Nailfold Videocapillaroscopy for Non-Invasive Assessment of Microcirculation and Prognostic Correlation with Endothelial Dysfunction, Cardiovascular Risk Factors, and Non-HLA Antibodies in Heart Transplant Recipients: A Pilot Study.

Early identification of allograft vasculopathy and the concomitant elimination of adverse risk factors is essential for improving the long-term prognosis of heart transplant (HTx) recipients with underlying cardiovascular disease (CVD). The major aim of this pilot study was to conduct a non-invasive imaging evaluation of the HTx patient microcirculation by employing nailfold video-capillaroscopy (NVC) in a well-characterized patient and control cohort, and to correlate these data with endothelial cell function, accompanied by studies of traditional cardiovascular risk factors and non-HLA antibodies in HTx recipients. Ten patients undergoing HTx (mean age of 38 ± 14 years) were recruited for the study and compared to a control group of 12 well-matched healthy volunteers (mean age 35 ± 5 years) with normal body mass index (BMI). Detailed medical records were collected from all individuals. NVC was performed using CapillaryScope 200 MEDL4N microscope. For functional readout and correlation analysis, endothelial cell network formation in conjunction with measurements of patient serum levels of vascular endothelial growth factor (VEGF) and non-HLA autoantibodies directed against the angiotensin II type-1-receptor (anti-AT1R-Ab), endothelin-1 type-A-receptor (anti-ETAR-Ab), protease-activated receptor-1 (anti-PAR-1-Ab), and VEGF-A (anti-VEGF-A-Ab) were studied. Our NVC analysis found that the average apical loop diameter of nailfold capillaries was significantly increased in HTx recipients (p = 0.001). In addition, HTx patients with more prominent changes in capillaroscopic patterns were characterized by the presence of traditional cardiovascular risk factors, and HTx patients had increased levels of anti-AT1R-ab, anti-ETAR-ab, and anti-VEGF-A-Ab (p = 0.017, p = 0.025, and p = 0.003, respectively). Capillary diameters most strongly correlated with elevated serum levels of troponin T and triglycerides (R = 0.69, p = 0.028 and R = 0.81, p = 0.004, respectively). In conclusion, we found that an abnormal NVC pattern in HTx patients is associated with traditional CVD risk factors and that NVC is a useful non-invasive tool to conveniently monitor changes in the microvasculature of HTx patients.

Assessment of Clinical Indicators Registered on Admission to the Hospital Related to Mortality Risk in Cancer Patients with COVID-19.

BACKGROUND: Oncology patients are a particularly vulnerable group to the severe course of COVID-19 due to, e.g., the suppression of the immune system. The study aimed to find links between parameters registered on admission to the hospital and the risk of later death in cancer patients with COVID-19. METHODS: The study included patients with a reported history of malignant tumor (n = 151) and a control group with no history of cancer (n = 151) hospitalized due to COVID-19 between March 2020 and August 2021. The variables registered on admission were divided into categories for which we calculated the multivariate Cox proportional hazards models. RESULTS: Multivariate Cox proportional hazards models were successfully obtained for the following categories: Patient data, Comorbidities, Signs recorded on admission, Medications used before hospitalization and Laboratory results recorded on admission. With the models developed for oncology patients, we identified the following variables that registered on patients' admission were linked to significantly increased risk of death. They are: male sex, presence of metastases in neoplastic disease, impaired consciousness (somnolence or confusion), wheezes/rhonchi, the levels of white blood cells and neutrophils. CONCLUSION: Early identification of the indicators of a poorer prognosis may serve clinicians in better tailoring surveillance or treatment among cancer patients with COVID-19.

The Summarized Assessment of Endothelin A Receptor Expression in Renal Transplant Compartments Associated with Antibody-Mediated Rejection.

The occurrence of anti-endothelin A receptor antibodies may be useful in diagnosis of transplant damage. We noticed that the presence of the endothelin A receptor (ETA receptor) in biopsy compartments is yet to be defined. We decided therefore to analysed the presence and relevance of the ETA receptor in biopsy to define the cause. Our study aims to evaluate the expression of ETA receptors in renal recipients after a biopsy due to the worsening of transplant function. METHODS: The expression of ETA receptors was analyzed in renal transplant biopsies using the immunohistochemical method. The evaluation of ETA receptors was performed on paraffin sections. ETA receptor expression was analyzed in four compartments of renal transplant biopsies: glomeruli; vessels; tubular epithelium; and interstitium. The assessment was presented using a three-step scale (0: lack of expression; 1: mild to moderate immunoreactivity; 2: high expression). The results of each compartment from a single biopsy were summarized and assessed in the context of antibody-mediated rejection (AMR). RESULTS: We analyzed 156 patients who had a renal allograft biopsy after renal transplantation. For each patient, we created a summarized ETA receptor expression score. The summarized ETA receptor expression score analysis showed statistically significant differences in patients with and without AMR. In addition, we noticed that patients with AMR had a significantly higher mean summarized expression of ETA receptor score of 3.28 ± 1.56 compared to patients who had a biopsy for other reasons with a mean summarized ETA receptor expression score of 1.47 ± 1.35 (p < 0.000001). ROC analysis of the ETA receptor expression score for detecting AMR status showed that the most appropriate cut-off for the test of the chosen binary classifier is between 2 and 3 of the summarized ETA receptor expression score. CONCLUSIONS: The expression of endothelin A receptors in renal transplant compartments may be associated with antibody-mediated rejection. The positive ETA receptor staining might be a vital feature in the diagnosis of damage in AMR. The summarized ETA receptor expression score seems to be an exciting diagnostic tool in transplant injury assessment.

Effect of Perioperative Optimization of Arterial Oxygen Content and Perfusion Pressure on the Function of the Transplanted Kidney in the Retrospective Study of Excretory Function and Assessment of New Markers of Kidney Damage: IL-18, Neutrophil Gelatinase-Associated Lipocalin, and Clusterin.

INTRODUCTION: The concept of anesthesia, in which kidney perfusion is optimized, the use of nephrotoxic drugs is avoided, and general anesthesia with protective and preconditioning properties of the graft is applied, is a key element of the therapeutic strategy in kidney transplantation (KTx). MATERIAL AND METHOD: A total of 86 patients (mean age: 49.4 ± 14.0 years, 66% men) with end-stage renal disease who underwent KTx between 2012 and 2015 were included in this retrospective study. Our aim was to assess the effect of oxygen content in arterial blood and selected hemodynamic parameters on the graft function and the occurrence of delayed graft failure. RESULTS: No differences were found in baseline characteristics, indication for transplantation, and surgical technique used among study population. No correlation was found between oxygen delivery exponents and both standard markers of renal function and new biochemical markers (eg, IL-18, clusterin, and neutrophil gelatinase-associated lipocalin [NGAL]). DISCUSSION: In our study, hemodynamic parameters measured at scheduled intervals did not exceed the physiological range, which might have been the reason for the lack of correlation between the function of graft and the described hemodynamic conditions. At the same time, in the observed ranges of perfusion pressure during optimization of the oxygen content, no correlations were found with the postoperative function of the transplanted kidney. That observation could be a valuable conclusion for reducing the tendency of maintaining high blood pressure with the abuse of catecholamines, especially vasoconstrictors, and volume therapy, whose negative effect on tissue perfusion is unequivocal.

Assessment of Hemoglobin Levels in Patients Qualified for Kidney Transplantation in the Perioperative Period and Its Impact on the Occurrence of Delayed Graft Function.

BACKGROUND: Anesthesia in patients undergoing kidney transplantation (KTx) should be aimed at creating optimal hemodynamic conditions for the newly implanted kidney. Changes in of blood count, caused mainly by intraoperative hemodilution, may adversely affect the perioperative course by strengthening the pathologic mechanisms of ischemia-reperfusion syndrome. METHODS: A total of 86 patients (mean age: 49.4 ± 14.0 years, 66% men) with end-stage renal disease who underwent KTx between 2012 and 2015 were included in this retrospective study. Our aim was to assess the hemoglobin level and the effect of fluctuations caused by the implemented fluid therapy on graft function and the occurrence of delayed graft failure. RESULTS: There was no difference in baseline characteristics, indication for transplantation, and surgical technique used among study population. Among the whole observation group, no correlation was found between fluid therapy causing hemodilution with a decrease in hemoglobin concentration and the occurrence of delayed graft failure. CONCLUSIONS: In our observations, we paid special attention to the problem of hemodilution in patients undergoing KTx. It is important to emphasize the importance of proper preparation of the patient for KTx by earlier implementation of anemia therapy, thus preventing exacerbation of anemia in the postoperative period, especially because the perioperative use of blood products is associated with numerous complications and a worse prognosis for the newly implanted kidney.

Living donor transplantation--the real gift of life. Procurement and the ethical assessment.

It has been observed during the past 10-15 years a greater disparity between the supply of kidneys for transplantation and the demand of patients on waiting lists. The number of cadaveric kidneys available for transplantation have not increased in many countries. Countries and their societies are faced with a choice, let patients with the end- stage renal disease stay on, dialysis giving a faster death and a lower quality of life, or decide to introduce the more active living donation program. There are countries, historically Scandinavian countries, the U.S.A. and U.K., which decided to change medical, social and ethical attitudes to help their citizens and patients on dialysis. For many other countries approval of the new approach of their donation seems to cause difficulties. The main problem for medical staff is the principle Primum non nocere (First do no harm), removal of a living kidney conflicts with this principle. From the other point of view is the human right of an individual to autonomy for donation of a kidney. The donor is completely informed for the risks involved in donation of a kidney to an awaiting recipient. The donors reasons for donation of the kidney must be understood and family pressure excluded. Where is the borderline between the paternalistic approach of the medical personnel preventing the altruistic attitude of the donor? How far is the role of the medical staff to extend in the assessment of the altruistic nature and goodwill of the donors?