Research Spotlight

Appiah, G. D., J. R. Chung, B. Flannery, F. P. Havers, R. K. Zimmerman, M. P. Nowalk, A. S. Monto, E. T. Martin, M. Gaglani, K. Murthy, L. A. Jackson, M. L. Jackson, H. Q. McLean, E. A. Belongia and A. M. Fry (2019). “Hospitalization following outpatient medical care for influenza: US influenza vaccine effectiveness network, 2011-12-2015-16.” Influenza Other Respir Viruses 13(2): 133-137.

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Over five seasons, we determined the proportion of outpatients with laboratory-confirmed, influenza-associated illness who were hospitalized within 30 days following the outpatient visit. Overall, 136 (1.7%) of 7813 influenza-positive patients were hospitalized a median of 4 days after an outpatient visit. Patients aged >/= 65 years and those with high-risk conditions were at increased risk of hospitalization. After controlling for age and high-risk conditions, vaccination status and infecting influenza virus type were not associated with hospitalization risk among adults.

Alvarez Villela, M., C. Y. Guerrero-Miranda, T. Chinnadurai, S. R. Patel and U. P. Jorde (2019). “Rate Response Pacing Left Ventricular Assist Device Patients.” ASAIO J Feb 22. [Epub ahead of print].

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Chronotropic incompetence (CI) is common in advanced heart failure and is associated with worse functional capacity. This impaired heart rate (HR) response during exercise is ameliorated but persists after left ventricular assist device (LVAD) implantation. Patients with continuous flow LVAD (CF-LVAD) suffer from significant exercise limitation despite restoration of resting cardiac output. Whether CI contributes to exercise limitation in this setting is unknown. We examined the role of CI and the effect of rate response pacing (RRP) on functional capacity in a group of stable patients with LVAD . . . Our findings demonstrate the association between CI and poor functional capacity in patients with advanced heart failure and CF-LVAD, in line with one small prior study. Findings in this cohort point out the inadequacy of current RRP technologies for sensing signals other than atrial rate during different types of physical activity. When RRP increased the HR promptly and in a sustained manner, replicating the activity of the sinus node, the effect on aerobic capacity was substantial, but this occurred in only a minority of patients. In contrast to the heterogeneous effect of RRP during treadmill-based CPX, its effect on 6 MWD was more homogeneous. This could represent a difference in CIED sensing efficacy since all of the employed devices in this study have an accelerometer-based RRP system. Ambulation, producing linear displacement of the body during 6 MWT could be more easily sensed by accelerometer-based systems than the more static motion during treadmill exercise. (Excerpts from advanced text; not paginated; no abstract available.)

Alonso-Hearn, M., G. Magombedze, N. Abendano, M. Landin and R. A. Juste (2019). “Deciphering the virulence of Mycobacterium avium subsp. paratuberculosis isolates in animal macrophages using mathematical models.” J Theor Biol 468: 82-91.

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Understanding why pathogenic Mycobacterium avium subsp. paratuberculosis (Map) isolates cause disparate disease outcomes with differing magnitudes of severity is important in designing and implementing new control strategies. We applied a suite of mathematical models: i) general linear, ii) and neurofuzzy logic, to explain how the host of origin of several Map isolates, Map genotype, host, macrophage-based in vitro model and time post-infection contributed to the infection. A logistic growth ordinary differential equation (ODE) model was applied to estimate within macrophage growth rates for the different Map isolates. The models revealed different susceptibilities of bovine and ovine macrophages to Map infection and confirmed distinct virulence profiles for the isolates, judged by their ability to grow within macrophages. Ovine macrophages were able to internalize Map isolates more efficiently than bovine macrophages. While bovine macrophages were able to internalize Map isolates from cattle with more efficiency, ovine macrophages were more efficient in internalizing ovine isolates. Overall, Map isolates from goat and sheep grew minimally within macrophages or did not grow but were able to persist by maintaining its initial population. In contrast, the ability of the bovine isolates and the non-domesticated animal isolates to grow to higher CFU numbers within macrophages suggests that these isolates are more virulent than the sheep and goat isolates, or that these isolates are better adapted to infect domestic ruminants. Overall, our study confirms the different virulence levels for the Map isolates and susceptibility profiles of host macrophages, which is crucial in increasing our understanding of Map infection.

Agbim, U. and S. K. Asrani (2019). “Non-invasive assessment of liver fibrosis and prognosis: an update on serum and elastography markers.” Expert Rev Gastroenterol Hepatol Feb 6: p. 1-14. [Epub ahead of print].

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INTRODUCTION: Non-invasive assessment of fibrosis is increasingly utilized in clinical practice to diagnose hepatic fibrosis. Non-invasive assessment of liver fibrosis relies on biologic and/or physical properties to assess tissue fibrosis. Serum markers estimate fibrosis by incorporating markers reflecting hepatic function (indirect markers) and/or markers measuring extracellular matrix degradation/fibrogenesis (direct markers). Radiology based techniques relay the mechanical properties and stiffness of a tissue, with increased stiffness associated with more advanced fibrosis. Areas covered: In this comprehensive review, the recent literature discussing serum markers and elastography-based techniques will be covered. These modalities are also explored in the setting of various liver diseases. Expert opinion: The etiology of liver disease and clinical context should be taken into consideration when non-invasive markers are incorporated in clinical practice. Non-invasive assessment of fibrosis has been most extensively utilized in hepatitis C, followed by hepatitis B and nonalcoholic fatty liver disease, but its role remains less developed in other etiologies of liver disease such as alcohol-associated liver disease and autoimmune liver disease. The role of non-invasive markers in predicting progression or regression of fibrosis, development of liver-related events and survival needs to be further explored.

Gregg, A. R. and A. Rajkovic (2019). “Cell-Free DNA Screening During Pregnancy.” JAMA 321(3): 308-309.

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The authors discussed 3 general approaches to cell-free DNA (cfDNA) screening using next-generation sequencing technology of single-nucleotide polymorphisms. However, they did not describe a fourth array-based approach platform. No approach is proven to outperform others under robust clinical conditions. All screening tests are imperfect. However, a high false-positive rate results in increased diagnostic testing. Although assay failures are more common with cfDNA screening, there is a much lower false-positive rate and a higher positive predictive value for common aneuploidies compared with conventional serum screening, resulting in fewer diagnostic tests. In addition, cfDNA screening is the only method to screen prenatally for sex chromosome aneuploidy. No valid trial shows that any combination of ultrasound nuchal translucency measurement and serum analyte screening is preferred for low-risk pregnancy and yields more genetic diagnoses than cfDNA screening. The authors referenced a hypothetical study that included a screening paradigm that is complex to implement statewide. The hypothetical comparison had a high false-positive rate and rate of diagnostic testing compared with cfDNA screening. The American College of Medical Genetics and Genomics (ACMG) was incorrectly included in the list of professional organizations that do not consider cfDNA screening “the standard approach in pregnancies that are not considered high risk.” The ACMG recommends informing all pregnant women that cfDNA screening is the most sensitive screening option for common aneuploidies, does not recommend age as a basis to choose between aneuploidy testing approaches, and does not recommend screening using serial screening tests. The ACMG recommends that patients receive accurate and balanced information to promote patient-centered, nondirective decision making. (Excerpt from comment on the article: Allyse MA, Wick MJ. Noninvasive prenatal genetic screening using cell-free DNA. JAMA. 2018;320(6):591-592.)