Research Spotlight

Elbehary, S., H. M. Szerlip and P. A. McCullough (2017). “Potassium excretion and outcomes in ckd: Is k intake ok?” Am J Kidney Dis 69(3): 325-327.

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Dietary potassium plays a pivotal role in blood pressure (BP), and higher potassium intake may subsequently decrease cardiovascular (CV) risk and mortality.1 In this issue of AJKD, Leonberg-Yoo et al 2 extend the epidemiologic evidence by relating dietary potassium intake with kidney disease progression and mortality in patients with chronic kidney disease (CKD).

Corzo, G. and G. P. Espino-Solis (2017). “Selected scorpion toxin exposures induce cytokine release in human peripheral blood mononuclear cells.” Toxicon 127: 56-62.

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A cytokine screening on human peripheral blood mononuclear cells (PBMCs) stimulated with selected scorpion toxins (ScTx’s) was performed in order to evaluate their effect on human immune cells. The ScTx’s chosen for this report were three typical buthid scorpion venom peptides, one with lethal effects on mammals Centruroides suffussus suffusus toxin II (CssII), another, with lethal effects on insects and crustaceans Centruroides noxius toxin 5 (Cn5), and one more without lethal effects Tityus discrepans toxin (Discrepin). A Luminex multiplex analysis was performed in order to determine the amounts chemokines and cytokines IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12-p40, IL-13, interferon alpha (IFN-alpha), interferon gamma (IFN-gamma), tumor necrosis factor alpha TNF-alpha, and interferon-inducible protein-10 (IP-10) secreted from human PBMCs exposed to these toxins. Although, the ScTx Cn5 is not lethal for mammals, it was able to induce the secretion of cytokines IL-1beta, IL-6, and TNF-alpha, IL-10 and IP-10 in comparison to the lethal CssII, which was able to induce only IP-10 secretion. Discrepin also was able to induce only IP-10. Interestingly, only low amounts of interferons alpha and beta were induced in the presence of the ScTx’s assayed. In a synergic experiment, the combination of Discrepin and Cn5 displayed considerable reverse effects on induction of IL-1beta, IL-6, IL-10 and TNF-alpha, but they had a slight synergic effect on IP-10 cytokine production in comparison with the single effect obtained with the Cn5 alone. Thus, the results obtained suggest that the profile of secreted cytokines promoted by ScTx Cn5 is highly related with a cytokine storm event, and also it suggests that the mammalian lethal neurotoxins are not solely responsible of the scorpion envenomation symptomatology.

Scherrer, J. F., J. Salas, F. D. Schneider, K. K. Bucholz, M. D. Sullivan, L. A. Copeland, B. K. Ahmedani, T. Burroughs and P. J. Lustman (2017). “Characteristics of new depression diagnoses in patients with and without prior chronic opioid use.” J Affect Disord 210: 125-129.

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Chronic use (>90 Days) of opioid analgesics significantly increases the risk of development of new depression episodes (NDE). It is unclear whether depression that develops in this manner is similar to or different from NDE in persons not exposed to opioid analgesic use (OAU). METHODS: VA patients were classified into two groups, those who did not receive an opioid and developed depression (non-OAU+NDE, n=4314) and those that had >90 days OAU and developed NDE (OAU+NDE, n=444). OAU+NDE patients were compared to non-OAU+NDE in terms of depression severity (PHQ-9 scores), incidence of PTSD, other anxiety disorders and substance use disorders after NDE, receipt of acute phase antidepressant treatment, dual antidepressant treatment, mood stabilizers and atypical antipsychotics. Prior to computing bivariate analysis, the prevalence of pain conditions and average maximum pain scores were equalized between the two groups using propensity scores and inverse probability of treatment weighting. RESULTS: Controlling for pain, OAU+NDE patients had more depression symptoms (p=.012), more incident PTSD (p=.04) and opioid abuse/dependence and were more likely to receive 12 weeks of antidepressant treatment (p<.0001). Last, non-OAU+NDE were more likely to have incident diagnoses for any other anxiety disorder (p=.014). CONCLUSIONS: Within the limitations of electronic medical record data, results indicate OAU+NDE patients have more depression symptoms, greater treatment adherence and different comorbid psychiatric conditions compared to non-OAU+NDE, independent of pain. Overall OAU related depression is as severe as non-OAU related depression and repeated depression screening in chronic opioid therapy may be warranted for pain patients, regardless of pain severity.

Thorud, J. C., S. Mortensen, J. L. Thorud, N. Shibuya, Y. M. Maldonado and D. C. Jupiter (2017). “Effect of obesity on bone healing after foot and ankle long bone fractures.” J Foot Ankle Surg 56(2): 258-262.

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As obesity has become more common, fractures in the obese population have become more frequent. Concern exists regarding alterations in bone health and healing in obese patients. A matched case-control study was performed at 1 institution to evaluate whether an association exists between nonunion and a high body mass index in metatarsal and ankle fractures. A total of 48 patients with nonunion were identified, and control patients matched 2 to 1 (n = 96) were selected. The control patients were matched for age, sex, and fracture type. No association was identified between nonunion and the continuous body mass index (p = .23) or morbid obesity, with a body mass index of >/=40 kg/m2 (p = .51). However, the results from both univariate and multivariate analysis suggested that patients with a current alcohol problem or a history of an alcohol problem might have a greater risk of nonunion. The odds ratio of a patient with a history of alcohol use experiencing nonunion was 2.7 (95% confidence interval 1.2 to 6.2). Further studies are warranted to confirm these findings.

Vasudevan, A., A. J. Singer, C. DeFilippi, G. Headden, J. M. Schussler, L. B. Daniels, M. Reed, M. P. Than, R. Birkhahn, S. W. Smith, T. W. Barrett, W. Arnold, W. F. Peacock and P. A. McCullough (2017). “Renal function and scaled troponin in patients presenting to the emergency department with symptoms of myocardial infarction.” Am J Nephrol 45(4): 304-309.

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BACKGROUND: Cardiac troponins are often found to be elevated in patients with renal dysfunction, even in the absence of acute myocardial injury. The objective of this report was to characterize the scaled troponin values and proportion of adjudicated acute myocardial infarction (AMI) among patients with and without renal dysfunction. METHODS: The data was from a multicenter prospective study including patients presenting to the emergency department with symptoms of AMI. Troponin measurements were standardized across various assays by calculating the observed results as multiples of the assay-specific 99th percentile upper limit of normal. Patients with an estimated glomerular filtration rate (eGFR; calculated by the Chronic Kidney Disease Epidemiology Collaboration formula) <60 mL/min/1.73 m2 were considered to have renal dysfunction. RESULTS: Of 430 included patients, 249 (58%) were male and 181 (42%) were female, with a mean age of 55.9 +/- 12.3 and 57.3 +/- 12.8 years, respectively. Eighty-seven (20.2%) had renal dysfunction. The proportions of patients with at least one scaled troponin value above the 99th percentile cut-off point among patients with and without renal dysfunction were 40 (45.9%) and 81 (23.6%) respectively (p < 0.001). The proportions of patients with an adjudicated diagnosis of AMI among those with and without renal dysfunction were 20.7 and 18.7%, respectively (p = 0.67). Using scaled troponins, by the second test there was >5X and by the third test >15X separation in the excursion of troponin among those with AMI compared to those without. CONCLUSIONS: One or more elevated troponin values are common in those with renal dysfunction. Scaled troponins for eGFR groups were similar, indicating that the use of this interpretative technique is applicable in discerning AMI for those with and without renal dysfunction.