INTRODUCTION:Recent studies in stroke patients from predominantly Asian populations have underscored the significance of trimethylamine N-oxide (TMAO) as a valuable blood biomarker for predicting incident strokes and major adverse cardiovascular events (MACE). However, its prognostic role after ischemic stroke in other populations is not yet comprehensively investigated. PATIENTS AND METHODS:We measured plasma TMAO levels in 1726 acute ischemic stroke patients (within 24 h from symptom onset) from the multicenter BIOSIGNAL cohort. Using cox and logistic regression models adjusting for demographic and vascular risk factors, we investigated the association of TMAO with recurrent stroke, MACE within 365 days and functional outcome at 90 days after stroke. RESULTS:TMAO levels were not associated with any risk of recurrent stroke (n = 108, unadj. HR per unit increase of log (TMAO) 1.15, 95% CI 0.88-1.51, adjust. HR 1.07, 95% CI 0.78-1.47) or MACE (n = 309, unadj. HR of log (TMAO) 1.10,95% CI 0.91-1.3, adjust. HR 0.90, 95% CI 0.74-1.09). There was an univariable positive association between higher TMAO plasma levels and unfavorable functional outcome, this association remained statistically significant in the multivariable analysis (unadj. OR of log (TMAO) 1.56, 95% CI 1.34-1.81, adjust. OR 1.28, 95% CI 1.04-1.57). CONCLUSION:In this large cohort of acute stroke patients from a predominantly White population, TMAO had no independent association with either recurrent stroke, or MACE or death. In univariable, and multivariable analysis, there was a significant association between TMAO and unfavorable functional outcome, which might not be clinically significant due to its low effect size. Therefore, TMAO seems not to be a clinically relevant biomarker for risk stratification after stroke.

Lipoprotein(a) (Lp(a)) is a causal risk-factor for atherosclerotic cardiovascular disease including acute ischemic stroke (AIS). The underlying pathomechanisms mediating this risk are less well understood, especially in AIS caused by large artery atherosclerosis (LAA). In this observational cohort study, we evaluated the association of Lp(a) with markers of LAA, namely carotid intima media thickness (cIMT) and the presence of extra- or intracranial vessel narrowing plaques. Among participants of the BIOSIGNAL cohort study we determined Lp(a) levels within 24 h after symptom onset in 1161 AIS patients from the single center of Zurich. cIMT was determined using a semi-automated computerized edge tracking software, internal carotid artery (ICA) stenosis was graded according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria, intracranial ultrasound was performed by transcranial color-coded duplex (TCCD). Higher Lp(a) levels were not associated with an increased cIMT in univariable or multivariable regression models containing known cardiovascular risk factors. Higher Lp(a) levels were not associated with the presence of neither extracranial high-grade ICA-stenosis nor significant intracranial stenosis assessed by neurovascular ultrasound. In AIS patients higher Lp(a) levels were not associated with clinical markers of atherosclerotic burden despite its association with LAA-stroke etiology and an increased risk for stroke recurrence. Date of registration: 17–10-2014. Registration-URL: http://www.clinicaltrials.gov; Unique identifier: NCT-02274727.

BACKGROUND:The role of Aldehyde Dehydrogenase 4 Family Member A1 (ALDH4A1) in atherosclerotic disease is unclear. Experimental data suggests a possible involvement in atherogenesis. We investigated the association between circulating ALDH4A1 and atherosclerotic disease outcome measures in acute stroke patients. METHODS:Multicenter study using data from the prospective BIOSIGNAL cohort (2014-2017). ALDH4A1 plasma concentrations were measured in stored samples collected within 24 h after stroke onset. Primary outcome measure was large artery atherosclerotic stroke (LAAS) origin. Secondary outcome measures were atherosclerotic disease outcomes such as the maximum intima-media-thickness (IMT), the degree of stenosis on ultrasound, and a composite for atherosclerotic disease burden (large artery atherosclerotic index stroke, history of myocardial infarction, coronary or peripheral artery disease). Logistic regression analyses were performed to examine the association between ALDH4A1 plasma concentrations (absolute and log-transformed) and the primary and secondary outcome measures. RESULTS:Of 1759 stroke patients, 84.5% had available ALDH4A1 measurements. Circulating ALDH4A1 plasma concentrations were neither significantly associated with LAAS (logALDH4A1 aOR 0.97, 95%CI 0.79-1.21, p = 0.81) nor any secondary outcome measure including the maximum IMT, stenosis degree or the composite for atherosclerotic disease burden. Sensitivity analysis using inverse probability of treatment weighting were in line with the main findings. CONCLUSIONS:In acute stroke patients, we found no clear evidence of an association between ALDH4A1 plasma concentrations and clinically relevant atherosclerotic disease outcome measures, including maximum IMT. However, due to the lack of validated and standardized ALDH4A1 assays, and the resulting limited comparability with other cohorts, a potential association cannot be excluded. TRIAL REGISTRATION:NCT02274727 (ClinicalTrials.gov).

BACKGROUND:Atrial fibrillation detected after stroke (AFDAS) affects secondary stroke prevention, yet identification can be challenging. Easily accessible cardiac blood biomarkers such as NT-proBNP (N-terminal pro-B-type natriuretic peptide) could guide diagnostic workup, but optimal cutoff values and the time-dependent relationship between NT-proBNP and AFDAS are unclear. We aimed (1) to externally validate earlier presented NT-proBNP cutoffs for atrial fibrillation prediction and (2) to assess the time-dependent relationship of NT-proBNP and early in-hospital AFDAS versus AFDAS after discharge. METHODS:We conducted a pooled data analysis of patients with ischemic stroke from the prospective international multicenter BIOSIGNAL (Biomarker Signature of Stroke Aetiology) cohort study (European Stroke Centers from October 2014 to October 2017) and the prospective single-center Graz stroke pathway study (Austria from May 2018 to August 2020). AFDAS was defined as ≥30-s atrial fibrillation/flutter diagnosed within 1 year post-admission and categorized in in-hospital versus after discharge. NT-proBNP was assessed ≤24 hours of symptom onset. The association between NT-proBNP and AFDAS was evaluated by a multivariable logistic regression analysis. RESULTS:AFDAS was diagnosed in 374 (16%) of 2292 patients with ischemic stroke (median age, 74 years; 42% female), 268 (72%) during hospitalization, and 106 (28%) after discharge (median duration of hospitalization, 15 days). NT-proBNP levels at admission had a good predictive capacity for in-hospital AFDAS (area under the receiver operating characteristic curve, 0.83 [95% CI, 0.81-0.86]). For patients diagnosed with AFDAS after discharge, the predictive capacity of NT-proBNP was poor (area under the receiver operating characteristic curve, 0.65 [95% CI, 0.60-0.70]), and 20% had normal NT-proBNP values <125 pg/mL at admission. The NT-proBNP cutoff of 505 pg/mL exhibited high sensitivity (82%) and specificity (71%) for in-hospital AFDAS, with a negative predictive value of 96%. CONCLUSIONS:In patients with ischemic stroke, the admission NT-proBNP cutoff of 505 pg/mL seems to be a reliable predictor for in-hospital AFDAS, while the predictive capacity of NT-proBNP for AFDAS after discharge is limited. Our results might influence the designs of future secondary stroke prevention trials.

BACKGROUND:Low concentrations of systemic folates have been associated with a higher risk of major depressive disorder (MDD) and more severe symptoms. Moreover, folate supplementation has been shown to increase the response to selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). Folates reach the brain through the choroid plexus via transcytosis mediated by the folate receptor alpha (FRα). FRα also represents the main mechanism of folate retrieval from the nascent urine. Autoantibodies against the FRα autoantibodies(FRAAs) have been found in the serum of individuals with cerebral folate deficiency. OBJECTIVES:This study aimed to assess the role of serum FRAA titer on serum folate concentration, disease severity, and response to the SSRI/SNRI treatment in adolescents with MDD. METHODS:Serum samples at baseline obtained from the participants of a large multicenter intervention trial in moderately to severely depressed youth were analyzed. Quantification of FRAA was performed by enzyme-linked immunosorbent assay. Serum folate concentration was determined by radioligand binding assay. RESULTS:FRAA titer in the patients with folate deficiency (≤3.0 ng/mL) was significantly higher than that in the patients with a normal folate concentration, and a low FRAA titer was associated with a reduced risk of folate deficiency. No correlation was found between the Children's Depression Rating Scale-Revised score and the serum folate concentration or the FRAA titer. In regression analysis, the effect size of the serum folate concentration on the response to SSRI/SNRI was larger than that of the FRAA titer. The response rate to the treatment in the high-folate group was ∼4 times that in the low-folate group (28.5% compared with 6.7%). CONCLUSIONS:In conclusion, patients with high-FRAA titers carry a higher risk of folate deficiency. Moreover, the response to SSRI/SNRI treatment is less likely in patients with folate deficiency.

Prolonged cardiac monitoring (PCM) increases atrial fibrillation (AF) detection after ischemic stroke, but access is limited, and it is burdensome for patients. Our objective was to assess whether midregional proatrial natriuretic peptide (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) could classify people who are unlikely to have AF after ischemic stroke and allow better targeting of PCM.

Background and objective Prostate-specific antigen (PSA) remains a critical marker for prostate cancer (PCa) detection and monitoring. Recognising historical variability in PSA assays and the evolution of assay technology and calibration, this study aims to reassess interassay variability using the latest generation of five assays in a contemporary cohort of men undergoing prostate biopsy. Methods Five different commercially available PSA assays were tested in a blood sample of 76 men before undergoing a prostate biopsy. Total PSA (tPSA) and free-to-total PSA ratio (%fPSA) were compared across assays, using Roche (Basel, Switzerland) as the benchmark, and correlated with biopsy outcome to analyse the impact on PCa diagnosis. The statistical analysis included Passing-Bablok regression and Bland-Altman plots, with a p value threshold of <0.05 for significance. Key findings and limitations Among the 76 men, 28 (36.8%) were diagnosed with significant PCa (defined as International Society of Urological Pathology grade ≥2). A high correlation was observed between tPSA and %fPSA values among the different PSA assays tested (r2 ≥ 0.9). The Passing-Bablok analysis showed that tPSA results varied substantially among the assays, with slopes ranging between 0.78 and 1.04. Compared with the tPSA of Roche, tPSA values were on average 20.7% lower by Beckman (Oststeinbeck, Germany), 15.2% lower by Abbott (Chicago, IL, USA), 6.1% lower by Diasorin (Saluggia, Italy), and 9.6% higher by Brahms (Hennigsdorf, Germany; p < 0.001 for all). The %fPSA values by Abbott and Brahms were higher at 15.7% and 10.6%, respectively (p < 0.001), while the Beckman and Diasorin values had minimal differences of -0.3% and 2.3%, respectively (p > 0.05). The variability across assays would have resulted in discrepancies in both the sensitivity and the specificity for tPSA and %fPSA by at least 14%, depending on the cut-offs applied. Conclusions and clinical implications Despite the use of the latest PSA assays, relevant variability of tPSA and %fPSA results can be observed among different assays. There is an urgent need for standardised calibration methods and greater awareness among practitioners concerning interassay variability. Clinicians should acknowledge that clinically relevant thresholds may depend on the specific PSA assay and that ideally the same assay is applied over time for better clinical decision-making. Patient summary Prostate-specific antigen (PSA) is a critical marker for prostate cancer (PCa) detection and monitoring. However, significant variations were observed in the results of the latest PSA assays. Thus, standardised calibration methods and greater awareness among practitioners concerning interassay variability are needed.

Background and Objectives Prolonged cardiac monitoring (PCM) increases atrial fibrillation (AF) detection after ischemic stroke, but access is limited, and it is burdensome for patients. Our objective was to assess whether midregional proatrial natriuretic peptide (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) could classify people who are unlikely to have AF after ischemic stroke and allow better targeting of PCM. Methods We analyzed people from the Biomarker Signature of Stroke Aetiology (BIOSIGNAL) study with ischemic stroke, no known AF, and >= 3 days cardiac monitoring. External validation was performed in the Preventing Recurrent Cardioembolic Stroke: Right Approach, Right Patient (PRECISE) study of 28 days of cardiac monitoring in people with ischemic stroke or transient ischemic attack and no known AF. The main outcome is no AF detection. We assessed the discriminatory value of MR-proANP and NT-proBNP combined with clinical variables to identify people with no AF. A decision curve analysis was performed with combined data to determine the net reduction in people who would undergo PCM using the models based on a 15% threshold probability for AF detection. Results We included 621 people from the BIOSIGNAL study. The clinical multivariable prediction model included age, NIH Stroke Scale score, lipid-lowering therapy, creatinine, and smoking status. The area under the receiver-operating characteristic curve (AUROC) for clinical variables was 0.68 (95% CI 0.62-0.74), which improved with the addition of log(10)MR-proANP (0.72, 0.66-0.78; p = 0.001) or log(10)NT-proBNP (0.71, 0.65-0.77; p = 0.009). Performance was similar for the models with log(10)MR-proANP vs log(10)NT-proBNP (p = 0.28). In 239 people from the PRECISE study, the AUROC for clinical variables was 0.68 (0.59-0.76), which improved with the addition of log(10)NT-proBNP (0.73, 0.65-0.82; p < 0.001) or log(10)MR-proANP (0.79, 0.72-0.86; p < 0.001). Performance was better for the model with log(10)MR-proANP vs log(10)NT-proBNP (p = 0.03). The models could reduce the number of people who would undergo PCM by 30% (clinical and log(10)MR-proANP), 27% (clinical and log(10)NT-proBNP), or 20% (clinical only). Discussion MR-proANP and NT-proBNP help classify people who are unlikely to have AF after ischemic stroke. Measuring MR-proANP or NT-proBNP could reduce the number of people who need PCM by 30%, without reducing the amount of AF detected.

Large bone defects after trauma demand for adequate bone substitutes. Bone void fillers should be antibacterial and pro-angiogenic. One viable option is the use of composite materials like the combination of PLGA and amorphous calcium phosphate (aCaP).Copper stimulates angiogenesis and has antibacterial qualities. Either copper oxide (CuO) nanoparticles (NPs) were therefore added to PLGA/aCaP/CuO in different concentrations (1, 5 and 10 w/w %) or copper-doped tricalcium phosphate NPs (TCP with 2% of copper) were electrospun into PLGA/CuTCP nanocomposites.Bi-layered nanocomposites of PLGA/aCaP with different copper NPs (CuO or TCP) and a second layer of pristine PLGA were fabricated. Two clinical bacterial isolates (Staphylococcus aureus and Staphylococcus epidermidis) were used to assess antibacterial properties of the copper-containing materials. For angiogenesis, the chorioallantoic membrane (CAM) assay of the chicken embryo was performed.The higher the CuO content, the higher were the antibacterial properties, with 10 % CuO reducing bacterial adhesion most effectively. Vessel and cell densities were highest in the 5 % CuO containing scaffolds, while tissue integration was more pronounced at lower CuO content. The PLGA/aCaP/CuO (1 % CuO) behaved similar like PLGA/CuTCP in all angiogenic and antibacterial readouts, based on the same copper fraction.We conclude that CuO NPs or CuTCP NPs are useful components to increase angiogenic properties of nanocomposites and at the same time exhibiting antibacterial characteristics.

Background and Aims: P-wave abnormalities in the 12-lead electrocardiogram (ECG) have been associated with a higher risk of acute ischemic stroke (AIS) as well as atrial fibrillation (AF). This study aimed to assess pre-determined ECG criteria during sinus rhythm in unselected AIS patients and their value for predicting newly diagnosed atrial fibrillation (NDAF) after hospital admission. Methods: P-wave alterations were measured on 12-lead ECG on admission in all consecutively enrolled patients without known AF between October 2014 and 2017. The outcome of interest was NDAF, identified by prolonged electrocardiographic monitoring within one year after the index AIS. Univariable and multivariable logistic regression was applied to assess the magnitude and independence of the association between pre-selected ECG markers and NDAF. The discriminatory accuracy was evaluated with the area under the receiver operating characteristic curve (AUC), and the incremental prognostic value was estimated with the net reclassification index. Results: NDAF was detected in 87 (10%) of 856 patients during a follow-up of 365 days. Out of the pre-selected ECG parameters, advanced interatrial block (aIAB) and PR interval in lead II were independently associated with NDAF in univariable regression analysis. Only aIAB remained a significant predictor in multivariable analysis. Adding aIAB to the best-performing multivariable regression model improved the discriminatory accuracy to predict NDAF from an AUC of 0.78 (95%-CI 0.77–0.80) to 0.81 (95%-CI 0.80–0.83, p < 0.001). Conclusion: aIAB is independently and highly associated with NDAF in patients with AIS, has high inter-rater reliability, and therefore may be helpful to refine diagnostic work-up to search for AF in AIS.

Background: Early identification of patients developing symptomatic intracranial hemorrhage and symptomatic brain edema after acute ischemic stroke is essential for clinical decision-making. Astroglial protein S-100B is a marker of blood-brain barrier disruption, which plays an important role in the formation of intracranial hemorrhage and brain edema. In this study, we assessed the prognostic value of serum S-100B for the development of these complications. Methods: Serum S-100B levels were measured within 24 h from symptom onset in 1749 consecutive acute ischemic stroke patients from the prospective, observational, multicenter BIOSIGNAL cohort study (mean age 72.0 years, 58.3% male). To determine symptomatic intracranial hemorrhage or symptomatic brain edema, follow-up neuroimaging was performed in all patients receiving reperfusion therapy or experiencing clinical worsening with an NIHSS increase of ⩾4. Results: Forty six patients (2.6%) developed symptomatic intracranial hemorrhage and 90 patients (5.2%) developed symptomatic brain edema. After adjustment for established risk factors, log10S-100B levels remained independently associated with both symptomatic intracranial hemorrhage (OR 3.41, 95% CI 1.7–6.9, p = 0.001) and symptomatic brain edema (OR 4.08, 95% CI 2.3–7.1, p < 0.001) in multivariable logistic regression models. Adding S-100B to the clinical prediction model increased the AUC from 0.72 to 0.75 ( p = 0.001) for symptomatic intracranial hemorrhage and from 0.78 to 0.81 ( p < 0.0001) for symptomatic brain edema. Conclusions: Serum S-100B levels measured within 24 h after symptom onset are independently associated with the development of symptomatic intracranial hemorrhage and symptomatic brain edema in acute ischemic stroke patients. Thus, S-100B may be useful for early risk-stratification regarding stroke complications.

Effective public health measures against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against three SARS-CoV-2 proteins. We used TRABI for continuous seromonitoring of hospital patients and blood donors (n = 72'250) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). We found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19. Crucially, we found no evidence of a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2-infected subjects represents a resource for the study of chronic and possibly unexpected sequelae.

Background Endotoxin adsorption is a promising but controversial therapy in severe, refractory septic shock and conflicting results exist on the effective capacity of available devices to reduce circulating endotoxin and inflammatory cytokine levels. Methods Multiarm, randomized, controlled trial in two Swiss intensive care units, with a 1:1:1 randomization of patients suffering severe, refractory septic shock with high levels of endotoxemia, defined as an endotoxin activity ≥ 0.6, a vasopressor dependency index ≥ 3, volume resuscitation of at least 30 ml/kg/24 h and at least single organ failure, to a haemoadsorption (Toraymyxin), an enhanced adsorption haemofiltration (oXiris) or a control intervention. Primary endpoint was the difference in endotoxin activity at 72-h post-intervention to baseline. In addition, inflammatory cytokine, vasopressor dependency index and SOFA-Score dynamics over the initial 72 h were assessed inter alia. Results In the 30, out of 437 screened, randomized patients (10 Standard of care, 10 oXiris, 10 Toraymyxin), endotoxin reduction at 72-h post-intervention-start did not differ among interventions (Standard of Care: 12 [1–42]%, oXiris: 21 [10–51]%, Toraymyxin: 23 [10–36]%, p = 0.82). Furthermore, no difference between groups could be observed neither for reduction of inflammatory cytokine levels ( p = 0.58), nor for vasopressor weaning ( p = 0.95) or reversal of organ injury ( p = 0.22). Conclusions In a highly endotoxemic, severe, refractory septic shock population neither the Toraymyxin adsorber nor the oXiris membrane could show a reduction in circulating endotoxin or cytokine levels over standard of care. Trial registration ClinicalTrials.gov. NCT01948778. Registered August 30, 2013. https://clinicaltrials.gov/study/NCT01948778

Background Prolonged cardiac monitoring (PCM) increases atrial fibrillation detection after stroke (AFDAS) but access is limited. We aimed to assess the utility of midregional pro-atrial natriuretic peptide (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) to identify people who are unlikely to have AFDAS and improve healthcare resource allocation for PCM.. Methods We analysed people from the BIOSIGNAL (Biomarker Signature of Stroke Aetiology) study with ischaemic stroke, no known AF and ≥3 days cardiac monitoring. External validation was in the PRECISE (Preventing Recurrent Cardioembolic Stroke: Right Approach, Right Patient) study of 28-days cardiac monitoring after stroke. The main outcome is no AFDAS. We assessed the discriminatory value of MR-proANP and NT-proBNP combined with clinical variables to identify people with no AFDAS. We determined the net reduction in people who would undergo PCM using the models with 15% AFDAS threshold probability. Results We included 621 people from BIOSIGNAL. The clinical model included age, National Institutes of Health Stroke Scale score, lipid-lowering therapy, creatinine and smoking status. The AUROC was 0.68 (95%CI 0.62-0.74) with clinical variables, which improved with log 10 MR-proANP (0.72,0.66-0.78;p=0.001) or log 10 NT-proBNP (0.71,0.65-0.77;p=0.009). Performance was similar for log 10 MR-proANP versus log 10 NT-proBNP (p=0.28). In 239 people from PRECISE, the AUROC for clinical variables was 0.68 (0.59-0.76), which improved with log 10 NT-proBNP (0.73,0.65-0.82;p<0.001) or log 10 MR-proANP (0.79,0.72-0.86;p<0.001). Performance was better with log 10 MR-proANP versus log 10 NT-proBNP (p=0.03). The models could reduce the number who would undergo PCM by 30% (clinical+log 10 MR-proANP), 27% (clinical+log 10 NT-proBNP) or 20% (clinical). Conclusions MR-proANP and NT-proBNP help classify people who are unlikely to have AFDAS and could reduce the number who need PCM by 30%.

BACKGROUND:Midregional pro-atrial natriuretic peptide (MR-proANP) is a promising biomarker to differentiate the underlying etiology of acute ischemic stroke (AIS). OBJECTIVES:This study aimed to determine the role of MR-proANP for classification as cardioembolic (CE) stroke, identification of newly diagnosed atrial fibrillation (NDAF), and risk assessment for major adverse cardiovascular events (MACE). METHODS:This study measured MR-proANP prospectively collected within 24 hours after symptom-onset in patients with AIS from the multicenter BIOSIGNAL (Biomarker Signature of Stroke Aetiology) cohort study. Primary outcomes were CE stroke etiology and NDAF after prolonged cardiac monitoring, as well as a composite outcome of MACE (recurrent cerebrovascular events, myocardial infarction, or cardiovascular death) within 1 year. Logistic/Poisson and subproportional hazard regression were applied to evaluate the association between MR-proANP levels and outcomes. Additionally, a model for prediction of NDAF was derived and validated as a decision tool for immediate clinical application. RESULTS:Between October 1, 2014, and October 31, 2017, this study recruited 1,759 patients. Log10MR-proANP levels were associated with CE stroke (OR: 7.96; 95% CI: 4.82-13.14; risk ratio: 3.12; 95% CI: 2.23-4.37), as well as NDAF (OR: 35.3; 95% CI: 17.58-71.03; risk ratio: 11.47; 95% CI: 6.74-19.53), and MACE (subdistributional HR: 2.02; 95% CI: 1.32-3.08) during follow-up. The model to predict NDAF including only age and MR-proANP levels had a good discriminatory capacity with an area under the curve of 0.81 (95% CI: 0.76-0.86), was well calibrated (calibration in the large: -0.086; calibration slope 1.053), and yielded higher net-benefit compared with validated scores to predict NDAF (AS5F score, CHA2DS2-VASc [Congestive Heart Failure, Hypertension, Age ≥65 or ≥75, Diabetes, Prior Cardioembolic Event, (female) Sex, or Vascular Disease] score). CONCLUSIONS:MR-proANP is a valid biomarker to determine risk of NDAF and MACE in patients with AIS and can be used as a decision tool to identify patients for prolonged cardiac monitoring. (Biomarker Signature of Stroke Aetiology Study: The BIOSIGNAL study [BIOSIGNAL]; NCT02274727).

Human lung cancer ranks among the most frequently treated cancers worldwide. As copper appears critical to angiogenesis and tumor growth, selective removal of copper represents a promising strategy to restrict tumor growth. To this end, we explored the activity of the novel high-affinity membrane-permeant Cu(I) chelator PSP-2 featuring a low-zeptomolar dissociation constant. Using H460 human lung cancer cells, we generated small tumors on the chorioallantoic membrane of the chicken embryo (CAM assay) and studied the effects of topical PSP-2 application on their weight and vessel density after one week. We observed a significant angiosuppression along with a marked decrease in tumor weight under PSP-2 application compared to controls. Moreover, PSP-2 exposure resulted in lower ki67+ cell numbers at a low dose but increased cell count under a high dose. Moreover, HIF-1α+ cells were significantly reduced with low-dose PSP-2 exposure compared to high-dose and control. The total copper content was considerably lower in PSP-2 treated tumors, although statistically not significant. Altogether, PSP-2 shows promising potential as an anti-cancer drug. Nevertheless, further animal experiments and application to different tumor types are mandatory to support these initial findings, paving the way toward clinical trials.

You have accessJournal of UrologyCME1 May 2022PD11-02 EVALUATION OF VARIETY AND PERFORMANCE BETWEEN PSA ASSAYS AND PHI IN A CLINICAL COHORT OF MEN UNDERGOING PROSTATE BIOPSY FOR SUSPECTED PROSTATE CANCER Basil Kaufmann, Paloma Pellegrino, Noémie Lautenbach, Katharina Spanaus, Arnold von Eckardstein, Thomas Hermanns, and Cédric Poyet Basil KaufmannBasil Kaufmann More articles by this author , Paloma PellegrinoPaloma Pellegrino More articles by this author , Noémie LautenbachNoémie Lautenbach More articles by this author , Katharina SpanausKatharina Spanaus More articles by this author , Arnold von EckardsteinArnold von Eckardstein More articles by this author , Thomas HermannsThomas Hermanns More articles by this author , and Cédric PoyetCédric Poyet More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002537.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate specific antigen (PSA) testing is of paramount importance as a diagnostic tool for detecting and monitoring patients with prostate cancer. Less is known about how different PSA tests perform in the same men and which additional tests (i.e., %fPSA and/or PHI) might help distinguish which men harbours significant prostate cancer and which do not. The aim of this study was to test different PSA assays and PHI in the same men undergoing prostate biopsy for suspected prostate cancer. METHODS: Clinical data from a consecutive group of men who underwent mpMRI/fusion and transperineal template prostate biopsy were prospectively gathered. Five different commercially available PSA assays (Roche, Diasorin, Brahms, Abott, Beckmann) and PHI (Beckmann) were tested in an additional blood sample taken before prostate biopsy. The results of all six assays were compared directly and in relation to clinical data and biopsy outcome. To study the different assay performance in predicting significant prostate cancer (defined as ISUP grading group ≥2), the area under the curve (ROC test) was used. RESULTS: Seventy-five men were available for final analysis. A total of 29 (38.7%) were diagnosed with significant PCa and in 46 (61.3%) the biopsy showed insignificant PCa (defined as ISUP 1) or no cancer. We found that some PSA assays consistently showed relevant higher or lower values across all PSA levels compared to our internal control assay from Roche. Compared to Roche, Brahms showed consistently higher values and Beckmann and Abott showed uniformly lower values, whereas Diasorin showed similar values in most blood samples tested. In contrast to total PSA, %FPSA showed less variety between the assays when tested in the same blood sample. The different assays including PHI, were then tested for their performance in detecting significant PCa using the AUC method. The average AUC value for the five PSA assays was 0.603 (ranging from 0.596 to 6.12), whereas PHI showed by far the highest AUC value with 0.808. CONCLUSIONS: We found relevant and constant differences in PSA levels between different tested PSA providers within the same blood sample. Thus, all clinical studies reporting PSA data should report the provider used. Furthermore, clinicians should know the specifics of the PSA test used in daily clinical practice for accurate and better interpretation of the test result. Finally, PHI outperformed all tested PSA assays in its ability to predict significant PCa before prostate biopsy and therefore could add value in intial PCa risk assessment. Source of Funding: This study received no financial support © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e189 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Basil Kaufmann More articles by this author Paloma Pellegrino More articles by this author Noémie Lautenbach More articles by this author Katharina Spanaus More articles by this author Arnold von Eckardstein More articles by this author Thomas Hermanns More articles by this author Cédric Poyet More articles by this author Expand All Advertisement PDF downloadLoading ...

AIMS Lipoprotein(a) [Lp(a)] is a recognized causal risk factor for atherosclerotic cardiovascular disease but its role for acute ischaemic stroke (AIS) is controversial. In this study, we evaluated the association of Lp(a) with large artery atherosclerosis (LAA) stroke and risk of recurrent cerebrovascular events in AIS patients. METHODS AND RESULTS For this analysis of the prospective, observational, multicentre BIOSIGNAL cohort study we measured Lp(a) levels in plasma samples of 1733 primarily Caucasian (98.6%) AIS patients, collected within 24 h after symptom onset. Primary outcomes were LAA stroke aetiology and recurrent cerebrovascular events (ischaemic stroke or transient ischaemic attack) within 1 year. We showed that Lp(a) levels are independently associated with LAA stroke aetiology [adjusted odds ratio 1.48, 95% confidence interval (CI) 1.14-1.90, per unit log10Lp(a) increase] and identified age as a potent effect modifier (Pinteraction =0.031) of this association. The adjusted odds ratio for LAA stroke in patients aged <60 years was 3.64 (95% CI 1.76-7.52) per unit log10Lp(a) increase and 4.04 (95% CI 1.73-9.43) using the established cut-off ≥100 nmol/l. For 152 recurrent cerebrovascular events, we did not find a significant association in the whole cohort. However, Lp(a) levels ≥100 nmol/l were associated with an increased risk for recurrent events among patients who were either <60 years [adjusted hazard ratio (HR) 2.40, 95% CI 1.05-5.47], had evident LAA stroke aetiology (adjusted HR 2.18, 95% CI 1.08-4.40), or had no known atrial fibrillation (adjusted HR 1.60, 95% CI 1.03-2.48). CONCLUSION Elevated Lp(a) was independently associated with LAA stroke aetiology and risk of recurrent cerebrovascular events among primarily Caucasian individuals aged <60 years or with evident arteriosclerotic disease.