Research Spotlight

Monticciolo, D. L. (2020). “2020 ACR Presidential Address: Quality, Ownership, and Our Role as Physicians.” J Am Coll Radiol Jul 6;S1546-1440(20)30643-8. [Epub ahead of print.].

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A story from long ago reminds us of the importance of quality in our practices, of taking ownership of our patients, and of our role as physicians. The coronavirus disease 2019 (COVID-19) pandemic has disrupted our practices. Before the pandemic, many practices were stretched thin by the amount of work that needed to be done. The work stoppage in many locations brought an unwelcome pause but gives us time to reflect on our practices. How can we maintain quality when high volumes return? The role of artificial intelligence, and our role in its development, needs to be considered. At the same time, we need to take more ownership of the patient and be more help to our referring providers. Our own ACR staff are great examples of taking ownership. Finally, we must recognize that patients and their families are important for optimal patient care. Making that connection is significant. Let us start where we began-in the service of our patients as their physicians. This role is rewarding and, together with a focus on quality and taking ownership, can lead to successful practices that are good for everyone, including ourselves.

Jarvis, J. L., V. Hamilton, M. Taigman and L. H. Brown (2020). “Using Red Lights and Sirens for Emergency Ambulance Response: How Often Are Potentially Life-Saving Interventions Performed?” Prehosp Emerg Care 2020 Aug 7;1-7. [Epub ahead of print.]. 1-7.

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BACKGROUND: Emergency Medical Services (EMS) often respond to 911 calls using red lights and sirens (RLS). RLS is associated with increased collisions and increased injuries to EMS personnel. While some patients might benefit from time savings, there is little evidence to guide targeted RLS response strategies. OBJECTIVE: To describe the frequency and nature of 911 calls that result in potentially life-saving interventions (PLSI) during the call. METHODS: Using data from ESO (Austin, Texas, USA), a national provider of EMS electronic health records, we analyzed all 911 calls in 2018. We abstracted the use of RLS, call nature, and interventions performed. A liberal definition of PLSI was developed a priori through a consensus process and included both interventions, medications, and critical hospital notifications. We calculated the proportion of calls with RLS response and with PLSI performed, both overall and stratified by call nature. RESULTS: There were 5,977,612 calls from 1,187 agencies included in the analysis. The majority (85.8%) of calls utilized RLS, yet few (6.9%) resulted in PLSI. When stratified by call nature, cardiac arrest calls had the highest frequency PLSI (45.0%); followed by diabetic problems (37.0%). Glucose was the most frequently given PLSI, n = 69,036. When including multiple administrations to the same patient, epinephrine was given most commonly PLSI, n = 157,282 administrations). CONCLUSION: In this large national dataset, RLS responses were very common (86%) yet potentially life-saving interventions were infrequent (6.9%). These data suggest a methodology to help EMS leaders craft targeted RLS response strategies.

Packer, M. (2020). “Mechanisms Leading to Differential Hypoxia Inducible Factor Signaling in the Diabetic Kidney: Modulation by SGLT2 Inhibitors and Hypoxia Mimetics.” Am J Kidney Dis Jul 22;S0272-6386(20)30849-0. [Epub ahead of print.].

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Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert important renoprotective effects in the diabetic kidney, which cannot be readily explained by their actions to lower blood glucose, blood pressure or glomerular filtration pressures. Their effects to promote erythrocytosis suggests that these drugs act on hypoxia inducible factors (specifically, HIF-1α and HIF-2α), which may underlie their ability to reduce the progression of nephropathy. Type 2 diabetes is characterized by renal hypoxia, oxidative and endoplasmic reticulum stress, and defective nutrient deprivation signaling, which (acting in concert) are poised to cause both activation of HIF-1α and suppression of HIF-2α. This shift in the balance of HIF-1α/HIF-2α activities promotes proinflammatory and profibrotic pathways in glomerular and renal tubular cells. SGLT2 inhibitors alleviate renal hypoxia and cellular stress and enhance nutrient deprivation signaling, which collectively may explain their actions to suppress HIF-1α and activate HIF-2α, and thereby, augment erythropoiesis, while muting organellar dysfunction, inflammation and fibrosis. Cobalt chloride, a drug conventionally classified as a hypoxia-mimetic, has a profile of molecular and cellular actions in the kidney that is similar to those of SGLT2 inhibitors. Therefore, many of renoprotective benefits of SGLT2 inhibitors may be related to their effect to promote oxygen deprivation signaling in the diabetic kidney.

Packer, M. (2020). “Beth Levine In Memoriam.” Eur Heart J 41(28): 2617.

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Beth Levine was widely recognized as a world leader in the field of autophagy research. Over a span of two decades, her findings repeatedly deciphered the mysteries of the molecular pathways that were essential to cellular health and survival. Her laboratory identified conserved mechanisms underlying the regulation of autophagy and provided the first evidence that autophagy genes are important in antiviral host defence, tumour suppression, lifespan extension, apoptotic corpse clearance, metazoan development, and the beneficial metabolic effects of exercise. In addition, she developed a potent autophagy-inducing cell permeable peptide, Tat-beclin 1, which has been shown to have numerous potential therapeutic applications in a range of human diseases. [No abstract; excerpt from article].

Olender, S. A., K. K. Perez, A. S. Go, B. Balani, E. G. Price-Haywood, N. S. Shah, S. Wang, T. L. Walunas, S. Swaminathan, J. Slim, B. Chin, S. De Wit, S. M. Ali, A. Soriano Viladomiu, P. Robinson, R. L. Gottlieb, T. Y. O. Tsang, I. H. Lee, R. H. Haubrich, A. P. Chokkalingam, L. Lin, L. Zhong, B. N. Bekele, R. Mera-Giler, J. Gallant, L. E. Smith, A. O. Osinusi, D. M. Brainard, H. Hu, C. Phulpin, H. Edgar, H. Diaz-Cuervo and J. I. Bernardino (2020). “Remdesivir for Severe COVID-19 versus a Cohort Receiving Standard of Care.” Clin Infect Dis Jul 24;ciaa1041. [Epub ahead of print.].

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BACKGROUND: We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe COVID-19 using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard-of-care. METHODS: GS-US-540-5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivir-cohort). GS-US-540-5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standard-of-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed SARS-CoV-2 infection, were hospitalized, had oxygen saturation 94% or lower on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard-of-care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality. RESULTS: After the inverse probability of treatment weighting procedure 312 and 818 patients were counted in the remdesivir- and non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio 2.03: 95% confidence interval 1.34-3.08, p<0.001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (adjusted odds ratio 0.38, 95% confidence interval: 0.22-0.68, p=0.001). CONCLUSIONS: In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19.