Stratification System Research Articles

Insights into Ultrasound Features and Risk Stratification Systems in Pediatric Patients with Thyroid Nodules.

Thyroid nodules in pediatric patients are less common than in adults but show a higher malignancy rate. Accordingly, the management of thyroid nodules in pediatric patients is more complex the younger the patient is, needing careful evaluation by physicians. In adult patients, specific ultrasound (US) features have been associated with an increased risk of malignancy (ROM) in thyroid nodules. Moreover, several US risk stratification systems (RSSs) combining the US features of the nodule were built to define the ROM. RSSs are developed for the adult population and their use has not been fully validated in pediatric patients. This study aimed to evaluate the available data about US features of thyroid nodules in pediatric patients and to provide a summary of the evidence regarding the performance of RSS in predicting malignancy. Moreover, insights into the management of thyroid nodules in pediatric patients will be provided.

Primary Prevention of Coronary and Other Cardiovascular Diseases: A Focused Review.

In 2022, the Japan Atherosclerosis Society (JAS) updated its prevention guidelines, the "Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2022" (JAS2022GL), expanding its scope from coronary artery disease (CAD) to atherosclerotic cardiovascular diseases (ASCVDs), including atherothrombotic stroke. The following year, the Japanese Circulation Society (JCS) updated its guidelines for primary prevention entitled "JCS 2023 Guideline on the Primary Prevention of Coronary Artery Disease" (JCS2023GL). Since those publications, scientific advancements in relevant fields have continued. This review article outlines the current recommendations provided by the guidelines, provides background information supporting these recommendations, introduces scientific findings subsequent to prior publications, and discusses future directions on select topics for the primary prevention of CVD. The topics covered in this review are traditional risk factors, including dyslipidemia and hypertension, the application of comprehensive risk stratification or risk scoring systems, patient-specific topics, salt and alcohol, and environmental factors. These topics were deliberate and selected by the authors, who were involved in the compilation of either or both JAS2022GL and JCS2023GL. This review not only emphasizes the pivotal role of continuously updated guidelines in shaping clinical practice but also stresses the urgent need for ongoing research to bridge existing knowledge and practice gaps.

Diagnostic efficacy of the contrast-enhanced ultrasound thyroid imaging reporting and data system classification for benign and malignant thyroid nodules.

The contrasted-enhanced ultrasound thyroid imaging reporting and data system (CEUS TI-RADS) is the first international risk stratification system for thyroid nodules based on conventional ultrasound (US) and CEUS. This study aimed to evaluate the diagnostic efficacy of CEUS TI-RADS for benign and malignant thyroid nodules and to assess the related interobserver agreement. The study recruited 433 patients who underwent thyroid US and CEUS between January 2019 and June 2023 at the Affiliated Hospital of Guangdong Medical University. A retrospective analysis of 467 thyroid nodules confirmed by fine-needle aspiration (FNA) and/or surgery was performed. Further, a CEUS TI-RADS classification was assigned to each thyroid nodule based on the CEUS TI-RADS scoring criteria for the US and CEUS features of the nodule. The nodules were grouped based on their sizes as follows: size ≤1 cm, group A; size >1 and ≤4 cm, group B; and size >4 cm, group C. Multivariate logistic regression was used to analyze independent risk factors for malignant thyroid nodules. Pathological assessment was the reference standard for establishing the sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) of CEUS TI-RADS in diagnosing malignant thyroid nodules. The area under the curve (AUC) in the receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic efficacy of the scoring system in predicting malignancy in three groups of nodules. The intragroup correlation coefficient (ICC) was adopted to assess the interobserver agreement of the CEUS TI-RADS score. Out of the 467 thyroid nodules, 262 were malignant and 205 were benign. Logistic regression analysis revealed that the independent risk factors for malignant thyroid nodules included punctate echogenic foci (P<0.001), taller-than-wide shape (P=0.015), extrathyroidal invasion (P=0.020), irregular margins/lobulation (P=0.036), hypoechoicity on US (P=0.038), and hypoenhancement on CEUS (P<0.001). The AUC for the CEUS TI-RADS in diagnosing malignant thyroid nodules was 0.898 for all nodules, 0.795 for group A, 0.949 for group B, and 0.801 for group C, with the optimal cutoff values of the CEUS TI-RADS being 5 points, 6 points, 5 points, and 5 points, respectively. Among these groups of nodules, group B had the highest AUC, with the SEN, SPE, ACC, PPV, and NPV for diagnosing malignant nodules being 95.9%, 88.1%, 92.8%, 92.6%, and 93.2%, respectively. The ICC of the CEUS TI-RADS classification between senior and junior physicians was 0.862 (P<0.001). In summary, CEUS TI-RADS demonstrated significant efficacy in distinguishing thyroid nodules. Nonetheless, there were variations in its capacity to detect malignant nodules across diverse sizes, and it demonstrate optimal performance in 1- to 4-cm nodules. These findings may serve as important insights for clinical diagnoses.

Mayo Clinic Validation of the AUA Risk Groups for Localized Renal Cell Carcinoma.

The AUA guidelines introduced a new risk group stratification system based primarily on tumor stage and grade to guide surveillance for patients treated surgically for localized renal cell carcinoma (RCC). We sought to evaluate the predictive ability of these risk groups using progression-free survival (PFS) and cancer-specific survival (CSS), and to compare their performance to that of our published institutional risk models. We queried our Nephrectomy Registry to identify adults treated with radical or partial nephrectomy for unilateral, M0, clear cell RCC, or papillary RCC from 1980 to 2012. The AUA stratification does not apply to other RCC subtypes as tumor grading for other RCC, such as chromophobe, is not routinely performed. PFS and CSS were estimated using the Kaplan-Meier method. Predictive abilities were evaluated using C indexes from Cox proportional hazards regression models. A total of 3191 patients with clear cell RCC and 633 patients with papillary RCC were included. For patients with clear cell RCC, C indexes for the AUA risk groups and our model were 0.780 and 0.815, respectively (P < .001) for PFS, and 0.811 and 0.857, respectively (P < .001), for CSS. For patients with papillary RCC, C indexes for the AUA risk groups and our model were 0.775 and 0.751, respectively (P = .002) for PFS, and 0.830 and 0.803, respectively (P = .2) for CSS. The AUA stratification is a parsimonious system for categorizing RCC that provides C indexes of about 0.80 for PFS and CSS following surgery for localized clear cell and papillary RCC.

Predictors of Response to Cognitive Behavioral Therapy in Patients With Tinnitus

Clinical guidelines recommend cognitive behavioral therapy (CBT) as a treatment for tinnitus. However, patient response to CBT is variable, and currently, there are no known predictors of response to CBT treatment for tinnitus. To identify the clinical predictors of patient response to CBT for treatment of tinnitus. This was a secondary cohort analysis of a single-arm clinical study including adults with chronic bothersome tinnitus recruited from Washington University School of Medicine in St Louis (Missouri) from September 2019 to February 2023. Participants completed an 8-week group CBT program with a licensed clinical psychologist. Each week consisted of 2.5 hours of CBT, amounting to 20 hours of total CBT participation, primarily delivered through a virtual platform. Conjunctive consolidation was used to create a predictive classification system for response to CBT based on tinnitus bother and anxiety levels. Response to CBT was predefined as a 13-point or greater decrease in the Tinnitus Functional Index (TFI) survey score. The study sample included 88 adult patients (median [IQR] age, 59 [49-66] years; 47 [53%] females and 41 [47%] males) with chronic bothersome tinnitus, of whom 53 (60%) had at least 13-point decrease in TFI and were considered to be responders. In univariable and multivariable logistic regression analyses, high to moderate anxiety level and severe tinnitus bother were associated with treatment response (adjusted odds ratio: anxiety, 3.33; 95% CI, 0.90-12.30; tinnitus bother, 12.08; 95% CI, 1.48-98.35). The clinical stratification system showed good predictive and discriminative ability (χ2 for linear trend = 20.0; C statistic = 0.75; 95% CI, 0.65-0.85). The findings of this study show that assessment of bother and anxiety levels in patients with tinnitus may be useful for identifying those who are more likely to respond to CBT. Before incorporation into clinical practice, future research should externally validate this finding in a separate population.

TDERS, an exosome RNA-derived signature predicts prognosis and immunotherapeutic response in clear cell renal cell cancer: A multicohort study

BackgroundTumor-derived exosomes are involved in tumor progression and immune invasion and might function as promising noninvasive approaches for clinical management. However, there are few reports on exosomal-based markers for predicting the progression and adjuvant therapy response rate among patients with clear cell renal cell carcinoma (ccRCC). MethodsThe signatures differentially expressed in exosomes from tumor and normal tissues from ccRCC patients were correspondingly deregulated in ccRCC tissues. We adopted a two-step strategy, including Lasso and bootstrapping, to construct a novel risk stratification system termed the TDERS (Tumor-Derived Exosome-Related Risk Score). During the testing and validation phase, we leveraged multiple external datasets containing over 2000 RCC cases from eight cohorts and one inhouse cohorts to evaluate the accuracy of the TDERS. In addition, enrichment analysis, immune infiltration signatures, mutation landscape and therapy sensitivity between the high and low TDERS groups were compared. Finally, the impact of TDERS on the tumor microenvironment (TME) was also analysed in our single-cell datasets. ResultsTDERS consisted of 12 mRNAs deregulated in both exosomes and tissues from patients with ccRCC. TDERS achieved satisfactory performance in both prognosis and immune checkpoint inhibitor (ICI) response across all ccRCC cohorts and other pathological types, since the average area under curve (AUC) to predict 5-year overall survival (OS) was larger than 0.8 across the four cohorts. Patients divided into the TDERS high group were resistant to ICIs, while mercaptopurine might function as a promising agent for those patients. Patients with a high TDERS were characterized by coagulation and hypoxia, which induced hampered tumor antigen presentation and relative resistance to ICIs. In addition, single cells from 12 advanced samples validated this phenomenon since the interaction between dendritic cells and macrophages was limited. Finally, PLOD2, which is highly expressed in fibro- and epi‑tissue, could be a potential therapeutic target for ccRCC patients since inhibiting PLOD2 altered the malignant phenotype of ccRCC in vitro. ConclusionAs a novel, non-invasive and repeatable monitoring tool, the TDERS could work as a robust risk stratification system for patients with renal cancer and precisely inform treatment decisions about ICI therapy.

Development and validation of competing risk nomograms for predicting cancer‑specific mortality in non-metastatic patients with non‑muscle invasive urothelial bladder cancer

We aimed to assess the cumulative incidences of cancer-specific mortality (CSM) in non-metastatic patients with non‑muscle invasive urothelial bladder cancer (NMIUBC) and establish competing risk nomograms to predict CSM. Patient data was sourced from the Surveillance, Epidemiology, and End Results database, as well as the electronic medical record system in our institution to form the external validation cohort. Sub-distribution proportional hazards model was utilized to determine independent risk factors influencing CSM in non-metastatic NMIUBC patients. Competitive risk nomograms were constructed to predict 3-year, 5-year, and 8-year cancer-specific survival (CSS) in all patients group, TURBT group and cystectomy group, respectively. The discrimination and accuracy of the model were validated through the concordance index (C-index), the area under the receiver operating characteristic curve (AUC), and calibration curves. Decision curve analysis (DCA) and a risk stratification system was employed to evaluate the clinical utility of the model. Race, age, marital status, surgery in other sites, tumor size, histological type, histological grade, T stage and N stage were identified as independent risk factors to predict CSS in all patients group. The C-index for 3-year CSS was 0.771, 0.770 and 0.846 in the training, testing and external validation sets, respectively. The ROC curves showed well discrimination and the calibration plots were well fitted and consistent. Moreover, DCA demonstrated well clinical effectiveness. Altogether, the competing risk nomogram displayed excellent discrimination and accuracy for predicting CSS in non-metastatic NMIUBC patients, which can be applied in clinical practice to help tailor treatment plans and make clinical decisions.

Assessing receptivity to malaria using case surveillance and forest data in a near-elimination setting in northeast Thailand

BackgroundThailand aimed to eliminate malaria by 2024, and as such is planning for future prevention of re-establishment in malaria free provinces. Understanding the receptivity of local areas to malaria allows the appropriate targeting of interventions. Current approaches to assessing receptivity involve collecting entomological data. Forest coverage is known to be associated with malaria risk, as an environment conducive to both vector breeding and high-risk human behaviours.MethodsGeolocated, anonymized, individual-level surveillance data from 2011 to 2021 from the Thai Division of Vector-Borne Disease (DVBD) was used to calculate incidence and estimated Rc at village level. Forest cover was calculated using raster maps of tree crown cover density and year of forest loss from the publicly available Hansen dataset. Incidence and forest cover were compared graphically and using Spearman’s rho. The current foci classification system was applied to data from the last 5 years (2017–2021) and forest cover for 2021 compared between the classifications. A simple risk score was developed to identify villages with high receptivity.ResultsThere was a non-linear decrease in annual cases by 96.6% (1061 to 36) across the two provinces from 2011 to 2021. Indigenous Annual Parasite Index (API) and approximated Rc were higher in villages in highly forested subdistricts, and with higher forest cover within 5 km. Forest cover was also higher in malaria foci which consistently reported malaria cases each year than those which did not. An Rc > 1 was only reported in villages in subdistricts with > 25% forest cover. When applying a simple risk score using forest cover and recent case history, the classifications were comparable to those of the risk stratification system currently used by the DVBD.ConclusionsThere was a positive association between forest coverage around a village and indigenous malaria cases. Most local transmission was observed in the heavily forested subdistricts on the international borders with Laos and Cambodia, which are where the most receptive villages are located. These areas are at greater risk of importation of malaria due to population mobility and forest-going activities. Combining forest cover and recent case surveillance data with measures of vulnerability may be useful for prediction of malaria recurrence risk.

Thyroid nodules as an incidental finding : Value of sonography and scintigraphy in primary diagnostics

Due to the widespread use of high-resolution sonography, numerous thyroid nodules are diagnosed, often as incidental findings. The challenge lies in evaluating various criteria such as size, shape, and echogenicity to assess the nodules' malignancy risk. Risk stratification systems have been developed to enable systematic assessment as well as to avoid unnecessary medical interventions and malignant findings being overlooked. This article provides an overview of the current diagnostic standards in primary assessment of thyroid nodules.

Utilization of the Caprini risk assessment model(RAM) to predict venous thromboembolism after primary hip and knee arthroplasty: an analysis of the Healthcare Cost and Utilization Project(HCUP)

PurposeThis study aims to investigate the potential role of Caprini risk assessment model (RAM) in predicting the risk of venous thromboembolism (VTE) in patients undergoing total hip or knee arthroplasty (THA/TKA). No national study has investigated the role of Caprini RAM after primary THA/TKA.MethodsData from The National Sample of Healthcare Cost and Utilization Project (HCUP) in 2019 were utilized for this study. The dataset consisted of 229,134 patients who underwent primary THA/TKA. Deep vein thrombosis (DVT) and pulmonary embolism (PE) were considered as VTE. The incidence of thrombosis was calculated based on different Caprini scores, and the risk of the Caprini indicator for VTE events was evaluated using a forest plot.ResultsThe prevalence of VTE after primary THA/TKA in the U.S. population in 2019 was found to be 4.7 cases per 1000 patients. Age, body mass index (BMI), and Caprini score showed a positive association with the risk of VTE (P < 0.05). The receiver operating characteristic (ROC) curve analysis indicated that a Caprini score of 9.5 had a sensitivity of 47.2% and a specificity of 82.7%, with an area under the curve (AUC) of 0.693 (95% CI, 0.677−0.710). The highest Youden index was 0.299. Multivariate logistic regression analysis revealed that malignancy, varicose vein, positive blood test for thrombophilia, history of thrombosis, COPD, hip fracture, blood transfusion, and age were significant risk factors for VTE. Based on these findings, a new risk stratification system incorporating the Caprini score was proposed.ConclusionsAlthough the Caprini score does not seem to be a good predictive model for VTE after primary THA/TKA, new risk stratification for the Caprini score is proposed to increase its usefulness.

Caste Transformation, Intracultural Communication, and Social Structure Dynamics in Kei Society, Southeast Maluku-Indonesia

This study investigates the system of social stratification and intracultural communication in the Kei people of Southeast Maluku, Indonesia, which is based on centuries-old caste traditions. Kei society is divided into three main classes: mel-mel (nobles), ren-ren (middle class), and iri-ri (lower class), each of which has roles and rights governed by local customary law, Larwul Ngabal. This caste system has created a recognized social balance despite certain dominance and hegemony. This research uses an ethnographic approach with a focus on direct observation, in-depth interviews, and document analysis to explore how stereotypes and social stratification are maintained through intracultural communication. The findings show that Kei people use language and cultural symbols to reinforce their caste position, while modernization and electoral politics open space for changes in social dynamics. The results of this study provide insights into how local communities adapt to modernization and democratization while maintaining traditional cultural structures. The implications of this study underscore the importance of understanding the dynamics of intracultural communication in the context of social stratification to maintain social order and promote inclusiveness in the social development of Kei society.

A novel prognostic index for extranodal natural killer/T-cell lymphoma in the era of pegaspargase/L-asparaginase.

Aim: This multicenter retrospective study aimed to develop a novel prognostic system for extranodal natural killer/T-cell lymphoma (ENKTL) patients in the era of pegaspargase/L-asparaginase.Materials & methods: A total of844 newly diagnosed ENKTL patients were included.Results: Multivariable analysis confirmed that Eastern Cooperative Oncology Group performance status, lactate dehydrogenase, Chinese Southwest Oncology Group and Asia Lymphoma Study Group ENKTL (CA) system, and albumin were independent prognostic factors. By rounding up the hazard ratios from foursignificant variables, a maximum of 7 points wereassigned. The model of Huaihai Lymphoma Working Group-Natural killer/T-cell Lymphoma prognostic index (NPI) was identified with four risk groups and the 5-year overall survival was 88.2, 66.7, 54.3and 30.5%, respectively.Conclusion: Huaihai Lymphoma Working Group-NPI provides a feasible stratification system for patients with ENKTL in the era of pegaspargase/L-asparaginase.

Tracking dynamic evolution of low- and intermediate-risk differentiated thyroid cancer: Identification of individuals at risk of recurrence.

The generally good prognosis of low- and intermediate-risk differentiated thyroid cancer (DTC) underscored the need to identify those few patients who relapse. Records of 299 low- or intermediate-risk DTC patients (mean follow-up 8.2 ± 6.2 years) were retrospectively reviewed. The sample was classified following the American Thyroid Association (ATA) dynamic risk stratification (DRS) system. After classifying patients according to DRS at the first visit following initial therapy (FU1), structural recurrence occurred in 2/181 (1.1%), 5/81 (6.2%) and 13/26 (50.0%) with excellent, indeterminate and biochemical incomplete response to treatment, respectively. All relapses but one happened within 5 years from FU1. Univariate analysis comparing excellent, indeterminate and biochemical incomplete with structural incomplete responses at the end of the follow-up, identified tumour size (p < .001), T status (<0.001), positive lymph nodes (N) (p < .01), multifocality (p < .004), need of additional radioactive iodine (RAI) (p < .0001) and first DRS status (p < .0003) as risk factors of recurrence. In the multivariate analysis, only RAI remained statistically significant (p < .02). Comparison between excellent and indeterminate with biochemical and structural incomplete responses, identified tumour size (p < .0004), T (p < .01), N (p < .0001), bilaterality (p < .03), first DRS status (p < .0001) and RAI (p < .001) as recurrence risk factors. T (p < .01) and first DRS (p < .0006) were confirmed in the multivariate analysis. Patients with DTC classified as low- or intermediate-risk of recurrence with excellent response to treatment at FU1 rarely develop structural disease and this occurs almost exclusively in the first 5 years. Initial DRS status is an accurate tool for determining the risk of recurrence.

The genomic and immunogenomic landscape of mechanics pathway informs clinical prognosis and response to mechanotherapy.

Mechanics shape cell and tissue plasticity and maintain their homeostasis. In cancers, mechanical signals regulate cancer hallmarks via mechanotransduction pathways, such as proliferation, metastasis and metabolic reprogramming. However, comprehensive characterization of mechanotransduction pathway genes and their clinical relevance across different cancer types remains untouched. Herein, we systematically portrayed the alterations of mechanotransduction pathway genes across 31 cancer types using The Cancer Genome Atlas (TCGA) databases. All the cancer types could be categorized into 6 subtypes based upon the transcriptional pattern of mechanics pathway genes. Each subtype has its own unique molecular expression pattern, mutation landscapes, immune infiltrates, and patient clinical outcome. We further found that the responses of two subtypes of cancers, one with the optimal outcome and the other with the worst prognosis, to a classical mechanotherapeutic agent (Fasudil, RhoA/ROCK inhibitor) were totally different, indicating that our cancer stratification system based upon mechanotransduction pathway genes could inform clinical responses of patients to mechanotherapeutic agents. Collectively, our study provides a novel pan-cancer landscape of the mechanotransduction pathways and underscores its potential clinical significance in the prediction of clinical prognosis and therapeutic responses to mechanotherapy among cancer patients.

Predicting outcomes in malignant ovarian germ cell tumors using the modified International Germ Cell Cancer Collaborative Group classification system

ObjectivesThe aim of our study was to evaluate the feasibility of the modified International Germ Cell Cancer Collaborative Group risk classification system in Chinese female patients with malignant ovarian germ...

ACUTE PANCREATITIS: IS THERE ANY RELATIONSHIP BETWEEN HEMATOCRIT AND SEVERITY OF THE DISEASE?

Introduction. Acute pancreatitis (AP) is one of the unsolved clinical problems in the practice of modern gastroenterology, surgery, and emergency medicine, which does not lose its relevance even with the advent of modern and high-tech diagnostic and therapeutic solutions. The failure of modern methods to diagnose and stratify the severity of the disease in the early stages after hospitalization of patients lead to the loss of precious time at the beginning of resuscitation measures in severe forms of AP. The aim. To assess the presence and strength of the correlation between hematocrit count and the severity of AP on the first day of the disease. Materials and methods. Polychoric analysis and receiver operating characteristic (ROC) analysis were used to assess the association and predictive value of hematocrit with the severity of AP. Only patients who arrived at the hospital within 24 hours of the onset of the disease were included in the study. Results. The correlation coefficient φ2 between hematocrit (at the reference value of 45%) and severity of AP is 0.34. The coefficient of mutual conjugation of K. Pearson (C) is equal to 0.5 which indicates the presence of a relationship between the hematocrit count and the severity of AP. After conducting the ROC analysis, it was determined that with the isolated use of hematocrit indicator provided its value of &gt; 44.4%, almost 70% of patients were diagnosed with severe AP; almost 90% of patients with a hematocrit level of £ 44.4% did not have severe AP. Also, due to the rather high values of the indicators of the prognostic capacity of the ROC analysis, it is possible to state about the presence of prognostic significance of hematocrit indicator for severe AP within the first day from the onset of the disease. Conclusions. Thus, the hematocrit number has a significant relationship with the severity of AP when calculated during the first day from the onset of the disease, which makes it promising for building systems of stratification of the severity of AP earlier than suggested by revised Atlanta criteria.

Simplifying risk stratification for thyroid nodules on ultrasound: validation and performance of an artificial intelligence thyroid imaging reporting and data system

PurposeTo validate the performance of a recently created risk stratification system (RSS) for thyroid nodules on ultrasound, the Artificial Intelligence Thyroid Imaging Reporting and Data System (AI TI-RADS). Materials and methods378 thyroid nodules from 320 patients were included in this retrospective evaluation. All nodules had ultrasound images and had undergone fine needle aspiration (FNA). 147 nodules were Bethesda V or VI (suspicious or diagnostic for malignancy), and 231 were Bethesda II (benign). Three radiologists assigned features according to the AI TI-RADS lexicon (same categories and features as the American College of Radiology TI-RADS) to each nodule based on ultrasound images. FNA recommendations using AI TI-RADS and ACR TI-RADS were then compared and sensitivity and specificity for each RSS were calculated. ResultsAcross three readers, mean sensitivity of AI TI-RADS was lower than ACR TI-RADS (0.69 vs 0.72, p < 0.02), while mean specificity was higher (0.40 vs 0.37, p < 0.02). Overall total number of points assigned by all three readers decreased slightly when using AI TI-RADS (5,998 for AI TI-RADS vs 6,015 for ACR TI-RADS), including more values of 0 to several features. ConclusionAI TI-RADS performed similarly to ACR TI-RADS while eliminating point assignments for many features, allowing for simplification of future TI-RADS versions.

Improving the Risk Prediction of the 2015 ATA Recurrence Risk Stratification in Papillary Thyroid Cancer.

Various prognostic factors are expected to refine the American Thyroid Association (ATA) recurrence risk stratification for patients with papillary thyroid cancer (PTC). However, it remains unclear to what extent integrating these factors improves patient treatment decision-making. We developed two predictive models for structural incomplete response (SIR) at the one-year follow-up visit, based on comprehensive clinical data from a retrospective cohort of 2539 patients. Model 1 included the recurrence risk stratification and lymph node features (i.e., number and ratio of metastatic lymph nodes, N stage). Model 2 further incorporated preablation stimulated thyroglobulin (s-Tg). An independent cohort of 746 patients was used for validation analysis. We assessed the models' predictive performance compared to the recurrence risk stratification using the integrated discrimination improvement (IDI) and the continuous net reclassification improvement (NRI). The clinical utility of the models was evaluated using decision curve analysis. Both Model 1 and Model 2 outperformed the recurrence risk stratification in predicting SIR, with improved correct classification rates (Model 1: IDI=0.02, event NRI=42.31%; Model 2: IDI=0.07, event NRI=53.54%). The decision curves indicated that both models provided greater benefits over the risk stratification system in clinical decision-making. In the validation set, Model 2 maintained similar performance while Model 1 did not significantly improve correct reclassification. The inclusion of lymph node features and s-Tg showed potential to enhance the predictive accuracy and clinical utility of the existing risk stratification system for PTC patients.

KRAS mutations in patients with AML: clinical characteristics and not reported mutations using NGS

ABSTRACT Background AML is a complex and heterogeneous disease. The KRAS gene is one of the important genes in the pathogenesis of acute myeloid leukemia (AML). Mutant RAS can promote oncogenesis via different mechanisms including oncogenic transcription, cell cycle progression, cellular survival, growth, metabolism, and cell migration. Therefore, it is important to identify the genomic landscape of AML. The aim of the study is to identify KRAS variants in AML and their association with clinic pathological criteria and possible effects on prognosis using NGS. Method Hotspot mutations in the KRAS gene were studied using Ion S5 next-generation sequencing system. Bone marrow samples of newly diagnosed AML patients were collected to identify hotspot mutations in the KRAS gene. DNA amplicons were subjected to sequencing and were analyzed using ion torrent software. Patients were classified according to the FAB classification system. Patients are also classified according to the cytogenetic groups and the ELN risk stratification system. Results KRAS mutations were detected in exon 2, 3, whereas no mutations in KRAS exon 1. Interestingly, Novel mutations were detected in KRAS in AML Egyptian patients. Also, there was no statistically significant association of RAS mutations with different clinical and prognostic parameters. However, KRAS mutant patients tended to have increased PB WBC counts, percentage of PB, and bone marrow blasts. Conclusion NGS is considered a useful tool to identify KRAS variants that could be useful for risk stratification and tailored therapy in AML patients

Lasso-Cox interpretable model of AFP-negative hepatocellular carcinoma.

In AFP-negative hepatocellular carcinoma patients, markers for predicting tumor progression or prognosis are limited. Therefore, our objective is to establish an optimal predicet model for this subset of patients, utilizing interpretable methods to enhance the accuracy of HCC prognosis prediction. We recruited a total of 508 AFP-negative HCC patients in this study, modeling with randomly divided training set and validated with validation set. At the same time, 86 patients treated in different time periods were used as internal validation. After comparing the cox model with the random forest model based on Lasso regression, we have chosen the former to build our model. This model has been interpreted with SHAP values and validated using ROC, DCA. Additionally, we have reconfirmed the model's effectiveness by employing an internal validation set of independent periods. Subsequently, we have established a risk stratification system. The AUC values of the Lasso-Cox model at 1, 2, and 3years were 0.807, 0.846, and 0.803, and the AUC values of the Lasso-RSF model at 1, 2, and 3years were 0.783, 0.829, and 0.776. Lasso-Cox model was finally used to predict the prognosis of AFP-negative HCC patients in this study. And BCLC stage, gamma-glutamyl transferase (GGT), diameter of tumor, lung metastases (LM), albumin (ALB), alkaline phosphatase (ALP), and the number of tumors were included in the model. The validation set and the separate internal validation set both indicate that the model is stable and accurate. Using risk factors to establish risk stratification, we observed that the survival time of the low-risk group, the middle-risk group, and the high-risk group decreased gradually, with significant differences among the three groups. The Lasso-Cox model based on AFP-negative HCC showed good predictive performance for liver cancer. SHAP explained the model for further clinical application.