Optimal Definition Research Articles

Game-theoretic algorithm for interdependent infrastructure network restoration in a decentralized environment.

Having reliable interdependent infrastructure networks is vital for well-being of a safe and productive society. Systems are vulnerable to failure or performance loss due to their interdependence among various networks, as each failure can propagate through the whole system. Although the conventional view has concentrated on optimizing the restoration of critical interdependent infrastructure networks using a centralized approach, having a lone actor as a decision-maker in the system is substantially different from the actual restoration decision environment, wherein infrastructure utilities make their own decisions about how to restore their network service. In a decentralized environment, the definition of whole system optimality does not apply as each decision-maker's interest may not converge with the others. Subsequently, this results in each decision-maker developing its own reward functions. Therefore, in this study, we address the concern of having multiple decision-makers with various payoff functions in interdependent networks by proposing a decentralized game theory algorithm for finding Nash equilibria solutions for network restoration in postdisaster situations.

Ningetinib plus gefitinib in EGFR-mutant non-small-cell lung cancer with MET and AXL dysregulations: A phase 1b clinical trial and biomarker analysis

BackgroundMET and AXL dysregulations are implicated in acquired resistance to EGFR-TKIs in NSCLC. But consensus on the optimal definition for MET/AXL dysregulations in EGFR-mutant NSCLC is lacking. Here, we investigated the efficacy and tolerability of ningetinib (a MET/AXL inhibitor) plus gefitinib in EGFR-mutant NSCLC, and evaluated the clinical relevance of MET/AXL dysregulations by different definitions. MethodsPatients in this phase 1b dose-escalation/dose-expansion trial received ningetinib 30 mg/40 mg/60 mg plus gefitinib 250 mg once daily. Primary endpoints were tolerability (dose-escalation) and objective response rate (dose-expansion). MET/AXL status were analyzed using FISH and IHC. ResultsBetween March 2017 and January 2021, 108 patients were enrolled. The proportion of MET focal amplification, MET polysomy, MET overexpression, AXL amplification and AXL overexpression is 18.1 %, 5.6 %, 55.8 %, 8.1 % and 45.3 %, respectively. 6.8 % patients have concurrent MET amplification and AXL overexpression. ORR is 30.8 % for tumors with MET amplification, 0 % for MET polysomy, 24.1 % for MET overexpression, 20 % for AXL amplification and 27.6 % for AXL overexpression. For patients with concurrent MET amplification and AXL overexpression, ningetinib plus gefitinib provides an ORR of 80 %, DCR of 100 % and median PFS of 4.7 months. Tumors with higher MET copy number and AXL expression tend to have higher likelihood of response. Biomarker analyses show that MET focal amplification and overexpression are complementary in predicting clinical benefit from MET inhibition, while AXL dysregulations defined by an arbitrary level may dilute the efficacy of AXL blockade. ConclusionsThis study demonstrates that combined blockade of MET, AXL and EGFR is a feasible strategy for a subset of EGFR-mutant NSCLC. Trial registrationChinadrugtrials.org.cn, CTR20160875.

The Dual Burden of Frailty and Heart Failure.

Frailty is highly prevalent among patients with heart failure (HF) and independently predicts adverse outcomes. However, optimal frailty definitions, assessments, and management in HF remain unclear. Frailty is common in HF, affecting up to 80% of patients depending on population characteristics. Even pre-frailty doubles mortality risk versus robust patients. Frailty worsens HF prognosis through systemic inflammation, neurohormonal changes, sarcopenia, and micronutrient deficiency. Simple screening tools like gait speed and grip strength predict outcomes but lack HF-specificity. Comprehensive geriatric assessment is ideal but not always feasible. Exercise, nutrition, poly-pharmacy management, and multidisciplinary care models can help stablize frailty components and improve patient-centred outcomes. Frailty frequently coexists with and exacerbates HF. Routine frailty screening should guide supportive interventions to optimize physical, cognitive, and psychosocial health. Further research on HF-specific frailty assessment tools and interventions is warranted to reduce this dual burden.

Degenerative Thoracic Myelopathy: A Scoping Review of Epidemiology, Genetics, and Pathogenesis.

Literature Review. Myelopathy affecting the thoracic spinal cord can arise secondary to several aetiologies which have similar presentation and management. Consequently, there are many uncertainties in this area, including optimal terminology and definitions. Recent collaborative cervical spinal research has led to the proposal and subsequent community adoption of the name degenerative cervical myelopathy(DCM), which has facilitated the establishment of internationally-agreed research priorities for DCM. We put forward the case for the introduction of the term degenerative thoracic myelopathy(DTM) and degenerative spinal myelopathy(DSM) as an umbrella term for both DCM and DTM. Following PRISMA guidelines, a systematic literature search was performed to identify degenerative thoracic myelopathy literature in Embase and MEDLINE. Conditions encompassed within DTM include thoracic spondylotic myelopathy, ossification of the posterior longitudinal ligament, ossification of the ligamentum flavum, calcification of ligaments, hypertrophy of ligaments, degenerative disc disease, thoracic osteoarthritis, intervertebral disc herniation, and posterior osteophytosis. The classic presentation includes girdle pain, gait disturbance, leg weakness, sensory disturbance, and bladder or bowel dysfunction, often with associated back pain. Surgical management is typically favoured with post-surgical outcomes dependent on many factors, including the causative pathology, and presence of additional stenosis. The clinical entities encompassed by the term DTM are interrelated, can manifest concurrently, and present similarly. Building on the consensus adoption of DCM in the cervical spine and the recent proposal of degenerative cervical radiculopathy(DCR), extending this common nomenclature framework to the terms degenerative spinal myelopathy and degenerative thoracic myelopathy will help improve recognition and communication.

GIS-based approach for optimizing biowaste collection services in rural small sized municipalities

Directive (EU) 2018/851 of the European Parliament and of the Council establishes the obligation for Member States to ensure, by 31 December 2023, that biowaste is separated and recycled at source or collected selectively. As this is a responsibility of the municipalities, studies to evaluate the best solutions and to ensure the rationality of the investments to be made to fulfill these objectives is of particular importance. Bearing in mind the new municipality’s responsibility, this article aims to demonstrate the applicability of GIS in supporting planning and decision of a new service provided to the population. The solutions found must be economically sustainable and feasible for small size municipalities, especially for those with no formal biowaste management system implemented and with reduced resources. It is therefore proposed an approach to analyze vehicle route optimization for the selective collection and transportation of biowaste in markedly rural municipalities with a strong forestry component, equating solutions that allow their recovery, as well as the promotion of the management of forest spaces. The Network Analyst extension of the ArcGIS® software was used to answer questions related to travel time route optimization, optimal location selection and definition of service areas. The analysis performed allowed to identify and evaluate the main factors that minimize the costs associated with the undifferentiated and selective collection and transportation of biowaste in the study area (Oleiros-Amieira parish, Portugal). It was determined the need to distribute the service through 3 different routes, as well as optimizing the location of a biomass plant fed by forest remnants deposited in community containers spread across the study area. Developing simpler and cost-effective instruments for reducing waste transport costs for small forest owners and municipalities, such as the proposed one, is essential to ensure a successful implementation of Directive (EU) 2018/851.

Production policy based on echelon base stocks for reverse logistics and industrial symbiosis: an IPA approach

Last years, the implementation of reverse loops in logistics and the deployment of industrial symbiosis becomes more important. However, these new activities management isn’t easy and it’s necessary to propose methodologies to facilitate the actors work. However, the existing studies are more at strategic level, aiming with implementation or cooperation. At the tactical/operational level, solutions are poorly effective and/or expensive. Our work targets an optimal production policy definition based on the base stock strategy adapted for an industrial symbiosis. The system is composed of two kinds of warehouses and three types of enterprises. The recovering depends on the kind of collected used finished products. All demands are uncertain such as the number of collected used finished products and generated waste. Then, the main objective is to minimize the sum of all economic, environmental and social costs by identifying the level of the base stocks. To do this, an infinitesimal perturbation analysis study is conducted to evaluate the gradient estimators of the objective function subject to an echelon base stock production policy. This result is then used in a simulation based-optimization algorithm to determine these stock levels and highlight our theoretical results by comparing with other replenishment strategy and mathematical programming.

Defining Arctic Stratospheric Polar Vortex Intensification Events

AbstractUsing the ERA5 reanalysis data, we identify seven easily calculable indices of the strength of the Arctic stratospheric vortex: zonal winds at 10 hPa and temperature or height anomalies at 10 , 50, and 100 hPa. We then compare the climatological statistics and meteorological properties of strong and weak events based on these indices. We particularly consider the sensitivity of the event statistics to the choice of thresholds, the use of these indices in capturing stratosphere–troposphere coupling, and meteorological conditions relevant to chemical ozone depletion. The frequency, seasonal distribution, and interdecadal variability of strong events is more sensitive to threshold or index choice compared to weak events. Composites of polar‐cap geopotential height anomalies are found to differ significantly based on the choice of index. In particular, height‐based events reveal a strong and immediate barotropic response near the central date due to surface pressure fluctuations, making it more difficult to regard central dates of height‐based events as purely stratospheric in origin. We further characterize the relationship of all indices to conditions relevant to chemical ozone depletion, finding that temperature‐based indices in the lower stratosphere perform best. Finally, we present four dynamical benchmarks used to assess and compare the representation of strong events in climate models. Our results highlight the challenges in determining the optimal definition for strong events and emphasize the implications of different choices, providing valuable insights for guiding future studies in defining strong events.

Variation in identifying children and adolescents with disability and developmental disability in population-based public health surveys

BackgroundThe term “developmental disability” (DD) is inconsistently defined and applied depending on purpose and across sources, including in legislation. ObjectiveThis project aimed to identify existing definitions of disability and DD and to determine the extent to which each definition could be operationalized to produce prevalence estimates using data from U.S. national surveys. MethodsUsing data among children <18 years from the 2016–2018 National Health Interview Survey (NHIS) and National Survey of Children's Health (NSCH), we estimated the prevalence of two definitions of disability (Washington Group Short Set on Functioning, American Community Survey) and seven definitions of DD [Health and Human Services (ever/current), Developmental Disabilities Assistance and Bill of Rights Act of 2000 (1+, 2+, or 3+ components), and Diagnostic and Statistical Manual of Mental Disorders, 5th ed (ever/current)]. Complex sample design variables and weights were used to calculate nationally representative prevalence. ResultsDisability (NHIS: 5.2–6.3%; NSCH: 9.2–11.9%) and DD prevalence (NHIS: 0.6–18.0% and NSCH: 0.2–22.2%) varied depending on the definition and data source. For the same definition, NSCH prevalence estimates tended to be higher than NHIS estimates. ConclusionsThe substantial variability in estimated prevalence of disability and DD among children in the United States may be in part due to the surveys not representing all components of each definition. Different or additional questions in national surveys may better capture existing definitions of disability and DD. Considering the data collection goals may help determine the optimal definition to provide useful information for public health action.

Abstract 12123: Descending Aortic Diastolic Flow Reversal in Aortic Regurgitation: Optimizing Definitions and Assessment on Cardiac Magnetic Resonance

Introduction: Holodiastolic flow reversal (HDR) in the descending aorta (DA) may indicate hemodynamically significant aortic regurgitation (AR). However, the optimal definition and quantification of flow reversal on cardiac magnetic resonance (CMR) is unknown. Methods: We studied 346 chronic AR patients with regurgitant volume (RegVol) ≥30 mL or regurgitant fraction (RegF) ≥30%. The presence of HDR and quantitation of reverse volume in the DA (DA-RVol) was performed by a blinded observer. The threshold for DA-RVol that identified ≥ moderate-severe AR (RegVol ≥45 mL and RegF ≥40%) was established by derivation (50% random sample), validation (50% remaining sample), and ROC curve analysis. Multivariable logistic regression models adjusting for age, gender, NYHA Class, and indexed left ventricular end-diastolic volume were performed to compare HDR and DA-RVol. Results: The median age was 61 (IQR 50-70) years, 79.2% men, and 30.3% with bicuspid aortic valve. The median RegF was 37% (IQR 32-44) and DA-RVol was 12 mL (IQR 5-27). HDR was observed in 150 (43.2%), with 63% sensitivity and 77% specificity for detecting ≥ moderate-severe AR. The threshold of DA-RVol which identified ≥ moderate-severe AR was 17 mL (AUC 0.82, sensitivity 68%, and specificity 87%). The ROC curve analysis revealed a higher AUC for DA-RVol ≥17 mL relative to HDR (0.78 vs 0.70, P &lt;0.001) for predicting ≥ moderate-severe AR. On multivariable analysis models, DA-RVol ≥17 mL was superior to HDR (AUC 0.83 vs 0.80, P =0.008). Conclusion: Quantitation of flow reversal in the descending aorta is a more reliable method to identify hemodynamically significant AR compared to simple presence of holodiastolic flow reversal.

Economic burden of premature deaths attributable to different heatwaves in China: A multi-site study, 2014–2019

It has been well documented that heatwaves are linked to elevated mortality and morbidity. However, the selection of optimal heatwave definitions for subsequent risk assessment has been inconsistent and there is no full picture of the effects of heatwaves with different intensities on economic losses due to mortality, which can provide important insights for public health considerations. Hence, we used a two-stage time series analysis, combined with values of statistical life (VSL) based on the value of a statistical life year to assess the economic burden of deaths associated with heatwaves of different intensities and durations and to identify the vulnerable populations and regions. We further conducted stratified analyses by age, sex, and region. We found 2.9% (95%CI: 0.0%, 6.5%)‒20.0% (95%CI: 2.9%, 34.2%) of VSL were attributable to heatwaves, corresponding to attributable economic losses (AELs) of 2.20 (95%CI: 0.32, 3.77)‒4.77 (95%CI: 1.53, 7.63) billion CNY. The economic burden of death was most sensitive to heatwave H99P_2D (99th percentile, at last 2 consecutive days), while H97·5P_2D (97.5th percentile, at last 2 consecutive days) caused the highest attributable economic losses. Females and elderly people aged ≥ 65 years were more sensitive. The AELs in the temperate zone and northern regions were larger than those in subtropical zone and southern regions during relatively low-intensity heatwaves, respectively. By contrast, the AELs in subtropical zone and southern regions were relatively higher than those in temperate zone and northern regions during relatively high-intensity heatwaves, respectively. The AELs were larger in urban areas than in rural areas. Tailored intervention strategies, primarily focusing on vulnerable populations and regions, should be formulated to reduce the economic loss due to heatwaves in the context of climate change.

Definitions, End Points, and Clinical Trial Designs for Bladder Cancer: Recommendations From the Society for Immunotherapy of Cancer and the International Bladder Cancer Group.

There is a significant unmet need for new and efficacious therapies in urothelial cancer (UC). To provide recommendations on appropriate clinical trial designs across disease settings in UC, the Society for Immunotherapy of Cancer (SITC) and the International Bladder Cancer Group (IBCG) convened a multidisciplinary, international consensus panel. Through open communication and scientific debate in small- and whole-group settings, surveying, and responses to clinical questionnaires, the consensus panel developed recommendations on optimal definitions of the disease state, end points, trial design, evaluations, sample size calculations, and pathology considerations for definitive studies in low- and intermediate-risk nonmuscle-invasive bladder cancer (NMIBC), high-risk NMIBC, muscle-invasive bladder cancer in the neoadjuvant and adjuvant settings, and metastatic UC. The expert panel also solicited input on the recommendations through presentations and public discussion during an open session at the 2021 Bladder Cancer Advocacy Network (BCAN) Think Tank (held virtually). The consensus panel developed a set of stage-specific bladder cancer clinical trial design recommendations, which are summarized in the table that accompanies this text. These recommendations developed by the SITC-IBCG Bladder Cancer Clinical Trial Design consensus panel will encourage uniformity among studies and facilitate drug development in this disease.

What MRI Sequences are Necessary for Automated Neural Network-Based Metastasis Segmentation ― An Ablation Study

Brain metastasis (BM) delineation is a time-consuming process in both daily clinical practice and research. Automated BM segmentation algorithms can be used to assist in this task. Most approaches to brain tumor segmentation, such as algorithms trained on the BraTS challenge, use four magnetic resonance imaging (MRI) sequences as input, making them susceptible to missing or corrupted sequences and increase the number of sequences necessary for MRI RT planning. The goal of this project is to compare neural networks with different combinations of input sequences for the segmentation of the contrast-enhancing metastasis and the surrounding FLAIR hyperintense edema. All models were tested in a multicenter international external test cohort. This allows us to determine which MRI sequences are needed for effective automated segmentations. In total, we had T1-weighted sequences without (T1) and with contrast enhancement (T1-CE), T2-weighted sequences (T2), and T2 fluid-attenuated inversion recovery (FLAIR) sequences from 339 patients with at least one brain metastasis from seven centers available. Preprocessing yielded co-registered, skull-stripped sequences with an isotropic resolution of 1 millimeter. The contrast-enhancing metastasis as well as the surrounding FLAIR hyperintense edema were manually segmented to create reference labels. A baseline 3D U-Net with all four sequences as well as six additional U-Nets with different clinically plausible combinations (T1-CE; T1; FLAIR; T1-CE+FLAIR; T1-CE+T1+FLAIR; T1-CE+T1) of input sequences were trained on a cohort of 239 patients from two centers and subsequently tested on an external cohort of 100 patients from the remaining five centers. All models that included T1-CE in their selected sequences showed similar performance for metastasis segmentation with a median Dice similarity coefficient (DSC) of 0.93-0.96. T1-CE alone likewise achieved a performance of 0.96 (IQR 0.93-0.97). The model trained with only FLAIR performed worse (DSC = 0.73, IQR 0.54-0.84). For edema segmentation, models that included both T1-CE and FLAIR performed best (median DSC = 0.93), while the remaining four models without simultaneous inclusion of these two sequences (T1-CE; T1; FLAIR; T1-CE+T1) reached a median DSC of 0.81-0.89. Automatic segmentation of brain metastases with less than four input sequences is feasible with minimal or no loss of quality. A T1-CE-only protocol suffices for metastasis segmentation. In contrast, for edema segmentation, the combination of T1-CE and FLAIR seems to be important. Missing either T1-CE or FLAIR decreases performance. These findings may improve future imaging routines by omitting unnecessary sequences, thus speeding up procedures in daily clinical practice while allowing for optimal neural network-based target definitions.

Local Time-to-Event Endpoint Under-Reporting and Variability in Pancreatic Cancer Trials Involving Radiotherapy

The role of radiotherapy (RT) for pancreatic adenocarcinoma (PDAC) remains controversial, with recent studies showing conflicting results. Importantly, endpoints used to evaluate efficacy in recent RT trials for PDAC have been highly variable. As variability in time-to-event (TTE) endpoint definitions is demonstrated to influence outcomes in other cancers, it is critical that radiation oncologists develop consensus around optimal endpoint definitions to use in future PDAC trial design. Thus, we conducted a systematic review of PDAC trials involving RT to characterize the frequency and variability in local TTE endpoint reporting. An electronic database search was conducted of PubMed, EMBASE, and Cochrane Library to identify phase 2 and 3 clinical trials published from 2010-2022 of localized PDAC involving RT that reported any TTE endpoint (e.g., local control). After excluding duplicates, two independent reviewers screened full-text manuscripts for inclusion. Trial characteristics and local TTE endpoints/definitions were tabulated. Three hundred twenty references were screened and 79 trials were included, of which 73 (92%) were phase 2 and 26 (33%) were randomized. Twenty (25%) trials reported a local TTE endpoint; these were local control (LC; N = 6), local progression-free survival (LPFS; N = 4), freedom from local progression (N = 6), locoregional progression-free interval (N = 1), cumulative incidence of local recurrence (N = 1), time to failure of sustained LC (N = 1), and local disease-free survival (N = 1). LC (N = 6) had 5 unique definitions and was undefined once; 1 definition included death as an event. LPFS (N = 4) had 3 definitions; 2 did not consider death an event. Among trials with local TTE endpoints, 9 trials specified the definition of a local recurrence/progression. Four trials defined local recurrence based on RT volumes; one counted clinical evidence of recurrence (e.g., tumor bleed); and one counted a rise in tumor markers without evidence of distant metastases. The index time ("time-zero") was defined for local TTE endpoints in 10 trials, including start of RT (N = 4) or chemo (N = 1), end of RT (N = 1), diagnosis (N = 1), enrollment (N = 1), and time of surgery (N = 1). Few pancreatic cancer trials involving RT report local TTE endpoints, with significant heterogeneity in endpoints used and their definitions. Development of consensus endpoint definitions will be critical for future PDAC trial design.

Prognostic and Pharmacotypic Heterogeneity of Hyperdiploidy in Childhood ALL.

High hyperdiploidy, the largest and favorable subtype of childhood ALL, exhibits significant biological and prognostic heterogeneity. However, factors contributing to the varied treatment response and the optimal definition of hyperdiploidy remain uncertain. We analyzed outcomes of patients treated on two consecutive frontline ALL protocols, using six different definitions of hyperdiploidy: chromosome number 51-67 (Chr51-67); DNA index (DI; DI1.16-1.6); United Kingdom ALL study group low-risk hyperdiploid, either trisomy of chromosomes 17 and 18 or +17 or +18 in the absence of +5 and +20; single trisomy of chromosome 18; double trisomy of chromosomes 4 and 10; and triple trisomy (TT) of chromosomes 4, 10, and 17. Additionally, we characterized ALL ex vivo pharmacotypes across eight main cytotoxic drugs. Among 1,096 patients analyzed, 915 had B-ALL and 634 had pharmacotyping performed. In univariate analysis, TT emerged as the most favorable criterion for event-free survival (EFS; 10-year EFS, 97.3% v 86.8%; P = .0003) and cumulative incidence of relapse (CIR; 10-year CIR, 1.4% v 8.8%; P = .002) compared with the remaining B-ALL. In multivariable analysis, accounting for patient numbers using the akaike information criterion (AIC), DI1.16-1.6 was the most favorable criterion, exhibiting the best AIC for both EFS (hazard ratio [HR], 0.45; 95% CI, 0.23 to 0.88) and CIR (HR, 0.45; 95% CI, 0.21 to 0.99). Hyperdiploidy and subgroups with favorable prognoses exhibited notable sensitivities to asparaginase and mercaptopurine. Specifically, asparaginase sensitivity was associated with trisomy of chromosomes 16 and 17, whereas mercaptopurine sensitivity was linked to gains of chromosomes 14 and 17. Among different definitions of hyperdiploid ALL, DI is optimal based on independent prognostic impact and also the large proportion of low-risk patients identified. Hyperdiploid ALL exhibited particular sensitivities to asparaginase and mercaptopurine, with chromosome-specific associations.

Lessons learned from the first national population-based genetic carrier-screening program for Duchenne muscular dystrophy

PurposeTo summarize the results of first year implementation of pan-ethnic screening testing for Duchenne muscular dystrophy (DMD) and present the ensuing challenges. MethodsData acquisition for this study was performed by retrospective search of Ministry of Health registry for reports of all laboratories performing genetic screening tests. DMD testing was performed by multiplex ligation-dependent probe amplification technology. In case of single-exon deletion, sequencing of the specific exon was performed to rule out underlying single-nucleotide variant. ResultsOf overall 85,737 DMD tests, 82 clinically significant findings were noted (0.095%, or 1:1,046 women). In addition, 80 findings with uncertain clinical significance were detected (0.093%, or 1:1072), as well as 373 cases (0.4%, or 1:230) of single-exon deletions subsequently identified as false positives because of underlying single-nucleotide variant, mostly variants in exon 8 in North African Jewish population, and in exon 48 in Arab Muslim population. ConclusionInterpretation of population-based DMD carrier screening is complex, occasionally requiring additional genetic testing methods and ethical considerations. Multicenter data registry, including ethnic origin and familial segregation in selected cases, is crucial for optimal definition of the results during genetic counseling and informed decisions regarding prenatal testing.

Identifying core MRI sequences for reliable automatic brain metastasis segmentation

BackgroundMany automatic approaches to brain tumor segmentation employ multiple magnetic resonance imaging (MRI) sequences. The goal of this project was to compare different combinations of input sequences to determine which MRI sequences are needed for effective automated brain metastasis (BM) segmentation. MethodsWe analyzed preoperative imaging (T1-weighted sequence ± contrast-enhancement (T1/T1-CE), T2-weighted sequence (T2), and T2 fluid-attenuated inversion recovery (T2-FLAIR) sequence) from 339 patients with BMs from seven centers. A baseline 3D U-Net with all four sequences and six U-Nets with plausible sequence combinations (T1-CE, T1, T2-FLAIR, T1-CE + T2-FLAIR, T1-CE + T1 + T2-FLAIR, T1-CE + T1) were trained on 239 patients from two centers and subsequently tested on an external cohort of 100 patients from five centers. ResultsThe model based on T1-CE alone achieved the best segmentation performance for BM segmentation with a median Dice similarity coefficient (DSC) of 0.96. Models trained without T1-CE performed worse (T1-only: DSC = 0.70 and T2-FLAIR-only: DSC = 0.73). For edema segmentation, models that included both T1-CE and T2-FLAIR performed best (DSC = 0.93), while the remaining four models without simultaneous inclusion of these both sequences reached a median DSC of 0.81–0.89. ConclusionsA T1-CE-only protocol suffices for the segmentation of BMs. The combination of T1-CE and T2-FLAIR is important for edema segmentation. Missing either T1-CE or T2-FLAIR decreases performance. These findings may improve imaging routines by omitting unnecessary sequences, thus allowing for faster procedures in daily clinical practice while enabling optimal neural network-based target definitions.

Prevalence of dilated mid-ascending aorta in individuals 15 years and older: In search of optimal diagnostic criteria and their effect on the burden of disease.

Controversy regarding the definition of the upper limit of normal (ULN) for dilated mid-ascending aorta (mAA) stems from variation in criteria, based on several small-sized studies with small datasets of normal subjects (DONS). The present study was carried out to demonstrate this variation in the prevalence of mAA dilation and to identify the optimal definition by creating the largest DONS. Echocardiographic studies of patients ≥ 15 years of age performed at a large tertiary care center over 4 years (n = 49,330) were retrospectively evaluated. The leading-edge-to-leading-edge technique was used to measure the mAA in diastole. The largest-to-date DONS (n = 2334) was created, including those who were normal on medical record review, did not have any of the 28 causes of dilated aorta, and had normal echocardiograms. Because age had the strongest correlation with mAA (multivariate adjusted R2 = 0.26), as compared with sex, height, and weight, we created a new ULN based on the DONS with narrow age stratification (10-year intervals). The prevalence of dilated mAA varied between 17% and 23% when absolute criteria were used with sex stratification, and it varied between 6% and 11% when relative criteria (relative to age, body surface area, and sex) were used. Based on new criteria from the DONS, it was 7.6%, with a ULN of 3.07-3.64 cm in women and 3.3-3.91 cm in men. These data demonstrate the undesirable variation in the prevalence of dilated mAA based on prior criteria and propose a new ULN for dilated mAA.

Optimal Definition of Pancreaticoduodenectomy in the International Classification of Diseases, 10th Revision, Procedure Coding System.

The implementation of the International Classification of Diseases, 10th Revision, Procedure Coding System (ICD-10-PCS) has created difficulty in identifying certain procedures, including pancreaticoduodenectomy. We sought to evaluate which combinations of ICD-10-PCS codes best identify pancreaticoduodenectomy. We used 2017-2018 Medicare data to identify acute care hospitalization claims of beneficiaries with both ICD-10-PCS and Current Procedural Terminology (CPT) codes available. We developed 12 candidate ICD-10-PCS definitions of pancreaticoduodenectomy and evaluated their test characteristics in identifying hospitalizations involving CPT codes 48150, 48152, 48153, 48154, or 48155 as the criterion standard. We selected one candidate definition with the best balance of test characteristics, then performed decision tree analysis and evaluated the conditional marginal sensitivity and positive predictive value of each individual code to understand which were most informative. Among 964,613 hospitalization claims from 4648 hospitals, 385 claims from 217 hospitals involved a CPT code for pancreaticoduodenectomy. The ICD-10-PCS definition with the best balance had a sensitivity of 92.2% (95% CI: 89.2%-94.4%), specificity of 99.9977% (95% CI: 99.9961%-99.9984%), positive predictive value of 93.7% (95% CI: 90.3%-95.9%), and negative predictive value of 99.9969% (95% CI: 99.9955%-99.9978%). The most informative procedure codes involved open nondiagnostic excision or resection of the duodenum (0DB90ZZ and 0DT90ZZ) and pancreas (0FBG0ZZ and 0FTG0ZZ). An ICD-10-PCS definition of pancreaticoduodenectomy using codes for (1) open or percutaneous endoscopic excision or resection of the pancreas and (2) similar codes for the duodenum, consistent with coding guidelines, has satisfactory test characteristics. We suggest researchers consider such characteristics in defining pancreaticoduodenectomy using ICD-10-PCS.

Discharge criteria for inpatient paediatric asthma: a narrative systematic review

IntroductionCriteria-led discharges (CLDs) and inpatient care pathways (ICPs) aim to standardise care and improve efficiency by allowing patients to be discharged on fulfilment of discharge criteria. This narrative systematic review...

Defining Small Intestinal Bacterial Overgrowth by Culture and High Throughput Sequencing

Despite accelerated research in small intestinal bacterial overgrowth (SIBO), questions remain regarding optimal diagnostic approaches and definitions. Here, we aim to define SIBO using small bowel culture and sequencing, identifying specific contributory microbes, in the context of gastrointestinal symptoms. Subjects undergoing esophagogastroduodenoscopy (without colonoscopy) were recruited and completed symptom severity questionnaires. Duodenal aspirates were plated on MacConkey and blood agar. Aspirate DNA was analyzed by 16S ribosomal RNA and shotgun sequencing. Microbial network connectivity for different SIBO thresholds and predicted microbial metabolic functions were also assessed. A total of 385 subjects with <103 colony forming units (CFU)/mL on MacConkey agar and 98 subjects with ≥103 CFU/mL, including ≥103 to <105 CFU/mL (N= 66) and ≥105 CFU/mL (N= 32), were identified. Duodenal microbial α-diversity progressively decreased, and relative abundance of Escherichia/Shigella and Klebsiella increased, in subjects with ≥103 to <105 CFU/mL and ≥105 CFU/mL. Microbial network connectivity also progressively decreased in these subjects, driven by the increased relative abundance of Escherichia (P < .0001) and Klebsiella (P= .0018). Microbial metabolic pathways for carbohydrate fermentation, hydrogen production, and hydrogen sulfide production were enhanced in subjects with ≥103 CFU/mL and correlated with symptoms. Shotgun sequencing (N= 38) identified 2 main Escherichia coli strains and 2 Klebsiella species representing 40.24% of all duodenal bacteria in subjects with ≥103 CFU/mL. Our findings confirm ≥103 CFU/mL is the optimal SIBO threshold, associated with gastrointestinal symptoms, significantly decreased microbial diversity, and network disruption. Microbial hydrogen- and hydrogen sulfide-related pathways were enhanced in SIBO subjects, supporting past studies. Remarkably few specific E coli and Klebsiella strains/species appear to dominate the microbiome in SIBO, and correlate with abdominal pain, diarrhea, and bloating severities.