Elevated serum mitochondrial DNA in females and lack of altered platelet mitochondrial methylation in patients with Parkinson´s disease.

Purpose: Mitochondrial dysfunction has long been considered in the pathogenesis of Parkinson's disease (PD). This is evident from the presence of mitochondrial DNA deletions in substantia nigra neurons and respiratory chain abnormalities in the skeletal muscle of PD patients. However, the contributing factors that potentially cause oxidative stress in PD are still elusive. To a certain extent, the identification of acquired changes in circulating mitochondrial DNA (mtDNA) content in blood samples may mirror the mitochondrial (dys-) function. Therefore, herein, we investigated the mtDNA concentrations in serum and cerebrospinal fluid (CSF) of PD patients.Materials and methods: We performed quantitative analysis (qPCR) at two mitochondrial regions (D-Loop; ATPase6) and evaluated the platelet mtDNA methylation levels (MT-TL1 ,MT-CO1, MT-CO2 and MT-CO3) by bisulfite-PCR pyrosequencing.Results: Our quantitative analysis at two mitochondrial regions (D-Loop; ATPase6) revealed an increase in mtDNA serum concentrations in PD females compared to healthy females. Of particular interest, these altered concentrations were restricted to females serum only. Thus, in males as well as CSF of PD patients no increase was detected. Additionally, mtDNA methylation in platelets isolated from the plasma of PD patients showed no altered methylation levels in the mitochondrial MT-TL1 and MT-CO1 regions. Besides, a complete lack of platelet mtDNA methylation was observed at MT-CO2 and MT-CO3 mitochondrial sites.Conclusions: Taken together, we found an increased mtDNA serum concentration exclusively in PD females. As of yet, it is unclear whether this might reflect specific changes or characteristics of female PD pathobiology. However, in context to the ongoing debate about mtDNA methylation, we could show that the mitochondrial epigenome does harbor detectable CpG methylation sites in platelets-derived DNA.

Biomarkers and postoperative cognitive function: could it be that easy?

PURPOSE OF REVIEW: Neurocognitive dysfunction after surgery is highly relevant in the elderly. The multifactorial manner of this syndrome has made it hard to define an ideal biomarker to predict individual risk and assess diagnosis and severity of delirium [postoperative delirium (POD)] and subsequent postoperative cognitive decline (POCD). This review summarizes recent literature on blood biomarkers for POD/POCD. RECENT FINDINGS: Markers for delirium have been searched for in the cerebrospinal fluid to examine the pathologic cascade. However, cerebrospinal fluid cannot be easily obtained in the perioperative setting. Thus, attention shifts toward prediction markers from patients' blood to determine the individual risk. In this regard, three major groups of peripheral blood markers could be distinguished: first, global, but unspecific markers associated with POD/POCD; second, specific and established markers related to neurocognitive function; and third, upcoming or newly described markers with less evidence. Solely neuron-specific enolase is an adequate biomarker based on recent literature. SUMMARY: Single markers for postoperative cognitive impairment cannot predict POD/POCD in geriatric patients. However, a wisely arranged battery of promising biomarkers might achieve a satisfying sensitivity and specificity for the preoperative assessment of subsequent cognitive decline. Adequately powered studies to prove this hypothesis are required.

Early prediction of acute kidney injury after transapical and transaortic aortic valve implantation with urinary G1 cell cycle arrest biomarkers.

BACKGROUND: Acute kidney injury (AKI) is a common complication following transcatheter aortic valve implantation (TAVI) leading to increased mortality and morbidity. Urinary G1 cell cycle arrest proteins TIMP-2 and IGFBP7 have recently been suggested as sensitive biomarkers for early detection of AKI in critically ill patients. However, the precise role of urinary TIMP-2 and IGFBP7 in patients undergoing TAVI is unknown. METHODS: In a prospective observational trial, 40 patients undergoing TAVI (either transaortic or transapical) were enrolled. Serial measurements of TIMP-2 and IGFBP7 were performed in the early post interventional course. The primary clinical endpoint was the occurrence of AKI stage 2/3 according to the KDIGO classification. RESULTS: Now we show, that ROC analyses of [TIMP-2]*[IGFBP7] on day one after TAVI reveals a sensitivity of 100 % and a specificity of 90 % for predicting AKI 2/3 (AUC 0.971, 95 % CI 0.914-1.0, SE 0.0299, p = 0.001, cut-off 1.03). In contrast, preoperative and postoperative serum creatinine levels as well as glomerular filtration rate (GFR) and perioperative change in GFR did not show any association with the development of AKI. Furthermore, [TIMP-2]*[IGFBP7] remained stable in patients with AKI ≤1, but its levels increased significantly as early as 24 h after TAVI in patients who developed AKI 2/3 in the further course (4.77 ± 3.21 vs. 0.48 ± 0.68, p = 0.022). Mean patients age was 81.2 ± 5.6 years, 16 patients were male (40.0 %). 35 patients underwent transapical and five patients transaortic TAVI. 15 patients (37.5 %) developed any kind of AKI; eight patients (20 %) met the primary endpoint and seven patients required renal replacement therapy (RRT) within 72 h after surgery. CONCLUSION: Early elevation of urinary cell cycle arrest biomarkers after TAVI is associated with the development of postoperative AKI. [TIMP-2]*[IGFBP7] provides an excellent diagnostic accuracy in the prediction of AKI that is superior to that of serum creatinine.

Role of anticoagulation therapy in modifying stroke risk associated with new-onset atrial fibrillation after non-cardiac surgery.

The role of antithrombotic therapy in the prevention of ischemic stroke after non-cardiac surgery is unclear. In this study, we tested the hypothesis that the association of new-onset postoperative atrial fibrillation (POAF) on ischemic stroke can be mitigated by postoperative oral anticoagulation therapy. Of 251,837 adult patients (155,111 female (61.6%) and 96,726 male (38.4%)) who underwent non-cardiac surgical procedures at two sites, POAF was detected in 4,538 (1.8%) patients. The occurrence of POAF was associated with increased 1-year ischemic stroke risk (3.6% versus 2.3%; adjusted risk ratio (RRadj) = 1.60 (95% confidence interval (CI): 1.37-1.87), P < 0.001). In patients with POAF, the risk of developing stroke attributable to POAF was 1.81 (95% CI: 1.44-2.28; P < 0.001) without oral anticoagulation, whereas, in patients treated with anticoagulation, no significant association was observed between POAF and stroke (RRadj = 1.04 (95% CI: 0.71-1.51), P = 0.847, P for interaction = 0.013). Furthermore, we derived and validated a computational model for the prediction of POAF after non-cardiac surgery based on demographics, comorbidities and procedural risk. These findings suggest that POAF is predictable and associated with an increased risk of postoperative ischemic stroke in patients who do not receive postoperative anticoagulation.