Should I consider treating my patient with heart failure with an SGLT2 inhibitor?

Absolutely! Although sodium glucose cotransporter 2 (SGLT2) inhibitors are often used for their antidiabetic properties, more recently they have been shown to have extraordinary benefits in patients with heart failure.

 In 2015, a large randomized controlled trial, EMPA-REG OUTCOME, showed that empagliflozin significantly lowered overall death, death from cardiovascular events, and hospitalizations for heart failure in patients who had type II diabetes (T2DM) and cardiovascular disease1.

Later, 2 other randomized controlled trials showed that patients with heart failure with reduced ejection fractions (HFrEF), irrespective of a diagnosis of T2DM, had lower rates of death from cardiovascular causes and better heart failure outcomes when treated with SGLT2 inhibitors2,3.

In 2021, the EMPEROR Preserved trial showed that SGLT2 inhibitors provide significant clinical benefit for patients with heart failure with preserved ejection fraction (HFpEF), irrespective of the presence of T2DM4. In addition, multiple studies have shown substantial benefit to starting SGLT2 inhibitors during or shortly after a hospitalization for heart failure.5,6,7

 The effectiveness of SGLT2 inhibitors in heart failure is also reflected in the updated guidelines from the American College of Cardiology/American Heart Association8  that recommend  use of SGLT2 inhibitors in patients with chronic symptomatic HFrEF.  In addition,  the guidelines state that SGLT2 inhibitors can be beneficial in decreasing heart failure hospitalizations and cardiovascular mortality for patients mildly reduced ejection fraction and those with HFpEF.

 Potential mechanisms of action of SGLT2 inhibitors in heart failure include reduction in myocardial oxidative stress, decrease cardiac preload and afterload, increase endothelial function, decrease arterial stiffness, and increase muscle free fatty acid uptake which leads to increased availability of ketones during times of stress.9 

So the data to date suggest that we should consider SGLT2 inhibitors as part of our armamentarium for treatment of heart failure unless, of course, there are contraindications, including pregnancy/risk of pregnancy, breastfeeding, eGFR <30mL/min/1.73 m2, symptoms of hypotension, systolic blood pressure <95mmHg, or a known allergic/other adverse reactions. 10

Bonus Pearl: Did you know that SGLT 2 inhibitors are derived from phlorizin, a naturally occurring phenol glycoside first isolated back in 1835 from the bark of apple tree in 1835? 11

Contributed by Yisrael Wallach, MD, St. Louis, Missouri

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., … & Inzucchi, S. E. (2015). Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. New England Journal of Medicine, 373(22), 2117-2128. https://pubmed.ncbi.nlm.nih.gov/26378978/
  2. McMurray, J. J., Solomon, S. D., Inzucchi, S. E., Køber, L., Kosiborod, M. N., Martinez, F. A., … & Langkilde, A. M. (2019). Dapagliflozin in patients with heart failure and reduced ejection fraction. New England Journal of Medicine, 381(21), 1995-2008. https://pubmed.ncbi.nlm.nih.gov/31535829/
  3. Packer, M., Anker, S. D., Butler, J., Filippatos, G., Pocock, S. J., Carson, P., … & Zannad, F. (2020). Cardiovascular and renal outcomes with empagliflozin in heart failure. New England Journal of Medicine, 383(15), 1413-1424. https://pubmed.ncbi.nlm.nih.gov/32865377/
  4. Anker, S. D., Butler, J., Filippatos, G., Ferreira, J. P., Bocchi, E., Böhm, M., … & Packer, M. (2021). Empagliflozin in heart failure with a preserved ejection fraction. New England Journal of Medicine, 385(16), 1451-1461. https://pubmed.ncbi.nlm.nih.gov/34449189/
  5. Cunningham, J. W., Vaduganathan, M., Claggett, B. L., Kulac, I. J., Desai, A. S., Jhund, P. S., … & Solomon, S. D. (2022). Dapagliflozin in Patients Recently Hospitalized With Heart Failure and Mildly Reduced or Preserved Ejection Fraction. Journal of the American College of Cardiology. https://pubmed.ncbi.nlm.nih.gov/36041912/
  6. Voors, A. A., Angermann, C. E., Teerlink, J. R., Collins, S. P., Kosiborod, M., Biegus, J., … & Ponikowski, P. (2022). The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nature medicine, 28(3), 568-574. https://pubmed.ncbi.nlm.nih.gov/35228754/
  7. Bhatt, D. L., Szarek, M., Steg, P. G., Cannon, C. P., Leiter, L. A., McGuire, D. K., … & Pitt, B. (2021). Sotagliflozin in patients with diabetes and recent worsening heart failure. New England Journal of Medicine, 384(2), 117-128. https://pubmed.ncbi.nlm.nih.gov/33200892/
  8. Heidenreich, P. A., Bozkurt, B., Aguilar, D., Allen, L. A., Byun, J. J., Colvin, M. M., … & Yancy, C. W. (2022). 2022 AHA/ACC/HFSA guideline for the management of heart failure: Executive summary: a report of the American College of Cardiology/American heart association joint Committee on clinical practice guidelines. Journal of the American College of Cardiology, 79(17), 1757-1780. https://pubmed.ncbi.nlm.nih.gov/35379504/
  9. Muscoli, S., Barillà, F., Tajmir, R., Meloni, M., Della Morte, D., Bellia, A., … & Andreadi, A. (2022). The New Role of SGLT2 Inhibitors in the Management of Heart Failure: Current Evidence and Future Perspective. Pharmaceutics, 14(8), 1730. https://pubmed.ncbi.nlm.nih.gov/36015359/
  10. Aktaa, S., Abdin, A., Arbelo, E., Burri, H., Vernooy, K., Blomström-Lundqvist, C., … & Gale, C. P. (2022). European Society of Cardiology Quality Indicators for the care and outcomes of cardiac pacing: developed by the Working Group for Cardiac Pacing Quality Indicators in collaboration with the European Heart Rhythm Association of the European Society of Cardiology. EP Europace, 24(1), 165-172. https://pubmed.ncbi.nlm.nih.gov/34455442/
  11. Petersen, C. (1835). Analyse des phloridzins. Annalen der pharmacie, 15(2), 178-178. 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

 

Should I consider treating my patient with heart failure with an SGLT2 inhibitor?

My patient complains of severe facial scarring from childhood acne that is not improving. How should I advise her?

Severe facial scarring after childhood acne is not uncommon, having been shown to affect 43% of acne patients.1 Fortunately, there are several evidence-based treatments available to improve their appearance.

One procedure that you could recommend to your patient is microneedling, also known as percutaneous collagen induction or collagen induction therapy.2 This therapy works by using extremely fine needles to create small puncture wounds in the epidermis and superficial dermis, leading to tissue proliferation and collagen remodeling with subsequent enhancement in scar appearance.3 In fact, one randomized clinical trial showed a statistically significant 41% mean improvement following the procedure4. Adverse effects are limited with this treatment, with participants experiencing no issues other than mild erythema and edema.4

Another highly effective solution is laser therapy, which includes resurfacing (carbon dioxide, CO2; erbium-doped yttrium aluminum garnet, Er:YAG) and fractional (nonablative, NAFL; and ablative, AFL) lasers. One study compared the efficacy of these different lasers. Improvement in scar appearance was measured with a scale graded from 0 to 10. The mean improvement scores of the CO2, Er:YAG, NAFL, and AFL groups were 6.0, 5.8, 2.2, and 5.2, respectively.5 The Er:YAG laser has even been shown to have significantly better results than microneedling (70% improvement vs 30% improvement).6 The biggest downside to laser therapy is that patients reported more erythema, swelling, and crusting when compared to microneedling; however, they experienced significantly less pain.6

Other potentially effective treatments for acne scars include dermal fillers and chemical peels, neither of which have been shown to be superior to microneedling or laser therapy individually. However, certain peels do seem to significantly improve the effects of microneedling when used together.7 The good news is that all four can be performed easily in the office setting, so a referral to a board-certified dermatologist or plastic surgeon would be a good first step to addressing your patient’s problem.

Request for treatment of scars years after onset of acne should not be surprising in a general medicine practice. Acne is the most common skin condition in the United States, affecting over 50 million people.8 Unfortunately, in severe cases, inflammation can lead to scarring in cosmetically sensitive areas, leading to a lower quality of life and higher rates of anxiety and depression.9

Bonus Pearl: Did you know that platelet-rich plasma (PRP), a concentrate of platelets and growth factors obtained from venipuncture, has been shown to enhance the effects of microneedling and laser therapy through increased protein synthesis, collagen remodeling, and accelerated wound healing? 10

Contributed by Aditya Nellore, MD,  St. Louis, Missouri

 

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References:

  1. Tan J, Kang S, Leyden J. Prevalence and Risk Factors of Acne Scarring Among Patients Consulting Dermatologists in the USA. J Drugs Dermatol. 2017 Feb 1;16(2):97-102. PMID: 28300850. https://pubmed.ncbi.nlm.nih.gov/28300850/
  2. Orentreich DS, Orentreich N. Subcutaneous incisionless (subcision) surgery for the correction of depressed scars and wrinkles. Dermatol Surg. 1995 Jun;21(6):543-9. doi: 10.1111/j.1524-4725.1995.tb00259.x. PMID: 7773602. https://pubmed.ncbi.nlm.nih.gov/7773602/
  3. Fabbrocini G, Fardella N, Monfrecola A, Proietti I, Innocenzi D. Acne scarring treatment using skin needling. Clin Exp Dermatol. 2009 Dec;34(8):874-9. doi: 10.1111/j.1365-2230.2009.03291.x. Epub 2009 May 22. PMID: 19486041. https://pubmed.ncbi.nlm.nih.gov/19486041/
  4. Alam M, Han S, Pongprutthipan M, Disphanurat W, Kakar R, Nodzenski M, Pace N, Kim N, Yoo S, Veledar E, Poon E, West DP. Efficacy of a needling device for the treatment of acne scars: a randomized clinical trial. JAMA Dermatol. 2014 Aug;150(8):844-9. doi: 10.1001/jamadermatol.2013.8687. PMID: 24919799. https://pubmed.ncbi.nlm.nih.gov/24919799/
  5. You HJ, Kim DW, Yoon ES, Park SH. Comparison of four different lasers for acne scars: Resurfacing and fractional lasers. J Plast Reconstr Aesthet Surg. 2016 Apr;69(4):e87-95. doi: 10.1016/j.bjps.2015.12.012. Epub 2016 Jan 7. PMID: 26880620. https://pubmed.ncbi.nlm.nih.gov/26880620/
  6. Osman MA, Shokeir HA, Fawzy MM. Fractional Erbium-Doped Yttrium Aluminum Garnet Laser Versus Microneedling in Treatment of Atrophic Acne Scars: A Randomized Split-Face Clinical Study. Dermatol Surg. 2017 Jan;43 Suppl 1:S47-S56. doi: 10.1097/DSS.0000000000000951. PMID: 28009690. https://pubmed.ncbi.nlm.nih.gov/28009690/
  7. El-Domyati M, Abdel-Wahab H, Hossam A. Microneedling combined with platelet-rich plasma or trichloroacetic acid peeling for management of acne scarring: A split-face clinical and histologic comparison. J Cosmet Dermatol. 2018 Feb;17(1):73-83. doi: 10.1111/jocd.12459. Epub 2017 Dec 10. PMID: 29226630. https://pubmed.ncbi.nlm.nih.gov/29226630/
  8. Bickers DR, Lim HW, Margolis D, Weinstock MA, Goodman C, Faulkner E et al. The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology. Journal of the American Academy of Dermatology 2006;55:490-500. https://pubmed.ncbi.nlm.nih.gov/16908356/
  9. Yazici K, Baz K, Yazici AE, Köktürk A, Tot S, Demirseren D, Buturak V. Disease-specific quality of life is associated with anxiety and depression in patients with acne. J Eur Acad Dermatol Venereol. 2004 Jul;18(4):435-9. doi: 10.1111/j.1468-3083.2004.00946.x. PMID: 15196157. https://pubmed.ncbi.nlm.nih.gov/15196157/
  10. Hashim PW, Levy Z, Cohen JL, Goldenberg G. Microneedling therapy with and without platelet-rich plasma. Cutis. 2017 Apr;99(4):239-242. PMID: 28492598. https://pubmed.ncbi.nlm.nih.gov/28492598/

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

 

My patient complains of severe facial scarring from childhood acne that is not improving. How should I advise her?

How is Monkeypox different than Covid-19?

Just like Covid-19, Monkeypox (MP) is caused by a virus (this time related to smallpox), but there are major differences between these 2 diseases. 1-11

First, in contrast to Covid-19 which can easily be transmitted by casual contact through air, MP is primarily transmitted by close skin-to-skin contact (or possibly through contaminated clothing/bed linens) and sexual contact,  with great majority of current cases occurring among men who have sex with men (MSM); airborne transmission does not appear to be an important source of spread. 2

Although there is an overlap, the incubation period of MP tends to be longer (3-17 days) than that of Covid-19 which can be as few as 2 days.  Common to both diseases are flu-like symptoms such as fever, chills, muscle aches and headache, but MP is characterized by a rash that may be located on or near the genitals or anus or other areas, including hands, feet, chest face or mouth. 4

The rash (Figure) can look like pimples or blisters initially and may be painful or itchy as well. MP rash can either precede or follow flu-like symptoms after 1-4 days, or be the sole manifestation of the disease. Lymph node swelling or eye involvement (advise infected patients not to touch their eyes) may occur.  Although respiratory symptoms such as sore throat, nasal congestion and cough may occur with both diseases, shortness of breath would be unusual in MP.  A person with MP is considered contagious from onset of illness until the rash scabs over completely, which usually takes 2-4 weeks. 4,5,7,8

In contrast to Covid-19, currently there are no specific proven effective therapy against MP. However, several therapeutic agents with known activity against smallpox may be considered for those particularly at high risk of complications (eg, immunosuppressed patients, those with severe disease, exfoliative skin conditions [eg, eczema, psoriasis, Darier disease] children <8 years of age, pregnant or breast feeding patients, those with complications {eg, bacterial skin infection, pneumonia, gastroenteritis) or concurrent comorbidities.  These include an antiviral drug, Tecovirimat (TPOXX, ST-246) which can be obtained under an expanded-access protocol through the CDC in the U.S. (https://www.cdc.gov/poxvirus/monkeypox/clinicians/obtaining-tecovirimat.html. opens in new tab) — and Vaccinia Immune Globulin Intravenous (VIGIV) also through the CDC. 3,10

There are some “good news” related to MP when compared to Covid-19. First, in contrast Covid-19, hospitalization or death from MP due to the current circulating West African strain of the virus are extremely uncommon to rare.   In fact, of more than 12,000 cases of MP in 68 countries during the first few weeks of the epidemic, only 3 deaths have been reported, none in the U.S. thus far. 2

Second, in contrast to Covid-19, a person with MP is not considered infectious before onset of symptoms. So from a public health standpoint, it may be easier to control the spread of MP in the population following identification of a case. 9

Third, vaccination of contacts with one of the 2 available vaccinia/smallpox vaccines following significant exposure to MP may prevent disease altogether or render the disease milder. Vaccines should be administered within 4 days of exposure and no longer than 14 days after.  The generally preferred vaccine against MP is a modified vaccinia virus Ankara vaccine (MVA; JYNNEOS in the U.S., Imvanex in the European Union, and Imamune in Canada) which is live but non-replicative and is associated with fewer adverse events and contraindications than the alternative, ACAM2000, a live smallpox vaccine. 3

Last, in contrast to lack of pre-existing immunity to Covid-19 in virtually everyone  when the pandemic hit over 2 years ago, a large proportion of the population who received smallpox vaccine as part childhood vaccination (ending in 1972 in the U.S.) may have at least partial immunity against MP, resulting in either no or milder disease.6,11  

Bonus Pearl: Did you know that despite its name, monkeys are not a natural host of Monkeypox, with the causative virus having been isolated from a wild monkey in Africa only once? Instead, the virus first got its name after it was identified in a colony of Asian monkeys in a laboratory in Denmark in 1958. Squirrels, rats and shrew species serve as its natural host.1

Figure: Monkeypox rash (Courtesy CDC). 

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. Cohen J. Monkeypox is a new global threat. African scientists know what the world is up against. Science. June 1 2022. Monkeypox is a new global threat. African scientists know what the world is up against | Science | AAAS
  2. Osterholm MT. Gellin B. Confronting 21st-century monkeypox. Science 2022;377:349. Confronting 21st-century monkeypox | Science
  3. Medical countermeasures available for the treatment of monkeypox. Treatment Information for Healthcare Professionals | Monkeypox | Poxvirus | CDC. Accessed August 2, 2022.
  4. Key characteristics for identifying monkeypox. Clinical Recognition | Monkeypox | Poxvirus | CDC. Accessed August 6, 2022
  5. Monkeypox signs and symptoms. Signs and Symptoms | Monkeypox | Poxvirus | CDC. Accessed August 6, 2022.
  6. Karem KL, Reynold M, Hughes C, et al. Monkeypox-induced immunity and failure of childhood smallpox vaccine to provide complete protection. Clin Vaccine Immunol 2007;14:1318-27. Monkeypox-induced immunity and failure of childhood smallpox vaccination to provide complete protection – PubMed (nih.gov)
  7. Monkeypox: Key facts. Monkeypox (who.int). Accessed August 6, 2022.
  8. Clinical presentations of Covid-19. Clinical Presentation | Clinical Care Considerations | CDC. Accessed August 6, 2022.
  9. How monkeypox spreads. How it Spreads | Monkeypox | Poxvirus | CDC. Accessed August 6, 2022.
  10. Sherwat A, Brooks JT, Birnkrant D, et al. Tecovirimat and the treatment of monkeypox—past, present, and future. N Engl J Med 2020. August 3, 2022. Tecovirimat and the Treatment of Monkeypox — Past, Present, and Future Considerations | NEJM
  11. Mandavilli A. Who is protected against monkeypox. NY Times. May 26, 2022. Who Is Protected Against Monkeypox? – The New York Times (nytimes.com)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

How is Monkeypox different than Covid-19?

Why do some patients with Covid-19 develop a rebound after completing a course of Paxlovid (nirmatrelvir/ritonavir) and how common is it?

Covid-19 rebound, characterized by the recurrence of Covid-19 symptom or a new positive viral test after having tested negative, is a poorly understood phenomenon that can occur after completion of therapy with Paxlovid, Molnupiravir (another antiviral Covid-19 drug) and even in patients with acute Covid-19 who never received any specific antiviral therapy. 1-6

Based on very limited number of studies, it appears that rebound is not caused by emergence of drug resistance or absence of neutralizing immunity, rather resumption of SARS-CoV-2 replication following completion of therapy, triggering a secondary immune-mediated response that’s associated with clinical symptoms.2,3

Recent studies suggest that rebound following Paxlovid treatment may not be as common as one may think.  In a cohort of 483 high-risk patients treated with Paxlovid for Covid-19, 0.8% experienced rebound of symptoms within 30 days of diagnosis, which were generally mild at a median of 9 days after treatment, all resolving without additional antiviral therapy.3  In this study, the median age was 63 years and 93% were fully vaccinated; there were no hospitalization related to rebound or deaths. In another study (pre-print) involving over 11,000 patients treated with Paxlovid, rebound symptoms occurred in 2.3% and 5.9% of patients  7 and 30 days following therapy, respectively, with similar rates reported in patients treated with Molnupiravir.4

Interestingly, a preprint article involving 568 untreated patients with mild-moderate Covid-19 found that 27% had symptom rebound after initial improvement with 12% having viral rebound based on nasal swabs with ≥0.5 log viral RNA copies/ml. 5 So antiviral therapy for Covid-19 is not a prerequisite for rebound symptoms.

Although some have suggested that insufficient drug exposure either due to individual pharmacokinetics or insufficient duration may be the cause of rebound in treated patients,2   there is currently no evidence that additional treatment for Covid-19 is needed in these patients.6

Despite reports of rebound, Paxlovid should still be considered in selected patients with mild-moderate Covid-19 at high risk of complications to minimize the risk of hospitalization and death from Covid-19. 

Bonus Pearl: Did you know that, according to CDC, Covid-19 rebound often occurs between 2-8 days following initial recovery? 1

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. Covid-19 rebound after paxlovid treatment. May 24, 2022. COVID-19 Rebound After Paxlovid Treatment (cdc.gov)
  2. Carlin AF, Clark AE, Chaillon A, et al. Virologic and immunologic characterization of Coronavirus Disease 2019 recrudescence after nirmatrelvir/ritonavir treatment. Clin Infec Dis 2022 (June 20). Virologic and Immunologic Characterization of Coronavirus Disease 2019 Recrudescence After Nirmatrelvir/Ritonavir Treatment | Clinical Infectious Diseases | Oxford Academic (oup.com)
  3. Ranaganath N, O’Horo JC, Challner DW, et al. Rebound phenomenon after nirmatrelvir/ritonavir treatment of Coronavirus Disease-2019 in high-risk persons. Clin Infect Dis 2022 (June 14). https://doi.org/10.1093/cid/ciac481 Rebound Phenomenon after Nirmatrelvir/Ritonavir Treatment of Coronavirus Disease-2019 in High-Risk Persons | Clinical Infectious Diseases | Oxford Academic (oup.com)
  4. Wang L, Berger NA, David PB, et al. Covid-19 rebound after Paxlovid and Molnupiravir during January-June 2022. MedRxiv 2022. COVID-19 rebound after Paxlovid and Molnupiravir during January-June 2022 | medRxiv
  5. Deo R, Choudhary MC, Moser C, et al. Viral and symptom rebound in untreated Covid-19 infection. Medrxiv 2022. Viral and Symptom Rebound in Untreated COVID-19 Infection (medrxiv.org)
  6. Covid-19 rebound after Paxlovid treatment. May 24, 2022. HAN Archive – 00467 | Health Alert Network (HAN) (cdc.gov)

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

 

Why do some patients with Covid-19 develop a rebound after completing a course of Paxlovid (nirmatrelvir/ritonavir) and how common is it?

What’s so “special” about SARS-CoV-2 Omicron subvariants BA.4 and BA.5?

BA.4 and BA.5 now account for the majority of Covid cases in the U.S.1  Several concerning features of BA.4 and BA.5 when compared to earlier strains of SARS-CoV-2 include:2-6

  1. High reproductive rate or R0 ie, the average number of new infections generated by an infectious person in a totally naïve population. BA.4/5 has an estimated R0 of 18.6, according to a one report.  For comparison, the R0 for the original Wuhan variant was estimated at 3.3, for Delta  5.1, early Omicron  9.5, BA.1 13.3, mumps 12, and measles 18.  So, it’s not surprising that we are currently experiencing higher rates of SARS-CoV-2 transmission in the population than just a few weeks ago.3
  2. Suboptimal existing immunity following prior infections due to Omicron variants BA.1 and BA.2, or prior vaccinations (including 3 doses of Pfizer vaccine).2,4
  3. More efficient spread than BA.2 when studied in human lung cells invitro. 2
  4. More pathogenic than BA.2 in hamsters. 2
  5. Reduced activity of SARS-CoV-2 therapeutic monoclonal antibodies.4
  6. Antigenically distant from other SARS-CoV-2 variants, with 50 mutations, including more than 30 on the spike protein, the viral protein targeted by Covid vaccines to induce immunity.5,6

Despite these potentially ominous traits, currently there is no evidence that  BA.4 or BA.5 is inherently more likely to cause severe disease than that caused by other Omicron subvariants.   The sheer number of infected persons in the population due to high transmission rates, however, will likely translate into higher hospitalization and deaths which has already happened in many areas.

High transmission rates also mean that we should not abandon the usual public health measures (eg, social distancing, masking indoors in public spaces) and vaccination with boosters for eligible persons with the aim of reducing hospitalization and death, if not infections.  

Bonus Pearl: Did you know that BA.4 and BA.5 became dominant in South Africa in April, 2022, despite 98% of the population reportedly having some antibodies from vaccination or previous infection or both?  

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. Leatherby L. What the BA.5 subvariant could mean for the United States. NY Times, July 7, 2022. https://theconversation.com/australia-is-heading-for-its-third-omicron-wave-heres-what-to-expect-from-ba-4-and-ba-5-185598
  2. Kimura I, Ymasoba D, Tamura T, et al. Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5. bioRxiv, preprint doi: https://doi.org/10.1101/2022.05.26.493539 , posted May 26, 2022. Accessed July, 13, 2022.
  3. Esterman D. The Conversation. Australia is heading for its third Omicron wave. Here’s what to expect from BA.4 and BA.5. July 4, 2022. https://theconversation.com/australia-is-heading-for-its-third-omicron-wave-heres-what-to-expect-from-ba-4-and-ba-5-185598
  4. Tuekprakhon A, Nutalai R, Dijokaite-Guraliuc A, et al. Antibody escape of SARS-COV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum.
  5. Katella K. Omicron and BA.5: A guide to what we know. YaleMedicine, July 6, 2022. https://www.yalemedicine.org/news/5-things-to-know-omicron
  6. Topol E. The BA.5 story. The takeover by this Omicron sub-variant is not pretty. Ground Truths. June 27, 2022. https://erictopol.substack.com/p/the-ba5-story

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

What’s so “special” about SARS-CoV-2 Omicron subvariants BA.4 and BA.5?

My elderly patient with UTI and E. coli bacteremia is ready to be switched from IV to oral antibiotic. Can I consider an oral beta-lactam in place of a fluoroquinolone or trimethoprim-sulfamethoxazole to complete an adequate course of antibiotic therapy at home.

Although oral fluoroquinolones (FQs) and trimethoprim-sulfamethoxazole (TMP-SMX) have been routinely recommended as step-down therapy for treatment of Enterobacterales bacteremia owing to their high bioavailability, increasing evidence suggests that beta-lactam (BL) antibiotics (particularly those with high bioavailability, such as cephalexin) are as effective without the attendant adverse risks associated with FQs—with increasing FDA warnings—and TMP-SMX.1,2

In the largest study to date involving a retrospective review of over 4,000 cases of Enterobacterales UTI-associated bacteremia (eg, E. coli, Proteus spp., Klebsiella spp) in Veterans Affairs hospitals, no significant difference in the main outcome (composite of 30-day all cause mortality or 30-day recurrent bacteremia) was found between the oral beta-lactam and FQ/TMP-SMX groups (4.4% vs 3.0%, respectively); additionally, when examined separately, no significant difference in mortality (3.0% vs 2.6%) or recurrent bacteremia (1.5% vs 0.4%) was found. 1

A meta-analysis of 8 retrospective studies (2019) also failed to find a significant difference in mortality or recurrent bacteremia between BLs and FQs or TMP-SMX groups; it did find a higher odds of any recurrent infection, however (5.5% vs 2.0% (O.R. 2.06, 1.18-3.61). 2

Before selecting an antibiotic, however, it’s important to recall that not all oral BLs are  created equal, with some having better bioavailability than others.   More specifically, it may not be common knowledge that cephalexin (“Keflex”), a commonly prescribed and inexpensive cephalosporin with great safety profile, has 90-100% bioavailability, rivaling those of FQs or TMP-SMX.

 Of interest, in a subset of patients who received cephalexin as step-down therapy (n=245) in the VA study above, the outcomes were nearly identical to those who received FQ or TMP-SMX, with a 30-d recurrent bacteremia of 0% and a 30-day mortality of 2% (vs 0.4% and 2.5% for ciprofloxacin and 1.0% and 2.4% for TMP-STX, respectively). Of note nearly one-half of the cephalexin group received a higher dose of 500 mg 4x/day, with the rest receiving less frequent dosing. 

These findings makes one wonder whether suboptimal oral BL dosing may not have contributed to the discrepant results from earlier studies suggesting the superiority of FQs or TMP-SMX over oral BLs as step-down therapy. 1,2

 

Bonus Pearl: Did you know that cephalexin may be given up to 4 gm/day in 4 divided doses with 90% of the drug excreted unchanged in the urine? 3

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. Sutton JD, Stevens VW, Chang NCN, Khader K, et al. Oral beta-lactam antibiotics vs fluoroquinolones or trimethoprim-sulfamethoxazole for definite treatment of Enterobacterales bacteremia from a urine source. JAMA Network Open 2020;3 (10):e20220166. Oral β-Lactam Antibiotics vs Fluoroquinolones or Trimethoprim-Sulfamethoxazole for Definitive Treatment of Enterobacterales Bacteremia From a Urine Source – PubMed (nih.gov)
  2. Punjabi C, Tien V, Meng L, et al. Oral fluoroquinolone or trimethoprim-sulfamethoxazole vs beta-lactams as step-down therapy for Enterobacteriaceae bacteremia: systematic review and meta-analysis. Open Forum Infect Dis 2019;6:ofz364 doi:10.1.1093/ofid/ofz364   https://pubmed.ncbi.nlm.nih.gov/31412127/
  3. Herman TF, Hasmi MF. Cephalexin. StatPearls (internet). https://www.ncbi.nlm.nih.gov/books/NBK549780/ Accessed July 10, 2022.

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My elderly patient with UTI and E. coli bacteremia is ready to be switched from IV to oral antibiotic. Can I consider an oral beta-lactam in place of a fluoroquinolone or trimethoprim-sulfamethoxazole to complete an adequate course of antibiotic therapy at home.

How would you answer these 7 most popular clinical questions of 2022 on Pearls4Peers??

Peers,

www.Pearls4Peers.com just turned 7 with 2022 poised to become its best year ever in viewership  (>30,000 views so far)!  To mark this “momentous” occasion, I thought I would share with you, loyal viewers and subscribers, the 7 most viewed posts  of 2022 at its midway point.  Imagine rounding on the wards with your team and someone asks you one or more of these questions.  Take a crack at answering them and compare your answers with those of P4P (Ctrl+Click)! Have fun!

  1. What is the significance of teardrop cells(dacrocytes) on the peripheral smear of my patient with newly-discovered pancytopenia?
  2.  My elderly patient developed a flare-up of her gout few days after receiving covid-19 vaccine. Is there a connection between immunization and gout flare? 
  3. What is the clinical relevance of the “SPICE” organisms? 
  4. What does an “indeterminate” result in QuantiFERON Gold in-Tube Test for latent tuberculosis really mean? 
  5. What is the difference between “moderate” and “high complexity” medical decision making under the Centers for Medicare and Medicaid Services (CMS) rule? 
  6. The urine culture of my female patient with urgency is growing Lactobacillus. Should I treat it?
  7. Why is serum AST levels generally higher than ALT in alcohol-induced liver injury?

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

How would you answer these 7 most popular clinical questions of 2022 on Pearls4Peers??

“Should I consider cardiac CT angiography in my 76-year-old male patient with chest pain of unclear origin?”  

Probably not!1-4 Although the 2021 AHA/ACC Chest Pain Guidelines have generally widened the scope of indications for cardiac CT angiography (CCTA) to patients at low to intermediate risk of coronary artery disease (CAD) presenting with acute coronary syndrome (ACS)1 (with or without known CAD), several caveats should be considered before ordering this test. In general preference is given to patients with the following characteristics: 

  • Age sixty-five years of age or younger.  Elderly are not ideal candidates for CCTA as the calcium burden may be too high, rendering the test non-diagnostic due to the interference with proper coronary artery lumen assessment. Women tend not to accumulate as much calcium and their age threshold may be increased to 70 years. Some studies like the ROMICAT II Trial extended the age up to 74 years.4 
  • BMI <40.2
  • Sinus rhythm. Atrial fibrillation can be circumvented with expanded padding techniques, albeit at higher radiation exposure.2
  • Without coronary stents, unless their stents are > 3.0 mm in diameter (eg, in left main, very proximal left anterior descending, circumflex or right coronary stents).2
  • Without high coronary calcium burden, or without multiple risk factors for CAD (eg, type 2 diabetes, hypertension, hyperlipidemia) in the setting of typical anginal chest pain.1
  • Other technical requirements: must be able to hold breath during procedure, not have contraindications to beta blockers (ideal heart rate <60 bpm), not have an iodinated contrast allergy, and have stable kidney function.2

Despite these caveats, many patients may still be able to undergo CCTA to help exclude coronary causes of their chest pain.  For example, a 49-year-old patient at low to intermediate risk of CAD presenting with atypical chest pain can potentially undergo CCTA and, if negative, be discharged the same day!4  

In our patient, however, given his older age, CCTA is likely to be non-diagnostic and proceeding to an alternative test, such as stress test or invasive coronary angiography (depending on circumstances and pre-test probability), may be a better option.  

Bonus Pearl: Did you know that, as a “bonus”,  CCTA provides a “free” look at the lungs, calcium score (used largely in asymptomatic patients to help weigh pros and cons of starting a statin)3, and other cardiopulmonary structures that may hint at alternative diagnoses for the cause of chest discomfort and/or dyspnea?

Contributed by Eldin Duderija MD, Cardiologist, Mercy Clinic, St. Louis, Missouri

 

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References:

  1. Gulati M, Levy P, et al. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain. J Am Coll Cardiol. 2021;78:e187–e285. https://pubmed.ncbi.nlm.nih.gov/34709879/
  2. Raff GL, Chinnaiyan KM, Cury RC, Garcia MT, Hecht HS, Hollander JE, O’Neil B, Taylor AJ, Hoffmann U; Society of Cardiovascular Computed Tomography Guidelines Committee. SCCT guidelines on the use of coronary computed tomographic angiography for patients presenting with acute chest pain to the emergency department: a report of the Society of Cardiovascular Computed Tomography Guidelines Committee. J Cardiovasc Comput Tomogr 2014;8:254-71. doi: 10.1016/j.jcct.2014.06.002. Epub 2014 Jun 12. PMID: 25151918. https://pubmed.ncbi.nlm.nih.gov/25151918/
  3. Hecht H, Blaha MJ, Berman DS, Nasir K, Budoff M, Leipsic J, Blankstein R, Narula J, Rumberger J, Shaw LJ. Clinical indications for coronary artery calcium scoring in asymptomatic patients: Expert consensus statement from the Society of Cardiovascular Computed Tomography. J Cardiovasc Comput Tomogr 2017;11:157-168. doi: 10.1016/j.jcct.2017.02.010. Epub 2017 Feb 24. PMID: 28283309. https://pubmed.ncbi.nlm.nih.gov/28283309/
  4. Hoffmann, Udo, et al. “Coronary CT angiography versus standard evaluation in acute chest pain.” N Engl J Med 2012;367:299-308. https://www.nejm.org/doi/full/10.1056/nejmoa1201161

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

“Should I consider cardiac CT angiography in my 76-year-old male patient with chest pain of unclear origin?”  

How do I assess the left ventricular (LV) systolic function by bedside point-of-care ultrasound (POCUS)?

You can assess the LV systolic function by POCUS by just zeroing in on the following cardiac parameters: 1. Anterior mitral valve leaflet motion in early diastole; 2. Change in LV chamber diameter; and 3. LV wall thickness during systole.1

First assess the anterior mitral valve leaflet motion towards the interventricular septum in early diastole in the parasternal long axis view (Figure). Estimated or measured distance between anterior mitral valve leaflet and the interventricular septum is called E-point septal separation (EPSS). When LV systolic function is normal, anterior mitral valve leaflet opens fully in early diastole, resulting in a small or minimal separation between it and the interventricular septum. Due to the fixed length of the chordae and the enlarged LV chamber size, anterior mitral valve leaflets are unable to fully open as systolic function worsens. This results in increased separation between the anterior mitral valve leaflet and the interventricular septum. An estimated EPSS greater than 10 mm is considered abnormal and suggests LV dysfunction.1,2

You can also estimate the LV ejection fraction (LVEF) quantitatively  by utilizing the following formula:3

LVEF (%)=75.5 – 2.5xEPSS (mm)

Keep in mind that aortic insufficiency and mitral stenosis can affect the accuracy of this formula.1

As for assessing the LV chamber diameter and wall thickness, recall that these parameters are also dynamic throughout the cardiac cycle. In systole, LV diameter should decrease by 30-40% while LV wall thickness should increase by approximately 40%. Using this as a guide, you can perform qualitative assessment by “eyeballing” the LV systolic function in parasternal long axis, parasternal short axis, apical 4-chamber and subcostal 4-chamber views. Beware that in parasternal long axis, apical 4-chamber and subcostal 4-chamber views, off axis of images can foreshorten the chamber size, resulting in overestimation of systolic function. Also be sure to use the midventricular papillary muscle view when assessing systolic function in the parasternal short axis.1   

Once you have obtained all the necessary images, feel free to categorize the systolic function as either “hyperdynamic”, “normal”, “reduced” or “severely reduced” (watch video below).1

Bonus pearl:  Did you know that qualitative assessment of the LV systolic function  following brief training sessions have been shown to significantly correlate with that obtained by formal echocardiography (k = 0.77, p <0.001).1,4,5 

Contributed by Woo Moon, D.O, Director POCUS Training Program, Mercy-St. Louis Hospital, St. Louis, Missouri

Figure: EPSS in normal vs reduced EF 

Note: EPSS (yellow arrows) is narrow in normal but wide in reduced EF

Video: Four categories of systolic function

 

References

  1. Soni MD MS NJ, Arntfield MD FRCPC R, Kory MD MPA P. Point of Care Ultrasound. 2nd ed. St. Louis, MO: Elsevier; 2019. . https://www.elsevier.com/books/point-of-care-ultrasound/soni/978-0-323-54470-2
  2. Kimura BJ, Yogo N, O’Connell CW, Phan JN, Showalter BK, Wolfson T. Cardiopulmonary limited ultrasound examination for “quick-look” bedside application. Am J Cardiol 2011;108(4):586–90. https://linkinghub.elsevier.com/retrieve/pii/S0002-9149(11)01424-X
  3. Silverstein JR, Laffely NH, Rifkin RD. Quantitative estimation of left ventricular ejection fraction from mitral valve E-point to septal separation and comparison to magnetic resonance imaging. Am J Cardiol 2006;97(1):137–40. https://www.ajconline.org/article/S0002-9149(05)01683-8/fulltext
  4. Melamed R, Sprenkle MD, Ulstad VK, Herzog CA, Leatherman JW. Assessment of left ventricular function by intensivists using hand-held echocardiography. Chest 2009;135(6):1416–20. https://journal.chestnet.org/article/S0012-3692(09)60341-X/fulltext 
  5. Johnson BK, Tierney DM, Rosborough TK, Harris KM, Newell MC. Internal medicine point-of-care ultrasound assessment of left ventricular function correlates with formal echocardiography. J Clin Ultrasound 2016;44(2):92–9. https://onlinelibrary.wiley.com/doi/10.1002/jcu.22272

 

 

 

 

 

 

 

How do I assess the left ventricular (LV) systolic function by bedside point-of-care ultrasound (POCUS)?

My patient with COPD on prednisone with recurrent pneumonia has a low serum IgG level.  Can corticosteroids lower serum immunoglobulin levels?

Yes! Both exogenous and endogenous hypercortisolism may be associated with a drop in serum immunoglobulin levels, particularly IgG, which may persist even after discontinuation of steroid treatment.1-4 This means that a low serum IgG level in a patient on corticosteroids should be interpreted with caution and may not necessarily suggest primary antibody deficiency.

Although some early studies did not find a significant impact of corticosteroids on immunoglobulin levels, several subsequent studies found otherwise.  A 1978 study involving atopic asthmatic patients (averaging 16.8 mg prednisone daily) found that mean serum IgG significantly decreased (-22%) with milder drop in IgA levels (-10%) and no drop in serum IgM levels.2 Of interest, IgE level increased significantly initially but later dropped as well. More importantly, mean serum IgG levels remained significantly decreased an average of 22 days after corticosteroids were discontinued.

More recently, in a study involving patients with giant cell arteritis and polymyalgia rheumatica on corticosteroids, 58% developed antibody deficiency with the great majority involving IgG, either alone or along with other immunoglobulins.3 The reduction of IgG persisted even after discontinuation of corticosteroids in nearly 50% of patients, and observed in nearly one-quarter of patients for at least 6 months! Whether low serum immunoglobulins due to corticosteroids alone significantly increase susceptibility to infections is unclear, however.

In our patient with COPD on prednisone, if serum IgG level is found to be low and a primary antibody deficiency is still suspected, a functional assessment of the antibody production after active immunization (eg, polysaccharide pneumococcal vaccine, tetanus toxoid) may be necessary. 1 An adequate antibody response to active immunization makes primary immunodeficiency unlikely. 

 

Bonus Pearl: Did you know that corticosteroid-induced hypogammaglobulinemia may be in part related to reduced IgG production as well as an increase in IgG catabolism?1,4

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

 

References

  1. Sarcevic J, Cavelti-Weder C, Berger CT, et al. Case report-secondary antibody deficiency due to endogenous hypercortisolism. Frontiers in Immunology 2020;11:1435. https://www.frontiersin.org/articles/10.3389/fimmu.2020.01435/full
  2. Settipane GA, Pudupakkam RK, McGowan JH. Corticosteroid effect on immunoglobulins. J Allergy Clin Immunol 1978;62: 162-6. https://www.jacionline.org/article/0091-6749(78)90101-X/pdf
  3. Wirsum C, Glaser C, Gutenberger S, et al. Secondary antibody deficiency in glucocorticoid therapy clearly differs from primary antibody deficiency. J Clin Immunol 2016;36:406-12. https://link.springer.com/article/10.1007/s10875-016-0264-7
  4. McMillan R, Longmire R, Yelenosky R. The effect of corticosteroids on human IgG synthesis. J Immunol 1976;116:1592-1595. https://www.jimmunol.org/content/116/6/1592

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My patient with COPD on prednisone with recurrent pneumonia has a low serum IgG level.  Can corticosteroids lower serum immunoglobulin levels?