Primecuts – This Week in the Journals

October 23, 2020

By Aaron Reyes, MD

Peer Reviewed

With medicine advancing at such a rapid pace, it is crucial for physicians to keep up with the medical literature.  This can quickly become an overwhelming endeavor given the sheer quantity and breadth of literature released on a daily basis. Primecuts helps you stay current by taking a shallow dive into recently released articles that should be on your radar. Our goal is for you to slow down and take a few small sips from the medical literature firehose.

Prognostic Value of Lung Ultrasound B-Lines in Systemic Sclerosis [1]

This prospective cohort study examined the utility of lung ultrasound (LUS) in providing prognostic value for the diagnosis or worsening of interstitial lung disease (ILD) in patients with systemic sclerosis (SSc). Two prominent lung manifestations of SSc include pulmonary artery hypertension (PAH) and ILD, which contribute to increasing morbidity and mortality. [7]

This study involved a cohort of 396 consecutive SSc adult patients presenting for routine office visits who received LUS examining 58 scan sites and quantifying the number of B-lines per site, observed by two cardiology fellows who received dedicated LUS training. These patients were 92% female, interquartile age of 44-66 years old, and had a median duration of disease of four years.

The authors found that patients with diffuse-type SSc, positive topoisomerase I antibodies (Scl-70), and high-resolution chest CT (HRCT) showing ILD had higher number of B-lines on LUS. As a screening tool, using ≥5 posterior B-lines as predictability of ILD development or worsening, LUS had a hazard ratio of 3.378 (95% CI 1.137-9.994), sensitivity of 92%, specificity of 28%, negative predictive value of 96%, positive predictive value of 16%, and a number needed to screen of 8.5.

Limitations of this study are LUS’s dependence on technique compared to other screening tests for SSc patients, such as pulmonary function tests and HRCT. It also required LUS trained providers to be present during the exams. Additionally, instead of standardized criteria, chart review was utilized to assess worsening of ILD.

ILD has become a major cause for mortality in SSc patients since angiotensin-converting enzyme inhibitors have decreased scleroderma renal crisis mortality [7]. Therefore, diagnosing ILD early is important for providers managing these patients. This cohort study provides evidence that LUS has strong sensitivity and negative predictive value as a screening tool that can decrease costs and radiation exposure; the latter becomes especially important for patients of reproductive age.

Patient Trajectories Among Persons Hospitalized for COVID-19: A Cohort Study [2]

Reflecting on time spent caring for admitted COVID-19 patients, providers noticed a broad range of clinical patterns. Admitting providers would collect and trend a large amount of clinical data to attempt to characterize a patient’s clinical course; however standardization of this information has yet to reach a gold standard.

The authors, from Johns Hopkins Health System, completed a retrospective cohort analysis of 24 demographic and clinical variables to attempt to find predictors for the clinical course of admitted COVID-19 patients. Outcomes were measured using the WHO Ordinal Scale for COVID-19, which is a numerical spectrum ranging from uninfected (0), ambulatory (1-2), hospitalized with mild disease (3-4), hospitalized with severe disease (5-7), and dead (8). [8]

The enrolled 832 patients were consecutively admitted at five different hospitals under the same hospital system. Only three patients were excluded for being under 18 years old. The final analyzed patients were 47% female, a median age of 63 years old, 41% Black, 32% White, 16% Latinx, and 64% with one or more comorbid conditions.

The primary development from this analysis was the creation of the COVID Inpatient Risk Calculator (CIRC), which was most useful in predicting progression to severe disease or death in the first two days of hospital admission. [9]

Age was an appreciable modifier for associations with other discrete variables on the calculator, suggesting that single variables are insufficient in providing prognostic data for COVID-19. Though, detectable troponin was significantly associated with progression to severe disease or death in patients 60 to 74 years old. Variables, independent of age, that were significant for disease progression or death included BMI, respiratory symptoms, respiratory rate, albumin level, and temperature > 38°C within 24 hours of admission. Conversely, constitutional symptoms and higher absolute lymphocyte count was associated with decreased risk for severe disease. Overall there were not enough events to reliably predict death alone.

As a retrospective cohort study, multiple limitations exist. The utilization of 24 variables without a standardized admission protocol led to multiple missing variables throughout analysis. Additionally, no data was available for co-infection rates or dates of symptom onset, which may be confounding variables in disease severity or death.

Caring for admitted COVID-19 patients can be challenging, especially as a large amount of clinical data can be made available for analysis. This cohort study has provided a unique tool, the CIRC, that may be useful in prognostication or expectation setting with patients and their families when initially admitted to the hospital due to COVID-19.

Effect of Ticagrelor Monotherapy vs Ticagrelor With Aspirin on Major Bleeding and Cardiovascular Events in Patients With Acute Coronary Syndrome: The TICO Randomized Clinical Trial [3]

For patients who undergo percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and receive a drug-eluting stent (DES), the standard of care has been to receive 12 months of dual-antiplatelet therapy (DAPT) usually consisting of aspirin and a P2Y12 inhibitor (i.e. cangrelor, clopidogrel, prasugrel, ticagrelor). Unfortunately, these patients are subsequently at increased risk for bleeding. This open-label RCT attempts to evaluate if three months of DAPT, followed by 9 months of monotherapy with ticagrelor is sufficient to prevent major adverse cardiac and cerebrovascular events with less major bleeding compared to usual 12 months of DAPT.

Patients (n=3056) were enrolled and randomized at 38 health centers in South Korea on a 1:1 basis to either DAPT (aspirin 100mg daily and ticagrelor 90mg BID) for 3 months followed by ticagrelor monotherapy or DAPT for 12 months. Each group was similar with a mean age of 61, 79-80% male, and similar comorbidity and history profiles. The primary exclusion criteria was increased bleeding risk, which included prior hemorrhagic stroke, traumatic brain injury, or brain surgery within the past 6 months, internal bleeding within the past 6 weeks, use of oral anticoagulation, and hemoglobin ≤ 8 g/dL. The primary outcome was a composite of major bleeding and adverse cardiac and cerebrovascular events within 12 months of PCI. Secondary outcomes included these variables individually.

The authors found a composite of adverse events of 3.9% versus 5.9% (hazard ratio 0.66, 95% CI 0.48 to 0.92), and when only analyzing month 3 to 12 the difference was 1.4% versus 3.5%. Major bleeding as a secondary outcome favored the intervention arm with a 1.7% versus 3.0% rate (0.2% versus 1.6% during months 3 to 12). There was no significant difference for major cardiac or cerebrovascular events. Subgroup analysis overall favored ticagrelor monotherapy in patients with less severe disease and with fewer comorbidities.

There were multiple limitations in this RCT. First was the initial exclusion of high bleed risk patients, whom these results would benefit most. Patients were also aware of their treatment arm. And standard aspirin dosage in South Korea was 100 mg daily. Lastly, the overall low event rate made it difficult to have high powered results.

In summary, monotherapy with a P2Y12 inhibitor during month 3 to 12 following PCI does not seem to increase cardiac or cerebrovascular events and has lower bleeding risk. Subgroup analysis suggests this may be beneficial in patients with less severe disease and fewer comorbidities. However, the low number of events and limited evaluation in high bleeding risk patients makes it difficult to extrapolate these findings without broader evaluation.


Genomewide Association Study of Severe Covid-19 with Respiratory Failure [4]

This retrospective genomewide association study (GWAS) examined patients with COVID-19 and respiratory failure in Italy and Spain and found two loci, 3p21.31 and 9q34.2, that correlated with lung tissue immunomodulator expression and ABO blood group, respectively. Of the blood groupings, blood group A was associated with high risk for respiratory failure and blood group O was protective. These findings can improve our understanding of the risk for worse COVID-19 outcomes in patients based on genetic factors and have implications for future research on more targeted therapeutics as more about this novel virus is uncovered.

Evaluating prophylactic heparin in ambulatory patients with solid tumors: a systematic review and individual participant data meta-analysis [5]

This systematic review and meta-analysis of 14 RCTs of ambulatory patients with solid tumors (56% lung, 15% colon or prostate, 10% pancreatic, 5% breast, and 15% other) found that prophylactic LMWH, compared to placebo, decreased the risk of any VTE and symptomatic VTE/DVT/PE by 3-4% (adjusted RR 0.58 to 0.59) with an increased risk of minor bleeding by 4% (adjusted RR 1.34) and with no significant impact on mortality, major bleeding, or thrombocytopenia. Clinically, this has a significant impact on solid tumor patients as hospitalization for VTE involves significant morbidity and mortality that may be avoided using LMWH without increased major bleeding risk. This prophylaxis option should be discussed and offered to patients undergoing follow up for solid tumors, especially lung cancer as these patients were the most represented in this analysis.

Daily Aspirin Use Associated With Reduced Risk For Fibrosis Progression In Patients With Nonalcoholic Fatty Liver Disease [6]

This prospective cohort study found that daily aspirin use for a minimum of two, but greatest effect at four, years in patients with biopsy-diagnosed NAFLD was associated with decreased progression of liver fibrosis based on multiple hepatic histology scoring calculators. Given the limited treatment options for NAFLD, which is primarily weight loss, this study provides evidence that providers may be able to curb fibrosis progression using daily aspirin, which may warrant a new indication for this common medication.

Dr. Aaron Reyes is a 2nd year resident at NYU Langone Health

Peer reviewed by Pam Boodram, associate editor, Clinical Correlations

Image courtesy of Wikimedia Commons


The COVID Inpatient Risk Calculator: CIRC. The Johns Hopkins University. 2020.