CLN Article

The Sample

Plasma Tau Elevations Persist Long After Traumatic Brain Injury

A study of military personnel who experienced traumatic brain injury (TBI) found they had elevated plasma tau levels months to years after their injuries (JAMA Neurology 2015; doi:10.1001/jamaneurol.2015.1383). Transient elevated tau levels previously had been reported in contact sport athletes, but the authors’ findings appear to be the first description of elevated tau levels persisting long after TBI.

The results provide an avenue for exploring plasma tau further as a predictive marker for individuals most likely to experience long-term TBI sequelae, according to the researchers. “Our findings may provide a framework for identifying patients who are most at risk for experiencing chronic symptoms related to TBI. Identifying those at risk early in the progression of the disease provides the best opportunity for therapies that can lessen the cognitive declines that may result from these long-term effects,” said lead author Jessica Gill, PhD, RN.

The authors also found higher plasma tau levels in participants who had more severe post-TBI symptoms. In addition, plasma tau levels correlated with three or more TBIs during deployment, compared with less than three TBIs.

The study involved 70 United States military personnel who had been deployed within the previous 18 months and who had a self-reported TBI, as well as 28 demographic- and deployment factor-matched control service members who had not experienced TBI. The authors used a novel ultrasensitive immunoassay with a lower limit of quantitation significantly lower than conventional tau assays, 0.012 pg/mL. By using results from this assay along with participants’ TBI histories and symptoms, they sought to provide evidence of a potential role for plasma tau in assessing long-term TBI symptoms.

Plasma tau levels in participants with TBI were significantly elevated in comparison to control subjects, 1.13 pg/mL versus 0.63 pg/mL. Plasma tau levels also were significantly associated with having a medical record associated with TBI versus merely a self-reported TBI (1.57 pg/mL versus 0.85 pg/mL); and having three or more TBIs compared with less than three (1.52 pg/mL versus 0.82 pg/mL). Severity of symptoms also correlated with total tau concentrations in participants with self-reported TBI. According to the authors, the findings suggest that tau accumulations may contribute to chronic neurological symptoms following TBI.

Change in Hb Levels More Informative Than Nadir Hb Level in Transfusion-Related Complications

Johns Hopkins University researchers reported that in patients undergoing major gastrointestinal surgery, change in hemoglobin level >50% was associated with complications, especially ischemic adverse events, even if the nadir hemoglobin stays above 7 g/dL, the guideline-recommended threshold for transfusion (JAMA Surg 2015; doi:10.1001/jamasurg.2015.1704).

The findings “imply that an exclusive focus on a nadir” hemoglobin as a transfusion threshold “may not always be appropriate,” according to the authors. They also called for future randomized clinical trials to explore both nadir hemoglobin and change in hemoglobin when considering how transfusion practices affect perioperative risks.

Despite guidelines suggesting a nadir hemoglobin of 7 g/dL as the trigger for packed red blood cell transfusions, the ideal criteria for transfusion has not been established, according to the authors. Recent research indicated that in cardiac surgery patients a >50% change in hemoglobin was associated with worse outcomes, even when hemoglobin remained above 7–8 g/dL. These findings prompted the authors to explore this association in non-cardiac patients.

The retrospective study involved 4,669 patients who underwent major gastrointestinal surgery. The median post-operative hemoglobin change was 40%. Compared with patients who had a hemoglobin change <50% and a hemoglobin nadir >7 g/dL, those with a hemoglobin change >50% or nadir hemoglobin <7 g/dL were at high risk of developing post-operative complications. A hemoglobin change >50% was strongly correlated with risk of ischemic complications, even if the nadir hemoglobin level was >7 g/dL.

An accompanying editorial suggested that “a patient’s [change in hemoglobin level] may just be a summative marker of preoperative risk factors and perioperative blood loss.” The editorial went on to suggest that “the best answer [for knowing when to transfuse patients] may be the establishment of a biomarker for inadequate oxygen delivery that would correlate with better outcomes after transfusion.”

Homocysteine, Dimethylarginine Possible Predictive Markers of Pre-Eclampsia

New research indicates that homocysteine (Hcy) and dimethylarginine (ADMA) levels increase 1 month prior to onset of pre-eclampsia, and may identify women at risk of developing this pregnancy-related condition (BJOG 2015; doi:10.1111/1471-0528. 13516).

Biomarkers commonly investigated in pre-eclampsia such as placental growth factor and vascular endothelial growth factor have not proven particularly informative in predicting pre-eclampsia, with sensitivities between 0.18 and 0.32. Hcy and ADMA previously have been shown to be elevated in conditions with endothelial alterations, including pre-eclampsia, so the authors sought to determine whether Hcy and ADMA elevations increased prior to pre-eclampsia symptoms, independent of maternal nutritional status.

The study involved 252 women with normal blood pressure and singleton pregnancy who enrolled before week 20 of pregnancy and underwent fasting blood sampling each month until they delivered. In all, 49 developed pre-eclampsia.

The authors found that both ADMA and Hcy levels increased 1 month prior to onset of pre-eclampsia symptoms, 124±27 nmol and 1,177±278 nmol, respectively, while women who did not develop pre-eclampsia did not have significant changes in either biomarker. ADMA increases of 80 nmol and Hcy increases of 1,000 nmol at 1 month prior to pre-eclampsia onset demonstrated the best predictive power.

Poor Concordance Among eGFR Equations

Italian researchers reported poor concordance among estimated glomerular filtration rate (eGFR) derived from the Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemio­logy (CKD-EPI) equation, and creatinine clearance (CrCl) measurement from 24h urine collection (Clin Biochem 2015; doi:10.1016/j.clinbiochem.2015.07.030). The authors were interested in exploring this issue because even though guidelines recommend determining eGFR via CKD-EPI and MDRD, creatinine clearance continues to be “used routinely in many settings.”

The authors conducted a retrospective analysis of laboratory data on creatinine clearance 24h urine collection and serum creatinine values as well as demographic information from 15,777 adult patients. They then calculated eGFR via both MDRD and CKD-EPI and normalized CrCl results to standard values of 1.73m2 body surface area and expressed CrCl as mL/min/1.73 m2.

eGFR concordance between the methods for patients ages 18 to 65 was 0.78, 0.34, and 0.41 for MDRD versus CKD-EPI, MDRD versus CrCl, and CKD-EPI versus CrCl, respectively. eGFR concordance between the methods for patients older than age 65 was 0.84, 0.38, and 0.36 for MDRD versus CKD-EPI, MDRD versus CrCl, and CKD-EPI versus CrCl, respectively. The authors concluded that using CrCl led to over-estimated eGFR, and that CrCl was inadequate and unreliable particularly in identifying chronic kidney disease subjects who have disease progression with GFR yearly decreases of 5 ml/min/1.73 m2.