Quantification of Circulating Cell-Free DNA in Idiopathic Parkinson's Disease Patients.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders globally and leads to an excessive loss of dopaminergic neurons in the substantia nigra of the brain. Circulating cell-free DNA (ccf-DNA) are double-stranded DNA fragments of different sizes and origins that are released into the serum and cerebrospinal fluid (CSF) due to cell death (i.e., necrosis and apoptosis) or are actively released by viable cells via exocytosis and NETosis. Using droplet digital polymerase chain reaction (ddPCR), we comprehensively analyzed and distinguished circulating cell-free mitochondrial DNA (ccf mtDNA) and circulating cell-free nuclear DNA (ccfDNA) in the serum and CSF of PD and control patients. The quantitative analysis of serum ccf-DNA in PD patients demonstrated a significant increase in ccf mtDNA and ccfDNA compared to that in healthy control patients and a significantly higher copy of ccf mtDNA when compared to ccfDNA. Next, the serum ccf mtDNA levels significantly increased in male PD patients compared to those in healthy male controls. Furthermore, CSF ccf mtDNA in PD patients increased significantly compared to ccfDNA, and ccf mtDNA decreased in PD patients more than it did in healthy controls. These decreases were not statistically significant but were in agreement with previous data. Interestingly, ccf mtDNA increased in healthy control patients in both serum and CSF as compared to ccfDNA. The small sample size of serum and CSF were the main limitations of this study. To the best of our knowledge, this is the first comprehensive study on serum and CSF of PD patients using ddPCR to indicate the distribution of the copy number of ccf mtDNA as well as ccfDNA. If validated, we suggest that ccf mtDNA has greater potential than ccfDNA to lead the development of novel treatments for PD patients.

Pharmacokinetics of dexmedetomidine during analgosedation in ICU patients.

Dexmedetomidine (DEX) is a fairly new alfa2-agonist which has been increasingly used in recent years for analgosedation, mostly because it offers a unique ability of providing both moderate level of sedation and analgesia without respiratory depression. Despite of many papers published, there are still only a few concerning the PK of the drug given as long-term infusion in ICU patients. The aim of this work was to characterize the population pharmacokinetics of dexmedetomidine and to investigate the potential benefits of individualization of drug dosing based on patient characteristics in the heterogeneous group of medical and surgical patients staying in intensive care unit. This study was performed in the group of 17 males and 10 females patients with a median age of 59.5 years and median body weight of 75 kg. Blood samples for dexmedetomidine assay were collected from arterial catheter, during and after discontinuation of a standard infusion, that ranged from 24 to 102 h. The following covariates were examined to influence dexmedetomidine PK: age, sex, body weight, patients' health status described by Sequential Organ Failure Assessment Score (SOFA), inotropes usage, and infusion duration. The dexmedetomidine PK was best described by a two-compartment model. The typical values of PK parameters were estimated as 27 L for the volume of the central compartment, 87.6 L for the volume of the peripheral compartment, 38.5 L/h (9.2 mL/min/kg for a 70 kg patient) for systemic clearance and 46.4 L/h for the distribution clearance. Those values are consistent with literature findings. We were unable to show any significant relationship between collected covariates and dexmedetomidine PK. This study does not provide sufficient evidence to support the individualization of dexmedetomidine dosing based on age, sex, body weight, SOFA, and infusion duration.

The role of simulation to support donation after circulatory death with extracorporeal membrane oxygenation (DCD-ECMO).

Maintaining the viability of organs from donors after circulatory death (DCD) for transplantation is a complicated procedure, from a time perspective in the absence of appropriate organizational capabilities, that makes such transplantation cases difficult and not yet widespread in Poland. We present the procedural preparation for Poland's first case of organ (kidney) transplantation from a DCD donor in which perfusion was supported by extracorporeal membrane oxygenation (ECMO). Because this organizational model is complex and expensive, we used advanced high-fidelity medical simulation to prepare for the real-life implementation. The real time scenario included all crucial steps: prehospital identification, cardiopulmonary resuscitation (CPR), advanced life support (ALS); perfusion therapy (CPR-ECMO or DCD-ECMO); inclusion and exclusion criteria matching, suitability for automated chest compression; DCD confirmation and donor authorization, ECMO organs recovery; kidney harvesting. The success of our first simulated DCD-ECMO procedure in Poland is reassuring. Soon after this simulation, Maastricht category II DCD procedures were performed, involving real patients and resulting in two successful double kidney transplantations. During debriefing, it was found that the previous simulation-based training provided the experience to build a successful procedural chain, to eliminate errors at the stage of identification, notification, transportation, donor qualifications and ECMO organ perfusion to create DCD-ECMO algorithm architecture.

Carbon dioxide as a potential danger to medical rescue teams at work - A case study.

Medical rescue teams might be exposed to the risk of accidental poisoning while performing rescue procedures. Exposure to the risk of lethal carbon dioxide (CO2) concentrations is a rare situation. This case study describes rescuing a patient who suffered from sudden cardiac arrest due to accidental CO2 poisoning. The victim was finally evacuated and resuscitated, but the circumstances of the rescue operation point to the need to equip ambulances with carbon dioxide detectors and hermetic oxygen masks. Med Pr 2017;68(1):135-138.

Introducing of the First DCD Kidney Transplantation Program in Poland.

In many countries, including Poland, the main problem with transplantation is the insufficiency of organ donors in relation to the demand for organs. Hence, the common aim globally is to increase the pool of donors. The prolonged survival of patients after transplantation, with respect to the survival time of patients on dialysis, makes the search much more intense. After the recourse of expanded criteria donors (ECD), the next step was obtaining kidneys from donors after irreversible cardiac death (DCD). Therefore, based on Dutch, British, and Spanish experience, it can be hypothesized that the introduction of DCD procedures in countries that have not launched these programs and the improvement of DCD procedures may shorten the waiting time for organ transplantation globally. The legal basis for the procurement of organs after irreversible cardiac arrest came into existence in Poland in 2010. Previously, such organ procurements were not in practice. Since 1984, when Poland published irreversible cardiac arrest as a criterion of brain death, it became the only way to determine death prior to the procurement of organs. The aim of this report was to evaluate the results of the first 19 transplantation cases involving harvested kidneys from donors after cardiac arrest, which was irreversible and clinically confirmed, without any doubt as per the ethical protocol of DCD. Understanding, support, and public perception are essential for this program's initiation and maintenance.

Increase of Soluble RAGE in Cerebrospinal Fluid following Subarachnoid Haemorrhage.

Receptors for advanced glycation end-products (RAGE) mediate the inflammatory reaction that follows aneurysmal subarachnoid haemorrhage. Soluble RAGE (sRAGE) may function as a decoy receptor. The significance of this endogenous anti-inflammatory mechanism in subarachnoid haemorrhage (SAH) remains unknown. The present study aims to analyse sRAGE levels in the cerebrospinal fluid (CSF) of SAH patients. sRAGE levels were assayed by ELISA kit in 47 CSF samples collected on post-SAH days 0-3, 5-7, and 10-14 from 27 SAH patients with acute hydrocephalus. CSF levels of sRAGE were compared with a control group and correlated with other monitored parameters. In the control group, the CSF contained only a trace amount of sRAGE. By contrast, the CSF of 20 SAH patients collected on post-SAH days 0-3 was found to contain statistically significant higher levels of sRAGE (mean concentration 3.91 pg/mL, p < 0.001). The most pronounced difference in CSF sRAGE levels between good and poor outcome patients was found on days 0-3 post-SAH but did not reach the significance threshold (p = 0.234). CSF sRAGE levels did not change significantly during hospitalisation (p = 0.868) and correlated poorly with treatment outcome, systemic inflammatory markers, and other monitored parameters. Our study revealed an early and constant increase of sRAGE level in the CSF of SAH patients.

Scaffolds from surgically removed kidneys as a potential source of organ transplantation.

End stage renal disease (ESRD) is a common disease, which relates to nearly 600 million people in the total population. What is more, it seems to be a crucial problem from the epidemiological point of view. These facts lead to a further necessity of renal replacement therapy development connected with rising expenditures for the health care system. The aim of kidney tissue engineering is to develop and innovate methods of obtaining renal extracellular matrix (ECM) scaffolds derived from kidney decellularization. Recently, progress has been made towards developing a functional kidney graft in vitro on demand. In fact, decellularized tissues constitute ideal natural scaffolds, due to the preservation of native ECM architecture, as well as of cell-ECM binding domains critical in promoting cell attachment, migration, and proliferation. One of the potential sources of the natural scaffolds is the kidney, which cannot be transplanted immediately after excision.