By: Kristie Bauman, MD
Researchers at the University of British Columbia may have solved our blood bank problems. After searching the human gut microbiome metagenomics library, Stephen Withers and colleagues found an enzyme that can convert A and B type red blood cells to type O. The enzyme is a glycosidase that cleaves sugars that attach A and B type antigenic residues to red blood cells. [1] While enzymes with similar function have been found in the past, this enzyme is 30 times more effective than its predecessors. Withers plans to further validate these results before beginning clinical testing. [2] While the enzyme might not completely solve blood bank shortages, it offers an interesting potential to expand the term “universal donor.”
A Randomized Trial of Epinephrine in Out of Hospital Cardiac Arrest (NEJM) [3]
Recent studies of epinephrine in cardiac arrest have questioned its effectiveness and its potential for neurologic harm, but few placebo controlled trials exist. A randomized, double-blind trial recently published in NEJM compared epinephrine to placebo in patients with out of hospital cardiac arrest who were given advanced cardiovascular life support by paramedics. If the initial trial of CPR with or without defibrillation was unsuccessful, patients were randomized to receive either 1 mg of epinephrine or 0.9% saline with subsequent doses every 3-5 minutes. This was continued until ROSC was achieved, resuscitation attempts were discontinued, or the patient was transitioned to hospital care. 30-day survival in the epinephrine and placebo groups were 3.2% and 2.4% respectively (odds ratio 1.39, 95% CI 1.06-1.82, p=0.02). However, rates of survival to hospital discharge with favorable neurologic outcome were not significantly different at 2.2% and 1.9% for the epinephrine and placebo groups respectively (odds ratio 1.18, 95% CI 0.86-1.61). Severe neurologic impairment, defined as a modified Rankin score of 4 or 5, was more common in the epinephrine group.
Bottom Line: Epinephrine increases survival in out of hospital cardiac arrest, however in those who survive there is increased risk of severe neurologic disability. Epinephrine has no effect on survival with favorable neurologic outcome.
Excess Mortality and Cardiovascular Disease in Young Adults with Type 1 diabetes in Relation to age at onset: a nationwide, register-based cohort study (The Lancet) [4]
Diabetes is a known cardiovascular risk factor, but does age at type 1 diabetes diagnosis alter this risk? This nationwide cohort study compares adults with type 1 diabetes to matched controls to study the effect of age of diagnosis, while controlling for duration of disease. Compared to controls, adults with type 1 diabetes had increased cardiovascular and non-cardiovascular mortality with increased incidence in patients diagnosed at younger ages. Hazard ratios for cardiovascular mortality were 3.64 (95%CI 2.34-5.66) for those diagnosed at 26-30 years versus 7.38 (CI 3.65-14.94) for those diagnosed at 0-10 years. Hazard ratios for non-cardiovascular mortality were 2.78 (CI 2.29-3.38) for those diagnosed at 26-30 years versus 3.96 (CI 3.06-5.11) for those diagnosed at 0-10 years. This trend of worse outcomes for people with earlier type 1 diabetes diagnosis was also seen for various other endpoints. Hazard ratios for those diagnosed at age 26-30 versus those diagnosed at 0-10 were as follows: 3.85 (CI 3.05-4.87) versus 11.44 (CI 7.95-16.44) for cardiovascular disease, 6.08 (CI 4.71-7.84) versus 30.50 (CI 19.98-46.57) for coronary heart disease, 5.77 (CI 4.08-8.16) versus 30.95 (CI 17.59-54.45) for acute myocardial infarction, 3.22 (CI 2.35-4.42) versus 6.45 (CI 4.04-10.31) for stroke, and 5.07 (CI 3.55-7.22) versus 12.90 (CI 7.39-22.51) for heart failure. Shockingly, these differences in risk were seen even though the mean age of study individuals was only 29 years.
Bottom Line: Patients with earlier onset of type 1 diabetes have an increased risk of mortality and cardiovascular disease even after controlling for disease duration.
Associated of Orthostatic Hypotension with Incident Dementia, Stroke, and Cognitive Decline (Neurology) [5]
Orthostatic hypotension is a common cause of syncope, but little is known about the long-term effects of these intermittent episodes of cerebral hypoperfusion. This prospective cohort study followed middle aged individuals with and without orthostatic hypotension to assess the risk of stroke, dementia, and cognitive decline. Patients with prior stroke or self-reported Parkinson’s disease were excluded. Orthostatic hypotension was checked only at the initial visit and defined as a drop in systolic blood pressure ≥ 20mmHg or a drop in diastolic blood pressure ≥ 10 mmHg when moving from supine to standing. The median length of follow up was 25 years. At follow-up, individuals with orthostatic hypotension at baseline were 2.08 times more likely to have an ischemic stroke (95% CI 1.65-2.62) and 1.54 times more likely to have dementia (95% CI 1.20-1.97). Interestingly, the increased risk for dementia persisted even after adjusting for stroke. There was no significant difference in the rate of cognitive decline. Notably, patients with orthostatic hypotension were more likely to be older, black, have hypertension, have lower cognitive scores at baseline, and die by the final follow up visit
Bottom Line: Middle aged patients with orthostatic hypotension are at an increased risk for dementia and ischemic stroke.
Assessment of the Safety of Discharging Select Patients Directly Home From the Intensive Care Unit (JAMA Internal Medicine) [6]
Patients in the ICU are typically transferred to the hospital wards before being discharged, but the safety of discharge directly from the ICU is unknown. This retrospective cohort study of 6,732 medical-surgical ICU patients from 9 hospitals compares healthcare utilization and patient outcomes in patients who were discharged directly from the ICU with those who were discharged after being transferred to the wards. Within the cohort, 14% of patients were discharged directly from the ICU and 86% were discharged from the hospital ward. Patients were more likely to be discharged directly from the ICU if their primary ICU admission diagnosis was overdose, withdrawal, seizures, or metabolic coma. Patients in both groups had a similar length of ICU stay, but those who were discharged directly from the ICU had a significantly shorter hospital stay (median 3.3 days vs. 9.2 days, p<0.001). Patients who were discharged directly from the ICU were younger (p<0.001), were more likely to leave against medical advice, were less likely to be have been transferred to the ICU in the post-operative setting (p<0.001), had a lower predicted mortality on ICU admission by APACHE II score (p<0.001), and were less likely to have received mechanical ventilation (p<0.001) or vasoactive medications (p<0.001) during their ICU stay. This study found that there was no difference in 30 day readmission rate, 30 day emergency department visit rate, or death within 1 year of discharge. Although this data suggests discharge directly from the ICU may be safe, the generalizability of this study may be limited, so it is important to use caution when making decisions at a local level.
Bottom Line: In a cohort study of medical-surgical ICU patients there was no difference in 30 day readmission and emergency department utilization or long term mortality between patients who were discharge after transfer to the hospital wards versus those who were discharged directly from the ICU.
Mini-Cuts:
Association of Cardiovascular Health Level in Older Age with Cognitive Decline and Incident Dementia (JAMA) [7]
Increased optimal cardiovascular health metrics are associated with a lower risk of dementia and cognitive decline. Cardiovascular health metrics for the study included measures of BMI, blood pressure, blood glucose, cholesterol, physical activity, diet, and overall cardiovascular health.
Medicare Spending on Brand-Name Combination Medications vs Their Generic Constituents (JAMA) [8]
Retrospective analysis of Medicare Part D expenditures notes that if 29 brand name combination products had been substituted for their generic components, $925 million could have been saved out of the $1.03 billion spent.
HIV Viral Suppression Trends Over Time Among HIV Infected Patients Receiving Care in the United States, 1997 to 2015: a Cohort Study (Annals of Internal Medicine) [9]
Viral suppression rates have increased from 32% to 86% from 1997 to 2015. Patients who were older or used an integrase strand transfer inhibitor had lower odds of having a detectable viral load, while black patients had higher odds of having a detectable viral load.
HLA-DQ:gluten tetramer test in blood gives better detection of coeliac patients than biopsy after 14-day gluten challenge (Gut) [10]
In a limited study of patients with prior biopsy verified diagnosis of celiac disease, increased frequency of blood CD4+ effector-memory gut-homing HLA-DQ:gluten tetramer-binding T cells on day 6 of gluten challenge was more sensitive than duodenal biopsy after a 14 day gluten challenge.
Kristie Bauman is a first year internal medicine resident at NYU Langone Health
Peer reviewed by Dana Zalkin, MD, an Associate Editor, Clinical Correlations
Image of Blood Transfusion Apparatus, United Kingdom, 1914-1918 courtesy of Wikimedia Commons
References
- News Staff. “Newly Found Enzymes Can Help Turn Type A and B Blood into Universal Type O | Medicine |.” Breaking Science News | Sci-News.com, August 21, 2018. http://www.sci-news.com/medicine/enzymes-turn-type-a-b-blood-into-universal-type-o-06324.html.
- Withers, Stephen. “CARB 105: Discovery of CAZYmes for Cell Surface Glycan Removal through Metagenomics: Towards Universal Blood.” American Chemical Society National Meeting 2018. Accessed August 24, 2018. https://plan.core-apps.com/acsboston18/abstract/fb1ee261-e80d-4602-9c36-aaafb789bf12.
- Perkins, Gavin D., Chen Ji, Charles D. Deakin, Tom Quinn, Jerry P. Nolan, Charlotte Scomparin, Scott Regan, et al. “A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest.” New England Journal of Medicine 379, no. 8 (August 23, 2018): 711–21. https://doi.org/10.1056/NEJMoa1806842.
- Rawshani, Araz, Naveed Sattar, Stefan Franzén, Aidin Rawshani, Andrew T. Hattersley, Ann-Marie Svensson, Björn Eliasson, and Soffia Gudbjörnsdottir. “Excess Mortality and Cardiovascular Disease in Young Adults with Type 1 Diabetes in Relation to Age at Onset: A Nationwide, Register-Based Cohort Study.” The Lancet 392, no. 10146 (August 11, 2018): 477–86. https://doi.org/10.1016/S0140-6736(18)31506-X.
- Rawlings, Andreea M., Stephen P. Juraschek, Gerardo Heiss, Timothy Hughes, Michelle L. Meyer, Elizabeth Selvin, A. Richey Sharrett, B. Gwen Windham, and Rebecca F. Gottesman. “Association of Orthostatic Hypotension with Incident Dementia, Stroke, and Cognitive Decline.” Neurology 91, no. 8 (August 21, 2018): e759. https://doi.org/10.1212/WNL.0000000000006027.
- Samieri, Cécilia, Marie-Cécile Perier, Bamba Gaye, Cécile Proust-Lima, Catherine Helmer, Jean-François Dartigues, Claudine Berr, Christophe Tzourio, and Jean-Philippe Empana. “Association of Cardiovascular Health Level in Older Age With Cognitive Decline and Incident Dementia.” JAMA 320, no. 7 (August 21, 2018): 657–64. https://doi.org/10.1001/jama.2018.11499.
- Sacks, Chana A., ChangWon C. Lee, Aaron S. Kesselheim, and Jerry Avorn. “Medicare Spending on Brand-Name Combination Medications vs Their Generic Constituents.” JAMA 320, no. 7 (August 21, 2018): 650–56. https://doi.org/10.1001/jama.2018.11439.
- Stelfox, Henry T., Andrea Soo, Daniel J. Niven, Kirsten M. Fiest, Hannah Wunsch, Kathryn M. Rowan, and Sean M. Bagshaw. “Assessment of the Safety of Discharging Select Patients Directly Home From the Intensive Care Unit: A Multicenter Population-Based Cohort Study.” JAMA Internal Medicine, August 20, 2018. https://doi.org/10.1001/jamainternmed.2018.3675.
- Nance, Robin M., J.A. Chris Delaney, Jane M. Simoni, Ira B. Wilson, Kenneth H. Mayer, Bridget M. Whitney, Frances M. Aunon, et al. “HIV Viral Suppression Trends Over Time Among HIV-Infected Patients Receiving Care in the United States, 1997 to 2015: A Cohort Study.” Annals of Internal Medicine, August 21, 2018. https://doi.org/10.7326/M17-2242.
- Sarna, Vikas K., Gry I. Skodje, Henrik M. Reims, Louise F. Risnes, Shiva Dahal-Koirala, Ludvig M. Sollid, and Knut E. A. Lundin. “HLA-DQ:Gluten Tetramer Test in Blood Gives Better Detection of Coeliac Patients than Biopsy after 14-Day Gluten Challenge.” Gut 67, no. 9 (September 1, 2018): 1606–13. https://doi.org/10.1136/gutjnl-2017-314461.