Low Number Of Events Research Articles

Adjuvant chemotherapy in T1a/bN0 breast cancer with a high 21-gene recurrence score (> 25): a 10-year follow-up in a real-world cohort.

In ER + /HER2- early breast cancer (BC), 21-Gene Recurrence Score (RS) > 25 indicates high-risk of distant-recurrence and predicts benefit from adjuvant chemotherapy (aCT) regardless of tumor-size. However, T1a/b (≤ 1cm) node-negative (N0) tumors, regarded as of low risk of recurrence, were under-represented in the RS trials. We therefore aimed to investigate the benefit of aCT in patients with T1a/bN0 BC, RS > 25, where clinical and genomic riskindicators are discordant. This retrospective observational cohort study utilized Israel's national Oncotest database to identify Clalit Health Services (CHS) members, diagnosed with T1a/bN0 HR + /HER2- BC, who underwent RS testing between February 2006, and December 2019. Patients with RS > 25 who received aCT were matched 1:1 by propensity-scoring to similarpatients receiving no aCT. Invasive disease-free survival (iDFS) and distant recurrence were the study endpoints. Patient demographic and clinical data were obtained from CHS's centralized database. Kaplan--Meier analysis with log-rank testing was used for comparing outcomes. During the study period, high-risk RS result (> 25) was identified in 156/9858 patients of the study cohort. aCTwas administered to 74 (47.4%) and median follow-up was 121months.Within the 148 matched-cases, eighteen iDFS-events occurred, nine (12.1%) in each group (χ2 = 0.72, p = 0.39). Four (5.4%) of the aCT treated and three (4.0%) of the untreated patients were diagnosed with distant recurrence (χ2 = 0.22, p = 0.64). In this study cohort, patients with T1a/bN0BC, RS > 25 that received aCT, did not have improved outcomes and the 21-Gene RS > 25 was not found to be predictive, possibly due to the low number of events observed.

Prediction Models for Perioperative Blood Transfusion in Patients Undergoing Gynecologic Surgery: A Systematic Review.

This systematic review aimed to evaluate prediction models for perioperative blood transfusion in patients undergoing gynecologic surgery. Given the inherent risks associated with blood transfusion and the critical need for accurate prediction, this study identified and assessed models based on their development, validation, and predictive performance. The review included five studies encompassing various surgical procedures and approaches. Predicting factors commonly used across these models included preoperative hematocrit, race, surgical route, and uterine fibroid characteristics. However, the review highlighted significant variability in the definition of perioperative periods, a lack of standardization in transfusion criteria, and a high risk of bias in most models due to methodological issues, such as a low number of events per variable, inappropriate handling of continuous and categorical predictors, inappropriate handling of missing data, improper methods of predictor selection, inappropriate measurement methods for model performance, and inadequate evaluations of model overfitting and optimism in model performance. Despite some models demonstrating good discrimination and calibration, the overall quality and external validation of these models were limited. Consequently, there is a clear need for more robust and externally validated models to improve clinical decision-making and patient outcomes in gynecologic surgery. Future research should focus on refining these models, incorporating rigorous validation, and adhering to standardized reporting practices.

The Impact of American Board of Urology Certification on Postoperative Outcomes for Patients in New York State.

Our goal was to determine if board certification status was associated with improved postoperative outcomes for certain urologic oncology operations. We performed a retrospective cohort study of patients aged 65 and over having radical prostatectomy (RP), radical cystectomy (RC), and radical or partial nephrectomy (RPN) by surgeons with New York State licenses from 2015 to 2021 using the Medicare limited dataset. Our primary exposure was surgeon American Board of Urology certification determined by the New York State Physician Profile. All surgeons were in practice for at least 5 years. Our primary outcomes were 90-day mortality, 30-day unplanned readmission, and hospital length of stay (LOS). We used multivariable linear and logistic regression adjusted for surgeon, hospital, and patient characteristics. We performed the analysis in R, and 2-sided P values < .05 were considered statistically significant. We identified 12,601 patients who had a procedure performed. At the time of the procedure, a minority of procedures (1.3%) were performed by nonboard-certified (NBC) urologists. Among the patient cohort, there were 262 and 1419 mortality and readmission events, respectively; median LOS was 2 days (interquartile range 1155). Patients operated on by NBC urologists tended to have lower-volume surgeons who were less likely to be fellowship trained and to have surgery at smaller hospitals. Patients treated by NBC urologists were more likely to have RP, and less likely to have RC and RPN. On multivariate analysis, board certification was protective against readmission for RP (P < .001) and RC (P = .02), longer LOS for RC (P = .001), and mortality for RPN (P = .008). Urology board certification was associated with fewer readmissions after RP and RC, a shorter LOS after RC, and a lower risk of mortality after RPN. Given low event numbers, these findings require validation with a larger dataset.

Primary localized malignant PEComa treated with surgery: A report of a large series of patients treated in a referral institution.

11582 Background: Perivascular Epithelioid Cell Tumors (PEComa) are mesenchymal neoplasms with a characteristic myomelanocytic immunophenotype. These tumors exhibit a broad anatomic distribution, and aggressive clinical behavior has been correlated with histological features such as tumor size and increasing mitotic activity. PEComas arising from the kidney are referred to as angiomyolipomas and usually lack metastatic potential, whereas epithelioid angiomyolipomas do have metastatic potential. Until now, only case reports or a limited number of patients have been documented in the literature, resulting in a lack of data regarding their clinical behavior. In this study, we present the outcomes of a large series of patients (pts) with primary localized malignant PEComa. Methods: This is a retrospective study involving all consecutive pts of any age affected by primary and localized malignant Pecoma surgically treated with curative intent at our institution from January 2000 to December 2023. Eligible pts had a pathologically confirmed diagnosis of malignant Pecoma. We present the outcome results in terms of Disease-Free Survival (that includes Local Recurrence (LR), Distant Metastases (DM), or death as first events) and Overall Survival (OS). Due to the low number of events only univariable analyses were performed. Results: 48 patients (19/48 M; 29/48 F) were identified. Median age at surgery was 50 yrs (range 18-80). Primary site was extremity and trunk in 19/48 pts, retroperitoneum in 13/48 pts and other in 16/48; median size of tumor was 11 cm (range 1-30 cm). At a m-FU of 57 mos (IQR:22-116), 8 pts died. Five- and 10-yr OS was 81.6% [95% Confidence Interval (CI): 70.1-94.9%)] and 77.3% (CI: 64.2-93.0%), respectively. One patient developed LR as first event, 9 developed DM and 3 died without any LR and DM; 3 and 1 patients developed DM as 2nd and 3rd event, respectively. Five- and 10-yr DFS was 69.4% [CI: 56.3-85.6%] and 65.1% (CI: 50.9-83.1%). Predictors of higher risk of DFS were age (&gt;64 yrs old) and site of origin [p=0.5; HR trunk and arms: 1.2 (CI: 0.38-3.81) vs. retroperitoneum and 3.49 (CI: 0.43-28.37) vs other]. Conclusions: In this series PEComas have a 30% risk of recurrence at 5 years. While age and the site of origin are associated with the natural history of the disease, better pathologic criteria are needed to stratify their risk.

Pfizer COVID19 vaccine is not associated with acute cardiovascular events excluding myocarditis– a national self-controlled case series study

BackgroundDespite publications assuring no increased risk for acute cardiovascular events (excluding myocarditis) and sudden death following administration of COVID19 vaccines, these issues still stir much public ado. We assessed the risk for acute cardiovascular events that require hospitalization (excluding myocarditis) and for mortality in the short-term following administration of the second dose of the Pfizer COVID19 vaccine in Israel.MethodsUsing a self-controlled case series (SCCS) study design and national databases, all second-dose vaccinees, who had not been diagnosed with COVID19 and who had an acute cardiovascular event (acute myocardial infarction/acute stroke/acute thromboembolic event) that required hospitalization in the 60 days following vaccine administration between Jan 11th, 2021 and Oct 31st 2021, were included. A similar analysis was carried out for mortality. The first 30 days following vaccination were defined as risk period while the next 30 days were defined as control period. The probability for an event between these periods was compared using a conditional logistic regression model, accounting for sex, age group, background morbidity and seasonal risk.ResultsOut of 5,700,112 second dose vaccinees, 4,163 had an acute cardiovascular event in the 60 days following vaccine administration. Following exclusion of 106 due to technical considerations, 1,979 events occurred during the risk period and 2,078 during the control period: Odds ratio, OR = 0.95, 95% confidence interval, CI 0.90–1.01, p = 0.12. Adjusted OR was similar (OR = 0.88, 95%CI 0.72–1.08). Stratifying by age showed no increased risk in any age group. Mortality assessment indicated low number of events in both periods. These results were consistent in sensitivity analyses.ConclusionsThere was no increased risk for acute cardiovascular events (excluding myocarditis) in the risk period compared to the control period following administration of the second dose of Pfizer COVID19 vaccine. Mortality data raised no concerns either, but may have been biased.

Machine learning approach for prediction of outcomes in anticoagulated patients with atrial fibrillation

BackgroundThe accuracy of available prediction tools for clinical outcomes in patients with atrial fibrillation (AF) remains modest. Machine Learning (ML) has been used to predict outcomes in the AF population, but not in a population entirely on anticoagulant therapy. Methods and aimsDifferent supervised ML models were applied to predict all-cause death, cardiovascular (CV) death, major bleeding and stroke in anticoagulated patients with AF, processing data from the multicenter START-2 Register. Results11078 AF patients (male n = 6029, 54.3%) were enrolled with a median follow-up period of 1.5 years [IQR 1.0–2.6]. Patients on Vitamin K Antagonists (VKA) were 5135 (46.4%) and 5943 (53.6%) were on Direct Oral Anticoagulants (DOAC). Using Multi-Gate Mixture of Experts, a cross-validated AUC of 0.779 ± 0.016 and 0.745 ± 0.022 were obtained, respectively, for the prediction of all-cause death and CV-death in the overall population. The best ML model outperformed CHA2DSVA2SC and HAS-BLED for all-cause death prediction (p < 0.001 for both). When compared to HAS-BLED, Gradient Boosting improved major bleeding prediction in DOACs patients (0.711 vs. 0.586, p < 0.001). A very low number of events during follow-up (52) resulted in a suboptimal ischemic stroke prediction (best AUC of 0.606 ± 0.117 in overall population). Body mass index, age, renal function, platelet count and hemoglobin levels resulted the most important variables for ML prediction. ConclusionsIn AF patients, ML models showed good discriminative ability to predict all-cause death, regardless of the type of anticoagulation strategy, and major bleeding on DOAC therapy, outperforming CHA2DS2VASC and the HAS-BLED scores for risk prediction in these populations.

Treatment Patterns, Effectiveness, and Safety of Originator Insulin Glargine versus Insulin Glargine-yfgn within the Veterans Health Administration

We described insulin glargine (originator) and insulin glargine-yfgn (biosimilar) treatment patterns, assessed effectiveness and safety outcomes, and identified reasons for switching back to the originator product from the biosimilar. This retrospective study included 328,463 Veterans 18 years of age and older who received one or more outpatient prescriptions for insulin glargine and/or insulin glargine-yfgn between 1 June 2021 and 31 December 2022. Patients were assigned to subgroups based on the initial prescription during the study period, prevalent versus incident use for originator insulin glargine, and prior versus no prior use of the originator before the biosimilar (i.e., prevalent originator non-switcher (n = 189,734), originator switch to biosimilar (n = 81,010), incident originator non-switcher (n = 49,401), and incident biosimilar (n = 8318)). There were no differences in the outcome of mean HbA1c (7.9% for all subgroups). There were also no differences in the unadjusted rates of hospitalization and/or emergency room visits for hyper- and hypoglycemia between the prevalent originator non-switcher and originator switched to biosimilar subgroups (p = 0.09 and 0.38, respectively) or the incident originator non-switcher and incident biosimilar subgroups (p = 0.054 and 0.61, respectively). Finally, none of the HbA1c or hyperglycemia outcomes adjusted for baseline characteristics were statistically different. Adjusted analyses for rates of hospitalization and/or emergency room visits for hypoglycemia could not be performed due to the low number of events. Overall, patients who received insulin glargine-yfgn had similar effectiveness and safety outcomes as patients who received the originator.

Prognostic Role of Multiparametric Cardiac Magnetic Resonance in Neo Transfusion-Dependent Thalassemia.

We prospectively evaluated the predictive value of multiparametric cardiac magnetic resonance (CMR) for cardiovascular complications in non-transfusion-dependent β-thalassemia (β-NTDT) patients who started regular transfusions in late childhood/adulthood (neo β-TDT). We considered 180 patients (38.25 ± 11.24 years; 106 females). CMR was used to quantify cardiac iron overload, biventricular function, and atrial dimensions, and to detect left ventricular (LV) replacement fibrosis. During a mean follow-up of 76.87 ± 41.60 months, 18 (10.0%) cardiovascular events were recorded: 2 heart failures, 13 arrhythmias (10 supraventricular), and 3 cases of pulmonary hypertension. Right ventricular (RV) end-diastolic volume index (EDVI), RV mass index (MI), LV replacement fibrosis, and right atrial (RA) area index emerged as significant univariate prognosticators of cardiovascular complications. The low number of events prevented us from performing a multivariable analysis including all univariable predictors simultaneously. Firstly, a multivariable analysis including the two RV size parameters (mass and volume) was carried out, and only the RV MI was proven to independently predict cardiovascular diseases. Then, a multivariable analysis, including RV MI, RA atrial area, and LV replacement fibrosis, was conducted. In this model, RV MI and LV replacement fibrosis emerged as independent predictors of cardiovascular outcomes (RV MI: hazard ratio (HR) = 1.18; LV replacement fibrosis: HR = 6.26). Our results highlight the importance of CMR in cardiovascular risk stratification.

Systematic Review and Meta-analysis of Fenestrated and Chimney/Snorkel Techniques for Endovascular Repair of Juxtarenal Aortic Aneurysms.

Comparative effectiveness of fenestrated endovascular aneurysm repair (FEVAR) and chimney graft endovascular aneurysm repair (ChEVAR) for juxtarenal aortic aneurysms (JAAs) remains unclear. Our objective was to identify and analyze the current body of evidence comparing the effectiveness of both techniques for JAA. We performed a systematic review and meta-analysis comparing the effectiveness of FEVAR and ChEVAR for JAA repair. We searched MEDLINE, EMBASE, and Cochrane Register for Controlled Trials from January 1, 1990, for randomized and non-randomized studies assessing outcomes of FEVAR and ChEVAR for JAA repair. Screening, data extraction, risk of bias assessment, and GRADE (Grading of Recommendations, Assessments, Development, and Evaluations) certainty of evidence were performed in duplicate. Data were pooled statistically where possible. Nine retrospective cohort studies comparing the use of FEVAR and ChEVAR for juxtarenal aneurysm were included for meta-analysis. The FEVAR and ChEVAR arms of the meta-analysis consisted of 726 participants and 518 participants, respectively. There were 598 (86.8%) and 332 (81.6%) men in each arm. The mean diameter was larger in the ChEVAR arm (59 mm vs 52.5 mm). Both techniques had similar rates of postoperative 30-day mortality, 3.38% (8/237) versus 3.52% (8/227), acute kidney injury, 16.76% (31/185) versus 17.31% (18/104), and major adverse cardiac events, 7.30% (46/630) versus 6.60% (22/333). The meta-analysis supported the use of FEVAR for most outcomes, with significant advantage for technical success (odds ratio [OR]: 3.24, 95% CI: 1.24-8.42) and avoidance of type 1 endoleak (OR: 5.76, 95% CI: 1.94-17.08), but a disadvantage for spinal cord ischemia (OR: 10.21, 95% CI: 1.21-86.11), which had a very low number of events. The quality of evidence was "moderate" for most outcomes. Both endovascular techniques had good safety profiles. The evidence does not support superiority of either FEVAR or ChEVAR for JAA. While lack of equipoise has hampered the design of randomised trials of open versus endovascular repair of juxtarenal aortic aneurysms, concern about the durability of endovascular repair highlights the need for stronger evidence of the comparative efficacy of endovascular techniques. This review performed meta-analysis and evidence appraisal of recent data from large observational studies comparing fenestrated and chimney techniques, using a comprehensive outcome set. Superiority of either intervention could not be established due to differences in participants' baseline risk in each study arm. However, data suggests that both techniques are safe and suitable for use when indicated.

Locoregional Breast Cancer Recurrence in the European Organisation for Research and Treatment of Cancer 10041/BIG 03-04 MINDACT Trial: Analysis of Risk Factors Including the 70-Gene Signature.

A number of studies are currently investigating de-escalation of radiation therapy in patients with a low risk of in-breast relapses on the basis of clinicopathologic factors and molecular tests. We evaluated whether 70-gene risk score is associated with risk of locoregional recurrence (LRR) and estimated 8-year cumulative incidences for LRR in patients with early-stage breast cancer treated with breast conservation. In this exploratory substudy of European Organisation for Research and Treatment of Cancer 10041/BIG 03-04 MINDACT trial, we evaluated women with a known clinical and genomic 70-gene risk score test result and who had breast-conserving surgery (BCS). The primary end point was LRR at 8 years, estimated by cumulative incidences. Distant metastasis and death were considered competing risks. Among 6,693 enrolled patients, 5,470 (81.7%) underwent BCS, of whom 98% received radiotherapy. At 8-year follow-up, 189 patients experienced a LRR, resulting in an 8-year cumulative incidence of 3.2% (95% CI, 2.7 to 3.7). In patients with a low-risk 70-gene signature, the 8-year LRR incidence was 2.7% (95% CI, 2.1 to 3.3). In univariable analysis, adjusted for chemotherapy, five of 12 variables were associated with LRR, including the 70-gene signature. In multivariable modeling, adjuvant endocrine therapy and to a lesser extent tumor size and grade remained significantly associated with LRR. This exploratory analysis of the MINDACT trial estimated an 8-year low LRR rate of 3.2% after BCS. The 70-gene signature was not independently predictive of LRR perhaps because of the low number of events observed and currently cannot be used in clinical decision making regarding LRR. The overall low number of events does provide an opportunity to design trials toward de-escalation of local therapy.

Post-marketing active surveillance of Guillain Barré Syndrome following COVID-19 vaccination in persons aged ≥12 years in Italy: A multi-database self-controlled case series study.

Recently published studies have reported association of COVID-19 vaccine ChAdOx1-S (Vaxzevria) with Guillain Barré Syndrome (GBS). Less is known about the safety of other COVID-19 vaccines with respect to GBS outcome. This study investigated the association of COVID-19 vaccines with GBS in more than 15 million persons aged ≥12 years in Italy. Study population was all individuals aged ≥12 years who received at least one dose of COVID-19 vaccines, admitted to emergency care/hospital for GBS from 27 December 2020-30 September 2021 in Italy. Identification of GBS cases and receipt of at least one dose of mRNA-1273 (Elasomeran), BNT162b2 (Tozinameran), ChAdOx1-S (Vaxzevria) and Ad26.COV2.S (Janssen) through record linkage between regional health care and vaccination registries. Relative Incidence (RI) was estimated Self-controlled case series method adapted to event-dependent exposure using in the 42-day exposure risk period after each dose compared with other observation periods. Increased risk of GBS was found after first (RI = 6.83; 95% CI 2.14-21.85) and second dose (RI = 7.41; 2.35-23.38) of mRNA-1273 and first dose of ChAdOx1-S (RI = 6.52; 2.88-14.77). Analysis by age found an increased risk among those aged≥60 years after first (RI = 8.03; 2.08-31.03) and second dose (RI = 7.71; 2.38-24.97) of mRNA-1273. The first dose of ChAdOx1-S was associated with GBS in those aged 40-59 (RI = 4.50; 1.37-14.79) and in those aged ≥ 60 years (RI = 6.84; 2.56-18.28). mRNA-1273 and ChAdOx1-S vaccines were associated with an increased risk of GBS however this risk resulted in a small number of excess cases. Limitations were loss of GBS outpatient cases and imprecision of the estimates in the subgroup analysis due to a low number of events.

Marrow Hypercellularity Does Not Exclude the Diagnosis of Essential Thrombocythemia (ET)

Background: The 2022 WHO criteria do not list bone marrow cellularity as a criterion for ET diagnosis (dx) 1, but a review discussing the International Consensus Classification criteria states that the marrow should be normocellular for age, with rare cases of mild hypercellularity 2. The ELN also cited normocellularity as a key factor in differentiating ET from polycythemia vera (PV) or prefibrotic myelofibrosis (MF), further suggesting that normocellularity is the expected standard in ET 3. However, we encountered a number of cases in our hematology practice with increased cellularity in bona fide ET patients (pts). Therefore, we decided to more systematically review the marrow cellularity and its prognostic impact. Methods: Medical records were queried for pts with ET per the ICD, versions 9-10. The dx of ET per WHO 2022 was confirmed by manual review. Cases lacking marrow biopsy were excluded. Structured query language was used for automated extraction of clinical, lab, and molecular findings. We utilized our previously described natural language processing pipeline to extract cellularity information from marrow reports 4. All hematopathology reports of hypercellular marrows were manually reviewed by 3 observers for confirmation and a randomly selected subset of the core and clot sections were reviewed for histomorphology and cellularity by 2 expert hematopathologists and 1 histomorphologist, blinded to pt age and clinical information prior to their review. Quantitative cellularity was determined independently and then congruently for consensus. Qualitative cellularity was defined using (100-age) ± 20% as the normal range with increases above this range considered hypercellular for age. Disease progression was defined as either progression to post-ET MF (PETMF) or direct transformation to acute myeloid leukemia. Transformation to PV was defined as pts with a JAK2 mutation for whom PV was thoroughly excluded at the time of ET dx but who developed absolute erythrocytosis and met the PV WHO diagnostic criteria later in their disease course. We performed univariable and multivariable analysis of progression, PV transformation, thrombosis and mortality risk using Cox proportional-hazards models. Overall (OS), progression-free (PFS), PV-free (PVFS) and thrombosis-free (TFS) survival were estimated using Kaplan-Meier methods. Results: 382 pts met WHO defined ET with marrow dx, of which 145 had pre-treatment diagnostic marrows available for review at Weill Cornell. In the other 237, the diagnostic biopsies had either been performed after treatment was initiated or only the report was available. Thirty-three (23%) were described as hypercellular and 112 (67%) were not. Review of 20 randomly selected marrows from the hypercellular group confirmed age-adjusted hypercellularity ranging from 30 to 80%. The hypercellular pts were significantly older at dx compared to those without hypercellularity (59 vs 50 yrs, p &amp;lt;0.001, Table 1). We identified no other significant differences in blood counts at dx, sex, driver mutation or thrombosis history between the groups. Univariate and multivariate analyses demonstrated no significant difference between the groups in PFS (HR 1.29, p=0.871), TFS (HR 1.39, p=0.671) or OS (HR 0.50, p=0.487) using age, thrombosis history and sex as covariates. A Cox model could not be generated for PVFS due to the low number of events. The 15-year PFS for pts with hypercellularity vs those without was 97% and 94% respectively ( p=0.56, Figure 1), 15-year PVFS was 100% and 67% respectively ( p=0.12), 15-year TFS was 79% and 87% respectively ( p=0.53) and 15-year OS was 84% and 81% respectively ( p=0.74). Conclusion: Our data to date suggests that hypercellularity is of importance diagnostically but not prognostically. Nearly a quarter of our pts with WHO ET had marrow that was hypercellular for age at dx. Pts with increased marrow cellularity tended to be older but were clinically indistinguishable from the remainder in terms of driver mutation, blood counts and thrombosis history. Univariate and multivariate analyses demonstrate that hypercellularity does not confer increased risk of progression, thrombosis or mortality. Thus, hypercellularity alone should not be used as a factor for excluding ET dx.

Optimization of Y-90 Radioembolization Imaging for Post-Treatment Dosimetry on a Long Axial Field-of-View PET/CT Scanner.

PET imaging after yttrium-90 (Y-90) radioembolization is challenging because of the low positron fraction of Y-90 (32 × 10-6). The resulting low number of events can be compensated by the high sensitivity of long axial field-of-view (LAFOV) PET/CT scanners. Nevertheless, the reduced event statistics require optimization of the imaging protocol to achieve high image quality (IQ) and quantification accuracy sufficient for post-treatment dosimetry. Two phantoms (NEMA IEC and AbdoMan phantoms, mimicking human liver) filled with Y-90 and a 4:1 sphere (tumor)-to-background ratio were scanned for 24 h with the Biograph Vision Quadra (Siemens Healthineers). Eight patients were scanned after Y-90 radioembolization (1.3-4.7 GBq) using the optimized protocol (obtained by phantom studies). The IQ, contrast recovery coefficients (CRCs) and noise were evaluated for their limited and full acceptance angles, different rebinned scan durations, numbers of iterations and post-reconstruction filters. The s-value-based absorbed doses were calculated to assess their suitability for dosimetry. The phantom studies demonstrate that two iterations, five subsets and a 4 mm Gaussian filter provide a reasonable compromise between a high CRC and low noise. For a 20 min scan duration, an adequate CRC of 56% (vs. 24 h: 62%, 20 mm sphere) was obtained, and the noise was reduced by a factor of 1.4, from 40% to 29%, using the full acceptance angle. The patient scan results were consistent with those from the phantom studies, and the impacts on the absorbed doses were negligible for all of the studied parameter sets, as the maximum percentage difference was -3.89%. With 2i5s, a 4 mm filter and a scan duration of 20 min, IQ and quantification accuracy that are suitable for post-treatment dosimetry of Y-90 radioembolization can be achieved.

Patients with AF and dementia are undertreated for their AF and cardiovascular comorbidities: results from the GARFIELD-AF registry

Abstract Background Oral anticoagulation (OAC) is key in preventing stroke in patients with atrial fibrillation (AF). However, patients with AF and dementia pose practical therapeutic challenges, such as compliance and haemorrhagic complications, resulting in possible underuse of cardiovascular (CV) treatment. Purpose The aim of this study is two-fold: a) to determine whether AF patients with dementia are undertreated for stroke prevention with OAC and for their CV comorbidities and b) to assess the risks and benefits of OAC in AF patients with dementia. Methods Analyses were conducted in newly diagnosed AF patients enrolled in GARFIELD-AF, the largest multinational prospective AF registry. Medical history of dementia was recorded at enrolment. Guideline-directed medical therapy (GDMT), defined according to ESC guidelines, was explored for coronary artery disease (CAD), diabetes, heart failure (HF), hypertension, and peripheral vascular disease (PVD). Propensity score weighting was applied to obtain estimates of OAC effect on all-cause mortality and stroke within two-year follow-up. Major bleeding occurrence is simply reported due to the low number of events. Results The study comprised 764 (1.5%) AF patients with dementia and 50,966 (98.5%) without dementia. Patients with dementia were more often female (58% vs 44%), older (median age 82 vs 71) and had higher prevalence of comorbidities, resulting in higher CHA2DS2-VASc (excl. sex; median 5.0 vs 3.0) and HAS-BLED score (median 2.0 vs 1.0) compared to patients without dementia. The proportion anticoagulated was lower among those with dementia (60% vs 70%), with fewer patients receiving VKA (27% vs 42%) (Fig. 1). Despite the increase in NOAC use among patients with dementia (17% in 2010-2013 vs 48% in 2015-2016), 35% remained non-anticoagulated in 2015-2016. Appropriate GDMT was lower among patients with dementia for the five considered comorbidities combined (35% vs 45%), with substantial differences observed for HF (35% vs 50%), CAD (27% vs 39%) and PVD (36% vs 48%) compared to patients without dementia. In patients with dementia, OAC usage was associated with lower all-cause mortality (HR 0.69; 95% CI 0.48-1.00). In contrast to patients without dementia, no evidence of a stroke risk reduction with OAC was observed among patients with dementia (HR 1.10; 95% CI 0.50-2.43) (Fig. 2). This finding might be explained by the higher proportion of patients with dementia receiving a reduced NOAC dose (73% vs 39% of NOAC receivers) and their lower VKA quality control (37% vs 46%, defined as time in therapeutic range &amp;gt;65%). Seven (1.6%) and eight (2.7%) major bleeding events occurred among patients with dementia who were on or not on OAC, respectively. Conclusions Despite their high risk of stroke, patients with AF and dementia are often undertreated for their AF and CV comorbidities. Our results support the use of OAC and should help inform treatment decisions in this vulnerable population.

A decision‐led evaluation approach for flood forecasting system developments: An application to the Global Flood Awareness System in Bangladesh

AbstractScientific and technical changes to flood forecasting models are implemented to improve forecasts. However, responses to such changes are complex, particularly in global models, and evaluation of improvements remains focussed on generalised skill assessments and not on the most relevant outcomes for those taking decisions. Recently, the Global Flood Awareness System (GloFAS) flood forecasting model has been upgraded from version 2.1 to 3.1 with a significant change to its hydrological model structure. In the updated version 3.1, a single fully configured hydrological model (LISFLOOD) has been adopted, including ground water and river routing processes, instead of two coupled models, a land surface and a simplified hydrological model, of the previous version 2.1. This study aims to evaluate changes in the simulated behaviour of floods and the forecast skill of the two GloFAS versions based on different decision criteria for early action. We evaluate GloFAS reforecasts for the Brahmaputra and the Ganges Rivers in Bangladesh for the period 1999–2018. For the Brahmaputra River, the old GloFAS 2.1 version performs better than the 3.1 version, especially in predicting low‐ (90th percentile) and medium‐level (95th percentile) floods. For the Ganges, GloFAS 3.1 shows improved probability of detection of low‐ to medium‐level floods compared to version 2.1, especially for lead times longer than 10 days. Both versions show limited skill for more extreme floods (99th percentile) but results are less robust for these less frequent floods given the lower number of events. Using lead‐time dependent thresholds improves the false alarm ratio while reducing the probability of detection. The changes in model structures influence the model performance in a complex and varied way and forecast skill needs further investigation across regions and decision‐making criteria. Understanding the skill changes between different model versions is important for decision‐makers; however, focused case studies such as this should also be used by model developers to guide future changes to the system to ensure that they lead to improvements in decision‐making ability.

Self as a prior: The malleability of Bayesian multisensory integration to social salience.

Our everyday perceptual experiences are grounded in the integration of information within and across our senses. Due to this direct behavioural relevance, cross-modal integration retains a certain degree of contextual flexibility, even to social relevance. However, how social relevance modulates cross-modal integration remains unclear. To investigate possible mechanisms, Experiment 1 tested the principles of audio-visual integration for numerosity estimation by deriving a Bayesian optimal observer model with perceptual prior from empirical data to explain perceptual biases. Such perceptual priors may shift towards locations of high salience in the stimulus space. Our results showed that the tendency to over- or underestimate numerosity, expressed in the frequency and strength of fission and fusion illusions, depended on the actual event numerosity. Experiment 2 replicated the effects of social relevance on multisensory integration from Scheller & Sui, 2022 JEP:HPP, using a lower number of events, thereby favouring the opposite illusion through enhanced influences of the prior. In line with the idea that the self acts like a prior, the more frequently observed illusion (more malleable to prior influences) was modulated by self-relevance. Our findings suggest that the self can influence perception by acting like a prior in cue integration, biasing perceptual estimates towards areas of high self-relevance.

Pulmonary Vasodilator and Inodilator Drugs in Cardiac Surgery: A Systematic Review With Bayesian Network Meta-Analysis

The authors performed a systematic review to evaluate the effect of pharmacologic therapy on pulmonary hypertension in the perioperative setting of elective cardiac surgery (PROSPERO CRD42023321041). Systematic review of randomized controlled trials with a Bayesian network meta-analysis. The authors searched biomedical databases for randomized controlled trials on the perioperative use of inodilators and pulmonary vasodilators in adult cardiac surgery, with in-hospital mortality as the primary outcome and duration of ventilation, length of stay in the intensive care unit, stage 3 acute kidney injury, cardiogenic shock requiring mechanical support, and change in mean pulmonary artery pressure as secondary outcomes. Twenty-eight studies randomizing 1,879 patients were included. Catecholamines and noncatecholamine inodilators, arterial pulmonary vasodilators, vasodilators, or their combination were considered eligible interventions compared with placebo or standard care. Ten studies reported in-hospital mortality and assigned 855 patients to 12 interventions. Only inhaled prostacyclin use was supported by a statistically discernible improvement in mortality, with a number-needed-to-treat estimate of at least 3.3, but a wide credible interval (relative risk 1.26×10-17 - 0.7). Inhaled prostacyclin and nitric oxide were associated with a reduction in intensive care unit stay, and none of the included interventions reached a statistically evident difference compared to usual care or placebo in the other secondary clinical outcomes. Inhaled prostacyclin was the only pharmacologic intervention whose use is supported by a statistically discernible improvement in mortality in the perioperative cardiac surgery setting as treatment of pulmonary hypertension. However, available evidence has significant limitations, mainly the low number of events and imprecision.

Incidence of and Risk Factors for Active Tuberculosis Disease in Individuals With Glomerular Disease: A Canadian Cohort Study

Kidney failure is an established risk factor for active tuberculosis (TB) but the risk of TB has not been reported in specific kidney diseases. We sought to determine the incidence of and risk factors for active TB in patients with glomerular disease. Observational cohort study. A provincial kidney pathology registry (2000-2012) was used to identify 3,079 adult patients with IgA nephropathy, focal segmental glomerulosclerosis (FSGS), antineutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis, lupus nephritis, membranous nephropathy, minimal change disease, or "other" glomerular diseases in British Columbia, Canada. Predictors included demographics, immigration status, comorbidities, immunosuppression use, estimated glomerular filtration rate (eGFR), and proteinuria. A diagnosis of active TB was ascertained using administrative data linkages and defined based on (1) the dispensation of 1 or more unique combinations of medications used to treat active TB, or (2) physician or hospital visits for active TB. The definition of TB was validated in an external cohort linked to the Provincial TB registry at the BC Centre for Disease Control (BCCDC). Standardized incidence ratios were calculated using the age-matched general population. Risk factors for active TB were identified using Cox proportional hazards regression analysis. The sensitivity and specificity of the outcome definition of active TB were 87.6% and 99.5%, respectively. During a median follow-up of 6.2 years, 41 patients developed active TB with an incidence of 197 of 100,000 person-years, approximately 23 times as high as the general population and>6 times higher than the threshold of 30 per 100,000 used to define high TB incidence. A high incidence was observed in all glomerular diseases (range, 110-403 per 100,000), in both Canadian- and foreign-born patients (range, 124-424 per 100,000), and in patients exposed or not to immunosuppression (282 vs 147 per 100,000). Factors associated with higher TB risk included immigration from a high-incidence country (HR, 3.90 [95% CI, 1.75-8.68]), diminished eGFR (HR, 2.81 [95% CI, 1.18-6.69]), higher levels of proteinuria (HR, 1.15 [95% CI, 1.04-1.27]), lupus nephritis (HR, 2.79 [95% CI, 1.37-5.68]), and immunosuppression use (HR, 2.13 [95% CI, 1.13-4.03]). A relatively low number of events contributed to uncertainty in risk estimates. Patients with glomerular disease have a high incidence of active TB irrespective of disease type, demographics, or use of immunosuppression. Prospective studies are needed to evaluate the utility of screening for latent TB infection in this population. Patients with kidney failure are at high risk of developing tuberculosis (TB), a major infection that can be prevented by identifying and treating patients who have had prior exposure to TB. The risk of TB in specific kidney diseases is unknown. In this Canadian study of 3,079 patients with glomerular disease, a group of autoimmune kidney conditions, the rate of TB was 23 times higher than in the general population. The rate was high irrespective of the use of immunosuppressive drugs or whether patients had immigrated to Canada from another country. These findings suggest that screening patients with glomerular disease for prior TB exposure may be beneficial; however, this needs to be evaluated in a prospective study.

484-P: Newer Glucose-Lowering Drugs and Risk of Parkinson’s Disease—A Meta-analysis of Randomized Outcome Trials

Background: Cumulative results from preclinical studies have shown that newer glucose-lowering drugs (GLDs), i.e., dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium-glucose co-transporter-2 (SGLT2) inhibitors, have been associated with a decreased risk of Parkinson’s disease (PD). The findings from clinical and epidemiological studies are however mixed. We aimed to evaluate the potential effect of newer GLDs on the risk of PD through a meta-analysis of randomized outcome trial data. Methods: We systematically searched Pubmed, Embase, and CENTRAL up to December 2022 for published randomized placebo-controlled outcome trials evaluating DPP-4 inhibitors, GLP-1RAs, and SGLT2 inhibitors. We extracted PD outcomes from clinicaltrials.gov. We estimated pooled odds ratios (OR) and 95% confidence interval (CI) using the Peto method and we performed a subgroup analysis by type of newer GLDs. Results: Of 24 trials that qualified for inclusion, there were 33 incident PD cases among 185,305 participants with or without type 2 diabetes over a median follow-up of 2.2 years. Newer GLDs were significantly associated with a lower risk of PD than placebo (OR, 0.50; 95%CI, 0.25-0.98). Our subgroup analysis showed that DPP-4 inhibitors (OR, 0.71; 95%CI, 0.23-2.22), GLP-1RAs (OR, 0.51; 95%CI, 0.10 - 2.55), or SGLT2 inhibitors (OR, 0.37; 95%CI, 0.13-1.01) were all associated with a decreased risk of PD, but the differences were marginally or not statistically significant. Conclusion: Newer GLDs may be associated with a decreased risk of developing PD. Given the low number of events and short duration of follow-up of existing clinical trials, comparative effectiveness studies using real-world data (RWD) are warranted. These RWD-based studies can pave the way for evaluating the potential drug repurposing value of these newer GLDs for PD, before moving to large-scale randomized controlled trials. Disclosure H.Tang: None. Y.Lu: None. W.T.Donahoo: None. M.S.Okun: None. F.Wang: None. J.Bian: None. J.Guo: Consultant; Pfizer Inc., Research Support; PhRMA Foundation, NIH - National Institutes of Health. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK133465)

Flow cytometry increases the proportion of valuable samples in cerebrospinal fluid with normal cell count in malignant blood diseases

The alteration of cerebrospinal fluid (CSF) in hematologic neoplasms is a poor prognostic marker. The characteristics of CSF are usually analyzed by flow cytometry or cytology. However, paucicellular CSF samples (≤5 cells/dL) can sometimes be considered unsuitable for analysis due to the low number of events. To evaluate the proportion of samples reported as suitable for analysis obtained by cytometry (FCM) and cytology in paucicellular CSF samples. 169 samples ofpaucicellular CSF corresponding to 115 patients with hematologic neoplasms were selected. The samples were obtained by lumbar puncture in tubes conditioned with EDTA and Transfix®. We characterized the immunophenotype ofCSF samples with an 8-color panel, and 55 samples (32%) were in a small sample tube (SST). In all cases, monocytes were identified by CD14 labeling and T lymphocytes by CD3 labeling. The acquisition was carried out in a FACSCantoII® cytometer, and the analysis was performed using Infinicyt® software. The proportion of samples suitable for analysis was higher in FCM compared to cytology (98% vs 61%, p < 0.000). We identified the presence of T lymphocytes and/or monocytes in most samples (98% and 90%, respectively). In the SST samples, the number of events recorded in low-volume samples (< 1 mL) was lower than in samples with higher volume (140 vs 556, p < 0.001), with a median of identification of 3 cell populations. FCM allows the analysis of a higher proportion ofpaucicellular CSF samples than cytology in hematologic neoplasms study.