Assessment of omeprazole and famotidine effects on the pharmacokinetics of tacrolimus in patients following kidney transplant-randomized controlled trial.

Tacrolimus is metabolized in the liver with the participation of the CYP3A4 and CYP3A5 enzymes. Proton pump inhibitors are used in kidney transplant patients to prevent duodenal and gastric ulcer disease due to glucocorticoids. Omeprazole, unlike famotidine, is a substrate and inhibitor of the enzymes CYP2C19, CYP3A4, CYP3A5. The aim of this study was to compare the impact of omeprazole and famotidine on the pharmacokinetics of tacrolimus. A randomized, non-blinded study involving 22 stabilized adult kidney transplant patients was conducted. Patients received the standard triple immunosuppression regimen and omeprazole 20 mg (n = 10) or famotidine 20 mg (n = 12). The study material consisted of blood samples in which tacrolimus concentrations were determined using the Chemiluminescent Microparticle Immuno Assay method. A single administration of omeprazole increased tacrolimus concentrations at 2 h (day 2) = 11.90 ± 1.59 ng/mL vs. 2 h (day 1 - no omeprazole administration) = 9.40 ± 0.79 ng/mL (p = 0.0443). AUC0-6 amounted to 63.07 ± 19.46 ng × h/mL (day 2) vs. 54.23 ± 10.48 ng × h/mL (day 1), (p = 0.0295). AUC2-6 amounted to 44.32 ± 11.51 ng × h/mL (day 2) vs. 38.68 ± 7.70 ng × h/mL (day 1), (p = 0.0130). Conversely, no significant changes in values of pharmacokinetic parameters were observed for famotidine. Omeprazole significantly increases blood exposure of tacrolimus. The administration of famotidine instead of omeprazole seems safer for patients following kidney transplantation. Clinical Trial Registration: clinicaltrials.gov, identifier NCT05061303.

The role of genetic risk factors, diet, and gut microbiota in type 1 diabetes mellitus, pancreas and pancreatic islet transplantation.

Despite advances in insulin delivery and glucose monitoring technology, prevention of the progression of secondary complications in patients with type 1 diabetes (T1DM) remains a challenge. Beta cell replacement therapy in the form of islet or pancreas transplantation can restore long-term normoglycaemia with sustained periods of insulin independence among T1DM patients. However, the same genetic, behavioural, or gut microbiota-related factors that promoted autoimmunity and primary islet destruction may also affect the function of transplanted islets and the ultimate results of transplant procedures. In such cases, identifying genetic risk factors and modifying behavioural factors and those related to gut microbiota may be beneficial for the outcomes of transplant procedures. Herein, we review related literature to the identified current gap in knowledge to be addressed in future clinical trials.

Impaired Expression of Humanin during Adrenocortical Carcinoma.

The discovery of mitochondria-derived peptides (MDPs) has provided a new perspective on mitochondrial function. MDPs encoded by mitochondrial DNA (mtDNA) can act as hormone-like peptides, influencing cell survival and proliferation. Among these peptides, humanin has been identified as a crucial factor for maintaining cell survival and preventing cell death under various conditions. Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy that results from adrenal hormone dysfunction. This study aimed to investigate humanin expression in the adrenal tissue and serum of patients with ACC. For the first time, our study revealed significant reduction in the mRNA expression of humanin in patients with ACC compared to healthy controls. However, no significant changes were observed in the serum humanin levels. Interestingly, we identified a positive correlation between patient age and serum humanin levels and a negative correlation between tumor size and LDL levels. While the impaired expression of humanin in patients with ACC may be attributed to mitochondrial dysfunction, an alternative explanation could be related to diminished mitochondrial copy number. Further investigations are warranted to elucidate the intricate relationship among humanin, mitochondrial function, and ACC pathology.

Effects of Isoflavonoid and Vitamin D Synergism on Bone Mineral Density-A Systematic and Critical Review.

Phytoestrogens are non-steroidal plant compounds, which bind to α and ß estrogen receptors, thereby causing specific effects. The best-known group of phytoestrogens are flavonoids, including isoflavonoids-genistein and daidzein. They play a role in the metabolism of bone tissue, improving its density and preventing bone loss, which contributes to reducing the risk of fractures. Vitamin D is found in the form of cholecalciferol (vitamin D3) and ergocalciferol (vitamin D2) and is traditionally recognized as a regulator of bone metabolism. The aim of this review was to evaluate the synergistic effect of isoflavonoids and vitamin D on bone mineral density (BMD). The MEDLINE (PubMed), Scopus and Cochrane databases were searched independently by two authors. The search strategy included controlled vocabulary and keywords. Reference publications did not provide consistent data regarding the synergistic effect of isoflavonoids on BMD. Some studies demonstrated a positive synergistic effect of these compounds, whereas in others, the authors did not observe any significant differences. Therefore, further research on the synergism of isoflavonoids and vitamin D may contribute to a significant progress in the prevention and treatment of osteoporosis.

Creating an Innovative Artificial Intelligence-Based Technology (TCRact) for Designing and Optimizing T Cell Receptors for Use in Cancer Immunotherapies: Protocol for an Observational Trial.

BACKGROUND: Cancer continues to be the leading cause of mortality in high-income countries, necessitating the development of more precise and effective treatment modalities. Immunotherapy, specifically adoptive cell transfer of T cell receptor (TCR)-engineered T cells (TCR-T therapy), has shown promise in engaging the immune system for cancer treatment. One of the biggest challenges in the development of TCR-T therapies is the proper prediction of the pairing between TCRs and peptide-human leukocyte antigen (pHLAs). Modern computational immunology, using artificial intelligence (AI)-based platforms, provides the means to optimize the speed and accuracy of TCR screening and discovery. OBJECTIVE: This study proposes an observational clinical trial protocol to collect patient samples and generate a database of pHLA:TCR sequences to aid the development of an AI-based platform for efficient selection of specific TCRs. METHODS: The multicenter observational study, involving 8 participating hospitals, aims to enroll patients diagnosed with stage II, III, or IV colorectal cancer adenocarcinoma. RESULTS: Patient recruitment has recently been completed, with 100 participants enrolled. Primary tumor tissue and peripheral blood samples have been obtained, and peripheral blood mononuclear cells have been isolated and cryopreserved. Nucleic acid extraction (DNA and RNA) has been performed in 86 cases. Additionally, 57 samples underwent whole exome sequencing to determine the presence of somatic mutations and RNA sequencing for gene expression profiling. CONCLUSIONS: The results of this study may have a significant impact on the treatment of patients with colorectal cancer. The comprehensive database of pHLA:TCR sequences generated through this observational clinical trial will facilitate the development of the AI-based platform for TCR selection. The results obtained thus far demonstrate successful patient recruitment and sample collection, laying the foundation for further analysis and the development of an innovative tool to expedite and enhance TCR selection for precision cancer treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04994093; https://clinicaltrials.gov/ct2/show/NCT04994093. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45872.

The Enhanced Expression of ZWILCH Predicts Poor Survival of Adrenocortical Carcinoma Patients.

Zwilch kinetochore protein (ZWILCH) plays a key role in proper cell proliferation. The upregulation of the ZWILCH gene was observed in many types of cancers, but the association of ZWILCH with adrenocortical carcinoma (ACC) was not investigated so far. The main aim of the presented study was to verify if the enhanced level of the ZWILCH gene can be used as a diagnostic marker for ACC development and progression, as well as a predictor of survival time for ACC patients. The performed analyses included investigation of the ZWILCH expression profile in tumors with publicly available TCGA (The Cancer Genome Atlas) datasets and transcriptomic data from the Gene Expression Omnibus (GEO) database, as well as, in human biological samples of normal adrenal, adrenocortical carcinoma and in commercially available tissue microarrays. The findings demonstrate statistically significant higher ZWILCH gene expression in ACC tissue in comparison with normal adrenal glands. Furthermore, there is a strong correlation between ZWILCH upregulation and tumor mitotic rate and the probability of patient survival. The enhanced ZWILCH level is also connected with the activation of genes involved in cell proliferation and the inhibition of genes related to the immune system. This work contributes to a better understanding of the role of ZWILCH as an ACC biomarker and diagnostic tool.

A Rare Case of Dedifferentiated Liposarcoma with Osteosarcomatous Differentiation-Diagnostic and Therapeutic Challenges.

INTRODUCTION: Liposarcomas are the most common of all sarcomas. A well-differentiated liposarcoma can transform into a dedifferentiated liposarcoma with myogenic, osteo- or chondrosarcomatous heterologous differentiation. Genomic amplification of MDM2 gene is then characteristic. Treatment usually involves surgical resection to radically remove the tumor. Other treatments such as chemotherapy and radiotherapy may also be used. CASE REPORT: A 60-year-old patient was admitted to the hospital for surgical treatment of a left renal mass. The true location of the tumor was discovered only intraoperatively. The lesion was completely removed laparoscopically with preservation of the capsule. Genomic amplification of MDM2 gene was confirmed. One and a half years after surgery, despite the removal of the tumor without the surrounding margin of healthy tissue, the patient remains without recurrence. CONCLUSION: Dedifferentiated liposarcoma with osteosarcomatous differentiation is a sporadic case and may occur in various locations of the retroperitoneal space, also mimicking a renal tumor. The laparoscopic technique is a safe surgical treatment for tumors of unclear origin. Removal of dedifferentiated liposarcoma with osteosarcomatous differentiation tumor with preservation of the lesion capsule without maintaining a margin of healthy tissue also allows for long-term cure. Precise immunohistochemical and molecular studies may have an impact on the effectiveness of further treatment and the prognosis of the patient. A patient after surgical treatment of liposarcoma requires constant outpatient follow-up for the reason of the high risk of local and distant recurrence.

Longitudinal Evaluation of Biomarkers in Wound Fluids from Venous Leg Ulcers and Split-thickness Skin Graft Donor Site Wounds Treated with a Protease-modulating Wound Dressing.

Venous leg ulcers represent a clinical challenge and impair the quality of life of patients. This study examines impaired wound healing in venous leg ulcers at the molecular level. Protein expression patterns for biomarkers were analysed in venous leg ulcer wound fluids from 57 patients treated with a protease-modulating polyacrylate wound dressing for 12 weeks, and compared with exudates from 10 acute split-thickness wounds. Wound healing improved in the venous leg ulcer wounds: 61.4% of the 57 patients with venous leg ulcer achieved a relative wound area reduction of ≥ 40%, and 50.9% of the total 57 patients achieved a relative wound area reduction of ≥ 60%. Within the first 14 days, abundances of S100A8, S100A9, neutrophil elastase, matrix metalloproteinase-2, and fibronectin in venous leg ulcer exudates decreased significantly and remained stable, yet higher than in acute wounds. Interleukin-1ß, tumour necrosis factor alpha, and matrix metalloproteinase-9 abundance ranges were similar in venous leg ulcers and acute wound fluids. Collagen (I) α1 abundance was higher in venous leg ulcer wound fluids and was not significantly regulated. Overall, significant biomarker changes occurred in the first 14 days before a clinically robust healing response in the venous leg ulcer cohort.

Biological response of adrenal carcinoma and melanoma cells to mitotane treatment.

A previous case report described an adrenal incidentaloma initially misdiagnosed as adrenocortical carcinoma (ACC), which was treated with mitotane. The final diagnosis was metastatic melanoma of unknown primary origin. However, the patient developed rapid disease progression after mitotane withdrawal, suggesting a protective role for mitotane in a non-adrenal-derived tumor. The aim of the present study was to determine the biological response of primary melanoma cells obtained from that patient, and that of other established melanoma and ACC cell lines, to mitotane treatment using a proliferation assay, flow cytometry, quantitative PCR and microarrays. Although mitotane inhibited the proliferation of both ACC and melanoma cells, its role in melanoma treatment appears to be limited. Flow cytometry analysis and transcriptomic studies indicated that the ACC cell line was highly responsive to mitotane treatment, while the primary melanoma cells showed a moderate response in vitro. Mitotane modified the activity of several key biological processes, including 'mitotic nuclear division', 'DNA repair', 'angiogenesis' and 'negative regulation of ERK1 and ERK2 cascade'. Mitotane administration led to elevated levels of DNA double-strand breaks, necrosis and apoptosis. The present study provides a comprehensive insight into the biological response of mitotane-treated cells at the molecular level. Notably, the present findings offer new knowledge on the effects of mitotane on ACC and melanoma cells.

Angiogenic Role of Mesothelium-Derived Chemokine CXCL1 During Unfavorable Peritoneal Tissue Remodeling in Patients Receiving Peritoneal Dialysis as Renal Replacement Therapy.

Peritoneal dialysis (PD) is a valuable 'home treatment' option, even more so during the ongoing Coronavirus pandemic. However, the long-term use of PD is limited by unfavourable tissue remodelling in the peritoneal membrane, which is associated with inflammation-induced angiogenesis. This appears to be driven primarily through vascular endothelial growth factor (VEGF), while the involvement of other angiogenic signaling pathways is still poorly understood. Here, we have identified the crucial contribution of mesothelial cell-derived angiogenic CXC chemokine ligand 1 (CXCL1) to peritoneal angiogenesis in PD. CXCL1 expression and peritoneal microvessel density were analysed in biopsies obtained by the International Peritoneal Biobank (NCT01893710 at www.clinicaltrials.gov), comparing 13 children with end-stage kidney disease before initiating PD to 43 children on chronic PD. The angiogenic potential of mesothelial cell-derived CXCL1 was assessed in vitro by measuring endothelial tube formation of human microvascular endothelial cells (HMECs) treated with conditioned medium from human peritoneal mesothelial cells (HPMCs) stimulated to release CXCL1 by treatment with either recombinant IL-17 or PD effluent. We found that the capillary density in the human peritoneum correlated with local CXCL1 expression. Both CXCL1 expression and microvessel density were higher in PD patients than in the age-matched patients prior to initiation of PD. Exposure of HMECs to recombinant CXCL1 or conditioned medium from IL-17-stimulated HPMCs resulted in increased endothelial tube formation, while selective inhibition of mesothelial CXCL1 production by specific antibodies or through silencing of relevant transcription factors abolished the proangiogenic effect of HPMC-conditioned medium. In conclusion, peritoneal mesothelium-derived CXCL1 promotes endothelial tube formation in vitro and associates with peritoneal microvessel density in uremic patients undergoing PD, thus providing novel targets for therapeutic intervention to prolong PD therapy.

Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial.

Many patients with venous leg ulcers do not reach complete healing with compression treatment alone, which is current standard care. This clinical trial HEAL LL-37 was a phase IIb double-blind, randomized, placebo-controlled study, with the aim to evaluate the efficacy and safety of a new drug LL-37 for topical administration, in combination with compression therapy, in 148 patients suffering from hard-to-heal venous leg ulcers. The study had three arms, consisting of two groups treated with LL-37 at concentrations of 0.5 or 1.6 mg/mL, and a placebo cohort. Patients had a mean age of 67.6 years, a median ulcer duration of 20.3 months, and a mean wound size at the time of randomization of 11.6 cm2 . Efficacy analysis performed on the full study population did not identify any significant improvement in healing in patients treated with LL-37 as compared with the placebo. In contrast, a post hoc analysis revealed statistically significant improvement with LL-37 treatment in several interrelated healing parameters in the subgroup of patients with large target wounds (a wound area of at least 10 cm2 at randomization), which is a known negative prognostic factor for healing. The study drug was well tolerated and safe in both dose strengths. In summary, this clinical trial did not detect any significant differences in healing of venous lower leg ulcers in the entire study cohort comparing patients treated with LL-37 versus placebo. A subgroup analysis provided an interesting observation that LL-37 could offer a treatment benefit in patients with large ulcers, exigently warranting a further study adequately powered to statistically assess the treatment outcome in this patient group.

Adropin Stimulates Proliferation and Inhibits Adrenocortical Steroidogenesis in the Human Adrenal Carcinoma (HAC15) Cell Line.

Adropin is a multifunctional peptide hormone encoded by the ENHO (energy homeostasis associated) gene. It plays a role in mechanisms related to increased adiposity, insulin resistance, as well as glucose, and lipid metabolism. The low adropin levels are strongly associated with obesity independent insulin resistance. On the other hand, overexpression or exogenous administration of adropin improves glucose homeostasis. The multidirectional, adropin-related effects associated with the regulation of metabolism in humans also appear to be attributable to the effects of this peptide on the activity of various elements of the endocrine system including adrenal cortex. Therefore, the main purpose of the present study was to investigate the effect of adropin on proliferation and secretory activity in the human HAC15 adrenal carcinoma cell line. In this study, we obtained several highly interesting findings. First, GPR19, the main candidate sensitizer of adrenocortical cells to adropin, was expressed in HAC15 cells. Moreover, GPR19 expression was relatively stable and not regulated by ACTH, forskolin, or adropin itself. Our findings also suggest that adropin has the capacity to decrease expression levels of steroidogenic genes such as steroidogenic acute regulatory protein (StAR) and CYP11A1, which then led to a statistically significant inhibition in cortisol and aldosterone biosynthesis and secretion. Based on whole transcriptome study and research involving transforming growth factor (TGF)-ß type I receptor kinase inhibitor we demonstrated that attenuation of steroidogenesis caused by adropin is mediated by the TGF-ß signaling pathway likely to act through transactivation mechanism. We found that HAC15 cells treated with adropin presented significantly higher proliferation levels than untreated cells. Using specific intracellular inhibitors, we showed that adropin stimulate proliferation via ERK1/2 and AKT dependent signaling pathways. We have also demonstrated that expression of GPR19 is elevated in adrenocortical carcinoma in relation to normal adrenal glands. High level of GPR19 expression in adrenocortical carcinoma may constitute a negative prognostic factor of disease progression.

Abnormal Nailfold Capillaries in Patients after Hand Transplantation.

BACKGROUND: The development of graft vasculopathy may play a role in the long-term deterioration of hand grafts. The aim of study was to examine the patterns of the nailfold capillaries in hand transplant recipients. METHODS: the study was performed on six patients who received hand transplantation. To normalize for the effect of immunosuppression an age- and sex-matched group of 12 patients with active kidney transplant was selected. As an additional control group, 12 healthy volunteers were recruited. Nailfold videocapillaroscopy was performed in all participants. Additionally, serum concentrations of vascular endothelial growth factor (VEGF) were measured. RESULTS: Videocapillaroscopic examination of the hand allografts revealed significant abnormalities: including capillary disorganization and microhaemorrhages. The number of capillaries was reduced, the vessels were enlarged and branched. Surprisingly, similar, albeit slightly less pronounced, changes were seen in the nailfolds of healthy hands of the limb transplant recipients. In kidney transplant recipients the capillaroscopic pattern was general normal and comparable to healthy individuals. Moreover, serum concentrations of VEGF in all participants correlated with average capillary diameter in capillaroscopy. CONCLUSIONS: in hand transplant recipients advanced microvascular abnormalities are found in nailfold capillaroscopic pattern in both transplanted and own extremities connected with elevated levels of VEGF.

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.

Ghrelin as a potential molecular marker of adrenal carcinogenesis: In vivo and in vitro evidence.

CONTEXT: Adrenal tumours belong to one of the most prevalent neoplasms. It is a heterogeneous group with different aetiology, clinical manifestation and prognosis. Its histopathologic diagnosis is difficult and identification of differentiation markers for tumorigenesis is extremely valuable for diagnosis. DESIGN: To assess ghrelin expression and the relationship among ghrelin, IGF2 and the clinicopathological characteristics of adrenal tumours. To investigate the influence of ghrelin on ACC cell line proliferation. MATERIALS AND METHODS: Expression of ghrelin and IGF2 in a total of 84 adrenal tissue samples (30 adenoma, 12 hyperplasia, 8 myelolipoma, 20 pheochromocytoma, 7 carcinoma and 7 unchanged adrenal glands) were estimated. Every operated patient from whom samples were obtained underwent clinicopathological analysis. All the parameters were compared among the groups examined and correlations between these were estimated. H295R cell line was incubated with ghrelin to assess its effect on proliferation and migration rate. RESULTS: The highest ghrelin expression was observed in carcinoma samples and the lowest in the control group. Ghrelin expression was 21 times higher in carcinoma (P = .017) and 2.4 times higher in adenoma (P = .029) compared with controls. There were no statistically significant differences between myelolipoma (P = .093) and pheochromocytoma (P = .204) relative to the control. Ghrelin level was significantly higher in carcinoma compared to adenoma (P = .049) samples. A positive correlation between ghrelin and IGF2 expression was observed only in myelolipoma (P = .001). Ghrelin at concentrations of 1 × 10-6  mol/L and 1 × 10-8  mol/L significantly stimulated proliferation and migration rate in the H295R cell line. CONCLUSION: Ghrelin appears to be an essential factor in driving adrenal tumours development.

Exposure to hepatitis E virus, hepatitis A virus and Borrelia spp. infections in forest rangers from a single forest district in western Poland.

BACKGROUND: Hepatitis E virus (HEV) infection is an emerging problem in developed countries. At least 2 zoonotic genotypes of the virus (HEV-3 and HEV-4) infect human beings. There are some data suggesting that forest rangers (FRs) can be at a higher risk of contact with HEV. OBJECTIVES: The aim of this study was to assess the prevalence of HEV exposure markers in FRs from a single forest district in Greater Poland in relation to anti-HAV (hepatitis A virus) IgG, and anti-Borrelia spp. IgM and IgG antibodies. MATERIAL AND METHODS: In total, 138 participants (48 FRs and 90 blood donors - BDs) were tested for anti-HEV IgM and IgG (EUROIMMUN Medizinische Labordiagnostika AG, Luebeck, Germany) and 96 individuals (48 FRs and 48 BDs) were tested for anti-HAV IgG (ARCHITECT immunoassays, Abbott Laboratories, Wiesbaden, Germany); anti-Borrelia IgM and IgG (EUROIMMUN kits) were assessed in FRs only. RESULTS: Anti-HEV markers were detected in 3 participants (2.2%; IgM in 1 FR, IgG in 2 BDs), less frequently than anti-HAV (16 out of 96 individuals, about 17%; FRs 19% vs BDs 15%) or anti-Borrelia antibodies (18 out of 48 individuals, 37.5%) (p < 0.0001 for both). Older study participants (≥45 years of age) were more frequently HAV-seropositive (29% vs 4% of the younger individuals; p = 0.0012). CONCLUSIONS: We failed to unequivocally prove HEV exposure in FRs. The HAV seroprevalence in this study paralleled the situation in the general population. Exposure to Borrelia spp. in FRs was common.

Neurologic complications in kidney transplant recipients.

Transplantology experiences continuous growth and kidney transplantation is the most frequently transplanted solid organ. Metabolic, cardiovascular, infectious or kidney function-related aspects are widely recognised and are of key interest for transplant doctors. Neurological complications seen in these patients, although known, are less covered in the literature. According to some reports, neurologic symptoms are experienced by almost 9 per 10 transplant recipients. The intensity, severity and type of abnormalities may vary, and most frequently the complications seem to be associated with a direct or indirect effect of immunosuppressive medications, including their direct effect on cells, on blood vessels, and susceptibility to infections. Increasing age of transplant recipients and relaxation of transplantation eligibility criteria enriches the population with patients already compromised, with a higher present risk of stroke, neuropathy, malignancy etc. Research on and introduction to clinical practice of new agents like belatacept, proteasome inhibitors, or modified release formulations of tacrolimus, changes the picture and type of abnormalities within the nervous or neuromuscular system but does not eliminate them. Thus, it seems justified to remind the society of the whole array of neurologic complications they can see in their practice despite advances in the field..

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.

The role of extracorporeal membrane oxygenation in patients after irreversible cardiac arrest as potential organ donors.

The number of people waiting for a kidney or liver transplant is growing systematically. Due to the latest advances in transplantation, persons after irreversible cardiac arrest and confirmation of death have become potential organ donors. It is estimated that they may increase the number of donations by more than 40%. However, without good organization and communication between pre-hospital care providers, emergency departments, intensive care units and transplantation units, it is almost impossible to save the organs of potential donors in good condition. Various systems, including extracorporeal membrane oxygenation (ECMO), supporting perfusion of organs for transplantation play a key role. In 2016 the "ECMO for Greater Poland" program was established. Although its main goal is to improve the survival rate of patients suffering from life-threatening cardiopulmonary conditions, one of its branches aims to increase the donation rate in patients with irreversible cardiac arrest. In this review, the role of ECMO in the latter group as the potential organ donors is presented.

Preliminary observations on the association between serum IL-6 and hydration status and cardiovascular risk in patients treated with peritoneal dialysis.

INTRODUCTION: Systemic inflammation, as defined by elevated blood IL-6, is a strong independent predictor of peritoneal dialysis (PD) patient survival. The present study has aimed to determine whether there exists a particular "phenotype" associated with high systemic IL-6 that characterizes PD patients in terms of their fluid status and cardiac parameters. METHODS: Fifty-seven prevalent PD patients were classified according to serum concentrations of IL-6. The degree of overhydration was assessed by bioimpedance analysis (BIA). Echocardiography and serum concentrations of NT-proBNP and troponin T were used to assess cardiovascular risk. RESULTS: Patients with high serum IL-6 were older, more often diabetic, treated with PD for longer, and significantly more overhydrated. There was a significant correlation between serum IL-6, hydration status (r=0.38; p=0.002) and serum albumin (r=-0.35; p=0.009). Multivariate regression analysis confirmed a strong association of overhydration, hypoalbuminemia, and systemic IL-6 concentration. Patients with high IL-6 had significantly increased levels of both NT-proBNP (r=0.36; p=0.006) and TnT (r=0.50; p<0.001) in the absence of abnormalities in echocardiography. CONCLUSIONS: High systemic IL-6 identifies PD patients with increased cardiovascular risk that is significantly related to overhydration. Thus, the measurement of serum IL-6 may contribute to the more accurate assessment of cardiovascular status in patients undergoing PD.