Prescribing Patterns and Outcomes of Edoxaban in Atrial Fibrillation Patients From Asia　- One-Year Data From the Global ETNA-AF Program.

Background: This study reports prescribing patterns and the 1-year effectiveness and safety of edoxaban in an Asian cohort of Edoxaban Treatment in routiNe clinical prActice (ETNA)-Atrial Fibrillation (AF) patients. Methods and Results: The Global ETNA-AF program integrates prospective, observational, noninterventional regional studies, collecting data on characteristics and clinical outcomes of patients with AF receiving edoxaban for stroke prevention. Baseline characteristics, medical history, and 1-year clinical event rates were assessed in patients from South Korea, Taiwan, Hong Kong, and Thailand. Clinically relevant events assessed at 12 months included all-cause death, cardiovascular death, ischemic and hemorrhagic stroke, systemic embolic events (SEEs), bleeding, and net clinical outcome (NCO). Overall, 3,359 patients treated with edoxaban 60 or 30 mg once daily completed 1-year follow-up; 70.9% of patients received recommended dosing according to local labels. Baseline mean±standard deviation age was 71.7±9.6 years, CHA2DS2-VASc score was 3.1±1.5, and modified HAS-BLED score was 2.3±1.1. Mean age and sex were similar across countries/regions. The 1-year event rate for all-cause death was 1.8%; major bleeding, 1.3%; ischemic stroke, 1.1%; cardiovascular mortality, 0.7%; hemorrhagic stroke, 0.3%; SEEs, 0%; and NCO, 4.1%; with differences observed between countries/regions and dosing groups. Conclusions: Most Asian patients with AF were prescribed recommended edoxaban dosing in routine care settings. At 1-year follow-up, this analysis supports the effectiveness and safety of edoxaban in these patients.

Preanalytical stability of molecular forms of prostate-specific antigen in serum samples (PSA, free PSA, [-2]proPSA) and their impact on fPSA/tPSA ratio and PHI.

BACKGROUND: Prostate cancer is a common cancer in men. Detection methods include the measurement of biomarkers: prostate-specific antigen (PSA), free PSA, [-2]proPSA, and the calculated indices: fPSA/tPSA ratio and Prostate Health Index (PHI). Proper preanalytical conditions are crucial for precise measurement and failure to adhere to protocols or regulations can influence the diagnostic algorithm. We assessed the stability of the above-mentioned biomarkers, fPSA/tPSA ratio and PHI, under various pre-analytical conditions. METHODS: Serum samples from 45 males were collected and stored under specific conditions before tPSA, fPSA, and [-2]proPSA were measured. Subsequently, the fPSA/tPSA and PHI were calculated. RESULTS: tPSA, fPSA, and [-2]proPSA remained stable during the two freeze-thaw cycles. Storage at 4°C and 22°C resulted in stable tPSA concentrations. However, fPSA levels decreased and [-2]proPSA levels increased over time. The fPSA/tPSA ratio remained stable for 72 h, at which point a decrease was observed in the samples kept at 4°C and 22°C. A gradual increase in PHI was observed in the samples kept at 4°C and 22°C. CONCLUSIONS: All biomarkers remained stable during two freeze-thaw cycles. tPSA was the most stable analyte when stored at 4°C, as well as at RT. A gradual increase of [-2]proPSA and a slight decrease in fPSA were observed during the storage test. This led to a decrease in the fPSA/tPSA ratio and an elevation in the PHI. We therefore recommend measuring prostate biomarkers promptly following blood collection. IMPACT: Understanding the pre-analytical stability of prostate biomarkers helps prevent false positive results and improve the accuracy of diagnostics for prostate cancer.

Outcomes of patients with atrial fibrillation on oral anticoagulation with and without heart failure: the ETNA-AF-Europe registry.

AIMS: Heart failure (HF) is a risk factor for major adverse events in atrial fibrillation (AF). Whether this risk persists on non-vitamin K antagonist oral anticoagulants (NOACs) and varies according to left ventricular ejection fraction (LVEF) is debated. METHODS AND RESULTS: We investigated the relation of HF in the ETNA-AF-Europe registry, a prospective, multicentre, observational study with an overall 4-year follow-up of edoxaban-treated AF patients. We report 2-year follow-up for ischaemic stroke/transient ischaemic attack (TIA)/systemic embolic events (SEE), major bleeding, and mortality. Of the 13 133 patients, 1854 (14.1%) had HF. Left ventricular ejection fraction was available for 82.4% of HF patients and was <40% in 671 (43.9%) and ≥40% in 857 (56.1%). Patients with HF were older, more often men, and had more comorbidities. Annualized event rates (AnERs) of any stroke/SEE were 0.86%/year and 0.67%/year in patients with and without HF. Compared with patients without HF, those with HF also had higher AnERs for major bleeding (1.73%/year vs. 0.86%/year) and all-cause death (8.30%/year vs. 3.17%/year). Multivariate Cox proportional models confirmed HF as a significant predictor of major bleeding [hazard ratio (HR) 1.65, 95% confidence interval (CI): 1.20-2.26] and all-cause death [HF with LVEF <40% (HR 2.42, 95% CI: 1.95-3.00) and HF with LVEF ≥40% (HR 1.80, 95% CI: 1.45-2.23)] but not of ischaemic stroke/TIA/SEE. CONCLUSION: Anticoagulated patients with HF at baseline featured higher rates of major bleeding and all-cause death, requiring optimized management and novel preventive strategies. NOAC treatment was similarly effective in reducing risk of ischaemic events in patients with or without concomitant HF.

Role of risk factors, scoring systems, and prognostic models in predicting the functional outcome in meningioma surgery: multicentric study of 552 skull base meningiomas.

Despite the importance of functional outcome, only a few scoring systems exist to predict neurologic outcome in meningioma surgery. Therefore, our study aims to identify preoperative risk factors and develop the receiver operating characteristics (ROC) models estimating the risk of a new postoperative neurologic deficit and a decrease in Karnofsky performance status (KPS). A multicentric study was conducted in a cohort of 552 consecutive patients with skull base meningiomas who underwent surgical resection from 2014 to 2019. Data were gathered from clinical, surgical, and pathology records as well as radiological diagnostics. The preoperative predictive factors of functional outcome (neurologic deficit, decrease in KPS) were analyzed in univariate and multivariate stepwise selection analyses. Permanent neurologic deficits were present in 73 (13.2%) patients and a postoperative decrease in KPS in 84 (15.2%). Surgery-related mortality was 1.3%. A ROC model was developed to estimate the probability of a new neurologic deficit (area 0.74; SE 0.0284; 95% Wald confidence limits (0.69; 0.80)) based on meningioma location and diameter. Consequently, a ROC model was developed to predict the probability of a postoperative decrease in KPS (area 0.80; SE 0.0289; 95% Wald confidence limits (0.74; 0.85)) based on the patient's age, meningioma location, diameter, presence of hyperostosis, and dural tail. To ensure an evidence-based therapeutic approach, treatment should be founded on known risk factors, scoring systems, and predictive models. We propose ROC models predicting the functional outcome of skull base meningioma resection based on the age of the patient, meningioma size, and location and the presence of hyperostosis and dural tail.

Vitamin D3 Supplementation: Comparison of 1000 IU and 2000 IU Dose in Healthy Individuals.

BACKGROUND: Scientific studies point to a significant global vitamin D deficiency. The recommended dose of vitamin D for the adult population in Central Europe is 800-2000 IU/day. The aim of our study was to determine whether doses of 1000 IU or 2000 IU of vitamin D3 are adequate to achieve the sufficiency reference values of [25(OH)D]. METHODS: Seventy-two healthy volunteers, average age twenty-two, took part in the study. The study was conducted from October to March in order to eliminate intra-dermal vitamin D production. Vitamin D3 in an oleaginous mixture was used. The participants used either 1000 IU or 2000 IU/daily for two 60-day periods with a 30-day break. RESULTS: The dose of 1000 IU, taken for 60 days, increased vitamin D levels relatively little. Furthermore, serum vitamin D levels decreased in the 30 days following the cessation of supplementation. Taking 2000 IU daily led to a sharp increase in serum levels which plateaued 30 days after the subjects stopped using vitamin D3 drops. CONCLUSIONS: Both doses, taken daily, can help maintain adequate vitamin D levels during the winter months. A daily dose of 2000 IU, however, maintained the desired levels of vitamin D for a longer period.

Prescribing Patterns and Outcomes of Edoxaban in Atrial Fibrillation: One-Year Data from the Global ETNA-AF Program.

Non-recommended dosing occurs in ~25-50% of non-vitamin K antagonist oral anticoagulant prescriptions, with limited data for edoxaban. We analyzed edoxaban dosing patterns in atrial fibrillation patients from the Global ETNA-AF program, relating patterns to baseline characteristics and 1-year clinical outcomes. The following dosing groups were compared: non-recommended 60 mg ("overdosed") vs. recommended 30 mg; non-recommended 30 mg ("underdosed") vs. recommended 60 mg. Most (22,166/26,823; 82.6%) patients received recommended doses. Non-recommended dosing was more frequent near label-specified dose-reduction thresholds. Ischemic stroke (IS; HR 0.85, 95% CI 0.50-1.47; p = 0.6) and major bleeding (MB; HR 1.47, 95% CI 0.97-2.71; p = 0.07) did not differ between recommended 60 mg and "underdosed" groups, whereas all-cause (HR 1.61, 95% CI 1.23-2.08; p = 0.0003) and cardiovascular deaths (HR 1.61, 95% CI 1.11-2.38; p = 0.01) were higher in the "underdosed" group. Compared with recommended 30 mg, the "overdosed" group had lower IS (HR 0.51, 95% CI 0.28-0.98; p = 0.04) and all-cause death (HR 0.74, 95% CI 0.55-0.98; p = 0.03) without higher MB (HR 0.74, 95% CI 0.46-1.22; p = 0.2). In conclusion: non-recommended dosing was infrequent, but more common near dose-reduction thresholds. "Underdosing" was not associated with better clinical outcomes. The "overdosed" group had lower IS and all-cause death without higher MB.

Assessment of Prostate Carcinoma Aggressiveness: Relation to 68Ga-PSMA-11-PET/MRI and Gleason Score.

BACKGROUND/AIM: To test the correlation of 68Ga-PSMA-11 uptake and the expression of PSMA (prostatic specific membrane antigen) with the Gleason score, apparent diffusion coefficient (ADC) and pharmacokinetic parameters obtained from dynamic contrast agent-enhanced MRI/PET. PATIENTS AND METHODS: Forty newly diagnosed, therapy naïve patients with prostatic carcinoma (PC) (mean age of 56.7, range=34-79), who were referred for 68Ga-PSMA-11-PET/MRI for primary staging and had undergone radical prostatectomy (RAPE) were included in this prospective study. Their blood samples were tested for serum levels of prostate-specific antigen (PSA) and proPSA. The patients' prostates were evaluated using whole-mount sections, which helped determine the extent and grade of the tumor; tests were performed to determine immunohistochemical PSMA expression. RESULTS: A correlation between PSMA expression and the accumulation of 68Ga-PSMA-11 was found using the Spearman correlation coefficient (p=0.0011). A stronger correlation was found between Gleason patterns 3 or 4 and PSMA expression (p=0.06). Furthermore, the correlation of Gleason score with the overall 68Ga-PSMA-11 accumulation within the tumor or non-tumor tissue was found to be significant (p=0.0157). A significant relation was found only with the Kep elimination rate constant, which was stronger in Gleason pattern 4 than in Gleason pattern 3. A weaker correlation was found between the accumulation of 68Ga-PSMA-11 and Ktrans in Gleason pattern 4: the most significant relation being between ADCmin and Gleason pattern 3 and 4 (p=0.0074). The total size of the tumor correlated with levels of proPSA (p<0.0001), and its extra prostatic extension correlated with levels of proPSA (p<0.0001). CONCLUSION: 68Ga-PSMA-11 correlates well with the expression of PSMA. Gleason pattern 3 and 4 had a higher correlation with 68Ga-PSMA-11 levels than did Gleason pattern 5. Either no correlation, or a weak correlation, was established with pharmacokinetics.

Heterogeneity of outcomes within diabetic patients with atrial fibrillation on edoxaban: a sub-analysis from the ETNA-AF Europe registry.

BACKGROUND: Recent data have suggested that insulin-requiring diabetes mostly contributes to the overall increase of thromboembolic risk in patients with atrial fibrillation (AF) on warfarin. We evaluated the prognostic role of a different diabetes status on clinical outcome in a large cohort of AF patients treated with edoxaban. METHODS: We accessed individual patients' data from the prospective, multicenter, ETNA-AF Europe Registry. We compared the rates of ischemic stroke/transient ischemic attack (TIA)/systemic embolism, myocardial infarction (MI), major bleeding and all-cause death at 2 years according to diabetes status. RESULTS: Out of an overall population of 13,133 patients, 2885 had diabetes (22.0%), 605 of whom (21.0%) were on insulin. The yearly incidence of ischemic stroke/TIA/systemic embolism was 0.86% in patients without diabetes, 0.87% in diabetic patients not receiving insulin (p = 0.92 vs no diabetes) and 1.81% in those on insulin (p = 0.002 vs no diabetes; p = 0.014 vs diabetes not on insulin). The annual rates of MI and major bleeding were 0.40%, 0.43%, 1.04% and 0.90%, 1.10% and 1.71%, respectively. All-cause yearly mortality was 3.36%, 5.02% and 8.91%. At multivariate analysis, diabetes on insulin was associated with a higher rate of ischemic stroke/TIA/systemic embolism [adjusted HR 2.20, 95% CI 1.37-3.54, p = 0.0011 vs no diabetes + diabetes not on insulin] and all-cause death [aHR 2.13 (95% CI 1.68-2.68, p < 0.0001 vs no diabetes]. Diabetic patients not on insulin had a higher mortality [aHR 1.32 (1.11-1.57), p = 0.0015], but similar incidence of stroke/TIA/systemic embolism, MI and major bleeding, vs those without diabetes. CONCLUSIONS: In a real-world cohort of AF patients on edoxaban, diabetes requiring insulin therapy, rather than the presence of diabetes per se, appears to be an independent factor affecting the occurrence of thromboembolic events during follow-up. Regardless of the diabetes type, diabetic patients had a lower survival compared with those without diabetes.

Edoxaban for stroke prevention in atrial fibrillation and age-adjusted predictors of clinical outcomes in routine clinical care.

AIMS: Patients with atrial fibrillation (AF) treated with oral anticoagulation still suffer from cardiovascular complications including cardiovascular death, stroke, and major bleeding. To identify risk factors for predicting stroke and bleeding outcomes in anticoagulated patients, we assessed 2-year outcomes in patients with AF treated with edoxaban in routine care. We also report the age-adjusted risk predictors of clinical outcomes. METHODS AND RESULTS: The Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular Atrial Fibrillation (ETNA-AF) Europe (NCT02944019) is a prospective, multi-centre, post-authorisation, observational study with an overall 4-year follow-up conducted in 825 centres enrolling edoxaban-treated patients in 10 European countries. Of the 13 133 patients with AF (mean age: 73.6 ± 9.5 years), 5682 (43.3%) were female. At the 2-year follow-up, 9017/13 133 patients were still on edoxaban; 1830 discontinued treatment including 937 who died (annualised event rate of all-cause death was 3.87%). 518 (2.14%) patients died of cardiovascular causes; 234 (0.97%) experienced major bleeding and 168 (0.70%) experienced stroke or systemic embolic events (SEE). Intracranial haemorrhage was noted in 49 patients (0.20%). History of transient ischaemic attack (TIA) at baseline was the strongest predictor of ischaemic stroke or SEE (Wald χ2: 73.63; P < 0.0001). Low kidney function at baseline was the strongest predictor of major bleeding (Wald χ2: 30.68; P < 0.0001). History of heart failure (HF) was the strongest predictor of all-cause (Wald χ2: 146.99; P < 0.0001) and cardiovascular death (Wald χ2: 100.38; P < 0.0001). CONCLUSION: Patients treated with edoxaban in ETNA-AF-Europe reported low 2-year event rates in unselected AF patients. Prior stroke, reduced kidney function, and HF identify patients at high risk of stroke, bleeding and all-cause/cardiovascular death, respectively.

Perceived vs. objective frailty in patients with atrial fibrillation and impact on anticoagulant dosing: an ETNA-AF-Europe sub-analysis.

AIMS: Frailty is common in patients with atrial fibrillation (AF), with possible impact on therapies and outcomes. However, definitions of frailty are variable, and may not overlap with frailty perception among physicians. We evaluated the prevalence of frailty as perceived by enrolling physicians in the Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular AF (ETNA-AF)-Europe registry (NCT02944019), and compared it with an objective frailty assessment. METHODS AND RESULTS: ETNA-AF-Europe is a prospective, multi-centre, post-authorization, observational study. There we assessed the presence of frailty according to (i) a binary subjective investigators' judgement and (ii) an objective measure, the Modified Frailty Index. Baseline data on frailty were available in 13 621/13 980 patients. Prevalence of perceived frailty was 10.6%, with high variability among participating countries and healthcare settings (range 5.9-19.6%). Conversely, only 5.0% of patients had objective frailty, with minimal variability (range 4.5-6.7%); and only <1% of patients were identified as frail by both approaches. Compared with non-frailty-perceived, perceived frail patients were older, more frequently female, and with lower body weight; conversely, objectively frail patients had more comorbidities. Non-recommended edoxaban dose regimens were more frequently prescribed in both frail patient categories. CONCLUSIONS: Physicians' perception of frailty in AF patients is variable, mainly driven by age, sex, and weight, and quite different compared with the results of an objective frailty assessment. Whatever the approach, frailty appears to be associated with non-recommended anticoagulant dosages. Whether this apparent inappropriateness influences hard outcomes remains to be assessed.

Long-Term Monitoring of the Antibody Response to a SARS-CoV-2 Infection.

A group of 110 patients from the West Bohemian region who had been infected with COVID-19 was monitored for the purposes of this study. We focused on cases of mild or moderate COVID-19; statistically the most likely to occur. Day zero was defined as the day on which a positive PCR test was first established. The mean length of observation was 6.5 months, the maximum length 12 months. The first blood samples were taken from a smaller cohort during the 1-3 months following the first positive PCR test. We assumed that SARS-CoV-2 antibodies would be present during this period and therefore a limited number of samples were taken for the purpose of detecting antibodies. More samples were collected, starting 4 months after the first positive PCR test. A subsequent set of blood samples were drawn, mostly 6 months after the first ones. Our study confirmed the presence of total IgG SARS-CoV-2 antibodies up to 1 year after the onset of the disease. The peak of antibody production was observed in the third month after the first positive PCR test. A mathematical estimate of the median duration of antibody positivity was calculated to be 18 months from the onset of the COVID-19 infection.

The Role of Serum Tumor Markers in Follow-up After Surgical Treatment of Malignant Lung Tumors.

AIM: The aim of this study was to evaluate the utility of selected tumor markers for the detection of lung cancer recurrence during follow-up. PATIENTS AND METHODS: The study group consisted of 109 patients and 109 healthy controls. The following biomarkers were selected: Carcinoembryonic antigen; cytokeratin fragment 19; neuron-specific enolase; tissue polypeptide-specific antigen; cytokeratin fragments 8, 18 and 19; insulin-like growth factor 1; pro-gastrin-releasing peptide; and 25-hydroxyvitamin D. The biomarkers were assessed individually or using a multivariate analysis. RESULTS: Carcinoembryonic antigen [area under the receiver operating characteristics curve (AUC)=0.6857, p<0.0001] and cytokeratin fragment 19 (AUC=0.6882, p<0.0001) proved best in detecting relapse. The multivariate model indicated insulin-like growth factor 1 (p=0.0006, AUC=0.6225) as the third most useful biomarker. The multivariate model using these three markers achieved the best AUC value of 0.7730 (p=0.0050). CONCLUSION: We demonstrated that carcinoembryonic antigen and cytokeratin fragment 19 play a key role in the detection of lung cancer recurrence. A multivariate approach can increase the effectiveness of detection.

Could the new coronavirus have infected humans prior November 2019?

The pandemic caused by the SARS-CoV-2 virus is believed to originate in China from where it spread to other parts of the world. The first cluster of diseased individuals was reported in China as early as in December 2019. It has also been well established that the virus stroke Italy later in January or in February 2020, hence distinctly after the outbreak in China. The work by Apolone et al. published in the Italian Medical Journal in November 2020 and retracted upon expression of concern on 22 March 2021, however propose that the virus could have stroke people already in September 2019, possibly following even earlier outbreak in China. By fitting an early part of the epidemic curve with the exponential and extrapolating it backwards, we could estimate the day-zero of the epidemic and calculated its confidence intervals in Italy and China. We also calculated how probable it is that Italy encountered the virus prior 1 January 2020. We determined an early portion of the epidemic curve representing unhindered exponential growth which fit the exponential model with high determination >0.97 in both countries. We conservatively suggest that the day-zero in China and Italy was 8 December 2019 (95% CI: 3 Dec., 20 Dec.) and 22 January 2020 (95% CI: 16 Jan., 29 Jan.), respectively. Given the uncertainty of the very early data in China and adjusting hence our model to fit the exponentially behaved data only, we can even admit that the pandemic originated through November 2019 (95% CI: 31 Oct., 22 Dec.). With high confidence (p <0.01) China encountered the virus prior Italy. We generally view any pre-pandemic presence of the virus in humans before November 2019 as very unlikely. The later established dynamics of the epidemics data suggests that the country of the origin was China.

Impact of Weight on Clinical Outcomes of Edoxaban Therapy in Atrial Fibrillation Patients Included in the ETNA-AF-Europe Registry.

BACKGROUND: Extremes of body weight may alter exposure to non-vitamin K antagonist oral anticoagulants and thereby impact clinical outcomes. This ETNA-AF-Europe sub-analysis assessed 1-year outcomes in routine care patients with atrial fibrillation across a range of body weight groups treated with edoxaban. METHODS: ETNA-AF-Europe is a multinational, multicentre, observational study conducted in 825 sites in 10 European countries. Overall, 1310, 5565, 4346 and 1446 enrolled patients were categorised into ≤60 kg, >60-≤80 kg (reference weight group), >80-≤100 kg and >100 kg groups. RESULTS: Patients weighing ≤60 kg were older, more frail and had a higher CHA2DS2-VASc score vs. the other weight groups. The rates of stroke/systemic embolism, major bleeding and ICH were low at 1 year (0.82, 1.05 and 0.24%/year), with no significant differences among weight groups. The annualised event rates of all-cause death were 3.50%/year in the overall population. After adjustment for eGFR and CHA2DS2-VASc score, the risk of all-cause death was significantly higher in extreme weight groups vs. the reference group. CONCLUSIONS: Low rates of stroke and bleeding were reported with edoxaban, independent of weight. The risk of all-cause death was higher in extremes of weight vs. the reference group after adjustment for important risk modifiers, thus no obesity paradox was observed.

Dendritic cell-based immunotherapy (DCVAC/OvCa) combined with second-line chemotherapy in platinum-sensitive ovarian cancer (SOV02): A randomized, open-label, phase 2 trial.

OBJECTIVE: DCVAC/OvCa is an active cellular immunotherapy designed to stimulate an immune response against ovarian cancer. We explored the safety and efficacy of DCVAC/OvCa plus carboplatin and gemcitabine in platinum-sensitive ovarian cancer. METHODS: In this open-label, parallel-group, phase 2 trial (ClinicalTrials.gov number NCT02107950), patients with platinum-sensitive ovarian cancer relapsing after first-line chemotherapy were randomized to DCVAC/OvCa and chemotherapy or chemotherapy alone. DCVAC/OvCa was administered every 3-6 weeks (10 doses). Endpoints included safety, progression-free survival (PFS; primary efficacy endpoint) and overall survival (OS; secondary efficacy endpoint). RESULTS: Between November 2013 and May 2015, 71 patients were randomized to chemotherapy in combination with DCVAC/OvCa or to chemotherapy alone. Treatment-emergent adverse events related to DCVAC/OvCa, leukapheresis and chemotherapy occurred in six (16.2%), two (5.4%), and 35 (94.6%) patients in the DCVAC/OvCa group. Chemotherapy-related events occurred in all patients in the chemotherapy group. Seven patients in the DCVAC/OvCa group were excluded from primary efficacy analyses due to failure to receive ≥1 dose of DCVAC/OvCa. PFS was not improved (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.42-1.28, P = 0.274, data maturity 78.1%). Median OS was significantly prolonged (by 13.4 months) in the DCVAC/OvCa group (HR 0.38, 95% CI 0.20-0.74, P = 0.003; data maturity 56.3%). A signal for enhanced surrogate antigen-specific T-cell activity was seen with DCVAC/OvCa. CONCLUSIONS: DCVAC/OvCa combined with chemotherapy had a favorable safety profile in patients with platinum-sensitive ovarian cancer. DCVAC/OvCa did not improve PFS, but the exploratory analyses revealed OS prolongation and enhanced surrogate antigen-specific T-cell activity.

Comparison of four routinely used vitamin D automated immunoassays.

BACKGROUND: To compare four automated immunoassays for the measurement of 25(OH)-vitamin D (25-OHD) and to assess the impact on the results obtained from a healthy population. METHODS: We analysed 100 serum samples on Unicel DxI 800 (Beckman Coulter), Architect i1000 (Abbott), Cobas e411 (Roche) and Liaison XL (DiaSorin). Passing-Bablok regression and Bland-Altman plots were used for method comparison. In order to categorise the obtained values, results were categorised into the following groups: 0-25 nmol/L, 25-50 nmol/L, 50-75 nmol/L and above 75 nmol/L and compared. The percentage of samples below 75 nmol/L, and below 50 nmol/L was then calculated for every method. RESULTS: According to paired comparisons, each method differs from others (p<0.0001) except Cobas vs Architect, which do not show a statistically significant difference (p=0.39). The strongest correlation was found between Liaison and Architect (ρ=0.94, p<0.0001). The percentage of samples below the recommended value of 75 nmol/L were: 70% (Architect), 92% (Liaison), 71% (Cobas) and 89% (Unicel). The percentage of samples below the value of 50 nmol/L were: 17% (Architect), 55% (Liaison), 28% (Cobas) and 47% (Unicel). CONCLUSIONS: The observed differences stem from the use of different analytical systems for 25-OHD concentration analysis and can result in different outcomes. The recommended values should be established for each assay in accordance with the data provided by the manufacturer or in the laboratory, in accordance with proper standardisation.

Long-term outcome of Simpson IV meningioma resection: Would it improve with adjuvant SRS?

OBJECTIVE: Subtotal meningioma resection (STR) is often performed to minimize surgical morbidity. Nevertheless, only a few studies have reported on patient outcome after STR. We studied the long-term outcome of SIV (Simpson grade IV) resection and identified predictive factors of overall survival (OS), progression-free survival (PFS) and time to progression (TTP). METHODS: A retrospective analysis was performed on 68 patients who underwent SIV resection of meningioma (grade I) from 2004 to 2010. Data were collected from clinical, surgical and pathology records and radiological imaging. Long-term outcomes were evaluated at least 10 years after surgery. RESULTS: Permanent morbidity was 11.8%, 30-day mortality 2.9% and progression rate 50.0% for a median follow-up duration of 126.6 months. Median TTP was 86.2 months. Adjuvant SRS was the only significant factor associated with longer PFS (p = 0.0052) and TTP (p = 0.0079). Higher age (p = 0.0022), KPS (p = 0.0182), postoperative ECOG score (p = 0.0182) were reliable predictors of shortened OS and aSRS (p = 0.0445) was reliable predictor of longer OS. CONCLUSION: STR in intracranial meningioma is still viable and often the only treatment option available in high-risk patients or high-risk tumors. Although surgical morbidity and mortality are high, the OS rate was 85.3% at 5 years and 79.4% at 10 years. Because of the considerable progression rate and rather a long term OS the adjuvant SRS should be considered following SIV resection.

Reclassification, Thromboembolic, and Major Bleeding Outcomes Using Different Estimates of Renal Function in Anticoagulated Patients With Atrial Fibrillation: Insights From the PREFER-in-AF and PREFER-in-AF Prolongation Registries.

BACKGROUND: The Cockcroft-Gault formula is recommended to determine a renal indication for dose reduction of dabigatran, edoxaban, and rivaroxaban. Nephrology guidelines now recommend the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae as more accurate estimates of glomerular filtration rate. METHODS: We analyzed anticoagulated patients with atrial fibrillation who were enrolled in the Prevention of Thromboembolic Events - European Registry in Atrial Fibrillation (PREFER in AF). The proportion of patients with dissimilar renal dosing indications was assessed when applying Cockcroft-Gault, MDRD, or CKD-EPI. Thromboembolic and major bleeding events at 1 year were compared in patients in whom Cockcroft-Gault and CKD-EPI provided concordant or discordant results around a threshold of 50 mL/minute. RESULTS: Out of 1288 patients with atrial fibrillation with chronic kidney disease in whom Cockcroft-Gault suggested a dose reduction of dabigatran, edoxaban, or rivaroxaban (creatinine clearance ≤50 mL/minutes), 19% and 16% were reclassified to the respective higher doses, and 24% and 23% to the respective lower doses by applying the MDRD and CKD-EPI formulae, respectively. In patients potentially receiving a different dose of dabigatran, edoxaban, or rivaroxaban when using CKD-EPI, we observed an excess of thromboembolic events (4.1% versus 0.8%; odds ratio, 5.5 [95% CI, 1.5-20.8]; P=0.01). Major bleeding rates were nonsignificantly different in the discordance versus concordance group (5.7% versus 2.7%; odds ratio, 2.2 [95% CI, 0.9-5.6]; P=0.09). CONCLUSIONS: The MDRD and CKD-EPI formulae suggest a different dosing in up to a quarter of anticoagulated patients with atrial fibrillation. This seems to impact hard outcomes.

Five Commercial Immunoassays for SARS-CoV-2 Antibody Determination and Their Comparison and Correlation with the Virus Neutralization Test.

There is an ongoing debate as to whether SARS-CoV-2 antibodies can be found in patients who have recovered from COVID-19 disease. Currently, there is no consensus on whether the antibodies, if present, are protective. Our regular measurements of SARS-CoV-2 antibodies, starting in July 2020, have provided us with the opportunity of becoming acquainted with the five different immunoassays. A total of 149 patients were enrolled in our study. We measured the samples using each immunoassay, then performing a virus neutralization test and comparing the results of SARS-CoV-2 antibodies with this test. We observed that the production of neutralizing antibodies is age-dependent. Elderly patients have a higher proportion of high neutralizing titers than young patients. Based on our results, and in combination with the literature findings, we can conclude that the serological SARS-CoV-2 antibody measurement is a helpful tool in the fight against COVID-19. The assays can provide information about the patient's previous contact with the virus. Anti-spike protein assays correlate well with the virus neutralization test and can be used in the screening of potential convalescent plasma donors.

Computed tomography with a full FOV photon-counting detector in a clinical setting, the first experience.

OBJECTIVES: to assess the feasibility of CT with an integrated photon-counting-detector system (PC-CT) in the body imaging of clinical patients. METHODS: 120 examinations using photon counting detector CT were evaluated in six groups: 1/ a standard-dose lung, 2/ low-dose lung, 3/ ultra-high resolution (UHR) lung, 4/ standard-dose abdominal, 5/ lower-dose abdominal, 6/ UHR abdominal CTA. All CT examinations were performed on a single-source prototype device equipped with a photon counting detector covering a 50 cm scan field of view. Standard dose examinations were performed with the use of detector element size of 0.4 mm, ultra-high-resolution examinations with the detector element size of 0.2 mm, respectively. The stability of the system during imaging was tested. The diagnostic quality of the acquired images was assessed based on the imaging of key structures and the noise level in five-point scale, the effective dose equivalent, dose length product and noise level, and also relation to body mass index and body surface area were compared with three similar groups of CT images made with energy integrating high end scanner. The parameters were evaluated using Wilcoxon test for independent samples, the independence was tested using Kruskal-Wallis test. RESULTS: When PC-CT images radiation dose is compared with the similar imaging using energy integrating CT, the PC-CT shows lower dose in ultra-high resolution mode, the dose is significantly lower (p < 0.0001), the standard dose examinations were performed with the comparable radiation doses. PC-CT exhibited the significantly higher ratio between parenchyma signal and background noise both in lung and in abdominal imaging (p < 0.0001). CONCLUSIONS: PC-CT showed imaging stability and excellent diagnostic quality at dose values that are comparable or better to the quality of energy integrating CT, the better signal and improved resolution is most important advantage of photon counting detector CT over energy integrating detector CT.