3-tier System Research Articles

Innovative Strategies and Insurance Consequences for Implementing Universal Health Insurance in the United States.

Universal Health Insurance does not exist in the United States for two reasons: (1) there is a general unwillingness to dismantle the historically grown framework of the world's most complex mix of public and private sector health coverage and (2) mere cost considerations. The first concern can be abated by establishing a Universal Health Insurance system which retains many or most of the historically grown infrastructure. Cost containment of such a reform is addressed herein in that the two proposed pathways comprise either (1) a leveled solution through Medicare-expansion for the uninsured only or (2) a more complex solution through a national, 2-tier healthcare system for all Americans. Both pathways are based on solid financing without major tax increases by using existing and/or yet untapped funding sources. The insurance consequences for both options are assessable. They are minor for the Medicare-expansion and more wide-ranging, yet also achievable, for a national, 2-tier healthcare system. Universal Health Insurance must no longer be an illusion that continues to haunt our society in the 21st century.

Re-Categorization and Risk of Malignancy of Atypical Effusions According to the International System for Reporting Serous Fluid Cytopathology (TIS): An Institutional Experience.

Serous effusion fluids serve as crucial cytological materials in diagnosing the underlying causes of fluid accumulation in various body cavities. The International System for Reporting Serous Fluid Cytopathology (TIS) outlined atypia of undetermined significance (AUS) and suspicious for malignancy (SFM) as two intermediate categories for atypical fluids. In our study, cases diagnosed as "atypical" by an experienced cytopathologist in the Hacettepe University Department of Pathology, between 2014 and 2023, were re-categorized according to TIS. The risk of malignancy (ROM) for AUS and SFM categories was calculated. Additionally, cases were re-evaluated according to the 5-tier categorical system by two observers with different level of experience. A total of 3501 effusion fluids were included in the study, evaluated between 2014 and 2023. 50.7% of the cases were male, and 49.3% were female. 55.2% of the cases were pleural fluid, 41.5% were peritoneal fluid, and 3.3% were pericardial fluid. Two hundred sixty five cases (7.6%) were non-diagnostic, 2160 (61.7%) were negative for malignancy, 111 (3.2%) were AUS, 83 (2.4%) were SFM, and 883 (25.2%) were malignant (M). ROM calculated 27% for AUS, 49% for SFM 49%. The interobserver agreement for AUS was 46% with kappa value of 0.162, and 42% for SFM with kappa value of 0.188. The differentiation of atypical cases into AUS and SFM is effective in determining the ROM. The interobserver agreement tends to be lower in intermediate categories compared to others, emphasizing the potential significance of clinical expertise in diagnosis.

Real-World evaluation of an AI triaging system for chest X-rays: A prospective clinical study

Chest X-rays (CXRs) are crucial for diagnosing and managing lung conditions. While CXR is a common and cost-effective diagnostic tool, interpreting the high volume of CXRs is challenging due to workforce limitations. Artificial intelligence (AI) offers promise in enhancing efficiency and accuracy. However, real-world applicability and generalizability across diverse patient cohorts remain areas of concerns. In our study, the LUNIT INSIGHT CXR Triage software was evaluated in a diverse patient cohort. Forty-three radiologists, blinded to AI results, assessed CXRs categorized into normal, non-urgent, and urgent using a 3-tier classification system. Performance metrics and turnaround times were analyzed.The AI system demonstrated sensitivity of 89% for normal CXRs, specificity of 93%, PPV of 83%, and NPV of 95%, with an F1 score of 0.86 and an AUC of 0.91. For non-urgent CXRs, sensitivity and specificity were 93% and 91%, with PPV and NPV at 94% and 89%, respectively, and an F1 score of 0.94 and an AUC of 0.92. In the urgent category, sensitivity was 82%, specificity 99%, PPV 90%, and NPV 98%. Subgroup analysis revealed consistently high accuracy across various age groups (Young, Adult, Senior), genders, and ethnicities (Chinese, Malay, Indian, Others), with sensitivity, specificity, and AUC consistently above 84%. The AI system also significantly reduced turnaround times across all subgroups, indicating its robust performance and generalizability in diverse healthcare settings.

The impact of Substantial LYMphovascular space invasion on sentinel lymph nodes status and recurrence in Endometrial Cancer patients: SLYM-EC a multicenter retrospective study

IntroductionTo evaluate the prognostic impact of substantial lymph vascular space invasion (LVSI) on the sentinel lymph node involvement and recurrence rate of patients with apparent uterine-confined endometrial cancer. Materials and methodsWe enrolled consecutive patients with apparent confined endometrial cancer who underwent surgical staging with sentinel node mapping from 14 European reference centers. LVSI was analyzed semi-quantitatively, according to a 3-tiered scoring system classified as absent, focal, and substantial. ResultsAmong 2352 eligible patients, 1980 were included in the analysis. Upon final pathology 226 patients (11.4 %) had SLNs involvement. LVSI was diagnosed focal in 152 patients (7.7 %), whereas 357 patients (18.0 %) showed substantial LVSI. Focal or substantial LVSI rate were significantly higher in patients with positive SLNs when compared to patients without SLNs involvement (p < 0.0001). On overall patient-based analysis, the sensitivity, specificity, positive predictive value, and negative predictive value of LVSI for sentinel lymph node metastases were 73 %, 80 %, 32 %, and 96 %, respectively. The 3-year multivariate analysis of recurrence-free survival showed that only the presence of substantial LVSI, and grade 3 disease were associated with relapse. Neither positive sentinel lymph node, deep myometrial infiltration, nor age at surgery were statistically significant. ConclusionsIn patients having undergone sentinel node biopsy, positive LVSI demonstrated moderate sensitivity and reasonable specificity in detecting SLN involvement. LVSI positivity does not correlate with nodal involvement. The presence of substantial LVSI remains a strong independent risk factor for recurrence, indicating a role for potential hematogenous dissemination in patients with early-stage disease.

Optimal Pediatric Outpatient Antibiotic Prescribing

In the US, 50% of all pediatric outpatient antibiotics prescribed are unnecessary or inappropriate. Less is known about the appropriateness of pediatric outpatient antibiotic prescribing. To identify the overall percentage of outpatient antibiotic prescriptions that are optimal according to guideline recommendations for first-line antibiotic choice and duration. This cross-sectional study obtained data on any clinical encounter for a patient younger than 20 years with at least 1 outpatient oral antibiotic, intramuscular ceftriaxone, or penicillin prescription filled in the state of Tennessee from January 1 to December 31, 2022, from IQVIA's Longitudinal Prescription Claims and Medical Claims databases. Each clinical encounter was assigned a single diagnosis corresponding to the lowest applicable tier in a 3-tier antibiotic tier system. Antibiotics prescribed for tier 1 (nearly always required) or tier 2 (sometimes required) diagnoses were compared with published national guidelines. Antibiotics prescribed for tier 3 (rarely ever required) diagnoses were considered to be suboptimal for both choice and duration. Primary outcome was the percentage of optimal antibiotic prescriptions consistent with guideline recommendations for first-line antibiotic choice and duration. Secondary outcomes were the associations of optimal prescribing by diagnosis, suboptimal antibiotic choice, and patient- and clinician-level factors (ie, age and Social Vulnerability Index) with optimal antibiotic choice, which were measured by odds ratios (ORs) and 95% CIs calculated using a multivariable logistic regression model. A total of 506 633 antibiotics were prescribed in 488 818 clinical encounters (for 247 843 females [50.7%]; mean [SD] age, 8.36 [5.5] years). Of these antibiotics, 21 055 (4.2%) were for tier 1 diagnoses, 288 044 (56.9%) for tier 2 diagnoses, and 197 660 (39.0%) for tier 3 diagnoses. Additionally, 194 906 antibiotics (38.5%) were optimal for antibiotic choice, 259 786 (51.3%) for duration, and 159 050 (31.4%) for both choice and duration. Acute otitis media (AOM) and pharyngitis were the most common indications, with 85 635 of 127 312 (67.3%) clinical encounters for AOM and 42 969 of 76 865 (55.9%) clinical encounters for pharyngitis being optimal for antibiotic choice. Only 257 of 4472 (5.7%) antibiotics prescribed for community-acquired pneumonia had a 5-day duration. Optimal antibiotic choice was more likely in patients who were younger (OR, 0.98; 95% CI, 0.98-0.98) and were less socially vulnerable (OR, 0.84; 95% CI, 0.82-0.86). This cross-sectional study found that less than one-third of antibiotics prescribed to pediatric outpatients in Tennessee were optimal for choice and duration. Four stewardship interventions may be targeted: (1) reduce the number of prescriptions for tier 3 diagnoses, (2) increase optimal prescribing for AOM and pharyngitis, (3) provide clinician education on shorter antibiotic treatment courses for community-acquired pneumonia, and (4) promote optimal antibiotic prescribing in resource-limited settings.

Improved Risk Prediction in Human Papillomavirus-Associated Endocervical Adenocarcinoma Through Assessment of Binary Silva Pattern-based Classification: An International Multicenter Retrospective Observational Study Led by the International Society of Gynecological Pathologists (ISGyP).

Endocervical adenocarcinomas (EACs) are a group of malignant neoplasms associated with diverse pathogenesis, morphology, and clinical behavior. As a component of the International Society of Gynecological Pathologists International Endocervical Adenocarcinoma Project, a large international retrospective cohort of EACs was generated in an effort to study potential clinicopathological features with prognostic significance that may guide treatment in these patients. In this study, we endeavored to develop a robust human papillomavirus (HPV)-associated EAC prognostic model for surgically treated International Federation of Gynecology and Obstetrics (FIGO) stage IA2 to IB3 adenocarcinomas incorporating patient age, lymphovascular space invasion (LVSI) status, FIGO stage, and pattern of invasion according to the Silva system (traditionally a 3-tier system). Recently, a 2-tier/binary Silva pattern of invasion system has been proposed whereby adenocarcinomas are classified into low-risk (pattern A/pattern B without LVSI) and high-risk (pattern B with LVSI/pattern C) categories. Our cohort comprised 792 patients with HPV-associated EAC. Multivariate analysis showed that a binary Silva pattern of invasion classification was associated with recurrence-free and disease-specific survival (P < 0.05) whereas FIGO 2018 stage I substages were not. Evaluation of the current 3-tiered system showed that disease-specific survival for those patients with pattern B tumors did not significantly differ from that for those patients with pattern C tumors, in contrast to that for those patients with pattern A tumors. These findings underscore the need for prospective studies to further investigate the prognostic significance of stage I HPV-associated EAC substaging and the inclusion of the binary Silva pattern of invasion classification (which includes LVSI status) as a component of treatment recommendations.

How Integrating the 5 Pillars of Community Practice Can Transform Physical Therapist Education and Reduce Health Disparities.

Patient history assists clinicians in determining the most appropriate tests to identify the symptoms' source and select appropriate interventions. Therefore, a subjective history is an essential component of patient management. When physical therapist practitioners transition into academia, they must understand how the history of the education system may affect learners. Health disparities are related to the lack of workforce diversity and skills in cultural responsiveness, and the education system is critical in addressing the impact of future providers on health disparities. Developing a doctor of physical therapy program to address health disparities requires an analysis of the historical context of the US educational and health care systems, along with traditional components of physical therapist education. This country's education system was built upon a 2-tiered system, where minoritized individuals struggled to overcome barriers imposed by legislation and societal beliefs. Jim Crow laws continued this unequal access to education, and the recent Supreme Court ruling to deny race-based affirmative action continues these inequities. This historical context informed the construction of the College of Saint Mary Doctor of Physical Therapy Program. The program's mission led to using less traditional educational approaches; thus, the pillars of practice took form. The 5 pillars evolved to include social determinants, inclusive faculty and student recruitment and retention practices, equitable grading, culturally responsive pedagogy, and community development. The purpose of this paper is to present a historical overview of the US education system and its influence on physical therapist education. Furthermore, it will illustrate how this historical context inspired the 5 Pillars of Community Practice from College of Saint Mary and discuss the challenges and interventions related to these pillars. There are tremendous disparities in educational outcomes and patient services in the United States. Disparities are most significant in those with historically marginalized identities. If those disparities are to improve, a change is required in the people providing care to patients. The best way to accomplish this is by transforming how future providers are educated.

Stanniocalcin-2 expression in glioblastoma - A novel prognostic biomarker: An observational study.

The objective of this study was to assess the prognostic relevance of Stanniocalcin-2 (STC2) expression, as determined via immunohistochemistry in tumor tissue, in a cohort of 83 patients diagnosed with glioblastoma who underwent maximal safe surgical resection followed by radiotherapy concurrent with adjuvant temozolomide. STC2 expression levels were categorized using a 3-tiered semiquantitative system: negative expression (level 0-), low expression (level 1+), and high expression (levels 2 + and 3+). Patients were categorized into 2 distinct groups according to their STC2 expression levels: negative STC2 (-/+) and positive STC2 (++/+++). The primary outcome measure was the relationship between STC2 expression and progression-free survival (PFS), with overall survival (OS) serving as the secondary endpoint. Kaplan-Meier survival analysis confirmed that patients exhibiting high STC2 expression had significantly shorter OS (8 vs 20 months, P < .001) and PFS (6 vs 18 months, P < .001) than those with low or negative STC2 expression. Multivariate analysis revealed that STC2 expression was an independent prognostic factor for both OS (hazard ratio: 0.4; 95% confidence interval: 0.2-0.8; P < .05) and PFS (hazard ratio: 0.3; 95% confidence interval: 0.2-0.4; P < .05) in patients with glioblastoma. Furthermore, elevated STC2 expression in GBM was correlated with several established aggressive clinicopathological characteristics, including advanced age (≥65 years), low ECOG PS (≥2), and isocitrate dehydrogenase mutation negativity. These findings underscore that heightened STC2 expression within the tumor tissue of GBM patients functions as an adverse prognostic marker, correlating with an elevated risk of progression and reduced OS. Therapeutic interventions targeting the AKT-mTOR, ERK1-2, and mitogen-activated protein kinase pathways as well as immune checkpoint inhibitors and vascular endothelial growth factor blockade, as well as potential forthcoming antibody-drug conjugates targeting the STC2 molecule, have the potential to broaden the scope of combined treatment strategies.

P-322 Development of a CD138-based histopathological scoring system to diagnose chronic endometritis

Abstract Study question Does a standardized histopathological classification system lead to a robust interobserver agreement to diagnose chronic endometritis (CE) and can an accurate computation algorithm be developed? Summary answer The proposed scoring system has a particularly good to excellent interobserver agreement among pathologists. A machine-learning algorithm outperformed pathologists in the clinically most relevant 2-tier-system. What is known already Plasma cell (PC) presence in the stromal endometrium has been proposed as a marker for CE, yet no standardized classification system that considers the amount or distribution of PCs exists. Also, interobserver agreement has been insufficiently reported in the previous publications on the topic. Without a robust histopathological score, the potential clinical impact of CE on ART treatment outcomes cannot be investigated. This issue is strongly reflected in the heterogeneity of the current diagnostic and therapeutic approaches, specifically for patients experiencing repeated implantation failure (RIF) or recurrent pregnancy loss (RPL). Study design, size, duration A 5-tier classification system based on CD138-positive PCs (Roche B-A38/automated Ventana system) was established: class0 (no PCs), classIPC (isolated PCs), class1 (³1 cluster of 5-19 PCs/0.25mm2), class2 (³1 cluster of 20-49 PCs/0.25mm2), class3 (³1 cluster of 50 or more PCs/0.25mm2). A test set of 78 endometrial biopsies (collected over two years) was selected by a certified pathologist who sorted &amp;gt;1000 biopsies to ensure the full spectrum of PC counts/distribution was accounted for. Participants/materials, setting, methods The 3DHistech-platform digitized the slides (pixel size 0.2738x0.2738mm) and a scoring session was set up in the Pathomation software suite. Six pathologists scored independently after training. Overall agreement was expressed by Fleiss’ Kappa values. Pairwise interobserver agreement was calculated using Cohen’s Kappa statistics. A supervised machine-learning algorithm was developed in QuPath(V0.4.2) and considered a seventh observer in the interobserver agreement calculations. Main results and the role of chance The CD138-based semiquantitative scoring system showed particularly good to excellent interobserver agreement among all observers. Overall agreement values were 0.722 for the 5-tier system and 0.858 for the 2-tier system (0+IPC versus 1 + 2+3, which was considered the clinically most relevant classification, i.e. CE absent versus diagnosed). Pairwise interobserver agreement was 0.871-0.951. Intra-class correlations varied from 0.727 to 0.839 in the 5-tier system and 0.893 to 0.965 in the 2-tier system. All findings were statistically significant (p &amp;lt; 0.001). The supervised machine-learning algorithm was able to compete with human pathologist observers and outperformed them in the 2-tier system. The proposed classification system provides a framework for assessing the presence and severity of endometrial PC infiltration and can guide further research. Limitations, reasons for caution Inconsistent staining intensity, non-specific epithelial staining and background interference are common problems that might limit interlaboratory use of the algorithm. Furthermore, the algorithm has not yet been associated to patient/clinical parameters. Accurate analysis of an endometrial biopsy might still be insufficient to provide a formal diagnosis of CE. Wider implications of the findings To unravel the association between PCs in endometrial biopsies (as a proxy for the diagnosis of CE) and the reproductive outcomes following ART, a standardized methodology is of crucial importance for future studies. Higher accuracy, efficieny and automation are advantages when using computer-aided diagnostics for CE. Trial registration number BUN 143202042810

MDB-17. A COMPARISON OF MAGNETIC RESONANCE IMAGING AND CEREBROSPINAL FLUID CYTOLOGY FOR DETECTING LEPTOMENINGEAL METASTASIS IN PATIENTS WITH MEDULLOBLASTOMA

Abstract BACKGROUND For medulloblastoma, CSF cytology and MRI together are considered to be superior to either modality alone in identifying leptomeningeal dissemination (LMD). However, MRI has vastly improved since the initial assessment of this approach. METHODS A retrospective medical record review of 130 patients (36.2% female) with medulloblastoma was performed. CSF samples and MR images (6.3% utilized FIESTA) obtained within 1 month of each other from 2000-2023 were analyzed. There were 302 CSF-MRI pairs (range: 1-12 pairs per patient) in total. A 3-tier system (negative, atypical/suspicious, positive) was utilized to account for equivocal findings. RESULTS The mean (SD) age at surgery was 13.2 (13.0) years. Mean (SD) postoperative follow-up time was 7.0 (5.2) years. 71.5% underwent gross or near-total resection, 80.8% received radiotherapy, and 93.1% received chemotherapy. The molecular subtypes were: SHH (24.6%), WNT (4.6%), non-WNT/non-SHH (38.5%), unknown (32.3%). MRI had an 89.8% sensitivity and CSF cytology had a 22.7% sensitivity for detecting LMD that was positive on CSF and/or MRI. MRI was positive in 23.1% of CSF negative cases. CSF was positive in 2.2% of MRI negative cases. For all CSF positive-MRI negative pairs, the CSF samples and MR images were obtained within 10 days of surgery. MRI was positive in 38.9% of CSF atypical cases. CSF was positive in 11.9% of MRI suspicious cases. MRI demonstrated greater or equal ability to CSF in 94.7% of pairs. MRI was more likely to exceed CSF at 3T versus 1.5T (51.3% vs. 27.4%; p&amp;lt;0.01). The overall concordance between CSF cytology and MRI was 61.3%, and this differed by subtype (75.4% SHH vs. 80.0% WNT vs. 52.3% NWNS; p&amp;lt;0.01). CONCLUSIONS Understanding the ability of CSF cytology and MRI to detect LMD is important. While MRI is superior overall, LMD detection varies by MRI Tesla, medulloblastoma subtype, and time since surgery.

The radiomorphological appearance of the invasive margin in pancreatic cancer is associated with tumor budding

PurposePancreatic cancer (PDAC) is characterized by infiltrative, spiculated tumor growth into the surrounding non-neoplastic tissue. Clinically, its diagnosis is often established by magnetic resonance imaging (MRI). At the invasive margin, tumor buds can be detected by histology, an established marker associated with poor prognosis in different types of tumors.MethodsWe analyzed PDAC by determining the degree of tumor spiculation on T2-weighted MRI using a 3-tier grading system. The grade of spiculation was correlated with the density of tumor buds quantified in histological sections of the respective surgical specimen according to the guidelines of the International Tumor Budding Consensus Conference (n = 28 patients).Results64% of tumors revealed intermediate to high spiculation on MRI. In over 90% of cases, tumor buds were detected. We observed a significant positive rank correlation between the grade of radiological tumor spiculation and the histopathological number of tumor buds (rs = 0.745, p < 0.001). The number of tumor buds was not significantly associated with tumor stage, presence of lymph node metastases, or histopathological grading (p ≥ 0.352).ConclusionOur study identifies a readily available radiological marker for non-invasive estimation of tumor budding, as a correlate for infiltrative tumor growth. This finding could help to identify PDAC patients who might benefit from more extensive peripancreatic soft tissue resection during surgery or stratify patients for personalized therapy concepts.

Combined spatial Keratin expression profiles at the invasive front represent a prognostic classifier for head and neck cancer

Keratin proteins are intermediate filaments that provide mechanical support and guide a plethora of important functions in epithelial cells. Although Keratins can be effectively used to characterize and differentiate cell lineages in many epithelia, it is still unclear if combinations of Keratin types and their spatial expression patterns can aid prognostication of head and neck squamous cell carcinoma (HNSCC). Here, we have assessed a panel of Keratin markers in four HPV negative HNSCC patient-derived organoid (PDO) models and their corresponding primary patient tissue to define spatial expression profiles of basal and supra-basal Keratins during invasion in Collagen-I matrices. Based on these profiles we have devised a scoring classification consisting of the following profiles: (i) no expression (Negative), (ii) uniform expression (Homogenous), (iii) heterogeneous expression (Mosaic), (iv) expression in the tumor core (Core), and (v) expression at the invasive front (Edge). Subsequently, this 5-tier system was validated in a well-documented tissue cohort of 157 HNSCC patients. We observe that patients with a Keratin 13 (K13) Edge profile have a significantly better prognosis than patients with K13 Core expression or K13 Negative tumors. Interestingly, we also find that K14 mosaicism strongly correlates with a favorable prognosis. We show that the absence of K13 from the tumor edge, in combination with K14 homogenous expression is a strong biomarker for poor prognosis in HNSCC. In short, our work indicates that defining the spatial expression patterns of basal and supra-basal markers in invasive HNSCC can benefit patient prognostication.

Serum chemistry profiling and prognostication in systemic mastocytosis: a registry-based study of the ECNM and GREM

AbstractCertain laboratory abnormalities correlate with subvariants of systemic mastocytosis (SM) and are often prognostically relevant. To assess the diagnostic and prognostic value of individual serum chemistry parameters in SM, 2607 patients enrolled within the European Competence Network on Mastocytosis and 575 patients enrolled within the German Registry on Eosinophils and Mast Cells were analyzed. For screening and diagnosis of SM, tryptase was identified as the most specific serum parameter. For differentiation between indolent and advanced SM (AdvSM), the following serum parameters were most relevant: tryptase, alkaline phosphatase, β2-microglobulin, lactate dehydrogenase (LDH), albumin, vitamin B12, and C-reactive protein (P < .001). With regard to subvariants of AdvSM, an elevated LDH of ≥260 U/L was associated with multilineage expansion (leukocytosis, r = 0.37, P < .001; monocytosis, r = 0.26, P < .001) and the presence of an associated myeloid neoplasm (P < .001), whereas tryptase levels were highest in mast cell leukemia (MCL) vs non-MCL (308μg/L vs 146μg/L, P = .003). Based on multivariable analysis, the hazard-risk weighted assignment of 1 point to LDH (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.1-4.0; P = .018) and 1.5 points each to β2-microglobulin (HR, 2.7; 95% CI, 1.4-5.4; P = .004) and albumin (HR, 3.3; 95% CI, 1.7-6.5; P = .001) delineated a highly predictive 3-tier risk classification system (0 points, 8.1 years vs 1 point, 2.5 years; ≥1.5 points, 1.7 years; P < .001). Moreover, serum chemistry parameters enabled further stratification of patients classified as having an International Prognostic Scoring System for Mastocytosis–AdvSM1/2 risk score (P = .027). In conclusion, serum chemistry profiling is a crucial tool in the clinical practice supporting diagnosis and prognostication of SM and its subvariants.

The 2-tier grading system identifies canine cutaneous and/or subcutaneous mast cell tumors with aggressive biological behavior regardless of growth model.

Histologic grading of canine cutaneous mast cell tumors (cMCTs) has prognostic and therapeutic implications, yet validation for subcutaneous MCTs (scMCTs) is lacking. For scMCTs with or without dermal invasion, determining their biological behavior remains poorly standardized and sometimes sparks controversy. This prospective study aimed to assess the prognostic utility of the 2-tier histologic grading system in MCTs with different growth models (GMs) and explore the prognostic impact of the GM itself. We assessed 6 histologic GM categories: solely cMCT (C-SC0), cMCT with superficial (C-SC1) or deep subcutaneous (C-SC2) involvement, solely scMCT (SC-C0), and scMCT with deep (SC-C1) or superficial (SC-C2) infiltration of the dermis. Ninety-one MCTs from 76 dogs undergoing excision and regional/sentinel lymphadenectomy were examined. GM classification identified 11 (12%) C-SC0 tumors, 12 (13%) C-SC1, 15 (16%) C-SC2, 21 (23%) SC-C0, 15 (16%) SC-C1, and 17 (19%) SC-C2. Mitotic count, 2-tier grade, nodal involvement, surgical margins, and outcome were stratified according to GM. scMCTs lacking dermal invasion, historically associated with a benign clinical course, had a poor prognosis in 10% of cases. cMCTs exhibiting deep subcutaneous involvement included the largest percentage of high-grade tumors (33%), had the highest occurrence of overt nodal metastases (33%), and had the lowest 1-year survival rate (86%). Histologic grade was confirmed as a relevant prognostic factor, surpassing nodal involvement and histologic margin status. The 2-tier histologic grading enabled the identification of all MCTs with aggressive biological behavior, regardless of their cutaneous or subcutaneous location.

925 Concordance Between CSF Cytology and MR Imaging in the Detection of Leptomeningeal Dissemination in Patients With Medulloblastomas

INTRODUCTION: In patients with medulloblastomas, the combination of CSF cytology and MR imaging is believed to be superior to either tool alone in detecting leptomeningeal dissemination (LMD). However, MRI has drastically improved since the initial assessment of this approach. METHODS: A retrospective review of 117 unique patients with medulloblastomas from a single institution was conducted. CSF samples and MR images obtained within 36 days of each other were included. A 3-tier system (negative, atypical/suspicious, positive) was utilized to account for equivocal findings. A total of 253 CSF-MRI pairs (range: 1-12 pairs per patient) obtained between 2000-2021 were analyzed. RESULTS: The mean (SD) age of this cohort was 14.1 (13.5) years (62.4% were male). Gross total resection with surgery was achieved in 64.5%, 83.7% received radiotherapy, 81.5% received chemotherapy. 16.2% were deceased, with the mean (SD) time till death being 4.6 (4.7) years following the first operation. The molecular subtypes were: SHH (17.0%), WNT (3.6%), non-WNT/non-SHH (46.6%), unknown (32.8%). There was a 60.5% concordance between CSF cytology and MRI, with no significant differences by molecular subtype. In 57.3% of cases, CSF cytology and MRI were both negative. In 1.2% of cases, CSF cytology and MRI were both equivocal. 26.9% of cases were positive on CSF cytology and/or MRI. MRI had an 86.8% sensitivity and CSF cytology had a 20.6% sensitivity for detecting LMD that was positive in CSF, MRI, or both. In 10 cases (4.0%), MRI was negative when CSF was atypical or positive. In 80 cases (31.6%), CSF was negative when MRI was positive or suspicious. In 94.5% of cases, MRI demonstrated greater or equal ability to CSF cytology in detecting LMD. CONCLUSIONS: MRI is superior to CSF cytology in detecting LMD but misses a small percentage of cases.

Development of Cyber Physical System Based Manufacturing System Design

Cyber Physical System (CPS) is Informatics and computer science. Cyber physical manufacturing system is a new research field. In the fields of computer science and manufacturing science and technology Promote the Fourth Industrial Revolution known as Industry 4.0. CPS is generally focused. About the integration of the physical world and cyberspace. It`s the integration of communication, Computational, control, and physical elements. Currently, CPS is Science, government and industry. Systematic literature review on cyber. The physical system of the manufacturing system is not available. The purpose of the chapters in this bookis to gain insight into manufacturing systems and develop cyber-physical systems. Physical systems for intelligent manufacturing. CPS is written using the concept of CPS. A 5-tier architecture system for manufacturing systems. Continuous Key Release. It also describes the technology of cyber physical manufacturing systems. Combined with manufacturing, CPS enables intelligent manufacturing and provides technical support for manufacturing upgrades and conversions. This can be summarized in three aspects: internet-based manufacturing, process intelligence, and product intelligence. Future manufacturing is said to be personalized manufacturing based on cyber physical systems, intelligent manufacturing, digital manufacturing, and network-based manufacturing. CPS continues to transform the manufacturing trends of the industry, creating even more amazing value for future global manufacturing scenarios

Abstract 83: Early Notification Using a Novel Three-Tiered Code Stroke System Reduces Neurointerventional Team Activation Times

Background: Although Code Stroke group page systems are essential to accelerate endovascular therapy (EVT), their design and implementation has not been well-studied. We assessed a novel 3-tiered system crafted to facilitate prompt, stepped activation. Methods: An escalating 3-tiered system was designed to provide salient services with both an a) alert-be ready page, and a b) go-go-go page while minimizing false alarms. Group page levels are: 1) pre-arrival notification of possible stroke by EMS to Neurology; 2) notification of possible large vessel occlusion (LVO) by Neurology (based on cortical signs) to Neurointerventional+/Anesthesia; and 3) post-imaging notification of confirmed LVO and angiosuite decision to all services. System performance was assessed over a 1 year period September 2022 to August 2023. Results: Among 798 Code Strokes, 75 (9.4%) patients received EVT, including 45 who were EMS-arriving. Among the 45 LVO strokes treated with EVT, 26 (58%) had an early notification (EN) Level 2 page pre-imaging and 19 (42%) only a late notification (LN) Level 2 page post-imaging. Patients in the EN vs LN group were nominally older (84 vs 74), more often female (61.5% vs 47.3%), and more severely affected (NIHSS 16 vs 13). Time metrics are presented in Table 1 and Figure 1. The EN group had a near 40 minute decrease in door-to-puncture (DTP) and 50 minute decrease in door-to-reperfusion (DTR) times. Conclusion: All levels of a 3-tier (pre-arrival, pre-imaging, and post-imaging) Code Stroke group page system were activated frequently in EVT patients and pre-imaging early notification of neurointerventional and anesthesia teams was associated with markedly reduced DTP and DTR times.

Nuclear morphology explained through digital morphometry: differentiating nuclear features across the three histological grades in cutaneous squamous cell carcinoma.

The accurate grading of cutaneous squamous cell carcinoma (cSCC) is crucial for effective treatment and patient care, but the current method, relying on pathologist visual assessment, can be subjective. This study aimed to quantitatively investigate nuclear morphometrics in cSCC tumor cells, specifically examining potential differences between established histological grades and exploring the utility of digital morphometrics in characterizing nuclear morphology. We analyzed 47 cSCC cases, utilizing whole slide images and CellProfiler software to extract nuclear morphometric features from a total of 519 828 nuclei. The results showed significant differences in nuclear size, shape, and spatial arrangement between different tumor grades. Notably, grade 3 tumors exhibited distinct characteristics compared to grades 1 and 2, suggesting a potential shift towards a simplified, 2-tier grading system. The study highlights the potential of digital morphometrics as a valuable tool for enhancing the accuracy and objectivity of cSCC grading, ultimately improving patient care.

Differential outcomes of re-stratified high-risk prostate cancer patients treated with external beam radiation therapy plus high-dose-rate brachytherapy boost.

We report outcomes of high-risk prostate cancer (PCa) patients, initially classified according to a 3-tier NCCN classification system, treated with external beam radiation therapy (EBRT) and high-dose-rate brachytherapy boost (HDR-BT). Patients were analyzed based on a re-stratification of their risk grouping using CAPRA score and a newer 5-tier NCCN classification. 471 high-risk PCa patients treated with EBRT, HDR-BT, and androgen deprivation therapy (ADT) between 1999 and 2018 were included. Competing risk survival analyses to compare individuals with CAPRA scores < 6 vs. ≥ 6 for biochemical relapse (BCR) and metastasis incidence were conducted. Also, overall survival (OS) for both groups using Kaplan-Meier analysis was assessed. The same analyses were repeated using a 5-tier NCCN stratification comparing those classified as high-risk vs. very high-risk patients. The median age was 71 years, and the median follow-up period was 72 months. The whole cohort received an EQD2 of 74 Gy or greater, with a median EQD2 of 106.89 Gy. Both a CAPRA score ≥ 6 and belonging to the NCCN very high-risk group were associated with BCR, with subdistribution hazard ratios (sHRs) of 3.04 (p = 0.015) and 2.53 (p = 0.013), respectively. For metastasis incidence, both the CAPRA and NCCN groups had similar sHRs of 2.60 (p = 0.094) and 2.71 (p = 0.037), respectively. For 10-year OS, patients with CAPRA score ≥ 6 and belonging to the NCCN very high-risk group presented similar HRs of 2.11 (p = 0.005) and 2.10 (p = 0.002). We showed that high-risk PCa patients classified according to the 3-tier NCCN system benefit from further stratification using the CAPRA score or the 5-tier NCCN stratification method. Patients with a CAPRA score ≥ 6 or classified as very high-risk demonstrate a higher hazard of BCR, metastasis, and death. These patients might benefit from further intensification of their investigations and treatment, based on ongoing research.

Inaccessibility, unresponsiveness, inconsistency, and invisibility of informal caregivers of older persons with cognitive impairment: community-based participatory research

BackgroundStudies on informal caregivers in Japan have been limited to family caregivers and largely conducted where family caregivers generally gather. Family caregivers who do not visit such places or non-family caregivers are generally overlooked, and data on these informal caregivers remains scant. Consequently, a framework is needed through which healthcare professionals can approach the informal caregivers of community-dwelling older persons. Therefore, this study approaches such informal caregivers and proposes a classification system for them from the starting point of older persons living in the community with cognitive impairment.MethodsIn 2016, we conducted an epidemiological survey of 7000 + community-dwelling older persons and identified 198 residents with Mini-mental state examination scores less than 23. A team of healthcare professionals contacted them regularly. By 2022, 92 people were still living in the community, and we systematically asked them about their informal caregivers. After approaching the caregivers and obtaining informed consent, we mailed separate questionnaires to older persons and informal caregivers.ResultsAmong the caregivers, 59%, 34%, and 3% were the child, spouse, and sibling of the older person, while the remaining 4% were non-family caregivers. Except for two daughters-in-laws, all children were biological children of the older person. Male caregivers (46%) tended to have full-time jobs, whereas female caregivers (54%) tended to face financial difficulties. Only 3% of the caregivers had joined a family caregivers’ association. Caregivers’ reason for not joining such organizations was a lack of time and knowledge. A 3-tiered classification system was developed for these informal caregivers: (1) the household form, (2) accessibility, and (3) the reciprocal awareness of caregiving. Furthermore, family caregivers who lived with the older person or visited them more than once a week with reciprocal awareness of caring and being cared, or “traditional caregivers,” accounted for 68% of the caregivers in this study.ConclusionCore family caregivers can be easily approached at places where such caregivers generally gather. However, there also exists a group of informal caregivers who are sometimes inaccessible, unresponsive, and invisible to healthcare professionals. Moreover, their awareness of caregiving is sometimes inconsistent.