Serum Levels Of S-100 Research Articles

Alda-1 alleviates brain injury after cardiopulmonary resuscitation by regulating acyl-CoA synthetase long-chain family member 4/glutathione peroxidase 4 pathway-mediated ferroptosis in swine

To investigate whether the acetaldehyde dehydrogenase 2 specific activator, Alda-1, can alleviate brain injury after cardiopulmonary resuscitation (CPR) by inhibiting cell ferroptosis mediated by acyl-CoA synthetase long-chain family member 4/glutathione peroxidase 4 (ACSL4/GPx4) pathway in swine. Twenty-two conventional healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 8), and Alda-1 intervention group (CPR+Alda-1 group, n = 8) using a random number table. The swine model of CPR was reproduced by 8 minutes of cardiac arrest induced by ventricular fibrillation through electrical stimulation in the right ventricle followed by 8 minutes of CPR. The Sham group only experienced general preparation. A dose of 0.88 mg/kg of Alda-1 was intravenously injected at 5 minutes after resuscitation in the CPR+Alda-1 group. The same volume of saline was infused in the Sham and CPR model groups. Blood samples were collected from the femoral vein before modeling and 1, 2, 4, 24 hours after resuscitation, and the serum levels of neuron specific enolase (NSE) and S100 β protein were determined by enzyme-linked immunosorbent assay (ELISA). At 24 hours after resuscitation, the status of neurologic function was evaluated by neurological deficit score (NDS). Thereafter, the animals were sacrificed, and brain cortex was harvested to measure iron deposition by Prussian blue staining, malondialdehyde (MDA) and glutathione (GSH) contents by colorimetry, and ACSL4 and GPx4 protein expressions by Western blotting. Compared with the Sham group, the serum levels of NSE and S100β after resuscitation were gradually increased over time, and the NDS score was significantly increased, brain cortical iron deposition and MDA content were significantly increased, GSH content and GPx4 protein expression in brain cortical were significantly decreased, and ACSL4 protein expression was significantly increased at 24 hours after resuscitation in the CPR model and CPR+Alda-1 groups, which indicated that cell ferroptosis occurred in the brain cortex, and the ACSL4/GPx4 pathway participated in this process of cell ferroptosis. Compared with the CPR model group, the serum levels of NSE and S100 β starting 2 hours after resuscitation were significantly decreased in the CPR+Alda-1 group [NSE (μg/L): 24.1±2.4 vs. 28.2±2.1, S100 β (ng/L): 2 279±169 vs. 2 620±241, both P < 0.05]; at 24 hours after resuscitation, the NDS score and brain cortical iron deposition and MDA content were significantly decreased [NDS score: 120±44 vs. 207±68, iron deposition: (2.61±0.36)% vs. (6.31±1.66)%, MDA (μmol/g): 2.93±0.30 vs. 3.68±0.29, all P < 0.05], brain cortical GSH content and GPx4 expression in brain cortical was significantly increased [GSH (mg/g): 4.59±0.63 vs. 3.51±0.56, GPx4 protein (GPx4/GAPDH): 0.54±0.14 vs. 0.21±0.08, both P < 0.05], and ACSL4 protein expression was significantly decreased (ACSL4/GAPDH: 0.46±0.08 vs. 0.85±0.13, P < 0.05), which indicated that Alda-1 might alleviate brain cortical cell ferroptosis through regulating ACSL4/GPx4 pathway. Alda-1 can reduce brain injury after CPR in swine, which may be related to the inhibition of ACSL4/GPx4 pathway mediated ferroptosis.

S100 as Serum Tumor Marker in Advanced Uveal Melanoma

S100 protein is routinely used as a serum tumor marker in advanced cutaneous melanoma. However, there is scarce and inconclusive evidence on its value in monitoring disease progression of uveal melanoma. In this monocenter study, we retrospectively assessed the connection between documented S100 protein levels of patients suffering from stage IV uveal melanoma and the clinical course of disease. Where available, we analyzed expression of S100 in melanoma metastases by immunohistochemistry. A total of 101 patients were included, 98 had available serum S100 levels, and in 83 cases, sufficient data were available to assess a potential link of S100 with the clinical course of the uveal melanoma. Only 12 of 58 (20.7%) patients had elevated serum levels at first diagnosis of stage IV disease. During progressive disease, 54% of patients showed rising serum S100 levels, while 46% of patients did not. Tumor material of 56 patients was stained for S100. Here, 26 (46.4%) showed expression, 19 (33.9%) weak expression, and 11 (19.6%) no expression of S100. Serum S100 levels rose invariably in all patients with strong expression throughout the course of disease, while patients without S100 expression in metastases never showed rising S100 levels. Thus, the value of S100 serum levels in monitoring disease progression can be predicted by immunohistochemistry of metastases. It is not a reliable marker for early detection of advanced disease.

Effects of early lumbar cistern drainage of cerebrospinal fluid and combination of edaravone and nimodipine on vasospasm, intracranial pressure, inflammatory factors in traumatic subarachnoid hemorrhage

Purpose: To investigate the effect of early lumbar cistern drainage (LCD) of cerebrospinal fluid (CSF) and combination of edaravone and nimodipine on vasospasm, intracranial pressure (ICP), serum inflammation, S100 and vascular endothelial growth factor (VEGF) levels in traumatic subarachnoid hemorrhage (tSAH).&#x0D; Methods: Treatment was administered to 136 patients divided into control group (n = 68) and study group (n = 68). Serum inflammation was determined by assessing the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) while nitric oxide (NO), endothelin-1 (ET-1), S100 and VEGF levels were determined by enzyme-linked immunosorbent assay (ELISA). Serum C-reactive protein (CRP) level was measured by immunoturbidimetry. Perfusion weighted imaging was performed and the mean transit time (MTT), cerebral blood flow (CBF), cerebral blood volume (CBV), mean flow velocity (Vm) and pulsatility index (PI) were recorded. Glasgow coma scale (GCS) score and Montreal cognitive assessment (MoCA) score were used to compare the differences in therapeutic effect.&#x0D; Results: Compared with values before treatment, Vm, PI, NO, CBF, CBV, GCS score and MoCA score were significantly increased (p &lt; 0.05), while ICP, serum levels of TNF-α, IL-6, CRP, ET-1, S100 and VEGF and MTT significantly decreased (p &lt; 0.05). Therapeutic response rate of the study group (89.71 %) was higher than that of control group (66.18%) (p &lt; 0.05).&#x0D; Conclusion: Early LCD of CSF and combination of edaravone and nimodipine reduces the degree of cerebral vasospasm and contribute to brain function recovery in the treatment of patients with tSAH. This therapeutic strategy requires further clinical trials before application in clinical practice.

OS01.5.A Neuron-specific enolase (NSE) and S100 serum levels in patients with active brain metastases from HER2-positive breast cancer treated with trastuzumab-deruxtecan (T-DXd): A biomarker analysis from the TUXEDO-1 trial

Abstract Background T-DXd is a novel antibody-drug conjugate with high activity in HER2-positive metastatic breast cancer. The prospective, single-arm, single-centre phase II TUXEDO-1 trial showed clinically relevant activity of T-DXd in HER2-positive BC pts with active BM with an intracranial response rate of 73.3%. This biomarker sub-study of TUXEDO-1 aimed to investigate changes in the extent of metastases-induced brain damage in patients with and without response to therapy by measuring the serum levels of two proteins constitutively expressed in the human brain and measurable upon brain damage in the blood serum: NSE and S100. Material and Methods We assessed serum NSE (sNSE) and serum S100 (sS100) levels in a total of 37 blood samples drawn at cycles 1, 4 and end of treatment (EOT) in all patients of the intent-to-treat population of the TUXEDO-1 trial using commercially available ELISA assays. Intracranial radiological response was centrally assessed by a board-certified neuro-radiologist using RANO criteria. sNSE and sS100 levels were compared between responders and non-responders using the Mann Whitney U test and a significance level of 0.05. Results At baseline, we detected no significant difference of sNSE or sS100 levels between T-DXd responders and non-responders, respectively. Baseline median sNSE level was 10.6 ng/ml (interquartile range (IQR) 8.6-12.2) in T-DXd responders as compared with median 12.5 ng/ml (IQR 12.2-12.9) in the non-responder group (n.s.). At cycle 4, corresponding numbers were 8.1 ng/ml in responding patients (IQR 7-11.2) and 12.7 ng/ml (IQR 12.2-12.9) in non-responders, respectively (p=0.009). No differences in sS100 levels were observed between the groups at any time point. Conclusion In patients showing intracranial objective response to T-Dxd, sNSE levels were significantly lower at cycle 4 as compared with non-responders, suggesting a reduction in metastases-induced brain damage as a direct treatment effect. sNSE may be a clinically useful biomarker for longitudinal assessment of brain metastasis burden.

Correlation of damage-associated molecular pattern molecules with age and body mass index

Objective: To explore the correlation of damage-associated molecular pattern molecules(DAMPs) serum S100, C-reactive protein (CRP), serum amyloid A (SAA) and uric acid (UA) with age and body mass index (BMI) to provide direction for further study of metabolic inflammation and inflammaging. Methods: The observational study method was used,and three hundred and sixty-six healthy people (131 males and 235 females) were selected from the physical examination center of the Second People's Hospital of Hunan Province from May to October 2020. They were divided into three age groups according to the age interval of 20 years, including 156 (53 males and 103 females) aged 20-40 years, 110 (36 males and 74 females) aged 41-60 years, and 100 (42 males and 58 females) aged 61-80 years. Kruskal Wallis H test was used to compare the differences of serum S100, CRP, SAA and UA levels among different age groups. According to the Health Industry Standards of the People's Republic of China-Weight Determination for Adults, the boundary is BMI =24 kg/m2. The healthy people were divided into non overweight (BMI<24 kg/m2) and overweight (BMI ≥ 24 kg/m2) two groups. The 1∶1 propensity score was used to match the age and gender. There were 96 non overweight subjects [43 males, 53 females, age 52 (35, 66) years], 96 overweight subjects [44 males, 52 females, age 52 (36, 64) years]. The serum levels of S100, CRP, SAA and UA in different BMI groups were compared by Mann-Whitney U test. Results: The median serum UA concentrations in males and females were 356 and 277 μmol/L, and the levels of serum UA of male was significantly higher than that of female (Z=-10.428, P<0.001); the median serum SAA concentrations in males and females were 3.1 mg/L and 4.4 mg/L, while the serum SAA level of female was significantly higher than that of male (Z=3.652, P<0.001); for 20-40, 41-60, and 61-80 years old group, the median concentration of serum S100 was 0.058, 0.057, 0.070 μg/L, and the median concentration of serum CRP was 0.32, 0.58, 0.93 mg/L; the median serum SAA concentrations were 3.2, 4.0, 5.2 mg/L; serum uric acid concentrations were (301.8±61.5), (298.6±69.8), (329.0±77.8) μmol/L. The levels of serum S100, CRP, SAA, UA in 61-80 years group were significantly higher than those of 20-40 years group (H=-2.749, H=-6.731, H=-5.033, H=-2.521, P=0.018, P<0.001, P<0.001, P=0.035) and 41-60 years old group (H=-2.719, H=-2.539, H=-2.540, H=-2.486, P=0.020, P=0.033, P=0.033, P=0.039).The levels of serum CRP of 41-60 years group was significantly higher than that of 20-40 years group (H=-4.108,P<0.001). There was no significant difference in levels of serum S100, SAA and UA between 20-40 years group and 41-60 years group (H=0.189, H=-2.360, H=-0.165, P=1.000, P=0.055, P=1.000); the levels of serum CRP and SAA were positively correlated with age (rs =0.342, rs =0.301, P<0.001, P<0.001); for overweight, non-overweight group, the median concentrations of serum S100 were 0.065 μg/L, 0.059 μg/L, the median concentrations of serum CRP were 0.92 mg/L, 0.47 mg/L, the median concentrations of serum SAA were 5.0 mg/L, 4.1 mg/L, the median concentrations of serum UA were 339.5 μmol/L, 301.5 μmol/L, the levels of CRP, SAA and UA in the overweight group were higher than those in the non-overweight group (Z=4.278, Z=2.025, Z=3.787, P<0.001, P=0.043, P<0.001); the levels of S100 in the overweight group was higher than those in the non-overweight group, but there was no significant difference in S100 between the two groups (Z=0.862, P=0.388); the levels of Serum CRP and UA were positively correlated with BMI (rs =0.348, rs =0.264, P<0.001, P=0.009). Conclusions: With the increase of age, the serum S100, CRP, SAA and UA levels of healthy people may be on the rise, especially the serum CRP and SAA levels are positively correlated with age; the serum S100, CRP, SAA and UA levels of overweight people may be higher than those of non-overweight people, especially the serum CRP, UA levels are positively correlated with BMI.

Determination of Cut-off Serum Values for Resistin and S100B Protein in Patients Who Survived a Cardiac Arrest.

IntroductionIn an attempt to identify patients who have successfully survived a resuscitated cardiac arrest (CA), attention is drawn to resistin and S100B protein, two biomarkers that have been studied in relation to CA.AimThe study aimed to identify the potential cut-off serum values for resistin and S100B in patients who had CA, compared to healthy volunteers, given that, currently, none of the markers have normal and pathological reference range limits for human assay levels related to this pathology.Materials and MethodsForty patients, resuscitated after out-of-hospital CA and forty healthy controls, were included in the study. All patients were followed up for seventy-two hours after CA or until death. Blood samples for biomarkers were collected on admission to the ED (0-time interval) and at 6, 12, 24, 48 and 72 hours following resuscitation. Only one blood sample was collected from the controls. The serum concentrations of biomarkers were measured.ResultsFor each time interval, median serum levels of resistin and S100 B were ​ significantly higher in patients with CA compared to healthy controls. The cut-of value for resistin in patients with CA, at the 12-hours versus controls, was > 8.2 ng/ml. The cut-of value for S100B in patients with CA versus controls recorded at 6 hours, was > 11.6 pg/ml.ConclusionSerum levels of resistin and S100B are higher among resuscitated CA patients compared to controls.

Application of the cerebral edema monitor on cardiopulmonary bypass in infants

ABSTRACTA diagnostic accuracy study was adopted to evaluate the ability of Cerebral edema monitor by comparing the index test results with those of the reference standard. The serum levels of astrocyte S100 protein and neuron-specific enolase (NSE) were determined. Changes in the cerebral electrical impedance coefficient (CEIC) was detected with the BORN-BE monitor. The left- and right-sided CEIC values, serum levels of S100, and serum NSE in the CPB group significantly increased from the beginning to the end of the operation (P < .05). Furthermore, left and right-sided CEIC values, serum levels of S100, and serum NSE in the CPB-B group were significantly higher than those of the CPB-A group (P < .05). Detection rates of cerebral edema in the CPB-B group at the 24 h post-operative time point were significantly higher than those in the CPB-A group (P < .05). The degree of brain damage is positively correlated with the CPB and aortic cross-clamping. CEIC is a sensitive index reflecting brain damage during CPB in infants.

Resistin-Can it be a new early marker for prognosis in patients who survive after a cardiac arrest? A pilot study.

AimThe aim of our study was to evaluate the potential role of resistin in estimating the 30 days prognosis in patients with hypoxic-ischemic organ injury who survived after a cardiac arrest (CA).Materials and methodsThe study included 40 patients resuscitated after a non-traumatic out-of-hospital CA admitted in Emergency Department (ED). All patients were followed for 30 days after CA or until death. Clinical data on admission were recorded. Blood samples were collected on admission in ED (0-time interval), and at 6, 12, 24, 48- and 72-hours following resuscitation. Serum concentrations of resistin, S100B and neuron specific enolase (NSE) were measured. Several predictive scores for the mortality at 30 days were created with logistic regressions.ResultsAt each time interval, median serum levels of resistin and S100 B were significantly higher in non-survivors compared to survivors. For NSE, plasma levels were significantly lower in survivors as compared to non-survivors at 48 and 72 hours, respectively. Accurate predictive scores for 30-days mortality were the ones which included the values of resistin and S100B measured at 12 hours after admittance [AUC 0.938 (0.813–0.989), sensitivity 85.71% (67.3%– 96%), specificity 91.67% (61.5%’99.8%), p<0.001], which included the values of all three markers measured at 12 hours after admittance [AUC 0.955 (0.839–0.995), sensitivity 82.14% (63.1%’93.9%), specificity 100.00% (73.5%’100.0%), p<0.001] and the that included the values of resistin and S-100B at 6 hours together with serum lactate on admission [AUC = 0.994 (0.901–1.0), sensitivity 96.4% (81.7%’99.9%), specificity 100.00% (73.5%’100.0%), p<0.001].ConclusionIn our study, serum levels of resistin or a combination of resistin with S-100B or resistin with S-100B and lactate, were highly predictive for 30 days mortality in resuscitated patients after CA. Further studies on large number of patients are needed to confirm our data.

Association between the simultaneous decrease in the levels of soluble vascular cell adhesion molecule-1 and S100 protein and good neurological outcomes in cardiac arrest survivors.

ObjectiveThis study aimed to determine whether simultaneous decreases in the serum levels of cell adhesion molecules (intracellular cell adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and E-selectin) and S100 proteins within the first 24 hours after the return of spontaneous circulation were associated with good neurological outcomes in cardiac arrest survivors.MethodsThis retrospective observational study was based on prospectively collected data from a single emergency intensive care unit (ICU). Twenty-nine out-of-hospital cardiac arrest survivors who were admitted to the ICU for post-resuscitation care were enrolled. Blood samples were collected at 0 and 24 hours after ICU admission. According to the 6-month cerebral performance category (CPC) scale, the patients were divided into good (CPC 1 and 2, n=12) and poor (CPC 3 to 5, n=17) outcome groups.ResultsNo difference was observed between the two groups in terms of the serum levels of ICAM-1, VCAM-1, E-selectin, and S100 at 0 and 24 hours. A simultaneous decrease in the serum levels of VCAM-1 and S100 as well as E-selectin and S100 was associated with good neurological outcomes. When other variables were adjusted, a simultaneous decrease in the serum levels of VCAM-1 and S100 was independently associated with good neurological outcomes (odds ratio, 9.285; 95% confidence interval, 1.073 to 80.318; P=0.043).ConclusionA simultaneous decrease in the serum levels of soluble VCAM-1 and S100 within the first 24 hours after the return of spontaneous circulation was associated with a good neurological outcome in out-of-hospital cardiac arrest survivors.

Protein S100 as outcome predictor after out-of-hospital cardiac arrest and targeted temperature management at 33\xa0\xb0C and 36\xa0\xb0C

BackgroundWe aimed to investigate the diagnostic performance of S100 as an outcome predictor after out-of-hospital cardiac arrest (OHCA) and the potential influence of two target temperatures (33 °C and 36 °C) on serum levels of S100.MethodsThis is a substudy of the Target Temperature Management after Out-of-Hospital Cardiac Arrest (TTM) trial. Serum levels of S100 were measured a posteriori in a core laboratory in samples collected at 24, 48, and 72 h after OHCA. Outcome at 6 months was assessed using the Cerebral Performance Categories Scale (CPC 1–2 = good outcome, CPC 3–5 = poor outcome).ResultsWe included 687 patients from 29 sites in Europe. Median S100 values were higher in patients with a poor outcome at 24, 48, and 72 h: 0.19 (IQR 0.10–0.49) versus 0.08 (IQR 0.06–0.11) μg/ml, 0.16 (IQR 0.10–0.44) versus 0.07 (IQR 0.06–0.11) μg/L, and 0.13 (IQR 0.08–0.26) versus 0.06 (IQR 0.05–0.09) μg/L (p < 0.001), respectively. The ability to predict outcome was best at 24 h with an AUC of 0.80 (95% CI 0.77–0.83). S100 values were higher at 24 and 72 h in the 33 °C group than in the 36 °C group (0.12 [0.07–0.22] versus 0.10 [0.07–0.21] μg/L and 0.09 [0.06–0.17] versus 0.08 [0.05–0.10], respectively) (p < 0.02). In multivariable analyses including baseline variables and the allocated target temperature, the addition of S100 improved the AUC from 0.80 to 0.84 (95% CI 0.81–0.87) (p < 0.001), but S100 was not an independent outcome predictor. Adding S100 to the same model including neuron-specific enolase (NSE) did not further improve the AUC.ConclusionsThe allocated target temperature did not affect S100 to a clinically relevant degree. High S100 values are predictive of poor outcome but do not add value to present prognostication models with or without NSE. S100 measured at 24 h and afterward is of limited value in clinical outcome prediction after OHCA.Trial registrationClinicalTrials.gov identifier: NCT01020916. Registered on 25 November 2009.

S100\u03b2 as a serum marker in endocrine resistant breast cancer

BackgroundEndocrine therapy is standard treatment for estrogen receptor (ER)-positive breast cancer. However, its efficacy is limited by intrinsic and acquired resistance. Here the potential of S100β as a biomarker and inhibition of its signaling network as a therapeutic strategy in endocrine treated patients was investigated.MethodsThe expression of S100β in tissue and serum was assessed by immunohistochemistry and an enzyme-linked immunosorbent assay, respectively. The S100β signaling network was investigated in cell line models of endocrine resistance by western blot, PCR, immunoprecipitation, and chromatin-immunoprecipitation. Endocrine resistant xenografts and tumor explants from patients with resistant tumors were treated with endocrine therapy in the presence and absence of the p-Src kinase inhibitor, dasatinib.ResultsTissue and serum levels of S100β were found to predict poor disease-free survival in endocrine-treated patients (n = 509, HR 2.32, 95% CI is 1.58–3.40, p < 0.0001 and n = 187, HR 4.009, 95% CI is 1.66–9.68, p = 0.002, respectively). Moreover, elevated levels of serum S100β detected during routine surveillance over the patient treatment period significantly associated with subsequent clinically confirmed disease recurrence (p = 0.019). In vivo studies demonstrated that endocrine treatment induced transcriptional regulation of S100β which was successfully disrupted with tyrosine kinase inhibition. In endocrine resistant xenografts and tumor explants from patients with endocrine resistant breast cancer, combined endocrine and dasatinib treatment reduced tumor proliferation and down-regulated S100β protein expression in comparison to endocrine treatment alone.ConclusionsS100β has potential as a new surveillance tool for patients with ER-positive breast cancer to monitor ongoing response to endocrine therapy. Moreover, endocrine resistant breast cancer patients with elevated S100β may benefit from combined endocrine and tyrosine-kinase inhibitor treatment.Trial registrationClinicalTrials.gov, NCT01840293). Registered on 23 April 2013. Retrospectively registered.

Serum protein S100 as marker of postoperative delirium after off-pump coronary artery bypass surgery: secondary analysis of two prospective randomized controlled trials.

To investigate the predictive value of S100 (biochemical marker of neuroglial injury) for the occurrence of postoperative delirium (POD) in patients undergoing off-pump coronary artery bypass (OPCAB)-surgery. We enrolled 92 patients older than 18 years undergoing elective OPCAB-surgery. Serum-levels of S100 were determined at baseline (BL), end of surgery (EOS) and on the first postoperative day (PD1). Postoperatively, all-patients were evaluated daily until PD5 for the presence of POD using the confusion assessment method (CAM) or the confusion assessment method for the intensive care unit (CAM-ICU) for patients in the intensive care unit (ICU). The overall incidence of POD was 21%. S100-values on PD1 significantly predicted the occurrence of POD during the later hospital stay [area under the curve (AUC)=0.724 (95% confidence interval (CI): 0.619-0.814); p=0.0001] with an optimal cut-off level of 123 pg mL-1 (sensitivity 100%, specificity 44%). Below this value, the absence of POD was predicted correctly in 43.66% of patients without POD [negative predictive value (NPV) of 100% (95%CI: 88.8%-100.0%) - positive predictive value of 29.8% (95%CI: 18.4%-43.4%) and likelihood ratio (LR) of the negative result of 0.0]. S100-levels <123 pg mL-1 measured on PD1 reliably rule out the development of POD after elective OPCAB-surgery. This finding warrants testing whether S100-levels could be used for a risk stratification of cardiac surgical patients and for the initiation of preventive measures against POD in patients with high postoperative S100-levels.

Therapeutic effects of various methods of MSC transplantation on cerebral resuscitation following cardiac arrest in rats.

In the present study, mesenchymal stem cells (MSCs) were transplanted into the brain of rats following cardiopulmonary resuscitation (CPR) by three different methods: Direct stereotaxic injection into the lateral cerebral ventricle (LV), intra-carotid administration (A), and femoral venous infusion (V). The three different methods were compared by observing the effects of MSCs on neurological function following global cerebral hypoxia-ischemia, in order to determine the optimum method for MSC transplantation. MSCs were transplanted in groups A, V and LV following the restoration of spontaneous circulation. Neurological deficit scale scores were higher in the transplantation groups, as compared with the control group. Neuronal damage, brain water content and serum levels of S100 calcium-binding protein B were reduced in the hippo-campus and temporal cortex of the transplantation groups, as compared with the control rats following resuscitation. MSCs were able to migrate inside the brain tissue following transplantation, and were predominantly distributed in the hippocampus and temporal cortex where the neurons were vulnerable during global cerebral ischemia. These results suggest that transplantation of MSCs may notably improve neurological function following CPR in a rat model. Of the three different methods of MSC transplantation tested in the present study, LV induced the highest concentration of MSCs in brain areas vulnerable to global cerebral ischemia, and therefore, produced the best neurological outcome.

CT imaging of bone and bone marrow infiltration in malignant melanoma—Challenges and limitations for clinical staging in comparison to 18FDG-PET/CT

Rationale of this study was the evaluation of the diagnostic value of computed tomography (CT) in the detection of bone marrow infiltration in comparison to PET/CT.Fifty patients (age 61±15.12years) with metastatic malignant melanoma underwent 18F-FDG-PET/CT, including contrast-enhanced CT. 2 readers evaluated the CT images in consensus for bone and bone marrow lesions focusing on lesion location, type and size. PET/CT was used as reference standard to estimate sensitivity, specificity, negative and positive predictive value. Moreover, the bone marrow density was estimated in the long bones and the sacral bone. Serum hamoglobin, thrombocyte level and S100 protein were correlated with the presence or absence of bone and bone marrow lesions.According to PET/CT as standard of reference, of 594 bone and medullary lesions 495 were considered malignant. Of these 77.8% were medullary, 20.4% lytic, 1% sclerotic and 0.8% mixed lytic/sclerotic. Contrast-enhanced CT yielded a lesion-based sensitivity of 36.8% and a specificity of 87.9% (PPV 93.8%; NPV 21.8%). Patient-based sensitivity and specificity were 78.8% and 82.4%, respectively. Of the missed lesions, most were medullary (95.8%). A disseminated bone marrow involvement (defined as >10 bone marrow lesions or diffuse infiltration of a whole body segment) was described in 11 cases, in 6 cases the disseminated involvement was underestimated or missed on CT. In cases with disseminated bone marrow involvement the bone marrow density was significantly higher in the humerus (p=0.04), but not in the femur or sacral bone (p=0.06). Multivariate analysis revealed no isolated effect of bone metastases on S100 serum and hemoglobin level, but both were significantly altered in patients with disseminated bone marrow involvement (p<0.05).In conclusion, the diagnostic value of computed tomography for the detection of bone marrow metastases in patients with melanoma, is limited. Especially in cases with disseminated bone marrow involvement about 50% of the cases were missed or underestimated.

Protective effect of erythropoietin on brain tissue in rats with cardiopulmonary resuscitation after asphyxia

To study the protective effect of erythropoietin (EPO) on brain tissue with cardiac arrest-cardiopulmonary resuscitation (CA-CPR) and its mechanism. 120 male Sprague-Dawley (SD) rats were randomly divided into three groups (each n = 40), namely: sham group, routine chest compression group, and conventional chest compression + EPO group (EPO group). The rats in each group were subdivided into CA and 6, 12, 24, 48 hours after restoration of spontaneous circulation (ROSC) five subgroups (each n = 8). The model of CA was reproduced according to the Hendrickx classical asphyxia method followed by routine chest compression, and the rats in sham group only underwent anesthesia, tracheostomy intubation and venous-puncture without asphyxia and CPR. The rats in EPO group were given the routine chest compression + EPO 5 kU/kg (2 mL/kg) after CA. Blood sample was collected at different time points of intervention for the determination the content of serum S100 β protein by enzyme linked immunosorbent assay (ELISA). All the rats were sacrificed at the corresponding time points, and the hippocampus was harvested for the calculation of the number of S100 β protein positive cells, and to examine the pathological changes and their scores at 24 hours after ROSC by light microscopy. With prolongation of ROSC time, the serum levels of S100 β protein (µg/L) in the routine chose compression group and the EPO group were significantly elevated, peaking at 24 hours (compared with CA: 305.7 ± 29.2 vs. 44.4 ± 6.2 in routine chest compression group, and 276.7 ± 28.9 vs. 44.7 ± 5.6 in the EPO group, both P < 0.05), followed by a fall. The levels of S100 β protein at each time point after ROSC in EPO group were significanthy lower than those of the routine chest compression group (83.2 ± 7.5 vs. 114.3 ± 15.3 at 6 hours, 123.9 ± 20.2 vs. 184.9 ± 22.2 at 12 hours, 276.7 ± 28.9 vs. 305.7 ± 29.2 at 24 hours, 256.3 ± 26.6 vs. 283.2 ± 23.6 at 48 hours, all P < 0.05). With the prolongation of ROSC time, the S100 β protein positive cell number in brain (cells/HP) in the routine chest compression group and the EPO group was significantly increased, peaking at 24 hours (compared with CA: 14.3 ± 2.2 vs. 6.7 ± 0.7 in the routine chest compression group, 11.3 ± 1.3 vs. 6.8 ± 0.9 in the EPO group, both P < 0.05), then it began to fall. The S100 β protein positive cell number in brain at each time point after ROSC in the EPO group was significantly lower than that of the routine chest compression group (7.0 ± 0.9 vs. 7.9 ± 1.9 at 6 hours, 8.4 ± 1.1 vs. 10.2 ± 2.2 at 12 hours, 11.3 ± 1.3 vs. 14.3 ± 2.2 at 24 hours, 8.3 ± 0.8 vs. 10.8 ± 2.0 at 48 hours, all P < 0.05). Under the light microscope, a serious brain cortex injury was found after reproduction of the model, and the degree of injury was reduced after EPO intervention. The pathological score at 24 hours after ROSC in EPO group was lower than that of routine chest compression group (3.83 ± 0.73 vs. 4.17 ± 0.75, P < 0.05). The S100 β protein level in serum and brain tissue was increased early in asphyxia CA-CPR rats. EPO intervention can reduce the expression of S100 protein and reduce the degree of brain injury.

Elevated S100A8/A9 and S100A12 Serum Levels Reflect Intraocular Inflammation in Juvenile Idiopathic Arthritis-Associated Uveitis: Results From a Pilot Study

Juvenile idiopathic arthritis-associated uveitis (JIAU) is the most common uveitis entity in childhood. As S100A8/A9 and S100A12 proteins are valuable biomarkers in childhood arthritis, we investigated the occurrence of these proteins in childhood uveitis. Serum samples from patients with JIAU (n = 79) or idiopathic anterior uveitis (IAU, n = 24), as well as from nonuveitic controls (n = 24), were collected. Furthermore, aqueous humor samples (JIAU n = 17, nonuveitic controls n = 16, IAU n = 12) were obtained. Samples were analyzed for S100A8/A9 and S100A12 protein levels by ELISA. Intergroup comparisons were performed, involving patient data, clinical data, and S100 levels. S100A8/A9 and S100A12 serum levels were elevated in IAU and JIAU patients as compared to nonuveitic controls (all P < 0.05). S100 serum levels in JIAU patients were higher in active arthritis (not significant; P = 0.289 for S100A8/A9 and P = 0.196 for S100A12) and active uveitis (P = 0.010 for S100A8/A9 and P = 0.026 for S100A12) than in controls. No significant differences in S100 levels were found in a subgroup analysis for sex, antinuclear antibody (ANA) status, disease duration, or presence of uveitis complications. In JIAU patients, S100 serum levels correlated with age and age at onset of uveitis. A longitudinal analysis in JIAU patients showed a correlation of serum S100A8/A9 and S100A12 levels with uveitis activity (both P = 0.03). S100A8/A9 levels in aqueous humor of patients with JIAU (P = 0.001) and IAU (P = 0.0002) were increased as compared to nonuveitic controls. Increased S100A8/A9 and S100A12 levels are found in the serum and aqueous humor of patients with autoimmune uveitis. Serum levels reflect activity of joint and eye disease.

Inhaled nitric oxide improves transpulmonary blood flow and clinical outcomes after prolonged cardiac arrest: a large animal study.

IntroductionThe probability to achieve a return of spontaneous circulation (ROSC) after cardiac arrest can be improved by optimizing circulation during cardiopulomonary resuscitation using a percutaneous left ventricular assist device (iCPR). Inhaled nitric oxide may facilitate transpulmonary blood flow during iCPR and may therefore improve organ perfusion and outcome.MethodsVentricular fibrillation was electrically induced in 20 anesthetized male pigs. Animals were left untreated for 10 minutes before iCPR was attempted. Subjects received either 20 ppm of inhaled nitric oxide (iNO, n = 10) or 0 ppm iNO (Control, n = 10), simultaneously started with iCPR until 5 hours following ROSC. Animals were weaned from the respirator and followed up for five days using overall performance categories (OPC) and a spatial memory task. On day six, all animals were anesthetized again, and brains were harvested for neurohistopathologic evaluation.ResultsAll animals in both groups achieved ROSC. Administration of iNO markedly increased iCPR flow during CPR (iNO: 1.81 ± 0.30 vs Control: 1.64 ± 0.51 L/min, p < 0.001), leading to significantly higher coronary perfusion pressure (CPP) during the 6 minutes of CPR (25 ± 13 vs 16 ± 6 mmHg, p = 0.002). iNO-treated animals showed significantly lower S-100 serum levels thirty minutes post ROSC (0.26 ± 0.09 vs 0.38 ± 0.15 ng/mL, p = 0.048), as well as lower blood glucose levels 120–360 minutes following ROSC. Lower S-100 serum levels were reflected by superior clinical outcome of iNO-treated animals as estimated with OPC (3 ± 2 vs. 5 ± 1, p = 0.036 on days 3 to 5). Three out of ten iNO-treated, but none of the Control animals were able to successfully participate in the spatial memory task. Neurohistopathological examination of vulnerable cerebral structures revealed a trend towards less cerebral lesions in neocortex, archicortex, and striatum in iNO-treated animals compared to Controls.ConclusionsIn pigs resuscitated with mechanically-assisted CPR from prolonged cardiac arrest, the administration of 20 ppm iNO during and following iCPR improved transpulmonary blood flow, leading to improved clinical neurological outcomes.

Abstract 12202: Inhaled Nitric Oxide Improves Artificial Circulation and Clinical Outcomes After Prolonged Cardiac Arrest

Introduction: Primary survival after cardiac arrest can be improved by optimizing circulation during CPR when using a minimal invasive left ventricular assist device (iCPR). Hypothesis: Inhaled nitric oxide may facilitate transpulmonary bloodflow during iCPR and thereby improve the functional outcome following cardiac arrest. Methods: Ventricular fibrillation (VF) was electrically induced in 20 anesthetized male pigs. Animals were left untreated for 10 minutes before iCPR was attempted. Subjects received either 20ppm of inhaled nitric oxide (iNO, n = 10) or 0ppm iNO (Control, n = 10), simultaneously started with iCPR until 5 hours following return of spontaneous circulation (ROSC). Animals were weaned from the respirator and followed up for five days using overall performance categories (OPC) and a spatial memory task. On day six, all animals were anesthetized again, and brains harvested for neurohistopathologic evaluation. Results: All animals in both groups achieved ROSC. iNO treated animals reached significantly higher iCPR flow during CPR (1.81 ± 0.30 L/min compared to 1.64 ± 0.51, p&lt;0.001), leading to significantly higher coronary perfusion pressure (CPP) values during the 6 minutes of CPR (25 ± 13 vs. 16 ± 6 mmHg, p = 0.002). iNO animals showed significantly lower S-100 serum levels thirty minutes post ROSC (0.26 ± 0.09 vs. 0.38 ± 0.15 ng/mL, p = 0.048), as well as lower blood glucose values 120-360 minutes following ROSC. Lower S-100 serum levels were reflected by superior clinical outcome of iNO treated animals as estimated with OPC (3 ± 2 vs. 5 ± 1, p = 0.036 on days 3 to 5). While n = 3 iNO treated animals were able to successfully participate in the spatial memory task, none of the controls were able to do so. Neurohistopathological examination of cerebral structures prone to ischemia-reperfusion injury revealed a trend towards less cerebral lesions in Neocortex, Archicortex, and Striatum when animals had been treated with iNO. Conclusions: In a model of prolonged cardiac arrest, the administration of 20ppm iNO during and following iCPR improved transpulmonary bloodflow and mitigated post-aggression metabolism, indicated by lower serum glucose levels. These effects translated into improved clinical outcomes in iNO treated animals.

CBM-07SERUM NSE, MMP-9 AND HER2 ARE PREDICTIVE OF BRAIN METASTASES IN METASTATIC BREAST CANCER PATIENTS

BACKGROUND: Breast cancer (BC) is the second leading cause of brain metastases (BM). Predictive factors for BM have been widely studied in metastatic BC; however, there is no known serum tumor marker to accurately predict BM in this population. Serum levels of protein S100, an astrocytic marker, are associated with stroke severity. Neuron Specific Enolase (NSE), a neuronal marker, has been associated with BM prognosis in lung cancer. Elevated serum levels of these markers could reflect the brain damages induced by BM. Matrix Metalloproteinase 9 (MMP-9) is involved in tumor invasion and metastatic dissemination, including BM. Finally, it has been shown that HER2-amplified breast tumors have a particular tropism for central nervous system. This study evaluates the predictive value of these four markers for BM in a population of metastatic BC patients. METHODS: In this case-control study, 88 consecutive BC patients with BM (cases) treated at the Montpellier Cancer Institute (2008-2015) were retrospectively selected, based on the availability of frozen serum samples for tumor markers determination. Cases were matched by age, tumor biology and number of previous metastatic treatment lines to 162 patients with metastatic BC but without CNS involvement (controls). RESULTS: Serum HER2, NSE and MMP-9 levels were significantly higher in cases than in controls (p= 0.0057, p = 0.0051 and p = 0.0062, respectively). Median HER2 (ng/ml) was 21.1 in cases compared to 12.3 in controls; median NSE (µg/l) was 10.8 compared to 8.70 in controls; median MMP-9 (ng/µl) was 422.9 in cases compared to 320.5 in controls. In multivariate analysis, serum HER2 and MMP-9 levels accurately discriminated cases from controls: odd ratio 4.4 (p = 0.000; 95%CI 1.9-9.6) for HER2 and 3.5 (p = 0.005; 95%CI 1.5-8.4) for MMP-9. CONCLUSIONS: Serum HER2 and MMP-9 seem to be predictive of BM in metastatic BC patients. These results need to be validated in further larger prospective studies.

Among the S100 proteins, S100A12 is the most significant marker for psoriasis disease activity.

Psoriasis is a chronic skin disease with deregulation of proteins in the immune system. These proteins include members of the heterogeneous S100 family, which have been discussed as potential biomarkers for disease severity. The aim of this study was to evaluate the impact of S100A7, S100A8, S100A9 and S100A12 as possible markers for disease activity in patients with psoriasis skin disease. S100A7, S100A8, S100A9 and S100A12 mRNA expression was determined in the skin of patients with psoriasis and controls (N=341) by gene expression analyses. In addition, S100 serum levels were investigated by ELISA in an independent cohort of psoriasis patients (i) untreated, with different manifestations (skin/joints), (ii) under treatment (etanercept) and (iii) healthy controls, (N=55). All S100-subtypes included are significantly upregulated in psoriasis skin lesions when compared with atopic dermatitis, lichen ruber and healthy donors. In untreated psoriasis patients, S100A12-serum levels showed the closest association with disease activity (PASI) (r=0.542; P<0.01). Serum levels decreased under treatment with etanercept (P<0.05). Among the investigated S100-proteins, S100A12 showed the closest association with disease activity and therapeutic response and might therefore provide a valuable biomarker for psoriasis.