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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. [ABSTRACT FROM AUTHOR]

Introduction: The precise etiology of Crohn's disease (CD) is still to be explained. Recent data suggest that CD is due to a loss of balance between pro- and anti-inflammatory agents and the overactivity of Th1 and Th17 cells. Aim of the study: Our project was aimed to investigate the Th1/Th2/Th17 serum cytokine profile in patients with CD. Material and methods: A group of 50 adults with diagnosed CD was enrolled. All the patients were classified according to the Crohn's Disease Activity Index as having an active, moderate-to-severe form of CD (CDAI ≥220). Serum samples were cytometrically tested for concentrations of IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α and IFN-γ. Results: Statistical analysis showed significantly higher serum levels of IL-2, IL-6, IL-17A, TNF-α and IFN-γ in CD patients comparing to the control group (p<0.05). No significant differences in IL-4 and IL-10 serum levels were observed. In our study, we demonstrated the predominance of Th1 cytokine profile in the serum of moderate-to-severe CD patients. We also found higher levels of IL-17A, suggesting a possible role of recently discovered Th17 cells in the pathogenesis of CD. Conclusions: Active moderate-to-severe Crohn's disease is characterized by Th1/ Th17 serum cytokine profile. The precise role of Th17 cells, however, is still not known, and further research is needed to elucidate it and to explore the potential of new therapeutic strategies in CD patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Acute rejection (AR) remains a major problem after kidney transplantation and crucial determinant of long-term graft function. Potent mediators of alloimmune response leading to AR are cytokines. To further explore the relation between cytokine pattern and frequency of AR episodes we analyzed Th1/Th2 cytokine concentrations in the urine of 44 patients prior to the kidney transplantation. During the 6-month period following the transplantation AR was diagnosed in 11 patients. Urine samples were collected 1day before the transplantation. Samples were cytometrically tested for concentrations of IL-2, IL-4, IL-5, IL-10, IFN-γ and TNF-α. Analysis showed significantly higher pretransplant concentrations of IFN-γ (P > .001), TNF-α (P < .05) and IL-10 (P < .001) in the urine of patients with diagnosed AR. No significant differences in the concentrations of IL-2, IL-4, IL-5 between the two groups were observed. Elevated pretransplant concentrations of urine IFN-γ and TNF-α in AR patients, not accompanied by higher concentrations of IL-2, may suggest an ongoing undetected and local, non-specific Th1 immune response, capable of amplifying the alloimmune response in the early phase postsurgery. While higher concentrations of IL-10 can partially result from activation of monocytes/macrophages, and partially from peripheral regulatory mechanisms controlling the ongoing immune reaction. [Copyright &y& Elsevier]

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-1β, tumour necrosis factor alpha, and matrix metalloproteinase-9 abundance ranges were similar in venous leg ulcers and acute wound fluids. Collagen (I) a1 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective The authors tested whether the anti-interleukin (IL)-17A monoclonal antibody secukinumab was safe and effective for the treatment of active Crohn’s disease. Design In a double-blind, randomised, placebocontrolled proof-of-concept study, 59 patients with moderate to severe Crohn’s disease (Crohn’s Disease Activity Index (CDAI) $220 to #450) were assigned in a 2:1 ratio to 2310 mg/kg intravenous secukinumab or placebo. The primary end point, addressed by Bayesian statistics augmented with historical placebo information, was the probability that secukinumab reduces the CDAI by $50 points more than placebo at week 6. Ancillary analyses explored associations of 35 candidate genetic polymorphisms and faecal calprotectin response. Results 59 patients (39 secukinumab, 20 placebo, mean baseline CDAI 307 and 301, respectively) were recruited. 18/59 (31%) patients discontinued prematurely (12/39 (31%) secukinumab, 6/20 (30%) placebo), 10/59 (17%) due to insufficient therapeutic effect (8/39 (21%) secukinumab, 2/20 (10%) placebo). Fourteen serious adverse events occurred in 10 patients (seven secukinumab, three placebo); 20 infections, including four local fungal infections, were seen on secukinumab versus none on placebo. Primary end point analysis estimated <0.1% probability (ƒ¢CDAI (SD) .33.9 (19.7), 95% credible interval 4.9 to 72.9) that secukinumab reduces CDAI by $50 points more than placebo. Secondary area under the curve analysis (weeks 4e10) showed a significant difference (mean DCDAI.49; 95% CI (2 to 96), p.0.043) in favour of placebo. Post hoc subgroup analysis showed that unfavourable responses on secukinumab were driven by patients with elevated inflammatory markers (CRP$10 mg/l and/or faecal calprotectin$200 ng/ml; mean DCDAI.62; 95% CI (-1 to 125), p.0.054 in favour of placebo). Absence of the minor allele of tumour necrosis factor-like ligand 1A was strongly associated with lack of response measured by baseline-adjusted changes in calprotectin at week 6 (p.0.00035 Bonferroni-corrected). Conclusions Blockade of IL-17A was ineffective and higher rates of adverse events were noted compared with placebo. INSET: Significance of this study. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]