Contributor: Geoff Hogan MD

Educational Pearls:

• Penicillin allergies are relatively uncommon despite their frequent reports

• • 10% of the population reports a penicillin allergy but only 5% of these cases are clinically significant

  • 90-95% of patients may tolerate a rechallenge after appropriate allergy evaluation

• Penicillin Allergy Decision Rule (PEN-FAST) on MD Calc

• • Useful tool to assess patients for penicillin allergies

  • Five years or less since reaction = 2 points (even if unknown)

  • Anaphylaxis or angioedema OR Severe cutaneous reaction = 2 points

  • Treatment required for reaction (e.g. epinephrine) = 1 point (even if unknown)

• A score of 0 on PEN-FAST indicates a less than 1% risk of a positive penicillin allergy test

• • A score of 1 or 2 indicates a 5% risk of a positive penicillin allergy test

• A low score on PEN-FAST should prompt clinicians to proceed with the best empiric antibiotic for the patient’s infection

References

1. Broyles AD, Banerji A, Barmettler S, et al. Practical Guidance for the Evaluation and Management of Drug Hypersensitivity: Specific Drugs [published correction appears in J Allergy Clin Immunol Pract. 2021 Jan;9(1):603. doi: 10.1016/j.jaip.2020.10.025.] [published correction appears in J Allergy Clin Immunol Pract. 2021 Jan;9(1):605. doi: 10.1016/j.jaip.2020.11.036.]. J Allergy Clin Immunol Pract. 2020;8(9S):S16-S116. doi:10.1016/j.jaip.2020.08.006

2. Piotin A, Godet J, Trubiano JA, et al. Predictive factors of amoxicillin immediate hypersensitivity and validation of PEN-FAST clinical decision rule [published correction appears in Ann Allergy Asthma Immunol. 2022 Jun;128(6):740. doi: 10.1016/j.anai.2022.04.005.]. Ann Allergy Asthma Immunol. 2022;128(1):27-32. doi:10.1016/j.anai.2021.07.005

3. Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and Management of Penicillin Allergy: A Review. JAMA. 2019;321(2):188-199. doi:10.1001/jama.2018.19283

4. Trubiano JA, Vogrin S, Chua KYL, et al. Development and Validation of a Penicillin Allergy Clinical Decision Rule. JAMA Intern Med. 2020;180(5):745-752. doi:10.1001/jamainternmed.2020.0403

Summarized & edited by Jorge Chalit, OMS3

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Contributor: Travis Barlock, MD

Educational Pearls:

• Key clinical considerations when managing heart transplant patients due to their unique pathophysiology

• 1. Arrhythmias

• • A transplanted heart is denervated, meaning it lacks autonomic nervous system innervation

  • • The lack of vagal tone results in an increased resting heart rate

    • Adenosine can be used since it primarily slows conduction through the AV node

    • Atropine is ineffective in treating transplant bradyarrhythmia because its mechanism is to inhibit the vagus nerve - but the heart lacks vagal tone

  • Allograft rejection can also cause tachycardia

  • • Consult transplant surgery - treatment is usually 500 mg methylprednisolone

• 2. Rejection

• • Transplant patients are administered immunosuppressants

  • Clinical presentation of acute rejection looks similar to heart failure with increased BNP, increased troponin, and pulmonary edema

  • Cardiac allograft vasculopathy is a form of chronic rejection

  • Patients will not report chest pain due to denervated heart

  • • Symptoms are usually weakness and fatigue

• 3. High risk of infection due to immunosuppression

• • Increased risk of infections which includes CMV, legionella, tuberculosis, etc

  • Immunosuppressants have side effects such as acute kidney injury or pancytopenia

• 4. Radiographic Cardiomegaly

• • A study found that radiographic cardiomegaly does not connote heart failure

  • They hypothesized it is instead the result of a mismatch between the size of the transplanted heart and the space in the thoracic cavity

References

1. Murphy JD, Mergo PJ, Taylor HM, Fields R, Mills RM Jr. Significance of radiographic cardiomegaly in orthotopic heart transplant recipients. AJR Am J Roentgenol. 1998 Aug;171(2):371-4. doi: 10.2214/ajr.171.2.9694454. PMID: 9694454.

2. Park MH, Starling RC, Ratliff NB, McCarthy PM, Smedira NS, Pelegrin D, Young JB. Oral steroid pulse without taper for the treatment of asymptomatic moderate cardiac allograft rejection. J Heart Lung Transplant. 1999 Dec;18(12):1224-7. doi: 10.1016/s1053-2498(99)00098-4. PMID: 10612382.

3. Pethig K, Heublein B, Wahlers T, Dannenberg O, Oppelt P, Haverich A. Mycophenolate mofetil for secondary prevention of cardiac allograft vasculopathy: influence on inflammation and progression of intimal hyperplasia. J Heart Lung Transplant. 2004 Jan;23(1):61-6. doi: 10.1016/s1053-2498(03)00097-4. PMID: 14734128.

Summarized by Meg Joyce, MS1 | Edited by Meg Joyce & Jorge Chalit, OMS3

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Contributor: Taylor Lynch, MD

Educational Pearls:

• Pediatric febrile seizures are defined as seizures that occur between the ages of six months to five years in the presence of a fever greater than or equal to 38.0 ºC (100.4 ºF). It is the most common pediatric convulsive disorder, with an incidence between 2-5%

• What are the types of seizures?

• • Simple: Tonic-clonic seizure, duration <15 minutes, only one occurrence in a 24-hour period, ABSENCE of focal features, ABSENCE of Todd’s paralysis

  • Complex: Duration >15 minutes, requires medication to stop the seizing, multiple occurrences in a 24-hour period, PRESENCE of focal features, PRESENCE of Todd’s paralysis

• What are the causes?

• • Caused by infectious agents leading to fever. Seen with common childhood infections.

  • It is debated whether the absolute temperature of the fever or the rate of change of temperature incites the seizure, but current evidence points to the rate of change of the temperature being the primary catalyst

• What are the treatment considerations?

• • For simple febrile seizures, work-up is similar to any pediatric patient presenting with a fever between the ages of six months and five years

  • Thorough physical exam to rule out any potential of meningeal or intracranial infections

  • Prophylactic antipyretics are not believed to prevent the occurrence of febrile seizures

• Disposition?

• • If the patient has returned to normal baseline behavior following a simple febrile seizure, and the physical exam is reassuring, the patient can be discharged home.

  • Additional labs, electroencephalogram, or lumbar punctures are not indicated in simple febrile seizures as long as the physical exam is completely normal

  • Any evidence of a complex seizure requires further workup

• Fast Facts:

• • Patients with a familial history of febrile seizures and developmental delays have a higher risk of developing febrile seizures

  • If a child has one febrile seizure, there is a 30-40% chance of another febrile seizure by age 5

  • Only 2-7% of children with febrile seizures go on to develop epilepsy

References:

1. Berg AT, Shinnar S, Hauser WA, Alemany M, Shapiro ED, Salomon ME, et al. A prospective study of recurrent febrile seizures. N Engl J Med. 1992 Oct 15;327(16):1122–7.

2. Schuchmann S, Vanhatalo S, Kaila K. Neurobiological and physiological mechanisms of fever-related epileptiform syndromes. Brain Dev. 2009 May;31(5):378–82.

3. Nilsson G, Westerlund J, Fernell E, Billstedt E, Miniscalco C, Arvidsson T, et al. Neurodevelopmental problems should be considered in children with febrile seizures. Acta Paediatr. 2019 Aug;108(8):1507–14.

4. Subcommittee on Febrile Seizures, American Academy of Pediatrics. Neurodiagnostic evaluation of the child with a simple febrile seizure. Pediatrics. 2011 Feb;127(2):389–94.

5. Pavlidou E, Panteliadis C. Prognostic factors for subsequent epilepsy in children with febrile seizures. Epilepsia. 2013 Dec;54(12):2101–7.

6. Huang CC, Wang ST, Chang YC, Huang MC, Chi YC, Tsai JJ. Risk factors for a first febrile convulsion in children: a population study in southern Taiwan. Epilepsia. 1999 Jun;40(6):719–25.

7. Hashimoto R, Suto M, Tsuji M, Sasaki H, Takehara K, Ishiguro A, et al. Use of antipyretics for preventing febrile seizure recurrence in children: a systematic review and meta-analysis. Eur J Pediatr. 2021 Apr;180(4):987–97.

Summarized by Dan Orbidan, OMS1 | Edited by Dan Orbidan & Jorge Chalit, OMS3

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Contributor: Aaron Lessen, MD

Educational Pearls:

• Point-of-care ultrasound (POCUS) is used to assess cardiac activity during cardiac arrest and can identify potential reversible causes such as pericardial tamponade

• Ultrasound could be beneficial in another way during cardiac arrest as well: pulse checks

• • Manual palpation for detecting pulses is imperfect, with false positives and negatives

  • Doppler ultrasound can be used as an adjunct or replacement to manual palpation for improved accuracy

• Options for Doppler ultrasound of carotid or femoral pulses during cardiac arrest:

• • Visualize arterial pulsation

  • Use color doppler

  • Numerically quantify the flow and correlate this to a BP reading - slightly more complex

• Doppler ultrasound is much faster than manual palpation for pulse check

• • Can provide information almost instantaneously without waiting the full 10 seconds for a manual pulse check

• The main priority during cardiac arrest resuscitation is to maintain quality compressions

• • If pulses are unable to be obtained through Doppler within the 10-second window, resume compressions and try again during the next pulse check

References

1. Cohen AL, Li T, Becker LB, Owens C, Singh N, Gold A, Nelson MJ, Jafari D, Haddad G, Nello AV, Rolston DM; Northwell Health Biostatistics Unit. Femoral artery Doppler ultrasound is more accurate than manual palpation for pulse detection in cardiac arrest. Resuscitation. 2022 Apr;173:156-165. doi: 10.1016/j.resuscitation.2022.01.030. Epub 2022 Feb 4. PMID: 35131404.

Summarized by Meg Joyce, MS1 | Edited by Meg Joyce & Jorge Chalit, OMS3

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Contributor: Travis Barlock, MD

Educational Pearls:

What is Hoover’s sign used to identify?

• This physical exam maneuver differentiates between organic vs. functional (previously known as psychogenic) leg weakness.

• Organic causes include disease processes such as stroke, MS, spinal cord compression, guillain-barre, ALS, and sciatica, among others

• In Functional Neurologic Disorder, the dysfunction is in brain signaling, and treatment relies on more of a psychiatric approach

How is Hoover's Sign performed?

• Place your hand under the heel of the unaffected leg and ask the patient to attempt to lift the paralyzed leg.

• If the paralysis is due to an organic cause, then you should feel the unaffected leg push down.

• This is due to the crossed-extensor reflex mechanism, an unconscious motor control function mediated by the corticospinal tract.

• If you don’t feel the opposite heel push down, that is a positive Hoover’s Sign.

How sensitive/specific is it?

• An unblinded cohort study in patients with suspected stroke found a sensitivity of 63% and a specificity of 100%

Fun Fact

• There’s also a pulmonary Hoover’s sign, named after the same doctor, Charles Franklin Hoover, which refers to paradoxical inward movement of the lower ribs during inspiration due to diaphragmatic flattening in COPD.

References

1. McWhirter L, Stone J, Sandercock P, Whiteley W. Hoover's sign for the diagnosis of functional weakness: a prospective unblinded cohort study in patients with suspected stroke. J Psychosom Res. 2011 Dec;71(6):384-6. doi: 10.1016/j.jpsychores.2011.09.003. Epub 2011 Oct 6. PMID: 22118379.

2. Stone J, Aybek S. Functional limb weakness and paralysis. Handb Clin Neurol. 2016;139:213-228. doi: 10.1016/B978-0-12-801772-2.00018-7. PMID: 27719840.

Summarized by Jeffrey Olson, MS3 | Edited by Jorge Chalit, OMS3

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Contributor: Jorge Chalit-Hernandez, OMS3

Educational Pearls:

• CYP enzymes are responsible for the metabolism of many medications, drugs, and other substances

• • CYP3A4 is responsible for the majority

  • Other common ones include CYP2D6 (antidepressants), CYP2E1 (alcohol), and CYP1A2 (cigarettes)

• CYP inducers lead to reduced concentrations of a particular medication

• CYP inhibitors effectively increase concentrations of certain medications in the body

• Examples of CYP inducers

• • Phenobarbital

  • Rifampin

  • Cigarettes

  • St. John’s Wort

• Examples of CYP inhibitors

• • -azole antifungals like itraconazole and ketoconazole

  • Bactrim (trimethoprim-sulfamethoxazole)

  • Ritonavir (found in Paxlovid)

  • Grapefruit juice

• Clinical relevance

• • Drug-drug interactions happen frequently and often go unrecognized or underrecognized in patients with significant polypharmacy

  • A study conducted on patients receiving Bactrim and other antibiotics found increased rates of anticoagulation in patients receiving Bactrim

  • Currently, Paxlovid is prescribed to patients with COVID-19, many of whom have multiple comorbidities and are on multiple medications

  • • Paxlovid contains ritonavir, a powerful CYP inhibitor that can increase concentrations of many other medications

• A complete list of clinically relevant CYP inhibitors can be found on the FDA website:

• • https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers

References

1. Glasheen JJ, Fugit RV, Prochazka AV. The risk of overanticoagulation with antibiotic use in outpatients on stable warfarin regimens. J Gen Intern Med. 2005;20(7):653-656. doi:10.1111/j.1525-1497.2005.0136.x

2. Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician. 2007;76(3):391-396.

3. PAXLOVID™. Drug interactions. PAXLOVIDHCP. Accessed March 16, 2025. https://www.paxlovidhcp.com/drug-interactions

Summarized & Edited by Jorge Chalit, OMS3

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Educational Pearls:

• Physiologic stimulation of ventilation occurs through changes in levels of:

• • Arterial carbon dioxide (PaCO2)

  • Arterial oxygen (PaO2)

• Hypercapnia is an elevated level of CO2 in the blood - this primarily drives ventilation

• Hypoxia is a decreased level of O2 in the body’s tissues - the backup drive for ventilation

• Patients at risk of hypercapnia should maintain an O2 saturation between 88-92%

• • Normal O2 saturation is 95-100%

• In patients who chronically retain CO2, their main drive for ventilation becomes hypoxia

• An audit was performed of SpO2 observations of all patients with a target range of 88–92% at a single hospital over a four-year period

• • This found that excessive oxygen administration was more common than insufficient oxygen and is associated with an increased risk of harm

• Individuals at risk of hypercapnia include but are not limited to patients with COPD, hypoventilation syndrome, or altered mental status

References

1. Homayoun Kazemi, Douglas C. Johnson, Respiration, Editor(s): V.S. Ramachandran, Encyclopedia of the Human Brain, Academic Press, 2002, Pages 209-216, ISBN 9780122272103, https://doi.org/10.1016/B0-12-227210-2/00302-2.

2. O'Driscoll BR, Bakerly ND. Are we giving too much oxygen to patients at risk of hypercapnia? Real world data from a large teaching hospital. Respir Med. 2025 Mar;238:107965. doi: 10.1016/j.rmed.2025.107965. Epub 2025 Jan 30. PMID: 39892771.

Summarized by Meg Joyce, MS1 | Edited by Meg Joyce & Jorge Chalit, OMS3

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Contributor: Aaron Lessen, MD

Educational Pearls:

Quick background info

• Cardiac arrest is when the heart stops pumping blood for any reason. This is different from a heart attack in which the heart is still working but the muscle itself is starting to die.

• One cause of cardiac arrest is when the electrical signals are very disrupted in the heart and start following chaotic patterns such as Ventricular tachycardia (VTach) and Ventricular fibrillation (VFib)

• One of the only ways to save a person whose heart is in VFib or VTach is to jolt the heart with electricity and terminate the dangerous arrhythmia.

A recent study in the Netherlands looked at how important the time delay is from when cardiac arrest is first identified to when a defibrillation shock from an Automated External Defibrillator (AED) is actually given.

• Their main take-away: each minute defibrillation is delayed drops the survival rate by 6%!

• These findings reinforce the importance of rapid AED deployment and early defibrillation strategies in prehospital cardiac arrest response.

References

1. Stieglis, R., Verkaik, B. J., Tan, H. L., Koster, R. W., van Schuppen, H., & van der Werf, C. (2025). Association Between Delay to First Shock and Successful First-Shock Ventricular Fibrillation Termination in Patients With Witnessed Out-of-Hospital Cardiac Arrest. Circulation, 151(3), 235–244. https://doi.org/10.1161/CIRCULATIONAHA.124.069834

Summarized by Jeffrey Olson, MS3 | Edited by Meg Joyce, MS1 & Jorge Chalit, OMS3

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