Stratification System Research Articles

Challenges in Risk Stratification of Solid Atypical Mixed Echogenicity Thyroid Nodules.

Background: To determine the prevalence and risk of malignancy (ROM) in solid atypical mixed echogenicity thyroid nodules (SAMENs) with sonographic patterns not classifiable by the 2015 American Thyroid Association Ultrasound Risk Stratification System (NC ATA). Methods: We searched our prospectively collected endocrine surgery thyroid nodule (TN) database, with particular attention to those solid nodules that were NC ATA. An algorithm assigned each into one of the five ATA risk groups per the 2015 American Thyroid Association Ultrasound Risk Stratification System (ATA USRSS). TNs that the algorithm could not assign to a risk group were deemed NC ATA and were subsequently analyzed. Additionally, we categorized this group using an algorithm based on the 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS). We were specifically interested in the characteristics that resulted in non-classification by the 2015 ATA USRSS and the fine needle aspiration biopsy (FNAB) cytology and surgical pathology results from the group. Results: We evaluated data from 5,040 nodules, of which 1,772 had surgical pathology. There were 150 solid nodules not classified by 2015 ATA USRSS, all of which demonstrated atypical features along with iso-, hetero-, hyper-and mixed echogenicity (solid atypical mixed echogenicity nodules-SAMENs). Sixty of these nodules were excised and sent for surgical pathology, while 90 were followed without surgical excision. Out of the 90 that did not undergo surgery, 82 underwent FNAB with cytologic evaluation. Of our 150 SAMENs, 40 were malignant by surgical histology and six were likely malignant by cytology (total SAMEN ROM without noninvasive follicular thyroid neoplasm with papillary-l ike nuclear features 31%). The most common sonographic pattern present in our SAMEN group consisted of an isoechoic solid component with microcalcifications (28/40-70% of all excised malignant nodules). In our excised malignant SAMENs, 50% demonstrated follicular-patterned neoplastic architecture while 48% displayed papillary architecture. Conclusion: Our study demonstrates that SAMENs with at least one suspicious sonographic feature: including (1) microcalcifications; (2) irregular or other suspicious margins,;opulation, and a higher ROM (31%) than the intermediate-risk group of the 2015 ATA USRSS (10-20%).

Clinical utility of pretreatment serum squamous cell carcinoma antigen for prognostication and decision-making in patients with early-stage cervical cancer.

To investigate the prognostic role of pretreatment squamous cell carcinoma antigen (SCCA) in early-stage cervical cancer (CC). We enrolled 487 cases of pathology-proven early-stage [International Federation of Gynecology and Obstetrics (FIGO) I/II] squamous or adenosquamous CC that were treated from 2012 to 2015. Restricted cubic splines (RCS) with a full Cox regression model were used to evaluate the association between SCCA levels and survival outcomes. Recursive partitioning analysis (RPA) was used to construct a risk stratification model for overall survival (OS). The performance of the RPA-based model was assessed using a receiver operating characteristic (ROC) curve. RCS analysis revealed an association between SCCA and OS and disease-free survival (DFS); SCCA ⩾2.5 ng/mL was robust for risk discrimination in our cohort. SCCA had an interaction effect with FIGO classification: Patients with FIGO I and SCCA ⩾2.5 ng/mL overlapped with those with FIGO II and SCCA < 2.5 ng/mL for OS [hazard ratio, 1.04 (95% confidence interval (CI): 0.49-2.24), p = 0.903] and DFS [1.05 (0.56-1.98), p = 0.876]. RPA modeling incorporating SCCA (<2.5 ng/mL and ⩾2.5 ng/mL) and FIGO classification divided CC into three prognostic groups: RPA I, FIGO stage I, and SCCA < 2.5 ng/mL; RPA II, FIGO stage I, and SCCA ⩾ 2.5 ng/mL, or FIGO stage II and SCCA < 2.5 ng/mL; and RPA III, FIGO stage II, and SCCA ⩾ 2.5 ng/mL; with 5-year OS of 94.0%, 85.1%, and 73.5%, respectively (p < 0.001). ROC analysis confirmed that the RPA model outperformed the FIGO 2018 stage with significantly improved accuracy for survival prediction [area under the curve: RPA versus FIGO, 0.663 (95% CI: 0.619-0.705] versus 0.621 (0.576-0.664), p = 0.045]. Importantly, the RPA groupings were associated with the efficacy of treatment regimens. Surgery followed by adjuvant treatment had a higher OS (p < 0.01) and DFS (p = 0.024) than other treatments for RPA III, whereas outcomes were comparable among treatment regimens for RPA I-II. Herein, the role of SCCA for prognostication was confirmed, and a robust clinicomolecular risk stratification system that outperforms conventional FIGO classification in early-stage squamous and adenosquamous CC was presented. The model correlated with the efficacy of different treatment regimes.

Representation of Karo Culture in the Early 20th Century in P. A. J Moojen’s Paintings

cultural and artistic point of view with a cultural studies approach. The results of the study show that Moojen's paintings represented the belief systems, social stratification systems, and art systems of Karo culture in the early 20th century. In conclusion, Moojen's paintings are able to provide an overview of the reality of the life of the Karo people who lived in the early 20th century that cannot be separated from elements of traditional Karo buildings.

Fashionable Dispositive in the Culture of XX–XXI Centuries as Alter Globalisation Strategy

The purpose of the article is to determine the harmonising intentions of fashion dispositive as a certain system of denial of globalisation influences in the form of leveling and simplification of modern cultural practices. The research methodology is determined by phenomenological and dialectical methods that help specify the figurative transformations of fashion as a systemic integrity of cultural creation. Scientific novelty of the article. The dispositive of fashion in a broad context as an opportunity to refer to one's own origins is an adequate way of self-realisation of the Ukrainian national ethos and of Ukrainian character. If one does not come to this globalism, the wide scale of the dialogue of cultures, the scale of opposition of nations, it is easy to fall prey to westernisation, colonisation of the culture of Ukraine. Cultural practices, particularly fashion, can stop leveling, westernisation as a type of western technological reincarnation of countries that blindly follow certain cultural patterns. Conclusions. Globalisation as the transcendence of boundaries, marketization, and transitology are certain systems of stratification of development that cannot be applied to culture as a whole. They can be indicated only within certain constellations of the economic model and production relations, but cannot characterise culture as a type of integrity. Everyday culture, which conditionally includes fashion, adapts extremely quickly to external influences, is oriented to fashionable discourse as a system of harmonising contradictions. Responsibility is formed for all dispositions, dispositives, which are formed as a permanent given of the dialogue, first of all, the dialogue of cultures. A planetary horizon is formed, which is a broad situational dimension of globalisation impulses, which is realised as a modern ideology of imagination and world-building in fashion. Key words: culture, globalisation, fashion, fashionable dispositive, discourse.

Evaluation of Alternative Risk Stratification Systems in a Large Series of Solitary Fibrous Tumors with Molecular Findings and Ki-67 Index Data: Do They Improve Risk Assessment?

The clinical evolution of solitary fibrous tumors (SFTs) is often uncertain and several risk stratification systems (RSS) have been proposed. The Demicco et al. RSS is the most frequently implemented. In this study we aim to validate two alternative RSS (Sugita et al. and G-Score) using results for the Demicco RSS from a previous study of 97 SFTs. In addition, we aim to determine whether reclassified cases had any distinctive molecular features. As the Sugita et al. system substitutes mitotic count with Ki-67 index we also investigated whether Ki-67 results for tissue microarrays are comparable to those obtained using whole tissue sections. In the present study we detected that many cases classified by Demicco RSS as low-risk were reclassified as intermediate risk using the new system (G-score RSS). Kaplan-Meier survival plots for G-Score RSS showed that the low-risk and intermediate-risk SFTs had a similar evolution that contrasted with the more aggressive high-risk group. Moreover, the similar evolution in both low and intermediate-risk groups occurred despite the G-score system being stricter in classifying low-risk tumors. We observed that Sugita RSS does not provide any better risk stratification in comparison with the Demicco RSS, and testing both RSS in our series produced similar Kaplan-Meier survival data. We found some discordant results when comparing whole sections and the corresponding tissue microarrays samples, finding the hotspot areas easier to locate in whole sections. Forty-one SFTs with initial low-risk assigned by the Demicco RSS were reclassified as intermediate-risk by G-score finding both TP53 and HTER mutations in four cases, only HTER mutation in 11 cases, and only TP53 mutation in 2 cases. All six cases of SFT classified as high-risk by both the Demicco and G-score RSS suffered recurrence/metastasis, and half showed both TP53 and HTER mutations. Five SFTs were categorized as low-risk by both Demicco and G-score, of which 4 cases revealed HTER mutation. Regarding the outcome of these 5 patients, two were lost to follow-up, and one of the remaining three patients suffered recurrence. We believe that although the presence of both TP53 and HTER mutations may confer or be related to poor evolution, the isolated presence of HTER mutation alone would not necessarily be related to poor outcome. The G-score RSS more accurately identified low-risk patients than the other two risk models evaluated in the present series. Late recurrence/metastasis may occasionally be observed even in low-risk SFTs categorized by stricter classification systems such as the G-score RSS. These findings support the possibility that additional, as yet unknown factors may influence the clinical evolution of SFTs. In conclusion, given the possibility of late recurrence, long-term follow-up is recommended for all SFT patients, even in cases classified as low risk by the stricter G-score system. An integration of clinical, radiological, pathological, and molecular findings may improve SFT risk stratification and better predict patient outcome.

Accuracy and reproducibility of the O-RADS MRI risk stratification system based on enhanced non-DCE MRI in the assessment of adnexal masses

ObjectiveEvaluation of the diagnostic performance and reproducibility of the Ovarian-Adnexal Reporting and Data System (O-RADS) Magnetic Resonance Imaging (MRI) risk stratification system based on enhanced non-dynamic contrast-enhanced (non-DCE) MRI in the diagnosis of adnexal masses. MethodsPatients who underwent conventional pelvic enhanced non-DCE MRI examination within one month prior to surgery formed the study population. Two experienced radiologists independently evaluated the images and assigned a score according to the O-RADS MRI risk stratification system. One of the radiologists reviewed the images and reassigned the scores after three months. Intra- and inter-observer agreement was evaluated with the k coefficient value. The adnexal masses that attained scores between 1 and 3 were considered benign, while those with scores of 4 or 5 were considered malignant. Analyses were conducted to determine the sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic (ROC) curve, which were then used for evaluating the diagnostic efficacy of the developed system based on enhanced non-DCE MRI scan. The reference standard was histology. ResultsA total of 308 patients (mean age: 42.09 ± 12.42 years, age range: 20–84 years) were enrolled in the study. Among the 362 adnexal masses from the included patients, there were 320 benign masses and 42 malignant masses. In the case of three readers, there were no malignant tumors scored 1–2. The O-RADS MRI score ≥ 4 was associated with malignancy resulted in a good diagnostic efficacy with the areas under the curve (AUC) values of 0.918 (95 % CI, 0.864–0.972), 0.905 (95 % CI, 0.842–0.968), and 0.882 (95 % CI, 0.815–0.950), the sensitivity values of 90.5 % (95 % CI, 87.5–93.5 %), 85.7 % (95 % CI, 82.1–89.3 %), and 83.3 % (95 % CI, 79.5–87.2 %), and the specificity values of 93.1 % (95 % CI, 90.5–95.7 %), 95.3 % (95 % CI, 93.1–97.5 %), and 93.1 % (95 % CI, 90.5–95.7 %) obtained for the three readers, respectively. Excellent intra-observer agreement and inter-observer agreement were observed with the k values of 0.883 (95 % CI, 0.814–0.952) and 0.848 (95 % CI, 0.770–0.926), respectively. ConclusionsThe O-RADS MRI risk stratification system based on enhanced non-DCE MRI scans exhibited high accuracy and reproducibility in the prediction of adnexal masses malignancy. Enhanced non-DCE MRI scan may offer an alternative diagnostic tool when DCE is not possible.

Downregulation of SMIM3 inhibits growth of leukemia via PI3K-AKT signaling pathway and correlates with prognosis of adult acute myeloid leukemia with normal karyotype

BackgroundAcute myeloid leukemia (AML) patients with normal karyotype (NK-AML) have significant variabilities in outcomes. The European Leukemia Net stratification system and some prognostic models have been used to evaluate risk stratification. However, these common standards still have some limitations. The biological functions and mechanisms of Small Integral Membrane Protein 3 (SMIM3) have seldomly been investigated. To this date, the prognostic value of SMIM3 in AML has not been reported. This study aimed to explore the clinical significance, biological effects and molecular mechanisms of SMIM3 in AML.MethodsRT-qPCR was applied to detect the expression level of SMIM3 in bone marrow specimens from 236 newly diagnosed adult AML patients and 23 healthy volunteers. AML cell lines, Kasumi-1 and THP-1, were used for lentiviral transfection. CCK8 and colony formation assays were used to detect cell proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. Western blot was performed to explore relevant signaling pathways. The biological functions of SMIM3 in vivo were validated by xenograft tumor mouse model. Survival rate was evaluated by Log-Rank test and Kaplan–Meier. Cox regression model was used to analyze multivariate analysis. The correlations between SMIM3 and drug resistance were also explored.ResultsThrough multiple datasets and our clinical group, SMIM3 was shown to be significantly upregulated in adult AML compared to healthy subjects. SMIM3 overexpression conferred a worse prognosis and was identified as an independent prognostic factor in 95 adult NK-AML patients. Knockdown of SMIM3 inhibited cell proliferation and cell cycle progression, and induced cell apoptosis in AML cells. The reduced SMIM3 expression significantly suppressed tumor growth in the xenograft mouse model. Western blot analysis showed downregulation of p-PI3K and p-AKT in SMIM3-knockdown AML cell lines. SMIM3 may also be associated with some PI3K-AKT and first-line targeted drugs.ConclusionsSMIM3 was highly expressed in adult AML, and such high-level expression of SMIM3 was associated with a poor prognosis in adult AML. Knockdown of SMIM3 inhibited the proliferation of AML through regulation of the PI3K-AKT signaling pathway. SMIM3 may serve as a potential prognostic marker and a therapeutic target for AML in the future.

A nomogram and risk classification system predicting esophageal stricture after endoscopic submucosal dissection of a large area for early esophageal cancer.

Esophageal stricture is a troublesome adverse effect of endoscopic submucosal dissection (ESD) for early esophageal cancer. However, risk factors of post-ESDesophagealstricture formation are incomprehensive. This study aimed to conduct a comprehensive analysis of independent risk factors and provide predictive tools. Patients who underwent ESD for early esophageal cancer between 2014 and 2021 at the Beijing Friendship Hospital, Capital Medical University, were recruited. A nomogram and risk classification system was established based on Cox proportional hazards analyses and validated using the concordance index (C-index), calibration curves, decision curve analysis (DCA), and Kaplan-Meier (K-M) curves. Stricture formed in 36 patients, while stricture was not observed in the remaining 112 patients. Operative time (odds ratio [OR]: 1.01; 95% confidence interval [CI]: 1.00-1.01; p < 0.01); lesions >3/4 circumferential range of esophagus (OR: 3.82; 95% CI: 1.90-7.66; p < 0.01), and tumor infiltration to the mucosal lamina propria (m2) or deeper (OR: 2.40; 95% CI: 1.24-4.66; p = 0.01) were independent predictive factors for post-ESD esophageal stricture. The nomogram and risk classification system was developed and validated with 0.79 C-index, good calibration curves, good DCA results, and good K-M curves. We developed a nomogram and risk stratification system to predict post-ESD esophageal stricture using three independent risk factors.

Evaluating Disease-specific Survival Prediction of Risk Stratification and TNM Systems in Differentiated Thyroid Cancer.

Many countries have national guidelines for the management of differentiated thyroid cancer (DTC), including a risk stratification system to predict recurrence of disease. Studies whether these guidelines could also have relevance, beyond their original design, in predicting survival are lacking. Additionally, no studies evaluated these international guidelines in the same population, nor compared them with the TNM system. Therefore, we investigated the prognostic value of 6 stratification systems used by 10 international guidelines, and the TNM system with respect to predicting disease-specific survival (DSS). We retrospectively studied adult patients with DTC from a Dutch university hospital. Patients were classified using the risk classification described in the British, Dutch, French, Italian, Polish, Spanish, European Society of Medical Oncology, European Thyroid Association, the 2009 and 2015 American Thyroid Association (ATA) guidelines, and the latest TNM system. DSS was analyzed using the Kaplan-Meier method, and the statistical model performance using the C-index, Akaike information criterion, Bayesian information criterion, and proportion of variance explained. We included 857 patients with DTC (79% papillary thyroid cancer, 21% follicular thyroid cancer). Median follow-up was 9 years, and 67 (7.8%) died because of DTC. The Dutch guideline had the worst statistical model performance, whereas the 2009 ATA/2014 British guideline had the best. However, the (adapted) TNM system outperformed all stratification systems. In a European population of patients with DTC, of 10 international guidelines using 6 risk of recurrence stratification systems and 1 mortality-based stratification system, our optimized age-adjusted TNM system (8th edition) outperformed all other systems.

A tissue miRNA expression pattern is associated with disease aggressiveness of localized prostate cancer.

Prostate cancer (PCa) is a heterogeneous malignancy with high variability in clinical course. Insufficient stratification according to the aggressiveness at the time of diagnosis causes unnecessary or delayed treatment. Current stratification systems are not effective enough because they are based on clinical, surgical or biochemical parameters, but do not take into account molecular factors driving PCa cancerogenesis. MicroRNAs (miRNAs) are important players in molecular pathogenesis of PCa and could serve as valuable biomarkers for the assessment of disease aggressiveness and its prognosis. In the study, in total, 280 PCa patients were enrolled. The miRNA expression profiles were analyzed in FFPE PCa tissue using the miRCURY LNA miRNA PCR System. The expression levels of candidate miRNAs were further verified by two-level validation using the RT-qPCR method and evaluated in relation to PCa stratification reflecting the disease aggressiveness. MiRNA profiling revealed 172 miRNAs dysregulated between aggressive (ISUP 3-5) and indolent PCa (ISUP 1) (p < 0.05). In the training and validation cohort, miR-15b-5p and miR-106b-5p were confirmed to be significantly upregulated in tissue of aggressive PCa when their level was associated with disease aggressiveness. Furthermore, we established a prognostic score combining the level of miR-15b-5p and miR-106b-5p with serum PSA level, which discriminated indolent PCa from an aggressive form with even higher analytical parameters (AUC being 0.9338 in the training set and 0.8014 in the validation set, respectively). The score was also associated with 5-year biochemical progression-free survival (bPFS) of PCa patients. We identified a miRNA expression pattern associated with disease aggressiveness in prostate cancer patients. These miRNAs may be of biological interest as the focus can be also set on their specific role within the molecular pathology and the molecular mechanism that underlies the aggressivity of prostate cancer.

Smooth muscle cell fate decisions decipher a high-resolution heterogeneity within atherosclerosis molecular subtypes

BackgroundMounting evidence has revealed the dynamic variations in the cellular status and phenotype of the smooth muscle cell (SMC) are vital for shaping the atherosclerotic plaque microenvironment and ultimately mapping onto heterogeneous clinical outcomes in coronary artery disease. Currently, the underlying clinical significance of SMC evolutions remains unexplored in atherosclerosis.MethodsThe dissociated cells from diseased segments within the right coronary artery of four cardiac transplant recipients and 1070 bulk samples with atherosclerosis from six bulk cohorts were retrieved. Following the SMC fate trajectory reconstruction, the MOVICS algorithm integrating the nearest template prediction was used to develop a stable and robust molecular classification. Subsequently, multi-dimensional potential biological implications, molecular features, and cell landscape heterogeneity among distinct clusters were decoded.ResultsWe proposed an SMC cell fate decision signature (SCFDS)-based atherosclerosis stratification system and identified three SCFDS subtypes (C1–C3) with distinguishing features: (i) C1 (DNA-damage repair type), elevated base excision repair (BER), DNA replication, as well as oxidative phosphorylation status. (ii) C2 (immune-activated type), stronger immune activation, hyper-inflammatory state, the complex as well as varied lesion microenvironment, advanced stage, the most severe degree of coronary stenosis severity. (iii) C3 (stromal-rich type), abundant fibrous content, stronger ECM metabolism, immune-suppressed microenvironment.ConclusionsThis study uncovered atherosclerosis complex cellular heterogeneity and a differentiated hierarchy of cell populations underlying SMC. The novel high-resolution stratification system could improve clinical outcomes and facilitate individualized management.

A prognostic nomogram to predict survival in elderly patients with small-cell lung cancer: a large population-based cohort study and external validation

BackgroundAge is an independent prognostic factor for small cell lung cancer (SCLC). We aimed to construct a nomogram survival prediction for elderly SCLC patients based on the Surveillance, Epidemiology, and End Results (SEER) database.MethodsA total of 2851 elderly SCLC patients from the SEER database were selected as a primary cohort, which were randomly divided into a training cohort and an internal validation cohort. Additionally, 512 patients from two institutions in China were identified as an external validation cohort. We used univariate and multivariate to determine the independent prognostic factors and establish a nomogram to predict survival. The value of the nomogram was evaluated by calibration plots, concordance index (C-index) and decision curve analysis (DCA).ResultsTen independent prognostic factors were determined and integrated into the nomogram. Calibration plots showed an ideal agreement between the nomogram predicted and actual observed probability of survival. The C-indexes of the training and validation groups for cancer-specific survival (CSS) (0.757 and 0.756, respectively) based on the nomogram were higher than those of the TNM staging system (0.631 and 0.638, respectively). Improved AUC value and DCA were also obtained in comparison with the TNM model. The risk stratification system can significantly distinguish individuals with different survival risks.ConclusionWe constructed and externally validated a nomogram to predict survival for elderly patients with SCLC. Our novel nomogram outperforms the traditional TNM staging system and provides more accurate prediction for the prognosis of elderly SCLC patients.

Validation of the novel International Association for the Study of Lung Cancer grading system and prognostic value of filigree micropapillary and discohesive growth pattern in invasive pulmonary adenocarcinoma

IntroductionThe Pathology Committee of the International Association for the Study of Lung Cancer (IASLC) proposed a new histological grading system based on the combination of predominant and high-grade patterns in 2020. Materials and MethodsPathological sections from 631 patients with stage I-III invasive lung adenocarcinoma were reviewed. We then determined the histological grade according to the new grading system and confirmed the pathological features that included the filigree micropapillary and discohesive growth pattern. Applying of the novel IASLC grading system in prognosis stratification was verified and the clinical significance of the pathological characteristics was explored. ResultsCox multivariable analysis revealed that in the stage I-III invasive lung adenocarcinoma, the IASLC grading system was significantly associated with disease-free survival (DFS) [hazard ratio (HR) = 1.419; 95 % confidence interval (CI): 1.040–1.937; P = 0.027] and overall survival (OS) (HR = 1.899; 95 % CI: 1.168–3.087; P = 0.010). In patients with IASLC Grades 1 and 2, the simultaneous presence of filigree micropapillary and discohesive growth pattern was significantly correlated with DFS (HR = 1.899; 95 % CI:1.168–3.087; P = 0.010). However, the filigree micropapillary and discohesive growth pattern did not affect the OS (HR = 2.786; P = 0.317). The competitive risk model revealed that in the stage I cohort, the simultaneous presence of filigree micropapillary and discohesive growth pattern was a risk factor for recurrence and metastasis [sub- distribution HR (SHR) = 1.987; 95 %CI: 1.122–3.518; P = 0.019]. ConclusionOur study verified that the new prognostic stratification system was an effective stratification tool. Filigree micropapillary and discohesive growth pattern may also be risk factors for DFS, postoperative recurrence and metastasis.

The diverging gender inequality across households: The case of Palestinian-Arab families in Israel

This article focuses on how the family’s position in the stratification system affects the division of housework and childcare in Palestinian-Arab society in Israel; a highly gendered society experiencing socioeconomic change. Recent studies carried out in economically developed countries have shown that the household position indicated by education, income, and employment, related to the way the household tasks are shared by the spouses. However, less is known about the phenomenon in the context of societies that maintain gendered norms regarding family roles while women improved their education and employment status. A multilogistic regression analysis for household tasks and logistic regression analysis for childcare were applied to data from Israeli Social Surveys to examine the effect of household strata in the social stratification system regarding the way Palestinian-Arab families in Israel manage their household’s demands. The main results show that upper-class households and couples with a higher education pose their gender roles as more egalitarian, which demonstrates selective gender equality. The gender boundaries in the sharing of caring tasks are less rigid by class in Palestinian-Arab families while they continued to be determined mainly by the couple’s relative education and attitudes toward gender roles.

Diagnostic Performance of ACR and Kwak TI-RADS for Benign and Malignant Thyroid Nodules: An Update Systematic Review and Meta-Analysis.

(1) Background: To determine the optimal cut-off values of two risk stratification systems to discriminate malignant thyroid nodules and to compare the diagnostic performance; (2) Methods: True and false positive and negative data were collected, and methodological quality was assessed for forty-six studies involving 39,085 patients; (3) Results: The highest area under the receiver operating characteristic (ROC) curve (AUC) of ACR and Kwak TI-RADS were 0.875 and 0.884. Based on the optimal sensitivity and specificity, the highest accuracy values of ROC curves or diagnostic odds ratios (DOR) were taken as the cut-off values for TR4 (moderate suspicious) and 4B. The sensitivity, specificity, DOR, and AUC by ACR (TR4) and Kwak TI-RADS (4B) for malignancy risk stratification of thyroid nodules were 94.3% and 96.4%; 52.2% and 53.7%; 17.5185 and 31.8051; 0.786 and 0.884, respectively. There were no significant differences in diagnostic accuracy in any of the direction comparisons of the two systems; (4) Conclusions: ACR and Kwak TI-RADS had good diagnostic performances (AUCs > 85%). Although we determined the best cut-off values in individual risk stratification systems based on statistical assessment, clinicians can adjust the optimal cut-off value according to the clinical purpose of the ultrasonography because raising or lowering cut-points leads to reciprocal changes in sensitivity and specificity.

External validation of a CT-based radiomics signature in oropharyngeal cancer: Assessing sources of variation

Background and purposeRadiomics is a high-throughput approach that allows for quantitative analysis of imaging data for prognostic applications. Medical images are used in oropharyngeal cancer (OPC) diagnosis and treatment planning and these images may contain prognostic information allowing for treatment personalization. However, the lack of validated models has been a barrier to the translation of radiomic research to the clinic. We hypothesize that a previously developed radiomics model for risk stratification in OPC can be validated in a local dataset. Materials and methodsThe radiomics signature predicting overall survival incorporates features derived from the primary gross tumor volume of OPC patients treated with radiation +/- chemotherapy at a single institution (n = 343). Model fit, calibration, discrimination, and utility were evaluated. The signature was compared with a clinical model using overall stage and a model incorporating both radiomics and clinical data. A model detecting dental artifacts on computed tomography images was also validated. ResultsThe radiomics signature had a Concordance index (C-index) of 0.66 comparable to the clinical model’s C-index of 0.65. The combined model significantly outperformed (C-index of 0.69, p = 0.024) the clinical model, suggesting that radiomics provides added value. The dental artifact model demonstrated strong ability in detecting dental artifacts with an area under the curve of 0.87. ConclusionThis work demonstrates model performance comparable to previous validation work and provides a framework for future independent and multi-center validation efforts. With sufficient validation, radiomic models have the potential to improve traditional systems of risk stratification, treatment personalization and patient outcomes.

Integrated analysis from multi-center studies identities m7G-derived modification pattern and risk stratification system in skin cutaneous melanoma.

The m7G modification has been proven to play an important role in RNA post-transcriptional modification and protein translation. However, the potential role of m7G modification patterns in assessing the prognosis of Skin cutaneous melanoma (SKCM) and tumor microenvironment (TME) has not been well studied. In this study, we investigated and finally identified 21 available m7G-related genes. We used hierarchical clustering (K-means) to classify 743 SKCM patients into three m7G-modified subtypes named m7G/gene cluster-A, B, C. We found that both m7G cluster B and gene cluster B exhibited higher prognosis and higher immune cell infiltration in TME compared to other subtypes. EIF4E3 and IFIT5, two m7G related genes, were both markedly elevated in Cluster B. Then, we constructed an m7G score system utilizing principal component analysis (PCA) in order to evaluate the patients' prognosis. High m7G score subtype was associated with better survival prognosis and active immune response. Overall, this article revealed that m7G modification patterns were involved in the development of the tumor microenvironment. Evaluating patients' m7G modification patterns will enhance our understanding of TME characteristics and help to guide personal treatment in clinics in the future.

Risk stratification of lateral neck recurrence for patients with pN1a papillary thyroid cancer

BackgroundLateral neck is not recommended for dissection in patients with pN1a papillary thyroid cancer (PTC), but its recurrence risk has not been well stratified. We aimed to develop a risk stratification system for lateral neck recurrence in patients with pN1a PTC.MethodsPatients with pN1a PTC who underwent thyroidectomy and unilateral central compartment dissection from 2000–2016 were enrolled. The association between number of central lymph node metastases (CLNMs) and lateral neck recurrence was comprehensively assessed using a Cox proportional hazards model with restricted cubic spline. Stratification was then performed based on CLNMs and other significant risk factors selected by multivariate analysis. Lateral neck recurrent-free survival (LRFS) rate of each stratification was estimated with Kaplan–Meier curve and comparison was performed using log-rank test.ResultsNinety-six (3.8%) lateral neck recurrences were identified during a median follow-up of 62 months among a total of 2500 admitted cases. An increasing number of CLNMs was associated with compromised LRFS for up to 6 CLNMs (P < 0.001), and CLNMs > 3 indicated significantly worse 5-year LRFS than that of CLNM ≤ 3 (90.6% vs. 98.1%, P < 0.001). When stratification with CLNMs and primary tumor size (selected by multivariate analysis, HR (95%CI) = 4.225(2.460–7.256), P < 0.001), 5-year LRFS rates of high- (CLNMs > 3 and primary tumor size > 2 cm), intermediate- (CLNMs > 3 and primary tumor size 1–2 cm) and low-risk (primary tumor size ≤ 1 cm or CLNMs ≤ 3) groups were 78.5%, 90.0% and 97.9%, respectively (P < 0.05).ConclusionsThe number of CLNMs combined with primary tumor size seems to effectively stratify lateral neck recurrence risk for patients with pN1a PTC.

Low-grade hepatocellular carcinoma characteristics, a practical nomogram and risk stratification system: a SEER population-based study

ABSTRACT Background The purpose of this study is to establish a nomogram and risk stratification system to predict OS in patients with low-grade HCC Research design and methods Data were extracted from the SEER database. C-index, time-dependent AUCs, and calibration plots were used to evaluate the effective performance of the nomogram. NRI, IDI, and DCA curves were adopted to compare the clinical utility of nomogram with AJCC. Results 3415 patients with low-grade HCC were available. The C-indices for the training and validation cohorts were 0.773 and 0.772. The time-dependent AUCs in the training cohort were 0.821, 0.817, and 0.846 at 1, 3 and 5 years. Calibration plots for 1-, 3- and 5-year OS showed good consistency between actual observations and that predicted by the nomogram. The values of NRI at 1, 3, and 5 years were 0.37, 0.66, and 0.64. The IDI values at 1, 3, and 5 years were 0.11, 0.16, and 0.23 (P< 0.001). DCA curves demonstrated that the nomogram showed better ability of predicting 1-, 3-, and 5-year OS probabilities than AJCC. Conclusions A nomogram and risk stratification system for predicting OS in patients with low-grade HCC were established and validated.

The Prospective Implementation of the 2015 ATA Guidelines and Modified ATA Recurrence Risk Stratification System for Treatment of Differentiated Thyroid Cancer in a Canadian Tertiary Care Referral Setting.

Objective: To present clinical outcomes of the prospective implementation of the 2015 American Thyroid Association (ATA) guidelines for the management of thyroid nodules and differentiated thyroid cancer (DTC) using the modified ATA recurrence risk (RR) stratification system. Methods: We prospectively analyzed 612 patients with DTC treated between April 2017 and December 2021 in Calgary, Alberta. Each patient was prospectively assigned a modified ATA RR and American Joint Committee Cancer 8th edition stage. Initial risk stratification and consideration of the 2015 ATA guidelines guided surgical management as well as the indication for and dose of radioiodine (RAI) and other adjuvant therapies. Patients were assessed for their response to treatment (RTT) at 2-years postoperatively. Results: There were 479 patients who had 2-year follow-up data and were included in the study. Of these patients, there were 253 (53%) low-, 129 (27%) intermediate-, and 97 (20%) high-RR patients. Of these, 227 patients (47%) underwent total thyroidectomy (TTX) plus RAI, 178 (37%) underwent TTX only, and 74 (16%) underwent lobectomy. The RTT at 2 years was excellent for 89% (66) of patients with lobectomy, 84% (149) for TTX only, and 53% (121) for TTX plus RAI. Among 253 patients who were deemed low RR, 85% (216) had excellent RTT, 13% (32) indeterminate RTT, 2% (4) biochemical incomplete RTT, and 1 patient had structural incomplete RTT. The intermediate RR group had the following RTT outcomes: 64% (83) excellent, 23% (30) indeterminate, 6% (7) biochemical incomplete, and 7% (9) structural incomplete. The high RR group had the worst RTT outcomes, with 38% (37) excellent, 19% (18) indeterminate, 10% (10) biochemical incomplete, and 33% (32) structural incomplete RTT. Conclusions: The 2015 ATA RR stratification system is useful for predicting disease status at 2-year post-treatment in patients with DTC. The 2015 ATA guidelines and modified ATA RR stratification treatment recommendations may reduce thyroid cancer overtreatment by including lobectomy as a definitive treatment option for low-risk thyroid cancers and selective use of RAI for intermediate and high-risk patients.