Medium Extracellular Vesicles-A Qualitative and Quantitative Biomarker of Prostate Cancer.

For years, the diagnosis of prostate cancer has been understated. Despite the relatively low mortality rate, prostate cancer is still one of the most common neoplasms in men, which proves the need for continuous improvements in the diagnostics of this disease. New biomarkers may address these challenges in the form of extracellular vesicles (EV) secreted by prostate cancer cells. The available literature in the PubMed, SCOPUS, and ResearchGate databases from the last ten years was analyzed using search phrases such as extracellular vesicles, microparticles, microvesicles, cancer biomarkers, and prostate cancer. Then, the research was selected in terms of the size of the tested EVs (the EV medium of 100-1000 nm diameter, was taken into account), the latest versions of the literature were selected and compiled, and their results were compared. The group of extracellular vesicles contain a substantial amount of genetic information that can be used in research on the specificity of prostate cancer and other cancers. So far, it has been shown that EVs produced by PCa cells express proteins specific for these cells, which, thanks to their specificity, can make EV useful biomarkers of prostate cancer. Moreover, the importance of the quantitative release of EV from PCa cells has been demonstrated, which may be necessary to diagnose prostate cancer malignancy. Each method positively correlates with Gleason's results and is even characterized by greater diagnostic sensitivity. Medium extracellular vesicles are a promising research material, and their specificity and sensitivity may allow them to be used in future prostate cancer diagnostics as biomarkers.

Neutrophil-to-Lymphocyte Ratio Predicts Early Neurological Deterioration after Endovascular Treatment in Patients with Ischemic Stroke.

The worsening of neurological status that occurs early after acute ischemic stroke (AIS) remains a serious issue, and the inflammatory response plays a key role in stroke pathobiology. Recently, endovascular treatment (EVT) has revolutionized the management and outcome of patients with AIS due to either extracranial carotid disease or intracranial disease. The neutrophil-to-lymphocyte ratio (NLR) represents an easily available inflammatory biomarker. The aim of the study was to assess the relationship between the NLR at admission and the occurrence of early neurological deterioration (END) in patients with AIS who underwent EVT. Patients with AIS and proximal arterial occlusion in the anterior circulation undergoing EVT were retrospectively identified. Absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) were collected from admission blood work to calculate the NLR. The study outcome was END defined as an increase in at least 4 points in NIHSS score or death between baseline and 24 h after the ischemic event. Patients included were 211, and END occurred in 30 (14.2%). Patients with older age (OR = 1.07, 95% CI: 1.02−1.13), higher serum glucose (OR = 1.01, 95% CI: 1.01−1.02), and higher NLR (OR = 1.011, 95% CI: 1.04−1.18) had an increased risk of END. The best predictive cut-off value of NLR was 6.4, and END occurred in 24.1% and 3.9% of the patients with NLR ≥ 6.4 and <6.4, respectively (p < 0.001). In patients with AIS undergoing EVT, higher NLR values predicted a higher risk of END. Biomarkers able to identify inflammatory mechanisms might identify novel treatment targets and enhance proof-of-concept trials of immunomodulation in stroke.

Does ASTRAL score at hospital admission predict symptomatic haemorrhagic transformation in acute ischaemic stroke after revascularisation? A pilot single-centre study.

INTRODUCTION: Accurately predicting outcomes after acute ischaemic stroke (AIS) is a major clinical goal. The aim of this pilot study was to evaluate the prognostic validity and accuracy of the Acute Stroke Registry and Analysis of Lausanne (ASTRAL) score in predicting symptomatic haemorrhagic transformation (sHT) in patients with AIS who have undergone revascularisation. MATERIAL AND METHODS: Consecutive patients hospitalised for AIS who underwent treatment with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) were identified, and their ASTRAL scores at hospital admission were estimated. The study endpoint was sHT within 24 hours of stroke onset. The predictive performance of the ASTRAL score was investigated through logistic regression analysis and discrimination and calibration tests. RESULTS: Sixty-eight AIS patients, with a median age of 69 (58-79) years, were included. sHT occurred in 20 (29.4%) of the 68 patients. The ASTRAL score was significantly higher in patients who developed sHT compared to non-sHT patients [36 (34-38) versus 24 (17-32); p<0.001]. The ASTRAL score was an independent predictor of sHT, and showed good discriminative power (area under the curve 0.88; 95% confidence interval, 0.789-0.965). CONCLUSIONS AND CLINICAL IMPLICATIONS: ASTRAL score is an independent predictor of sHT and shows high predictive accuracy in patients with AIS. Future studies are warranted to confirm these results.

Biomarkers in the Prediction of Hemorrhagic Transformation in Acute Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Hemorrhagic transformation (HT) is a complication that occurs spontaneously or after thrombolysis in acute ischemic stroke (AIS) and can increase morbidity and mortality. The association of biomarkers with the risk of HT has been variably reported. We conducted a systematic review of the literature and meta-analysis and sought to compare blood biomarkers associated with HT and its subtypes by evaluating its predictability and correlation with outcome in AIS. METHODS: The study protocol was registered in the PROSPERO database (CRD42020201334) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Among 2,230 articles identified from Cochrane Library, PubMed, and Web of Science databases, 30 quality-appraised articles were found eligible. Meta-analysis was conducted for matrix metalloproteinase-9 (MMP-9), cellular fibronectin (c-Fn), ferritin, S100 calcium-binding protein B (S100B), and neutrophil-lymphocyte ratio (NLR). We also reviewed biomarkers for correlation with the functional outcome at 90 days from stroke onset (poor outcome modified Rankin scale >2). RESULTS: The pooled diagnostic odds ratio (DORpooled) was the highest for baseline c-Fn levels (299.253 [95% CI, 20.508-4,366.709]), followed by MMP-9 (DORpooled, 29.571 [95% CI 17.750-49.267]) and ferritin (DORpooled, 24.032 [95% CI 2.557-225.871]). However, wide confidence intervals for ferritin and c-Fn suggested lesser reliability of the markers. Patients with MMP-9 levels ≥140 ng/mL were 29.5 times at higher risk of developing symptomatic HT after AIS (area under the curve = 0.881). S100B (DORpooled, 6.286 [95% CI, 1.861-21.230]) and NLR (DORpooled, 5.036 [95% CI, 2.898-8.749]) had lower diagnostic accuracies. Among the markers not included for meta-analysis, caveolin-1, thrombin-activated fibrinolysis inhibitor, plasminogen activator inhibitor-1, and soluble ST2 were highly sensitive. Elevated levels of MMP-9, ferritin, and NLR were found to be associated with poor functional outcomes and mortality. CONCLUSION: Of the 5 biomarkers, there was enough evidence that MMP-9 has higher diagnostic accuracy for predicting the risk of HT before thrombolysis. MMP-9, ferritin, and NLR also predicted poor short-term outcomes.

Mechanical Thrombectomy in Stroke. Experience from Switching from Stent Retriever Only to Stent Retriever Combined with Aspiration Catheter.

Endovascular treatment is a rapidly evolving technique; therefore, there is a constant need to evaluate this method and its modifications. This paper discusses a single-center experience and the results of switching from the stent retriever only (SO) mechanical thrombectomy (MT) to the combined approach (CA), with a stent retriever and aspiration catheters. METHODS: The study involved a retrospective analysis of 70 patients undergoing MT with the use of either SO or CA. The primary endpoint was the frequency of perfect reperfusion defined as grade 3 of the modified Thrombolysis in Cerebral Infarction scale (mTICI) after the first pass. The secondary endpoints were the procedure success, defined as mTICI grades 2b-3; time of the procedure; clinical outcome, measured by 90 days' modified Rankin Scale (mRS) score; Δ NIHSS, defined as the difference between National Institutes of Health Stroke Scale (NIHSS) score at patients' admission and discharge; and the total number of device passes. RESULTS: Out of the 70 patients included, 33 were treated with SO and 37 with CA. In both groups, a total number of 42 patients received intravenous recombined tissue plasminogen activator (iv-rTPA: 20 patients (60.6%) in the SO group and 22 patients (59.5%) in the CA group (p = 1.000). There was a significant difference between the groups regarding first-pass success rate, with 46% in the CA group and 18% in the SO group, (OR 3.83, 95% CI 1.28 to 11.44, p = 0.016). Complete procedure success tended to be more frequent in the CA group than in the SO group-94.6% vs. 84.8% (OR 3.13, 95% CI 0.56 to 17.34, p = 0.193)-and CA tended to require a lower number of passes than SO (mean 1.76 vs. 2.09 passes per procedure, p = 0.114), yet these differences did not reach statistical significance. Mean duration of the procedure was significantly shorter in the CA group than in the SO group (49 min vs. 64 min, p = 0.017). There was a significant difference in clinical outcomes, with higher Δ NIHSS (9.3 in the CA group vs. 6.7 in the SO group, p = 0.025) after the procedure and 90-day mRS (median 2 in the CA group vs. 4 in the SO group, p = 0.031). CONCLUSIONS: Combining stent retrievers with aspiration catheters may offer a beneficial effect on angiographic results and clinical outcomes in stroke patients undergoing endovascular treatment.

Tractography Alterations in the Arcuate and Uncinate Fasciculi in Post-Stroke Aphasia.

Fiber tractography based on diffuse tensor imaging (DTI) can reveal three-dimensional white matter connectivity of the human brain. Tractography is a non-invasive method of visualizing cerebral white matter structures in vivo, including neural pathways surrounding the ischemic area. DTI may be useful for elucidating alterations in brain connectivity resulting from neuroplasticity after stroke. We present a case of a male patient who developed significant mixed aphasia following ischemic stroke. The patient had been treated by mechanical thrombectomy followed by an early rehabilitation, in conjunction with transcranial direct current stimulation (tDCS). DTI was used to examine the arcuate fasciculus and uncinate fasciculus upon admission and again at three months post-stroke. Results showed an improvement in the patient's symptoms of aphasia, which was associated with changes in the volume and numbers of tracts in the uncinate fasciculus and the arcuate fasciculus.

The Impact of Electrical Stimulation of the Brain and Spinal Cord on Iron and Calcium-Phosphate Metabolism.

BACKGROUND: Deep-brain stimulation (DBS) electrically modulates the subcortical brain regions. Under conditions of monopolar cerebral stimulation, electrical current flows between electrode's contacts and an implantable pulse generator, placed in the subclavicular area. Spinal cord stimulation (SCS) delivers an electrical current to the spinal cord. Epidural electrical stimulation is associated with the leakage of current, which can cause a generalized reaction. The aim of our study was to investigate whether the electrical stimulation of the cerebrum and spinal cord could have generalized effects on biochemical parameters. MATERIALS AND METHODS: A total of 25 patients with Parkinson's disease (PD, n = 21) and dystonia (n = 4), who underwent DBS implantation, and 12 patients with chronic pain, who had SCS, received electrical stimulation. The blood levels of selected biochemical parameters were measured before and after overnight stimulation. RESULTS: After DBS, the mean ± interquartile range (IQR) values for iron (off 15.6 ± 13.53 µmol/L; on: 7.65 ± 10.8 µmol/L; p < 0.001), transferrin (off: 2.42 ± 0.88 g/L; on: 1.99 ± 0.59 g/L; p < 0.001), transferrin saturation (off: 23.20 ± 14.50%; on: 10.70 ± 11.35%; p = 0.001), phosphate (off: 1.04 ± 0.2 mmol/L; on: 0.83 ± 0.2 mmol/L; p = 0.007), and total calcium (off: 2.39 ± 0.29 mmol/L; on: 2.27 ± 0.19 mmol/L; p = 0.016) were significantly reduced, whereas ferritin (off: 112.00 ± 89.00 ng/mL; on: 150.00 ± 89.00 ng/mL; p = 0.003) and C-reactive protein (off: 0.90 ± 19.39 mg/L; on: 60.35 ± 35.91 mg/L; p = 0.002) were significantly increased. Among patients with SCS, significant differences were observed for ferritin (off: 35 ± 63 ng/mL; on: 56 ± 62 ng/mL; p = 0.013), transferrin (off: 2.70 ± 0.74 g/L; on: 2.49 ± 0.69 g/L; p = 0.048), and C-reactive protein (off: 31.00 ± 36.40 mg/L; on: 36.60 ± 62.030 mg/L; p = 0.018) before and after electrical stimulation. No significant changes in the examined parameters were observed among patients after thalamotomy and pallidotomy. CONCLUSIONS: Leaking electric current delivered to the subcortical nuclei of the brain and the dorsal column of the spinal cord exposes the rest of the body to a negative charge. The generalized reaction is associated with an inflammatory response and altered iron and calcium-phosphate metabolism. Alterations in iron metabolism due to electrical stimulation may impact the course of PD. Future research should investigate the influence of electric current and electromagnetic field induced by neurostimulators on human metabolism.

Endovascular Treatment of Stroke Caused by Carotid Artery Dissection.

Ischemic stroke due to large vessel occlusion (LVO) is a devastating condition. Most LVOs are embolic in nature. Arterial dissection is responsible for only a small proportion of LVOs, is specific in nature and poses some challenges in treatment. We describe 3 cases where patients with stroke caused by carotid artery dissection were treated with mechanical thrombectomy and extensive stenting with good outcome. We believe that mechanical thrombectomy and stenting is a treatment of choice in these cases.

Neutrophil-to-Lymphocyte Ratio and Symptomatic Hemorrhagic Transformation in Ischemic Stroke Patients Undergoing Revascularization.

OBJECTIVES: Symptomatic hemorrhagic transformation (sHT) is a life-threatening complication of acute ischemic stroke (AIS). The early identification of the patients at increased risk of sHT can have clinically relevant implications. The aim of this study was to explore the validity and accuracy of the neutrophil-to-lymphocyte ratio (NLR) in predicting sHT in patients with AIS undergoing revascularization. METHODS: Consecutive patients hospitalized for AIS who underwent intravenous thrombolysis, mechanical thrombectomy or both were identified. The NLR values were estimated at admission. The study endpoint was the occurrence of sHT within 24 h from stroke treatment. RESULTS: Fifty-one patients with AIS were included, with a median age of 67 (interquartile range, 55-78) years. sHT occurred in 10 (19.6%) patients. Patients who developed sHT had higher NLR at admission. NLR was an independent predictor of sHT and showed good discriminatory power (area under the curve 0.81). In a multivariable analysis, NLR and systolic blood pressure were independently associated with sHT. CONCLUSIONS: NLR at admission can accurately predict sHT in patients with AIS undergoing revascularization.

Prevalence of Lower Extremity Arterial Disease as Measured by Low Ankle-Brachial Index in Patients with Acute Cerebral Ischemic Events.

BACKGROUND: Low ankle-brachial index (ABI) of ≤0.9 is diagnostic of lower extremity arterial disease (LEAD). It is also a strong marker of generalized atherosclerosis. The objective of this study was to assess the prevalence of low ABI in patients with acute cerebral ischemic events (ACIE): ischemic stroke (IS) or transient ischemic attack (TIA). METHODS: We compared 150 inpatients with ACIE to 50 inpatient controls and assessed risk factors, ABI measurements, and Duplex ultrasound of the cervical vessels. RESULTS: Low ABI was seen in 69 patients (46%) in the ACIE group and in 8 (16%) in the control group; p < 0.01. The mean and median ABI values in the ACIE group were 0.88 (SD = 0.22) and 0.91 (0.24-1.33), which were significantly lower than in the control group: 1.04 (SD = 0.16) and 1.0 (0.66-1.36); p < 0.0001, respectively. Coronary artery disease, carotid stenosis of ≥50% and smoking were risk factors, which were associated with significantly lower ABI in the study group; the ABI with risk factors vs. without was 0.85 vs. 0.92 (coronary artery disease); p < 0.05, 0.7 vs. 0.92; (carotid stenosis) p < 0.001 and 0.83 vs. 0.98; (smoking) p < 0.001, respectively. CONCLUSION: Our study demonstrated that patients with ACIE have significantly higher involvement of another vascular bed as LEAD. Coronary artery disease, carotid stenosis ≥50% and smoking were main risk factors associated with coexistence of LEAD and ACIE.

Association of Neutrophil-to-Lymphocyte Ratio and Lymphocyte-to-Monocyte Ratio with Treatment Modalities of Acute Ischaemic Stroke: A Pilot Study.

Background and Objectives: Ischaemic stroke (IS) is the leading cause of death and disability worldwide. All stages of cerebral ischaemia, but especially acute phase, are associated with inflammatory response. Recent studies showed that neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) may be used to assess inflammation in IS. To test whether there is a relationship between these parameters and type of stroke treatment, we analysed NLR and LMR in IS patients treated with three different modalities. Materials and Methods: The study included 58 adults with acute IS. A total of 28 patients received intravenous thrombolysis. In another 10 patients, the thrombolytic therapy was followed by thrombectomy and 20 patients did not undergo causal treatment. Blood samples were obtained within 24 h of the stroke diagnosis to calculate NLR and LMR. Next, NLR and LMR of the study subgroups were compared. Results: Our study revealed that NLR was significantly higher in patients treated with thrombectomy following thrombolysis, compared to no causal treatment. Statistical analysis demonstrated that patients with high National Institutes of Health Stroke Scale (NIHSS) scores presented higher NLR than in those with low NIHSS scores. Additionally, patients with high-sensitivity C-reactive protein (hs-CRP) ≥ 3 mg/L presented with significantly higher NLR and significantly lower LMR than the group of patients with lower hs-CRP (<3 mg/L). Conclusions: The main finding of this pilot study was that NLR in IS patients treated using thrombectomy following thrombolysis was markedly higher than that in other treatment groups, which was associated with increased severity of the disease in these patients. Therefore, patients with higher NLR may be expected to have more severe stroke. The link between stroke severity and NLR deserves further study.

Effectiveness of tonic and burst motor cortex stimulation in chronic neuropathic pain.

Background: Motor cortex stimulation (MCS) is an intracranial, invasive method for treatment of chronic pain. Main indications for MCS are central post stroke pain, neuropathic facial pain, phantom limb pain and brachial plexus or spinal cord injury pain. Spinal cord stimulation (SCS) with burst waveform has been proved to be more effective than tonic mode in chronic pain. Necessity to replace depleted batteries of motor cortex tonic stimulators gave us an opportunity of applying burst stimulation. The objective of the pilot study was to evaluate the effects of burst stimulation applied on motor cortex in patients with chronic pain syndromes as well as comparison to tonic mode. Materials and methods: We have evaluated 6 patients (females N=3, males N=3) belonging to the group of 14 cases (females N=5, males N=9) who had undergone surgical procedure of MCS in years 2005-2017. Selected for the study were 6 patients with thalamic pain N=3, with facial pain N=3 (anaesthesia dolorosa and neuropathic trigeminal neuralgia). The patients were subjected to both modes of stimulation then they chose which one was better in relieving pain: tonic or burst. Pain intensity was assessed with the visual analogue scale (VAS) before the replacement of implanted pulse generator (IPG) and after the stimulation with tonic and burst modes. Results: In the study, 5 out of 6 patients with MCS found burst mode more effective than tonic mode. Baseline VAS score in patients that had at least 3 months depleted battery of tonic IPG was 95 mm. After implantation of a new IPG mean VAS score on tonic stimulation was 72 mm, on burst 53 mm. Conclusions: The most preferred option of MCS in selected group of patients was burst stimulation. This study has shown, that the burst stimulation of cerebral cortex is a promising modality when tonic stimulation is not sufficient in refractory, neuropathic pain.

Assessing Circulating Factor VIIa-Antithrombin Complexes in Acute Ischemic Stroke: A Pilot Study.

AIM: The goal of this study was to determine the levels of factor VII (FVII), factor VIIa-antithrombin complexes (FVIIa-AT), total tissue factor (TF), and tissue factor-bearing microparticles (MPs-TF) in patients with acute ischemic stroke. Further, we sought evidence of an association between hemostatic markers, time of blood sampling, type of treatment, and patient outcomes. METHODS: Venous blood samples were collected from 33 patients on the first day and on the seventh day after stroke diagnosis. Age-matched controls were also included (n = 20). Plasma levels of FVII, FVIIa-AT, total TF, and MPs-TF were measured by enzyme-linked immunosorbent assay. We divided patients into 2 groups: thrombolysis group (n = 13) and nonthrombolysis group (n = 20). Furthermore, evaluation of the National Institutes of Health Stroke Scale and the Barthel Index was performed on the first day and the seventh day. RESULTS: Patients with ischemic stroke showed significantly lower plasma FVII, FVIIa-AT, and total TF levels than controls (median, 112.25% vs 132.05%, P = .004; 107.97 pmol/L vs 154.94 pmol/L, P < .001; 81.74 pg/mL vs 105.71 pg/mL, P < .001, respectively). In contrast, levels of plasma MPs-TF were significantly higher in patients with stroke compared to healthy controls (1.60 pg/mL vs 0.74 pg/mL, P < .001). Additionally, the thrombolysis group had lower FVII levels on the seventh day compared to the first day (median, 109.80% vs 115.74%, P = .04). CONCLUSION: Factor VII, FVIIa-AT, and total TF are decreased, while MPs-TF are elevated in patients with ischemic stroke. We observed a slight but significant effect of alteplase on FVII plasma levels.

Haemostatic factors do not account for worse outcomes from ischaemic stroke in patients with higher C-reactive protein concentrations.

Background Although the role of microparticles was recently implicated in stroke pathophysiology, the association between microparticles and inflammation is still not fully understood. The aim of this cohort study of 66 patients was to assess a relation between haemostatic factors, C-reactive protein and clinical outcome of ischaemic stroke. Methods Plasma microparticles procoagulant activity, concentrations of tissue factor-bearing microparticles, tissue factor and tissue factor pathway inhibitor in ischaemic stroke patients were determined with enzyme-linked immunosorbent assays at the time of initial diagnosis, along with serum C-reactive protein concentrations. Patients were divided into two groups depending on their C-reactive protein concentrations (C-reactive protein <3 mg/L; n = 28 vs. C-reactive protein ≥3 mg/L; n = 38). The analysed clinical outcome measures included the National Institutes of Health Stroke Scale and the Barthel Index. Results The two C-reactive protein groups did not differ significantly in terms of microparticles procoagulant activities, tissue factor-bearing microparticles, tissue factor and tissue factor pathway inhibitor concentrations. A significant correlation was observed between tissue factor pathway inhibitor and National Institutes of Health Stroke Scale score at admission ( R = 0.3, P = 0.03). Patients with C-reactive protein ≥3 mg/L presented with significantly higher National Institutes of Health Stroke Scale scores (median, 9.00 vs. 5.50, P = 0.002) and lower Barthel Index scores (median, 20.00 vs. 65.00, P = 0.002) than individuals with C-reactive protein <3 mg/L. The C-reactive protein concentrations correlated positively with National Institutes of Health Stroke Scale scores ( R = 0.3, P = 0.02) and inversely with Barthel Index scores ( R = - 0.4, P = 0.002). Conclusions Altogether, these findings imply that haemostatic parameters (microparticles, tissue factor-bearing microparticles, tissue factor, tissue factor pathway inhibitor) do not account for elevated C-reactive protein concentrations in ischaemic stroke patients.

Hepcidin Levels Are Increased in Patients with Acute Ischemic Stroke: Preliminary Report.

BACKGROUND: Our current understanding of iron balance in acute ischemic stroke (AIS) is still limited. The objective of this study was to evaluate levels of iron homeostasis proteins-hepcidin (25-amino acid form) and soluble hemojuvelin (sHJV) together with hepcidin/sHJV ratio (Hepc/sHJV) and soluble transferrin receptor (sTfR) in patients with AIS. In addition, the effect of timing of blood collection, type of stroke treatment, and scores on the National Institutes of Health Stroke Scale were investigated. METHODS: Participants comprised 31 patients diagnosed with AIS and 20 matched healthy controls. Venous blood samples were drawn on the first day and on the seventh day after stroke onset. Individuals who had experienced a stroke were subdivided according to type of treatment (thrombolysis group, n = 12 versus nonthrombolysis group, n = 19). Plasma hepcidin, sHJV, and sTfR levels were determined by the enzyme-linked immunosorbent assay method. RESULTS: We found that plasma hepcidin levels were significantly higher in ischemic stroke patients compared with the control group (median, 19.82 versus 12.62 ng/mL, P = .04). Furthermore, levels of hepcidin on the seventh day (1 week after diagnosis) were significantly higher in patients treated with thrombolysis than in patients not treated with thrombolysis (median, 22.16 versus 16.21 ng/mL, P = .04). CONCLUSIONS: The study provides evidence that AIS is associated with increased hepcidin levels. Stroke treatment may have an influence on hepcidin synthesis.