Multiple Cutoffs Research Articles

Base rates of failure on various performance validity tests as a function of age in adults referred for neuropsychological assessment.

This study aimed to investigate the relationship between age and base rates of failure (BRFail) on various performance validity tests (PVTs) administered in medical-legal settings. Archival data were analyzed from 3,297 adults (Mage = 42.3 years; Meducation = 11.2) referred for psychological or neuropsychological assessments in a medical-legal or forensic civil disability context who passed the Word Memory Test. BRFail on 10 PVTs (three freestanding and seven embedded) were reported at multiple cutoffs across five age groups ranging from 16 years to 69 years. BRFail increased with age on most embedded PVTs, with a couple of notable exceptions. Reliable Digit Span was unrelated to age at ≤6 but produced elevated BRFail among older examinees at ≤7. Within freestanding PVTs, a positive relationship emerged between age and BRFail on most instruments/cutoffs. Older age is associated with an increased risk of false positive errors on many embedded PVTs that rely on raw scores. Although freestanding PVTs tend to be more resistant to the effects of age, several commonly used cutoffs may still produce increased false positive rates in older examinees. Taken together, results suggest that PVT scores should be interpreted in the context of patient characteristics, in an evidence-based manner, rather than by rigidly applying omnibus cutoffs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

PD-L1 Immunohistochemistry in Gastric Cancer: Comparison of Combined Positive Score and Tumor Area Positivity Across 28-8, 22C3, and SP263 Assays.

The clinical application of PD-L1 immunohistochemistry (IHC) testing is complicated by the availability of multiple IHC assays, scoring algorithms, and cutoffs. This study assessed the analytical comparability of three commercially available PD-L1 assays and two scoring algorithms used to assess PD-L1 status in gastric cancer (GC) samples. Serial sections of 100 resected GC samples, with PD-L1 expression levels across the dynamic range, were stained with three in vitro diagnostic-grade PD-L1 assays (28-8, 22C3, and SP263). Three trained pathologists blindly and independently scored slides using combined positive score (CPS) and tumor area positivity (TAP) algorithms. Comprehensive statistical analyses were performed to evaluate analytical concordance. Digital image analysis (DIA) was used to objectively compare the technical performance of each assay by simulating CPS and TAP. Comparable staining patterns were observed with these three PD-L1 assays. Despite discernible variation in staining intensity, reproducible evaluations of PD-L1 positivity were observed. Inter- and intra-assay assessments of all three assays, using either CPS or TAP and the same PD-L1 cutoffs, demonstrated moderate to almost-perfect (interassay Cohen's kappa [κ] range, 0.47-0.83) and substantial to almost-perfect (intra-assay κ range, 0.77-1.00) agreement. Interpathologist assessment exhibited a significant level of concordance (intraclass correlation coefficient ≥0.92). No difference in technical performance was observed using DIA. This study highlights analytical concordance in PD-L1 testing between three major PD-L1 assays when TAP and CPS are applied. Comparability of the technical assay performance was further supported by independent DIA. These observations support cross-application flexibility of the different PD-L1 assays and scoring algorithms to characterize PD-L1 expression in GC.

The role of regulatory policies in organizational culture: Insights from the education industry.

On February 26, 2018 and July 24, 2021, the Chinese government respectively issued two significant regulatory policies to address the problems caused by off-campus training institutions in terms of students' extra-curricular and family financial burdens. These policies have had a tremendous and far-reaching impact on the off-campus training industry in China. With the help of these two events, we explored the role of industry-level regulatory policies in shaping and forming organizational culture. This paper adopts a text analysis method, combined with the dimensions of the Denison Organizational Culture Survey (DOCS) and MAXQDA 18 software, to obtain data on corporate culture. Then, the approaches of regression discontinuity in time (RDiT) and regression discontinuity (RD) designs with multiple cutoffs are used to estimate the policy treatment effect. This empirical research suggests that regulatory policies have a significant impact on corporate culture. Moreover, regulatory policies of varying degrees of strictness have differential effects on different dimensions of corporate culture. The research findings contribute to the theories of corporate culture and can guide enterprises to evaluate the impact of policies on corporate culture more clearly, thereby enabling them to make wiser operation decisions.

Distribution and Positive Predictive Value of Follicle Stimulating Hormone Among Nonazoospermic Men.

Our goal was to characterize the distribution of follicle stimulating hormone (FSH) in fertile and subfertile nonazoospermic men, and to determine the ability of various FSH thresholds to predict fertility status. We performed a retrospective cohort study of 1389 nonazoospermic men who presented for fertility evaluation. Men with at least 2 semen analyses and 1 FSH level were included. Men were dichotomized into fertile and subfertile groups based on total motile sperm count. FSH was evaluated within a multivariable model, and positive predictive values (PPVs) for subfertility were used to assess the clinical utility of various FSH thresholds. One thousand fifteen (80%) men were classified as fertile and 274 (20%) as subfertile. Age, presence of varicocele, and testosterone levels were not statistically different between the groups. Median FSH was 4.0 vs 6.0 (P < .001) among fertile vs subfertile men. Multiple FSH thresholds ranging from 2.9 to 9.3 performed similarly in predicting fertility status (PPV 0.49-0.59). Only FSH thresholds above the 95th percentile (12.1) had PPVs greater than 0.7. The highest PPV (0.84) was seen at an FSH of 20.8 (99th percentile). While there were significant differences in FSH levels among fertile and subfertile nonazoospermic men, multiple FSH cutoffs between 2.2 and 9.3 performed poorly for prediction of fertility status as determined by total motile sperm count. It was not until the 95th percentile FSH value that a clinically useful level of predictability for subfertility was reached, indicating that FSH should not be used as a standalone test of fertility status. Nonetheless, FSH testing remains clinically useful and may be most informative in the setting of extreme values or discordant FSH and semen analysis results.

An empirical comparison of statistical methods for multiple cut-off diagnostic test accuracy meta-analysis of the Edinburgh postnatal depression scale (EPDS) depression screening tool using published results vs individual participant data

BackgroundSelective reporting of results from only well-performing cut-offs leads to biased estimates of accuracy in primary studies of questionnaire-based screening tools and in meta-analyses that synthesize results. Individual participant data meta-analysis (IPDMA) of sensitivity and specificity at each cut-off via bivariate random-effects models (BREMs) can overcome this problem. However, IPDMA is laborious and depends on the ability to successfully obtain primary datasets, and BREMs ignore the correlation between cut-offs within primary studies.MethodsWe compared the performance of three recent multiple cut-off models developed by Steinhauser et al., Jones et al., and Hoyer and Kuss, that account for missing cut-offs when meta-analyzing diagnostic accuracy studies with multiple cut-offs, to BREMs fitted at each cut-off. We used data from 22 studies of the accuracy of the Edinburgh Postnatal Depression Scale (EPDS; 4475 participants, 758 major depression cases). We fitted each of the three multiple cut-off models and BREMs to a dataset with results from only published cut-offs from each study (published data) and an IPD dataset with results for all cut-offs (full IPD data). We estimated pooled sensitivity and specificity with 95% confidence intervals (CIs) for each cut-off and the area under the curve.ResultsCompared to the BREMs fitted to the full IPD data, the Steinhauser et al., Jones et al., and Hoyer and Kuss models fitted to the published data produced similar receiver operating characteristic curves; though, the Hoyer and Kuss model had lower area under the curve, mainly due to estimating slightly lower sensitivity at lower cut-offs. When fitting the three multiple cut-off models to the full IPD data, a similar pattern of results was observed. Importantly, all models had similar 95% CIs for sensitivity and specificity, and the CI width increased with cut-off levels for sensitivity and decreased with an increasing cut-off for specificity, even the BREMs which treat each cut-off separately.ConclusionsMultiple cut-off models appear to be the favorable methods when only published data are available. While collecting IPD is expensive and time consuming, IPD can facilitate subgroup analyses that cannot be conducted with published data only.

Concordance among three programmed death-ligand 1 (PD-L1) scoring methods and their association with clinical outcomes of tislelizumab (TIS) monotherapy in esophageal squamous cell carcinoma (ESCC).

390 Background: Multiple scoring methods and cutoffs have been developed to evaluate tumor PD-L1 expression status in patients with ESCC, and PD-L1 expression level has been associated with the degree of response to anti-programmed cell death protein 1 (PD-1)/PD-L1 therapy. Here, we retrospectively investigated concordance between three PD-L1 scoring methods and their association with clinical outcomes in RATIONALE-302, a phase 3 study of the anti-PD-1 antibody TIS vs investigator-chosen chemotherapy (ICC) as second-line treatment for advanced unresectable/metastatic ESCC (NCT03430843). Methods: Patients enrolled in RATIONALE-302 with evaluable PD-L1 expression by the tumor area positivity (TAP) score (based on visual estimation of positive tumor cells [TCs] and tumor-associated immune cells [ICs]) using the VENTANA PD-L1 (SP263) assay were categorized at a 10% cutoff. Stained slides from those patients were rescored post hoc using both combined positive score (CPS; based on counting positive TCs and ICs) at cutoff 10 and TC (based on counting positive TCs only) score at a 1% cutoff, thresholds currently used in ESCC for anti-PD-(L)1 therapy. Concordance at these thresholds was investigated. Clinical efficacy (overall survival [OS]) for PD-L1 subgroups was assessed. Results: Of 512 pts enrolled, 364 had evaluable TAP scores (TIS, n=180; ICC, n=184), of whom 355 had evaluable post-hoc CPS and TC scores (TIS, n=175; ICC, n=180). TAP score and CPS showed high concordance in terms of overall percentage agreement (OPA; 90% [95% confidence interval (CI): 86, 93]) and Cohen’s Kappa (0.79 [95% CI: 0.72, 0.85]), while TAP and TC scores had lower concordance (OPA: 78% [95% CI: 73, 82]; Cohen’s Kappa: 0.56 [95% CI: 0.47, 0.64]). OS benefit with TIS vs ICC in PD-L1 subgroups defined by TAP, CPS, and TC score cutoffs were generally similar (Table). Conclusions: OS subgroup analysis showed comparable treatment effect by TAP score at 10% cutoff, CPS at cutoff 10, and TC score at 1% cutoff based on SP263 staining. TAP score and CPS at these cutoffs exhibited substantial concordance. The results indicate that the less time-consuming, visually estimated TAP score and CPS may be interchangeable for clinical measurement of PD-L1 expression in patients with ESCC. Clinical trial information: NCT03430843 . [Table: see text]

PD-L1 as a predictor of chemo-immunotherapy response in biliary tract cancers: A systematic review and meta-analysis.

541 Background: Advanced biliary tract cancers (BTCs) are rare and aggressive malignancies with limited treatment options. Recently, immune checkpoint inhibitors in combination with chemotherapy (ICI-C) gained approval as first-line therapy for unresectable or metastatic BTCs. Two large phase III clinical trials of ICI-C in BTCs did not show a significant correlation between PD-L1 expression and therapeutic response. However, in a phase II study of single-agent nivolumab, there was an association. In light of these conflicting findings, we conducted a comprehensive systematic review and meta-analysis of clinical trials investigating ICI-C in BTCs to assess whether PD-L1 expression could predict treatment response. Methods: We searched PubMed, Web of Science, EMBASE, and Cochrane databases to identify relevant studies. Patient characteristics, method of PD-L1 assessment, and measures of treatment response including hazard ratio (HR), objective response rate (ORR), progression-free-survival (PFS), and overall survival (OS) were extracted. Pooled ORR and HR were calculated using random effect model and assessed for study heterogeneity. Results: Among the 4,882 studies screened, seven clinical trials evaluating the efficacy of ICI-C in BTCs were identified. Of these trials, two randomized phase III trials report HR between PD-L1 positive and negative patients, while five phase II clinical trials reported ORR based on PD-L1 expression. Out of the 1,069 patients included in these trials, 954 underwent assessment for PD-L1 expression. 66.4% (n=634) exhibited PD-L1 expression level ≥ 1% as determined by either tumor proportion score (TPS) or combined positive score (CPS), while 33.5% (n=320) were classified as PD-L1 negative. Notably, 115 patients were not tested for PD-L1 expression, a variety of PD-L1 assays were used across the studies, and only some studies reported multiple PD-L1 cutoffs. Pooled analysis of two-phase III trials demonstrated that PD-L1 expression ≥ 1% was associated with improved OS (pooled HR 0.83, 95% CI 0.72-0.95) compared to PD-L1 &lt; 1% (pooled HR 0.85, 95% CI 0.67-1.07). Additionally, pooled ORR from five phase II studies showed a trend towards an improved response in patients with PD-L1 expression ≥ 1% (pooled ORR 64%, 95% CI 52-74%) compared to PD-L1 &lt;1% (pooled ORR 46%, 95% CI 31-62%) with a subgroup difference p-value of 0.08. Conclusions: This meta-analysis suggests that BTCs patients with PD-L1 expression ≥ 1% may exhibit a more favorable response to chemo-immunotherapy, and that a majority of BTCs have this level of expression. These findings support further investigation of the use of PD-L1 as a biomarker, and in particular investigation of different PD-L1 levels, which may inform treatment for patients with relative contraindications to immunotherapy use.

CROSS-COUNTRY VALIDATION OF ANTHROPOMETRIC AGE (ANTHROPOAGE) AS A MEASURE OF BIOLOGICAL AGING

Abstract Aging occurs at unique rates at an individual and population-level. In contrast to chronological age (CA), biological age (BA) is better at capturing functional decline and risk of age-related diseases, disability, and death. Nonetheless, it is still unclear how this phenomenon changes across adults from different races/ethnicities. We recently developed a BA metric using anthropometric measurements (AnthropoAge) in participants from NHANES-III. Here, we aim to validate AnthropoAge across countries and to determine whether it displays population-specific patterns using harmonized cohorts from the U.S. and Mexico from the Gateway to Global Aging Data Team, including the Mexican Health and Aging Study and the Health and Retirement Study. We found that AnthropoAge is a robust predictor of overall mortality risk in both American (AUROC=0.797; 95%CI 0.786-0.808) and Mexican (0.776; 0.740-0.812) adults, and this was consistent across multiple cutoffs of time. Notably, we found that the prediction improved in participants aged 50-75 years in comparison to older adults aged 75-100 years. AnthropoAge was also associated with number of comorbidities and disability in activities of daily living independently of CA. Finally, we observed marked changes of AnthropoAge and its acceleration across the years in both countries, with a significant interaction with Mexican ethnicity (beta for interaction: 0.2034; p=5.94E-05). AnthropoAge is a robust and reproducible measure of BA, however, new studies are required to decipher the heterogeneity of anthropometric aging in specific ethnicities and age categories.

A multiple cut-off diagnostic meta-analysis to identify the atrial high-rate episodes threshold that better relates to thromboembolic events

Abstract Background Despite the high prevalence of atrial high-rate episodes (AHRE) detected by cardiac implantable electronic devices (CIED), clinical guidelines and consensus documents have failed to agree on a universal AHRE definition. Clear evidence on the best management strategy is lacking. Purpose The present is a diagnostic test accuracy meta-analysis aiming to derive from available literature the optimal AHRE threshold to predict thromboembolic events. Methods PubMed/MEDLINE and EMBASE databases were screened for studies on CIED patients reporting incidence of thromboembolic events referred to at least one AHRE definition. A random-effect diagnostic test accuracy meta-analysis with multiple cut-offs was performed: duration of AHRE was the "diagnostic test" (positive test if the patients experienced an AHRE lasting at least as long as the time cut-off under examination) whose performance in predicting the "disease" (thromboembolic events) was evaluated across multiple cut-offs. Two analyses, according to AHRE definition (longest episode vs. cumulative burden), were performed. Results 23 studies were included in the analyses (Fig. 1 Panel A), encompassing 46,189 patients: 19 considering the longest single AHRE and 4 the AHRE burden, respectively. Median follow-up was 40.75 (IQR 28.25-52.80) months. The analysis on the longest single AHRE indicated 0.07 minutes as the optimal cut-off to differentiate AHRE associated or not to thromboembolic events [sensitivity 65.4% (95% CI 48.8-79.0%), specificity 52.7% (95%CI 46.0-59.4%), area under the summary receiver operating characteristic curve (AUC-SROC): 0.62; Fig. 1 Panel B]. The analysis on AHRE burden indicated, instead, 1.4 minutes as the optimal cut-off [sensitivity 58.2% (95%CI 25.6-85.0%), specificity 57.5% (95% CI 42.0-71.7%), AUC-SROC 0.60; Fig. 1 Panel C]. PPV and NPV for 6 minutes and 24 hours cut-offs were similar in each analysis (Figure 2). Sensitivity analyses exclusively considering studies reporting data on patients without previous AF diagnosis and high-quality studies only yield similar results. Conclusion The present evidence-based approach suggests the presence (or not) of AHRE, rather than a specific duration, relates to an increased thromboembolic risk in CIED patients. A linear relationship between AHRE duration (both in terms of single longest episode than cumulative burden) and thromboembolic events was not observed.

Role of atrial high-rate episodes in stratifying thromboembolic risk: a multiple cut-off diagnostic meta-analysis.

Despite the high prevalence rate of atrial high-rate episodes (AHREs) detected using cardiac implantable electronic devices (CIEDs), clinical guidelines and consensus documents have disagreed on a universal AHRE definition and a temporal cut-off related to subsequent thromboembolic events. This diagnostic test accuracy meta-analysis aims to derive the optimal temporal threshold of clinically significant AHREs from the available literature. The PubMed/MEDLINE and EMBASE databases were screened for studies on CIED patients reporting the incidence of thromboembolic events related to at least one AHRE temporal cut-off. A total of 23 studies were included: 19 considering the longest single AHRE and four the AHRE burden, respectively. A random-effect diagnostic test accuracy meta-analysis with multiple cut-offs was performed. Two analyses were performed according to the AHRE temporal cut-off subtype (longest episode vs. cumulative burden). The analysis on the longest single AHRE indicated 0.07 min as the optimal duration to differentiate AHRE associated or not with thromboembolic events [sensitivity 65.4% (95% CI 48.8%-79.0%), specificity 52.7% (95% CI 46.0%-59.4%), and area under the summary receiver operating characteristic curve (AUC-SROC): 0.62]. The analysis on AHRE burden indicated 1.4 min as the optimal cut-off [sensitivity 58.2% (95% CI 25.6%-85.0%), specificity 57.5% (95% CI 42.0%-71.7%), and AUC-SROC 0.60]. A sensitivity analysis excluding patients with a history of atrial fibrillation and including high-quality studies only yielded similar results. The presence of AHRE, rather than a specific duration, relates to an increased, albeit low, thromboembolic risk in CIED patients. Any AHRE should constitute an additional element in patient-specific thromboembolic risk assessment.

Machine learning using multimodal and autonomic nervous system parameters predicts clinically apparent stroke-associated pneumonia in a development and testing study.

Stroke-associated pneumonia (SAP) is a preventable determinant for poor outcome after stroke. Machine learning (ML) using large-scale clinical data warehouses may be able to predict SAP and identify patients for targeted interventions. The aim of this study was to develop a prediction model for identifying clinically apparent SAP using automated ML. The ML model used clinical and laboratory parameters along with heart rate (HR), heart rate variability (HRV), and blood pressure (BP) values obtained during the first 48h after stroke unit admission. A logistic regression classifier was developed and internally validated with a nested-cross-validation (nCV) approach. For every shuffle, the model was first trained and validated with a fixed threshold for 0.9 sensitivity, then finally tested on the out-of-sample data and benchmarked against a widely validated clinical score (A2DS2). We identified 2390 eligible patients admitted to two-stroke units at Charité between October 2020 and June 2023, of whom 1755 had all parameters available. SAP was diagnosed in 96/1755 (5.5%). Circadian profiles in HR, HRV, and BP metrics during the first 48h after admission exhibited distinct differences between patients with SAP diagnosis vs. those without. CRP, mRS at admission, leukocyte count, high-frequency power in HRV, stroke severity at admission, sex, and diastolic BP were identified as the most informative ML features. We obtained an AUC of 0.91 (CI 0.88-0.95) for the ML model on the out-of-sample data in comparison to an AUC of 0.84 (CI 0.76-0.91) for the previously established A2DS2 score (p < 0.001). The ML model provided a sensitivity of 0.87 (CI 0.75-0.97) with a corresponding specificity of 0.82 (CI 0.78-0.85) which outperformed the A2DS2 score for multiple cutoffs. Automated, data warehouse-based prediction of clinically apparent SAP in the stroke unit setting is feasible, benefits from the inclusion of vital signs, and could be useful for identifying high-risk patients or prophylactic pneumonia management in clinical routine.

Circulating Tumor DNA Monitoring on Chemo-immunotherapy for Risk Stratification in Advanced Non-Small Cell Lung Cancer.

Chemoimmunotherapy (chemoIO) is a prevalent first-line treatment for advanced driver-negative non-small cell lung cancer (NSCLC), with maintenance therapy given after induction. However, there is significant clinical variability in the duration, dosing, and timing of maintenance therapy after induction chemoIO. We used circulating tumor DNA (ctDNA) monitoring to inform outcomes in patients with advanced NSCLC receiving chemoIO. This retrospective study included 221 patients from a phase III trial of atezolizumab+carboplatin+nab-paclitaxel versus carboplatin+nab-paclitaxel in squamous NSCLC (IMpower131). ctDNA monitoring used the FoundationOne Tracker involving comprehensive genomic profiling of pretreatment tumor tissue, variant selection using an algorithm to exclude nontumor variants, and multiplex PCR of up to 16 variants to detect and quantify ctDNA. ctDNA was detected (ctDNA+) in 96% of pretreatment samples (median, 93 mean tumor molecules/mL), and similar ctDNA dynamics were noted across treatment arms during chemoIO. ctDNA decrease from baseline to C4D1 was associated with improved outcomes across multiple cutoffs for patients treated with chemoIO. When including patients with missing plasma or ctDNA- at baseline, patients with ctDNA- at C4D1 (clearance), had more favorable progression-free survival (median 8.8 vs. 3.5 months; HR, 0.32;0.20-0.52) and OS (median not reached vs. 8.9 months; HR, 0.22; 0.12-0.39) from C4D1 than ctDNA+ patients. ctDNA monitoring during induction chemoIO can inform treatment outcomes in patients with advanced NSCLC. Importantly, monitoring remains feasible and informative for patients missing baseline ctDNA. ctDNA testing during induction chemoIO identifies patients at higher risk for disease progression and may inform patient selection for novel personalized maintenance or second-line treatment strategies.

Cutoffs and Characteristics of Abnormal Bowel Dilatation in Pediatric Short Bowel Syndrome.

Although excessive intestinal dilatation associates with worsened outcomes in pediatric short bowel syndrome (SBS), little is known about the natural history and definition of pathological dilatation. We addressed fore-, mid-, and hind-gut dilatation in children with SBS, who had not undergone autologous intestinal reconstructive (AIR) surgery, in relation to controls. SBS children without history of AIR surgery (n = 59) and age-matched controls without any disclosed intestinal pathology (n = 140) were included. Maximum diameter of duodenum, small bowel (SB), and colon were measured in each intestinal contrast series during 2002 to 2020 and expressed as diameter ratio (DR) to L5 vertebrae height. Predictive ability of DR for weaning off parenteral nutrition (PN) was analyzed with Cox proportional hazards regression models using multiple cutoffs. Duodenum (DDR), SB (SBDR), and colon (CDR) DR were 53%, 183%, and 23% higher in SBS patients compared to controls ( P < 0.01 for all). The maximal DDR and SBDR measured during follow-up is associated with current PN dependence and young age. DDR correlated with SBDR ( r = 0.586, P < 0.01). Patients with maximal DDR less than 1.5, which was also the 99th percentile for controls, were 2.5-fold more likely to wean off PN ( P = 0.005), whereas SBDR and CDR were not predictive for PN duration. All segments of remaining bowel, especially SB, dilate above normal levels in children with SBS. In SBS children without AIR surgery, PN dependence and young age is associated with duodenal and small intestinal dilatation, while duodenal dilatation also predicted prolonged PN.

Quantitative Late Gadolinium Enhancement Cardiac Magnetic Resonance and Sudden Death in Hypertrophic Cardiomyopathy: A Meta-Analysis

BackgroundQuantitative late gadolinium enhancement (LGE) cardiac magnetic resonance provides important prognostic information for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). However, it has not been fully integrated into clinical practice. ObjectivesThe purpose of this study was to assess the prognostic value of LGE extent in predicting SCD in adults with HCM across different methods of quantification, thresholds, and patients’ clinical profile. MethodsThe authors searched PubMed, Web of Science, and Cochrane Library for studies investigating the prognostic value of LGE% in predicting SCD in HCM. Pooled ORs were calculated with 95% CIs. The optimal threshold was determined using a multiple cutoffs model. ResultsEleven studies were included in the meta-analysis with a total of 5,550 patients and a median follow-up time of 5.2 years. Two studies quantified LGE manually, 7 studies used the 6 SD technique, 1 study used the 4 SD technique, and 1 study the 2 SD technique. There was no statistically significant difference in predicting SCD between these 4 methods (P = 0.443). Optimal cutoff could be determined only for the 6 SD technique. LGE 10% was the optimal threshold of the 6 SD technique with sensitivity 0.73 and specificity 0.67. ConclusionsThe different LGE quantification techniques have comparable accuracy in predicting SCD. When the more extensively studied 6 SD technique is used, LGE 10% is the optimal cutoff and can effectively restratify intermediate-risk patients. LGE extent can improve HCM risk stratification, but it is unlikely to become a standalone tool.

Sediment preservation and accretion rates of fluvial meander-belt deposits: variations with temporal scale and river size

Abstract The preservation and accretion rates of fluvial meander-belt deposits appear to vary with the time over which they are evaluated, but the drivers of this effect are not fully understood. Using channel trajectories tracking the temporal evolution of meandering rivers, constrained with data on past river planforms, a numerical model is used to simulate planform evolutions of meander-belt reaches that underwent different types of meander transformation behaviours and bend cutoffs. Sediment preservation and bar accretion rates are quantified for three hierarchies of depositional products: (i) accretion stages reflecting intervals of bend migration by a certain meander-transformation style, (ii) meander-belt segments encompassing multiple stages but no bend cutoffs and (iii) meander-belt segments that experienced one or multiple cutoffs. Results show that distinct power-law relationships between the accretion rate and the time of sedimentation exist for river systems of different magnitudes in scale. Within each order of magnitude in river-system size, a single power-law relationship fails to effectively capture all depositional hierarchies. Sediment preservation varies with the time over which it is computed, but systematic variations in accretion rates with time primarily portray an apparent dependency of river migration rates on time: these variations largely reflect the temporal resolution and timespan of the modelled examples, highlighting an inherent issue affecting studies of river evolutions.

CE-452776-3 IS RATE CONTROL EVER ADEQUATE? CATHER ABLATION IN RATE CONTROLLED ATRIAL FIBRILLATION WITH REDUCED EJECTION FRACTION

The optimal rate control target for atrial fibrillation (AF) in the setting of heart failure with reduced ejection fraction (HFrEF) is not defined. Prior clinical trials have demonstrated benefits of AF ablation for patients with HFrEF, including recovery in left ventricular ejection fraction (LVEF). However, it is unknown if degree of rate control prior to ablation affects outcomes. To evaluate whether degree of pre-ablation rate control impacts LVEF recovery following AF ablation in patients with HFrEF. A single center, retrospective cohort study of 75 consecutive patients with LVEF ≤35% who underwent first-time ablation for persistent AF at NYU Langone Health between January 2014 and January 2021. Patients were classified as having a LVEF recovery if their post-ablation LVEF was >35%. Proportion of patients with LVEF recovery were compared between multiple rate control cutoffs: 110 bpm, 90 bpm, and 70 bpm. A binomial logistic regression analysis was then performed examining the relationship of pre-ablation HR on LVEF recovery. The mean pre-ablation HR was 90±25 bpm, baseline LVEF was 27±6%, and 64% (48/75) of patients had at least 3 months of maximal GDMT prior to ablation (Table 1A). Significant improvement in LVEF was observed in all patient subgroups irrespective of rate control status (Figure 1A) and regardless of prior GDMT (Figure 1B). Overall, LVEF recovery to >35% occurred in 59% (44/75) of patients. Compared to patients with pre-ablation HR faster than evaluated rate control cutoffs (Table 1B), there were no differences in frequency of LVEF recovery when using ≤110 bpm (controlled: 58% vs. not controlled: 63%, p=0.73) or ≤90 bpm (controlled: 52% vs. not controlled: 66%, p=0.21). In contrast, patients achieving rate control ≤70 bpm were significantly less likely to have LVEF recovery (41%) compared to those with HR above the cutoff (66%; p=0.04). Binomial logistic regression analysis did not reveal HR as a significant predictor of LVEF recovery (OR=1.01; CI 95%=0.99-1.03; p=0.16). Catheter ablation of persistent in AF in patients with HFrEF frequently resulted in improvement in LVEF, irrespective of achieved rate control. LVEF recovery >35% following catheter ablation was reduced only with rate control of HR 70bpm. Catheter ablation should be considered in HFrEF patients regardless of degree of rate control achieved. Heart rate 70bpm should be evaluated as a goal for adequate rate control in patients with HFrEF in whom rhythm control is not pursued.

Visuospatial Dysfunction in Alzheimer’s Disease Maps to a Brain Network (P12-6.009)

<h3>Objective:</h3> Localize visuospatial dysfunction in Alzheimer’s disease (AD) using atrophy and network mapping techniques, and identify whether clock-draw or clock-copy is a better test of parietal lobe dysfunction. <h3>Background:</h3> Visuospatial dysfunction in AD is common and a direct contributor to falls, car accidents and loss of independence. Better understanding of visuospatial network dysfunction in AD allows for earlier intervention and improved safety. Atrophy mapping studies have localized visuospatial dysfunction to multiple brain regions suggesting it maps to a network. Here, cortical thickness and atrophy network maps were created and compared to clock-copy and clock-draw scores to identify the network underlying visuospatial dysfunction in AD using the Alzheimer’s Disease Neuroimaging Initiative (ADNI). <h3>Design/Methods:</h3> Initial analyses were run using ADNI1 then validated using independent subjects in ADNI2. Cortical thickness was directly compared to clock-draw and clock-copy scores identifying brain regions directly associated with performance. A general-linear-model was generated from each cohort’s healthy controls and used to estimate expected cortical thickness for AD subjects. Atrophy maps were generated using multiple Z-score cutoffs at a voxel-wise level. Atrophy network maps were generated using the normative connectome and compared to clock-copy and clock-draw scores. <h3>Results:</h3> Single-subject cortical thickness maps compared directly to clock-copy or clock-draw scores did not identify any voxels that correlated with scores meeting FWE p&lt;0.05. Atrophy network maps compared to clock-draw scores identified a network but not voxels meeting FWE p&lt;0.05. However, atrophy network mapping identified a map centered on the bilateral angular gyri significantly correlating with clock-copy scores. Clock-copy atrophy network maps showed higher reproducibility than clock-draw. <h3>Conclusions:</h3> Our results show that clock-draw and clock-copy scores map to networks rather than single brain regions. Clock-draw maps to a distributed brain network while clock-copy maps to the angular gyrus and is more reproducible. Clock-copy is a more specific measure of parietal lobe function in AD than clock-draw. <b>Disclosure:</b> Dr. Baratono has stock in moderna. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley. Mr. Drew has nothing to disclose.

MP41-01 EVALUATION OF GROWTH RATES FOR SMALL RENAL MASSES IN ELDERLY PATIENTS UNDERGOING ACTIVE SURVEILLANCE

You have accessJournal of UrologyCME1 Apr 2023MP41-01 EVALUATION OF GROWTH RATES FOR SMALL RENAL MASSES IN ELDERLY PATIENTS UNDERGOING ACTIVE SURVEILLANCE Ridwan Alam, Sunil Patel, Peter Chang, Andrew Wagner, James McKiernan, Phillip Pierorazio, Mohamad Allaf, and Nirmish Singla Ridwan AlamRidwan Alam More articles by this author , Sunil PatelSunil Patel More articles by this author , Peter ChangPeter Chang More articles by this author , Andrew WagnerAndrew Wagner More articles by this author , James McKiernanJames McKiernan More articles by this author , Phillip PierorazioPhillip Pierorazio More articles by this author , Mohamad AllafMohamad Allaf More articles by this author , and Nirmish SinglaNirmish Singla More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003279.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Emerging data suggests that tumor microenvironments may differ among patients based on age, which can be of concern to patients who are enrolled in active surveillance (AS) for a prolonged period. We sought to examine if particular age cutoffs were associated with an increased growth rate (GR) for patients enrolled in AS for small renal masses (SRMs). METHODS: The Delayed Intervention and Surveillance for Small Renal Masses registry is a prospective, multi-institutional study examining outcomes in patients undergoing AS for SRMs. Two definitions of GR were examined: growth rate from the initial image (GRi) and growth rate from the prior image (GRp). Image measurements were dichotomized based on patient age at the time of imaging. Multiple age cutoffs were examined: 65, 70, 75, and 80 years. Mixed effects linear regression examined associations between age and GR, with controlling to account for multiple measurements from the same individual. RESULTS: We examined 2542 measurements from 571 patients [Figure]. The median age of patients at enrollment was 70.9 years (IQR 63.2-77.4) with a median tumor diameter of 1.8 cm (IQR 1.4-2.5). When examined as a continuous variable, age was not associated with GRi (-0.0001 cm/year, 95% CI -0.007 – 0.007, P=0.97) or GRp (0.008 cm/year, 95% CI -0.004 – 0.020, P=0.17) after adjustment. The only age thresholds associated with an increased GR were 65 years for GRi and 70 years for GRp[Table]. Patients who underwent delayed intervention had increased GRi (0.282 cm/year, 95% CI 0.078 – 0.487, P=0.007) but no difference in GRp (0.319 cm/year, 95% CI -0.032 – 0.670, P=0.07) compared to those who remained on AS. CONCLUSIONS: Patients with SRMs on AS do not exhibit a clear association between tumor GR and patient age, suggesting that AS is a safe and durable management option for aging patients with SRMs. Source of Funding: None. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e554 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ridwan Alam More articles by this author Sunil Patel More articles by this author Peter Chang More articles by this author Andrew Wagner More articles by this author James McKiernan More articles by this author Phillip Pierorazio More articles by this author Mohamad Allaf More articles by this author Nirmish Singla More articles by this author Expand All Advertisement PDF downloadLoading ...

Mach cutoff phenomenon of sonic boom in temperature inversion layers

The Mach cutoff of sonic boom occurs when shock waves propagate from supersonic to subsonic regions in a stratified atmosphere. In this study, numerical simulations are performed to clarify Mach cutoff behaviors in atmospheric temperature inversion layers, which have not yet been investigated. The two-dimensional Euler equations with a gravitational source term are solved in a horizontally stratified atmosphere. Surface and non-surface temperature inversion layers include three and four supersonic–subsonic mixing layers, respectively. Computations are made to analyze the propagation characteristics of a conventional N-shaped waveform. The results show that multiple upward and downward cutoffs occur owing to atmospheric temperature inversions, with multiple outgoing and evanescent waves, and multiple shock wave focusing. The upward and downward cutoffs act similarly. The positive- and negative-pressure regions are inversed when a cutoff occurs twice; thus, each cutoff shifts a phase by π/2, as expressed in the linear theory of caustics. A waveform transition occurs owing to wave splitting in a cutoff region, in addition to the phase shift. For surface temperature inversion, upward cutoffs make the waves between the cutoff and ground surfaces persist, resulting in rumbling. For non-surface temperature inversion, upward and downward cutoffs occur alternately, and the waves between them persist as well. Therefore, multiple cutoffs in temperature inversion layers play an important role in sonic boom evaluation during low supersonic flight.

Evaluation of Growth Rates for Small Renal Masses in Elderly Patients Undergoing Active Surveillance

BackgroundAs the adoption of active surveillance (AS) for small renal masses (SRMs) grows, the number of elderly patients enrolled for a prolonged period of time will increase. However, our understanding of comparative growth rates (GRs) in aging patients with SRMs remains poor. ObjectiveTo examine whether particular age cutoffs are associated with an increased GR for patients undergoing AS for SRMs. Design, setting, and participantsWe identified all patients with SRMs enrolled in the multi-institutional, prospective Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry since 2009 who elected for AS. Outcome measurements and statistical analysisTwo definitions of GR were examined: GR from the initial image (GRi) and GR from the prior image (GRp). Image measurements were dichotomized based on patient age at the time of imaging. Multiple age cutoffs were examined: 65, 70, 75, and 80 yr. Mixed-effect linear regression examined the associations between age and GR, with controlling to account for multiple measurements from the same individual. Results and limitationsWe examined 2542 measurements from 571 patients. The median age at enrollment was 70.9 yr (interquartile range [IQR] 63.2–77.4) with a median tumor diameter of 1.8 cm (IQR 1.4–2.5). As a continuous variable, age was not associated with GRi (–0.0001 cm/yr, 95% confidence interval [CI] –0.007 to 0.007, p = 0.97) or GRp (0.008 cm/yr, 95% CI –0.004 to 0.020, p = 0.17) after adjustment. The only age thresholds associated with an increased GR were 65 yr for GRi and 70 yr for GRp. Limitations include the one-dimensional nature of the measurements used. ConclusionsIncreased age for patients on AS for SRMs is not associated with increased GRs. Patient summaryWe examined whether patients undergoing active surveillance (AS) exhibited accelerated growth of their small renal masses (SRMs) after a certain age. No demonstrable change was seen, suggesting that AS is a safe and durable management option for aging patients with SRMs.