Research Spotlight

Posted January 15th 2020

Novel dietary and pharmacologic approaches for acid-base modulation to preserve kidney function and manage uremia.

Donald E. Wesson, M.D.
Donald E. Wesson, M.D.

Goraya, N. and D. E. Wesson (2020). “Novel dietary and pharmacologic approaches for acid-base modulation to preserve kidney function and manage uremia.” Curr Opin Nephrol Hypertens 29(1): 39-48.

Full text of this article.

PURPOSE OF REVIEW: We review mechanisms for chronic kidney disease (CKD) progression that might be addressed with nonpharmacologic and novel pharmacologic interventions as strategies by which to slow or even prevent CKD progression. RECENT FINDINGS: Evolving data support the contribution of the broad spectrum of disorders of acid (H) accumulation, which we refer to as ‘H stress’, to CKD progression. Recent studies support that amelioration of H stress, including spectra of H accumulation that are insufficient to cause metabolic acidosis, is kidney-protective. In addition, gut-derived toxins appear to contribute to CKD progression and to the well described increased cardiovascular disease (CVD) risk in patients with CKD. Dietary and novel pharmacologic interventions hold promise as strategies to slow CKD progression through reducing levels of these gut-derived toxins. In addition, oxidative stress appears to mediate CKD progression and contributing factors like diet and cigarette smoking can exacerbate oxidative stress. Dietary changes and smoking cessation hold promise to favorably affect CKD progression by reducing kidney oxidative stress. SUMMARY: The urgent need to add to the traditional armamentarium of blood pressure control and antiangiotensin II pharmacologic therapy for kidney protection has led to investigations into additional kidney-protective strategies. Acid stress, a disordered gut microbiome, and oxidative stress each appear to contribute to CKD progression and can be potentially addressed by nonpharmacologic and novel pharmacologic interventions.


Posted January 15th 2020

Spread of Antigenically Drifted Influenza A(H3N2) Viruses and Vaccine Effectiveness in the United States During the 2018-2019 Season.

Manjusha Gaglani M.D.
Manjusha Gaglani M.D.

Flannery, B., R. J. G. Kondor, J. R. Chung, M. Gaglani, M. Reis, R. K. Zimmerman, M. P. Nowalk, M. L. Jackson, L. A. Jackson, A. S. Monto, E. T. Martin, E. A. Belongia, H. Q. McLean, S. S. Kim, L. Blanton, K. Kniss, A. P. Budd, L. Brammer, T. J. Stark, J. R. Barnes, D. E. Wentworth, A. M. Fry and M. Patel (2020). “Spread of Antigenically Drifted Influenza A(H3N2) Viruses and Vaccine Effectiveness in the United States During the 2018-2019 Season.” J Infect Dis 221(1): 8-15.

Full text of this article.

BACKGROUND: Increased illness due to antigenically drifted A(H3N2) clade 3C.3a influenza viruses prompted concerns about vaccine effectiveness (VE) and vaccine strain selection. We used US virologic surveillance and US Influenza Vaccine Effectiveness (Flu VE) Network data to evaluate consequences of this clade. METHODS: Distribution of influenza viruses was described using virologic surveillance data. The Flu VE Network enrolled ambulatory care patients aged >/=6 months with acute respiratory illness at 5 sites. Respiratory specimens were tested for influenza by means of reverse-transcriptase polymerase chain reaction and were sequenced. Using a test-negative design, we estimated VE, comparing the odds of influenza among vaccinated versus unvaccinated participants. RESULTS: During the 2018-2019 influenza season, A(H3N2) clade 3C.3a viruses caused an increasing proportion of influenza cases. Among 2763 Flu VE Network case patients, 1325 (48%) were infected with A(H1N1)pdm09 and 1350 (49%) with A(H3N2); clade 3C.3a accounted for 977 (93%) of 1054 sequenced A(H3N2) viruses. VE was 44% (95% confidence interval, 37%-51%) against A(H1N1)pdm09 and 9% (-4% to 20%) against A(H3N2); VE was 5% (-10% to 19%) against A(H3N2) clade 3C.3a viruses. CONCLUSIONS: The predominance of A(H3N2) clade 3C.3a viruses during the latter part of the 2018-2019 season was associated with decreased VE, supporting the A(H3N2) vaccine component update for 2019-2020 northern hemisphere influenza vaccines.


Posted January 15th 2020

Hepatic Encephalopathy and Nutrition Influences: A Narrative Review.

Mohammad A. Fallahzadeh, M.D.
Mohammad A. Fallahzadeh, M.D.

Fallahzadeh, M. A. and R. S. Rahimi (2019). “Hepatic Encephalopathy and Nutrition Influences: A Narrative Review.” Nutr Clin Pract Dec 23. [Epub ahead of print].

Full text of this article.

Hepatic encephalopathy (HE) is a potentially reversible neurocognitive condition seen in patients with advanced liver disease. The overt form of HE has been reported in up to 45% of patients with cirrhosis. This debilitating condition is associated with increased morbidity and mortality and imposes a significant burden on the caregivers and healthcare system. After providing an overview of HE epidemiology and pathophysiology, this review focuses on the interaction of HE and frailty, nutrition requirements and recommendations in cirrhotic patients with HE, and current dietary and pharmacologic options for HE treatment.


Posted January 15th 2020

Prevalence of 25-Hydroxyvitamin D deficiency in the acute rehabilitation population following traumatic brain injury1.

Simon Driver Ph.D.
Simon Driver Ph.D.

Dubiel, R., B. Williams, E. Sullivan, L. Callender, M. Bennett and S. Driver (2019). “Prevalence of 25-Hydroxyvitamin D deficiency in the acute rehabilitation population following traumatic brain injury1.” NeuroRehabilitation Dec 18. [Epub ahead of print].

Full text of this article.

OBJECTIVE: To determine the prevalence of vitamin D deficiency among individuals with traumatic brain injury (TBI) undergoing acute inpatient rehabilitation. SETTING: Inpatient Rehabilitation. PARTICIPANTS: Participants were admitted from November 1st, 2010 through June 30th, 2015 with diagnosis of mild-severe TBI and had serum 25 OH vitamin D levels checked upon admission. 369 out of 845 met inclusion. DESIGN: Retrospective cohort. MAIN MEASURES: 25 OH vitamin D, vitamin D treatment. RESULTS: The majority of patients were male (67%), Caucasian (89%) with private insurance (61%) and a mean age of 43.5+/-21.0 years. 25 OH vitamin D levels were categorized: deficient (<20 ng/mL), insufficient (20-29.9 ng/mL), and sufficient (>/=30 ng/mL). There were 95 (26%) patients that were deficient, 131 (36%) that were insufficient, and 143 (39%) that were sufficient. Race/ethnicity was found to be significant (p = 0.0145) with the largest percentage of Hispanics found in the insufficient and deficient categories, and the largest percentage of Blacks in the deficient category. Most patients with deficient or insufficient vitamin D levels were prescribed vitamin D replacement during their rehab stay (p < 0.0001). CONCLUSION: The majority of patients undergoing acute inpatient rehabilitation were found to have insufficient or deficient vitamin D levels, therefore it should be routinely screened and treated as indicated.


Posted January 15th 2020

Relationship between heart rate and outcomes in patients in sinus rhythm or atrial fibrillation with heart failure and reduced ejection fraction.

Milton Packer M.D.
Milton Packer M.D.

Docherty, K. F., L. Shen, D. Castagno, M. C. Petrie, W. T. Abraham, M. Bohm, A. S. Desai, K. Dickstein, L. V. Kober, M. Packer, J. L. Rouleau, S. D. Solomon, K. Swedberg, A. Vazir, M. R. Zile, P. S. Jhund and J. J. V. McMurray (2019). “Relationship between heart rate and outcomes in patients in sinus rhythm or atrial fibrillation with heart failure and reduced ejection fraction.” Eur J Heart Fail Dec 17. [Epub ahead of print].

Full text of this article.

AIMS: To investigate the relationship between heart rate and outcomes in heart failure and reduced ejection fraction (HFrEF) patients in sinus rhythm (SR) and atrial fibrillation (AF) adjusting for natriuretic peptide concentration, a powerful prognosticator. METHODS AND RESULTS: Of 13 562 patients from two large HFrEF trials, 10 113 (74.6%) were in SR and 3449 (25.4%) in AF. The primary endpoint was the composite of cardiovascular death or heart failure hospitalization. Heart rate was analysed as a categorical (tertiles, T1-3) and continuous variable (per 10 bpm), separately in patients in SR and AF. Outcomes were adjusted for prognostic variables, including N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), and also examined using change from baseline heart rate to 1 year (/= +10 bpm, < +/-10 bpm). SR patients with a higher heart rate had worse symptoms and quality of life, more often had diabetes and higher NT-proBNP concentrations. They had higher risk of the primary endpoint [T3 vs. T1 adjusted hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.35-1.66; P < 0.001; per 10 bpm: 1.12, 95% CI 1.09-1.16; P < 0.001]. In SR, heart rate was associated with a relatively higher risk of pump failure than sudden death (adjusted HR per 10 bpm 1.17, 95% CI 1.09-1.26; P < 0.001 vs. 1.07, 95% CI 1.02-1.13; P = 0.011). Heart rate was not predictive of any outcome in AF. CONCLUSIONS: In HFrEF, an elevated heart rate was an independent predictor of adverse cardiovascular outcomes in patients in SR, even after adjustment for NT-proBNP. There was no relationship between heart rate and outcomes in AF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifiers NCT01035255 and NCT00853658.