.5492/wjccm.v5.i1.57. PMID: 26855894; PMCID: PMC4733456.

3. Reynolds PM, MacLaren R. Re-evaluating the Utility of Stress Ulcer Prophylaxis in the Critically Ill Patient: A Clinical Scenario-Based Meta-Analysis. Pharmacotherapy. 2019 Mar;39(3):408-420. doi: 10.1002/phar.2172. Epub 2018 Sep 6. PMID: 30101529.

ketamine and suicidal ideation

Q: 32 years old male with severe depression is admitted to ICU with active suicidal ideation. A family member suggested Ketamine, as he read an advertisement on the Ketamine infusion clinic as a "feel good" substance. You should tell the family member that this is a bad idea. Ketamine increases the risk of suicidal ideation and should never be used in these patients.

A) True 

B) False

Answer: B

Interestingly, studies have suggested that a single infusion of ketamine may mitigate suicidal ideation within an hour. Moreover, this effect may last up to seven days.

Similarly, related compound esketamine can be given intranasally, which may be a preferred route when a patient is resistant to provide an intravenous line, though the evidence is not as robust as for ketamine infusion.

Said that, another objective of this question is to identify the evil of this 'feel good' effect. Lately, there has been a mushrooming of ketamine infusion clinics in many urban areas of the USA. These centers may not have proper oversight to deal with side effects or any untoward incidents with such infusions in outpatient settings.

#pharmacology

#psychiatry

References:

1. Abbar M, Demattei C, El-Hage W, Llorca PM, Samalin L, Demaricourt P, Gaillard R, Courtet P, Vaiva G, Gorwood P, Fabbro P, Jollant F. Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial. BMJ. 2022 Feb 2;376:e067194. doi: 10.1136/bmj-2021-067194. PMID: 35110300; PMCID: PMC8808464.

2. Kishimoto T, Chawla JM, Hagi K, et al. Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. Psychol Med 2016; 46:1459.

3. Hochschild A, Grunebaum MF, Mann JJ. The rapid anti-suicidal ideation effect of ketamine: A systematic review. Prev Med. 2021 Nov;152(Pt 1):106524. doi: 10.1016/j.ypmed.2021.106524. Epub 2021 Sep 16. PMID: 34538369.

Pox, orthopox viruses and general symptoms

Q: Systemic symptoms are more common in? (select one)

A) poxvirus (Molluscum contagiosum virus-MCV) 

B) monkeypox (orthopox virus)

Answer: B

There has been a renewed interest in pox and orthopox viruses since the outbreak in mid-2022. Clinical exams and knowing the characteristic dermal appearances play an important role in differentiating different pox and orthopox viruses. 

Molluscum contagiosum generally causes "hard bumps," whereas monkeypox lesions are usually pus-filled. But frequently, it is hard to differentiate monkey pox from molluscum contagiosum just based on dermal appearance but systemic symptoms like fever, chills, and myalgias are more frequently present in monkeypox infection.

Other dermal appearances that require differential diagnoses are warts, condyloma acuminatum, condylomata lata, pyogenic granuloma, adnexal tumors, Langerhans cell histiocytosis, basal cell carcinoma, and amelanotic melanoma. A skin biopsy may be required to establish these clinical conditions.

Also, dermal lesions due to cryptococcosis, histoplasmosis, and Talaromyces marneffei infections may resemble molluscum lesions, particularly in immunosuppressed patients. 

#ID

#dermatology

References:

1. Hussain A, Kaler J, Lau G, Maxwell T. Clinical Conundrums: Differentiating Monkeypox From Similarly Presenting Infections. Cureus. 2022 Oct 4;14(10):e29929. doi: 10.7759/cureus.29929. PMID: 36348880; PMCID: PMC9634140.

2. De Clercq E, Jiang Y, Li G. Therapeutic strategies for human poxvirus infections: Monkeypox (mpox), smallpox, molluscipox, and orf. Travel Med Infect Dis. 2023 Mar-Apr;52:102528. doi: 10.1016/j.tmaid.2022.102528. Epub 2022 Dec 17. PMID: 36539022; PMCID: PMC9758798.

autonomic dysfunction in Guillain-Barré syndrome

Q: Which autonomic dysfunction is more common in Guillain-Barré syndrome(GBS)? (select one)

A) Ileus 

B) Urinary retention

Answer: A

Dysautonomia is present in most of the patients with GBS. Ileus is present in almost half of the patients, whereas urinary retention is present in about one out of four patients. Other autonomic dysfunctions may be present with various frequencies, such as hypertension and hypotension, tachycardia and bradycardia, and fever. Patients with dysautonomia have higher mortality, including sudden death.

Hyponatremia can also be found in lab findings due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH), occurring secondary to autonomic involvement.

#neurology

References:

1. Flachenecker P. Autonomic dysfunction in Guillain-Barré syndrome and multiple sclerosis. J Neurol 2007; 254 Suppl 2:II96.

2. Chakraborty T, Kramer CL, Wijdicks EFM, Rabinstein AA. Dysautonomia in Guillain-Barré Syndrome: Prevalence, Clinical Spectrum, and Outcomes. Neurocrit Care 2020; 32:113.

3. Anandan C, Khuder SA, Koffman BM. Prevalence of autonomic dysfunction in hospitalized patients with Guillain-Barré syndrome. Muscle Nerve 2017; 56:331.

Brain abscess

Q: 30 years old male is brought to the Emergency Department (ED) with headache, fever, an episode of seizure at home, and focal deficit in the Right upper extremity. A STAT scan of the head showed a probable brain abscess. Per family, the patient was on a road trip in Latin America and returned from vacation two weeks ago. Lumbar Puncture (LP) is indicated.

A) Yes

B) No

Answer: B

Though seems surprising, LP has no role in patients with suspicion of brain abscess. In fact, it can cause brainstem herniation if the abscess is large and already causing a mass effect. Also, cerebrospinal fluid (CSF) is usually not very helpful. 

Further neurological imaging such as MRI, brain biopsy, and abscess drainage is indicated.

#procedures

#neurology

#ID

References:

1. Nadvi SS, Nathoo N, van Dellen JR. Lumbar puncture is dangerous in patients with brain abscess or subdural empyema. S Afr Med J. 2000 Jun;90(6):609-10. PMID: 10918891.

2. Sonneville R, Ruimy R, Benzonana N, Riffaud L, Carsin A, Tadié JM, Piau C, Revest M, Tattevin P; ESCMID Study Group for Infectious Diseases of the Brain (ESGIB). An update on bacterial brain abscess in immunocompetent patients. Clin Microbiol Infect. 2017 Sep;23(9):614-620. doi: 10.1016/j.cmi.2017.05.004. Epub 2017 May 10. PMID: 28501669.

A note on "Rebound" COVID-19 after nirmatrelvir-ritonavir treatment

Patients who have been treated with nirmatrelvir-ritonavir are more prone to develop "Rebound" COVID-19 symptoms within 10 days to a few weeks. This calls for close clinical judgment for clinicians to decide which patients should be treated with nirmatrelvir-ritonavir. It would be prudent to prescribe nirmatrelvir-ritonavir to patients who are highly symptomatic or at high risk for deterioration. It should not be prescribed just to decrease the duration of mild symptoms or viral shedding.

The "Rebound" phenomenon correlates with repeat higher antigen positivity, and the peak viral levels can be higher with a rebound. Irrespective of vaccination status, it can occur in both vaccinated and unvaccinated patients. Recurrent symptoms are generally mild, but severe complications may occur. A case of acute pulmonary emboli has been reported following the rebound phenomenon after Nirmatrelvir/Ritonavir treatment for COVID-19.

Patients experiencing rebound should be isolated.

#ID

#COVID

References:

1. Ranganath N, O'Horo JC, Challener DW, et al. Rebound Phenomenon After Nirmatrelvir/Ritonavir Treatment of Coronavirus Disease 2019 (COVID-19) in High-Risk Persons. Clin Infect Dis 2023; 76:e537.

2. Anderson AS, Caubel P, Rusnak JM, EPIC-HR Trial Investigators. Nirmatrelvir-Ritonavir and Viral Load Rebound in Covid-19. N Engl J Med 2022; 387:1047.

3. Wong GL, Yip TC, Lai MS, et al. Incidence of Viral Rebound After Treatment With Nirmatrelvir-Ritonavir and Molnupiravir. JAMA Netw Open 2022; 5:e2245086.

4. Pandit JA, Radin JM, Chiang DC, et al. The Coronavirus Disease 2019 Rebound Study: A Prospective Cohort Study to Evaluate Viral and Symptom Rebound Differences in Participants Treated With Nirmatrelvir Plus Ritonavir Versus Untreated Controls. Clin Infect Dis 2023; 77:25.

5. Birabaharan M, Martin TCS. Acute pulmonary emboli following rebound phenomenon after Nirmatrelvir/Ritonavir treatment for COVID-19. Am J Emerg Med 2022; 61:235.e5.

treatment-resistant schizophrenia

Q: 34 years old male with an established diagnosis of schizophrenia is admitted to ICU with exacerbation of his symptoms. Patient's meds have been recently changed by his outpatient physician due to probable treatment-resistant schizophrenia. Spouse reports that lately, the patient has increased his smoking habit due to stress at work. Which medicine probably has been prescribed? (select one)

A) Carbamazepine 

B) Amisulpride

C) Paliperidone

D) Clozapine 

E) Risperidone

Answer: D

This question aims to cover two objectives. 

First, The drug of choice for treatment-resistant schizophrenia is clozapine. This is the only drug approved so far by the FDA for this indication.

Second: Tobacco smoking decreases the level/effect of olanzapine due to stimulation of cytochrome P450 1A2 enzyme that is involved in the antipsychotics’ metabolism.

Carbamazepine (choice A) is not used for treatment-resistant schizophrenia, though it has the potential to reduce the levels of all antipsychotics.

Amisulpride is excreted by the kidney (choice B), and levels can be affected in patients with renal insufficiency.

Paliperidone (choice C) does not undergo first-pass metabolism, and levels are usually unaffected.

Risperidone (choice E) is metabolized by the cytochrome P450 2D6 enzyme. Its level can be elevated by co-treatment with fluoxetine and paroxetine, which are metabolized by the same enzyme system.

#psychiatry

#pharmacology

References:

1. Potkin SG, Kane JM, Correll CU, Lindenmayer JP, Agid O, Marder SR, Olfson M, Howes OD. The neurobiology of treatment-resistant schizophrenia: paths to antipsychotic resistance and a roadmap for future research. NPJ Schizophr. 2020 Jan 7;6(1):1. doi: 10.1038/s41537-019-0090-z. PMID: 31911624; PMCID: PMC6946650.

2. Kane JM, Agid O, Baldwin ML, Howes O, Lindenmayer JP, Marder S, Olfson M, Potkin SG, Correll CU. Clinical Guidance on the Identification and Management of Treatment-Resistant Schizophrenia. J Clin Psychiatry. 2019 Mar 5;80(2):18com12123. doi: 10.4088/JCP.18com12123. PMID: 30840788.

3. Ying J, Chew QH, McIntyre RS, Sim K. Treatment-Resistant Schizophrenia, Clozapine Resistance, Genetic Associations, and Implications for Precision Psychiatry: A Scoping Review. Genes (Basel). 2023 Mar 10;14(3):689. doi: 10.3390/genes14030689. PMID: 36980961; PMCID: PMC10048540.

Electrolyte abnormality, Neostigmine and Oglivie's syndrome

Q: Which electrolyte abnormality may prevent Neostigmine from resolving Ogilvie's syndrome?

Answer; Potassium

Acute colonic pseudo-obstruction or Ogilvie syndrome, is an acute large bowel obstruction with no evidence of mechanical colonic obstruction. It is said to be due to invasion and destruction of the splanchnic nerves, superior mesenteric ganglion, and celiac nerve plexus.

Neostigmine, an acetylcholinesterase inhibitor, increases acetylcholine concentrations at the enteric nervous system neuromuscular junctions, enabling smooth muscle to contract. Neostigmine is given as intravenous, 2 mg over 5 minutes. A repeat dosage may be given if necessary. Side effects of neostigmine include sweating, salivation, bradycardia, hypotension, and bronchospasm. Due to possible bradycardia, atropine should be available at the bedside. The neostigmine is eliminated by the kidney and should be used with caution in renal failure.

Reports indicate that patients with hypokalemia, may not respond to neostigmine. 

#GI

#electrolytes

References:

1. Dolkar T, Adhikari S, Devi P, Nwani SO, Dogar M. Persistent Hypokalemia in a Patient With Ogilvie's Syndrome. Cureus. 2022 Nov 30;14(11):e32056. doi: 10.7759/cureus.32056. PMID: 36600873; PMCID: PMC9802540.

2. van Dinter TG Jr, Fuerst FC, Richardson CT, et al. Stimulated active potassium secretion in a patient with colonic pseudo-obstruction: a new mechanism of secretory diarrhea. Gastroenterology 2005; 129:1268.

3. Bazerbachi F, Haffar S, Szarka LA, et al. Secretory diarrhea and hypokalemia associated with colonic pseudo-obstruction: A case study and systematic analysis of the literature. Neurogastroenterol Motil 2017; 29.

Protamine induced Pulmonary Vasoconstriction

Case: 48 years old male with coronary artery disease has been taken for an elective heart-bypass surgery. In the end, protamine reversal was instituted. After a few minutes of protamine infusion, the PAP (pulmonary artery pressure) suddenly increased to 90/40 mm Hg. The protamine was discontinued. PAP was noted to return to normal. The protamine was restarted but the PAP again rapidly increased to 85/37 mm Hg, and the patient became hypotensive. 

Answer: Protamine-induced acute pulmonary hypertension.

Mechanism of action: Complement activation, leading to thromboxane A2 generation causing acute pulmonary hypertension.

Treatment is the application of inhaled Nitric Oxide and hemodynamic support as required. Interestingly, Protamine can be restarted if needed to complete surgery under the protection of inhaled NO! By using iNO, a full reversal dose of protamine can be successfully administered to a patient. Nitric Oxide can be weaned in the next 24 hours after surgery.

Alternatives to protamine for heparin reversal, such as heparinase or recombinant platelet factor 4 can be applied but are usually unavailable.

#cardiovascular

#pulmonary

#pharmacology

References: 

1. Ralley FE. The use of nitric oxide for managing catastrophic pulmonary vasoconstriction arising from protamine administration. Anesth Analg. 1999 Mar;88(3):505-7. doi: 10.1097/00000539-199903000-00007. PMID: 10071995.

2. Lowenstein E. Lessons from studying an infrequent event: adverse hemodynamic response associated with protamine reversal of heparin anticoagulation. J Cardiothorac Anesth. 1989 Feb;3(1):99-107. doi: 10.1016/0888-6296(89)90019-7. PMID: 2520647.

3. 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.

‘Rule of 20s’ in cardiac tamponade

Q: What is the ‘Rule of 20s’ in cardiac tamponade?

Answer: Although nothing is hard and fast in clinical medicine, if the following five 20s are present on clinical exam, it speaks of cardiac tamponade proved otherwise.

• CVP more than 20 cm H2O
• HR increases more than 20 beats/minute
• Pulsus paradoxes more than 20
• SBP decreased by more than 20 mmHg and
• Pulse pressure less than 20

Some students/intensivists may also like another 'rule of 20s' related to Pulmonary Artery Catheter insertion.

• Right atrium (or SVC) should be entered within 20 cm of the skin
• Right ventricle should be entered within 40 cm of the skin
• Pulmonary artery should be entered within 60 cm of the skin

#procedures

#cardiology

Further reading:

1. Ariyarajah V, Spodick DH. Cardiac tamponade revisited: a postmortem look at a cautionary case. Tex Heart Inst J. 2007;34(3):347-51. PMID: 17948086; PMCID: PMC1995065.

2. Curtiss EI, Reddy PS, Uretsky BF, Cecchetti AA. Pulsus paradoxus: definition and relation to the severity of cardiac tamponade. Am Heart J. 1988 Feb;115(2):391-8. doi: 10.1016/0002-8703(88)90487-5. PMID: 3341174.

IBD and smoking

Q: 34 years old male with an established diagnosis of ulcerative colitis is advised by his primary care physician to stop smoking. His ulcerative colitis may get? (select one)

A) better

B) worse

Answer: B

It may be a surprise to some that nicotine has a protective effect on the symptoms of ulcerative colitis. Unfortunately, patients with ulcerative colitis who also smoke, if quit smoking may get exacerbation of ulcerative colitis. Moreover, it may also be more challenging to treat. Symptoms may get better or resolve with the resumption of cigarette smoking. These patients are at a rock and a hard place.

Clinicians haven't yet resolved the mystery of why similar inflammatory bowel disease (IBD), i.e., Crohn's disease, may get exacerbated with smoking? Smoking increases the risk of strictures and fistulas in Crohn's disease.

#GI

#tobacco

References:

1. Mahid SS, Minor KS, Soto RE, et al. Smoking and inflammatory bowel disease: a meta-analysis. Mayo Clin Proc 2006; 81:1462.

2. Cosnes J, Beaugerie L, Carbonnel F, Gendre JP. Smoking cessation and the course of Crohn's disease: an intervention study. Gastroenterology 2001; 120:1093.

3. Boyko EJ, Perera DR, Koepsell TD, et al. Effects of cigarette smoking on the clinical course of ulcerative colitis. Scand J Gastroenterol 1988; 23:1147.

4. Beaugerie L, Massot N, Carbonnel F, et al. Impact of cessation of smoking on the course of ulcerative colitis. Am J Gastroenterol 2001; 96:2113.

SVR

Q: Systemic Vascular Résistance (SVR) is primarily governed by all of the following EXCEPT? (select one)

A) Extravascular edema

B) Vessel length

C) Blood viscosity

D) Vessel diameter

E) Vessel tone

Answer: A

The formula to understand hemodynamics is relatively simple. The three significant determinants are:

• systemic blood pressure (BP)
• cardiac output (CO), and 
• systemic vascular resistance (SVR)

The simple formula is: BP = CO X SVR

Where CO = HR X SV

HR = Heart rate

SV = Stroke Volume

The stroke volume depends on the following:

• Preload
• Myocardial contractility
• Afterload

SVR is governed by:

• Vessel length
• Blood viscosity
• Vessel diameter and tone 

Alteration in any of the above may cause hemodynamic instability or may be a reactive process to an insult in a body.

Extravascular edema (choice A) has no primary role in determining SVR.

#hemodynamics

References:

1. Secomb TW. Hemodynamics. Compr Physiol. 2016 Mar 15;6(2):975-1003. doi: 10.1002/cphy.c150038. PMID: 27065172; PMCID: PMC4958049.

2. De Hert S. Physiology of hemodynamic homeostasis. Best Pract Res Clin Anaesthesiol. 2012 Dec;26(4):409-19. doi: 10.1016/j.bpa.2012.10.004. PMID: 23351228.

3. Chawla LS, Ince C, Chappell D, Gan TJ, Kellum JA, Mythen M, Shaw AD; ADQI XII Fluids Workgroup. Vascular content, tone, integrity, and haemodynamics for guiding fluid therapy: a conceptual approach. Br J Anaesth. 2014 Nov;113(5):748-55. doi: 10.1093/bja/aeu298. Epub 2014 Sep 17. PMID: 25231767.

Insulinoma

Q: In insulinoma, hypoglycemia is primarily due to? (select one)

A) increased glucose utilization

B) reduced hepatic glucose output

Answer: B

There is a common misconception that as insulinoma causes high insulin output, symptoms occur due to increased glucose utilization. In reality, this is due to reduced hepatic glucose output. The fasting state tends to pronounce symptoms more intense, though a large number of patients report postprandial hypoglycemia. Symptoms are usually subtle and may go undiagnosed. One out of five patients get mislabeled as having a neurologic or psychiatric disorder. Some may even develop seizures.

Once a clinician suspects insulinoma, the meticulous application of the 'art' of differential diagnosis helps establish the diagnosis coupled with invasive and non-invasive testing. Treatment is usually surgical.

One exciting test worth mentioning regarding the question above is selective arterial calcium stimulation (SACT). The test is based on the belief that calcium stimulates insulin release from hyperfunctional beta cells but not the normal beta cells. Calcium stimulates insulin release in the same arterial territory as the abnormal beta cells, which helps localize the operative boundaries. The test is carried out by selective injection of calcium gluconate into the gastroduodenal, splenic, and superior mesenteric arteries with subsequent sampling of the hepatic venous effluent for insulin. This test also helps in differentiating between insulinoma and nesidioblastosis.

#endocrinology

References:

1. Rizza RA, Haymond MW, Verdonk CA, et al. Pathogenesis of hypoglycemia in insulinoma patients: suppression of hepatic glucose production by insulin. Diabetes 1981; 30:377.

2. Dizon AM, Kowalyk S, Hoogwerf BJ. Neuroglycopenic and other symptoms in patients with insulinomas. Am J Med 1999; 106:307.

3. Doppman JL, Miller DL, Chang R, et al. Insulinomas: localization with selective intraarterial injection of calcium. Radiology 1991; 178:237.

4. Okabayashi T, Shima Y, Sumiyoshi T, Kozuki A, Ito S, Ogawa Y, Kobayashi M, Hanazaki K. Diagnosis and management of insulinoma. World J Gastroenterol. 2013 Feb 14;19(6):829-37. doi: 10.3748/wjg.v19.i6.829. PMID: 23430217; PMCID: PMC3574879.

Drawing K

Q: The potassium level is more reliable via? (select one)

A) arterial line 

B) venous puncture

Answer: B

Potassium levels via arterial line may not be as reliable as through peripheral venous puncture. It is postulated that the tip of the cannula could get impinged against the vessel wall so that during withdrawal of the sample, a high shear rate may cause hemolysis of red blood cells leading to an increased potassium concentration in drawn blood samples.

#electrolytes

#lab-medicine

References:

1. Mehta V, Ahmed Z. Apparent hyperkalaemia from blood sampled from an arterial cannula. Br J Anaesth. 2004 Sep;93(3):456-8. doi: 10.1093/bja/aeh199. Epub 2004 Jun 11. PMID: 15194630.

2. Asirvatham JR, Moses V, Bjornson L. Errors in potassium measurement: a laboratory perspective for the clinician. N Am J Med Sci. 2013 Apr;5(4):255-9. doi: 10.4103/1947-2714.110426. PMID: 23724399; PMCID: PMC3662091.

prevalence of bicuspid aortic valves

Q: The bicuspid aortic valve is more common in males.

A) True
B) False



Answer: A

The bicuspid aortic valve is common in about 1 percent of the population. The male-to-female ratio has been described as 2 to 3:1. The Copenhagen Baby Heart Study which screened more than 25,0000 babies found the prevalence of bicuspid aortic valve found it in 0.8 percent of the babies with a 2:1 male-to-female ratio.

Said that few subsets of patients may have a higher prevalence of bicuspid aortic valves like in coarctation of the aorta 30 to 50 percent of patients may have it, and in females with Turner syndrome, it can be up to 30 percent.


#cardiology
#epidemiology




References:


1. Braverman AC, Cheng A. The bicuspid aortic valve and associated aortic disease. In: Valvular Heart Disease, 5th ed, Otto CM, Bonow RO (Eds), Saunders/Elsevier 2021. p. 197.


2. Sillesen AS, Vøgg O, Pihl C, et al. Prevalence of Bicuspid Aortic Valve and Associated Aortopathy in Newborns in Copenhagen, Denmark. JAMA 2021; 325:561.