Intermediate-risk Group Research Articles

Prognostic staging system correctly identifies high risk groups in cardiac transthyretin amyloidosis treated with tafamidis

Abstract Background The development of different multiparametric staging systems improved the risk assessment of cardiac transthyretin amyloidosis (ATTR-CA) patients substantially. However, to date, all staging systems were validated in treatment-naive ATTR-CA patients. The introduction of tafamidis led to significant changes in the disease trajectory of ATTR-CA, indicating that it may also have an impact on the prognostic accuracy of these staging systems. Purpose Thus, we sought to assess whether the prognostic value of the National Amyloidosis Centre (NAC) staging system, currently considered as the most accurate, is sustained in ATTR-CA patients treated with tafamidis. Methods This retrospective observational study included ATTR-CA patients treated with tafamidis. Patients were continuously followed from treatment initiation to time of death. NT-proBNP and eGFR data collected at baseline were used to stratify patients into low (stage I), intermediate (stage II) and high-risk (stage III) subgroups according to the NAC staging system. Kaplan-Meier analyses were conducted to illustrate overall survival. Differences in overall survival between subgroups were assessed by log rank tests. P-values <0.05 were considered statistically significant. Results A total of 166 ATTR-CA patients (95.2% wild-type) were enrolled. 81 (48.8%), 51 (30.7%) and 34 (20.5%) patients were stratified into stages I, II and III, respectively. Median follow-up was 539 [323-865] days, during which 20 deaths were recorded. Overall survival of the subgroups over time is demonstrated in figure 1. The probability of overall survival was significantly lower for patients in stage III compared to patients in stages I (log rank; p=0.002) and II (log rank; p=0.031). However, no differences in the probability of overall survival were identified between patients in stage I and II (log rank; p=0.679). Conclusions In this cohort of ATTR-CA patients treated with tafamidis, the NAC staging system effectively identified patients at elevated risk of mortality. However, the distinction in survival rates between low- and intermediate-risk groups was less pronounced, suggesting that tafamidis may have a stronger prognostic impact in these groups.Overall Survival across NAC Stages

Prediction of mortality, future arrhythmia and cardiovascular disease: an artificial intelligence-enhanced electrocardiography platform

Abstract Background Artificial intelligence-enhanced electrocardiography (AI-ECG) can be used to identify existing disease, but could additionally be used to predict occurrence of future disease and death. Purpose We developed an AI-ECG platform that predicts mortality and a wide spectrum of future arrhythmia and cardiovascular disease. Methods The AI-ECG risk estimation platform (AIRE) was developed in a dataset of 1,163,401 ECGs from 189,539 patients from a secondary care setting in the USA. Uniquely, AIRE uses deep learning with a residual convolutional neural network with a discrete-time survival loss function to output subject-specific survival curves (Fig 1A). AIRE was fine-tuned to additionally predict the endpoints described below. Results AIRE accurately predicts risk of all-cause mortality (C-index 0.775 (0.773-0.776) and can differentiate prognosis in high- and low-risk subjects, even when only cardiologist-defined normal ECGs are considered (Fig 2B). Additionally, in Cox regression analyses, AIRE was superior to conventional risk factors (Fig 1B). AIRE accurately predicted future ventricular arrhythmia (c-index 0.760 (0.756-0.763)), future complete heart block (CHB) (0.809 (0.805-0.814), future atrial fibrillation (0.753 (0.751-0.756), future atherosclerotic cardiovascular disease (0.696 (0.694-0.698)) and future heart failure (0.787 (0.785-0.789)) . AIRE was superior to left ventricular ejection fraction (LVEF) in predicting risk of future ventricular arrhythmias in subjects with LVEF <50% (C-index 0.649 (0.638 – 0.660) vs 0.615 (0.603 – 0.626) p < 0.0001 ). For CHB prediction, AIRE was able to further risk stratify subjects with bifascicular block and syncope into low (1.9% 5 year CHB), intermediate (8.8%), and high risk (20.7%) groups, and could guide treatment decisions. We externally validated our findings in four diverse, transnational cohorts from Brazil and the UK, including volunteers, primary care subjects and patients with Chagas disease, and found AIRE accurately predicted all-cause mortality in all four external cohorts (Fig 2). Non-mortality endpoints were successful externally validated in the UKB. In explainability analyses, we found features of QRS morphology, low QRS voltage, poor precordial R wave progression, inverted and biphasic T waves and ST segment changes were the most significant morphological features associated with high predicted mortality (Fig 1D). Through phenome- and genome-wide association studies (GWAS), we identified candidate biological pathways including changes in cardiac structure (LV mass, LV trabeculation and left atrial size). GWAS identified variants adjacent to VGLL2, KCNQ1, CCDC91 and TBX3 which have been described in association with QT interval, biological aging and metabolic syndrome (Fig 1E). Conclusion AIRE could be used worldwide across a range of clinical contexts for risk estimation of not only mortality but a wide spectrum of future arrhythmia and cardiovascular diseases.Figure 1Figure 2

Polygenic risk score for prediction of atrial fibrillation according to presence of the hypertrophic cardiomyopathy

Abstract Background The significance of genetic predisposition in predicting atrial fibrillation (AF) is well recognized, yet its role in hypertrophic cardiomyopathy (HCM) patients remains less clear. Objective In this study, we aimed to elucidate the impact of genetic risk on the development of AF in both HCM and non-HCM patients. Methods This retrospective analysis examined 1,180 HCM patients (mean age 61.1±7.1, 63.0% male) and 476,238 non-HCM patients (mean age 57.0±8.1, 45.3% male) from the UK Biobank. Participants were stratified based on their validated polygenic risk score (PRS) for AF: the bottom 10% constituted the low genetic risk group, the top 10% comprised the high genetic risk group, and the remainder fell into the intermediate genetic risk group. We assessed the incidence of AF and major cardiovascular events and analyzed predictors, including genetic risk. Results Among HCM patients, no significant differences in baseline characteristics were observed based on genetic risk, except for the rate of CIED implantation (P=0.036). Conversely, among non-HCM patients, variations in age, gender, and comorbidities were noted according to genetic risk. The HCM patients were categorized into three groups based on risk, with respective AF incidence rates of 2.4, 3.6, and 5.4 events per 100 person-years, respectively. In non-HCM patients, the incidence of AF per 100 person-years was 0.2, 0.5, and 1.0, respectively. Genetic risk emerged as a significant predictor of AF in both HCM and non-HCM patients, although with a higher hazard ratio observed in non-HCM patient (HR, 2.51; 95% CI, 1.59–3.98 vs. HR, 4.77; 95% CI, 4.47–5.09) (P=0.003 for interaction). In non-HCM patients, predictors of AF included age, male sex, body mass index, smoking history, and a history of hypertension, diabetes, heart failure, stroke, and myocardial infarction, in addition to PRS. However, in HCM patients, only age, diabetes, and a history of stroke were identified as independent predictors of AF. Moreover, high genetic risk was significantly associated with the risk of major adverse cardiovascular events. Conclusions In conclusion, our study indicates associations between genetic predisposition and AF occurrence in both HCM and non-HCM patients.

Post-ROsc ecG pREdictS Survival after out-of hospital cardiac arrest: validation of the PROGRESS score

Abstract Background Prognostication is crucial for patients with an out-of-hospital cardiac arrest (OHCA) both during resuscitation and after return of spontaneous circulation (ROSC) and early prognostication is still a challenge. At this regard, we proposed the PROGRESS score: a post-ROSC 12-lead ECG features’-based score to predict 30-day survival. Purpose The aim of the present study is to validate the PROGRESS score on a larger population of post-OHCA patients and to test its performance even after correction for patients’ and events’ characteristics, contained in the UB-ROSC score, could increase its discrimination ability. Methods Cardiac arrest cases were retrieved from the Lombardy Cardiac Arrest Registry (LombardiaCARe) from January 2015 to December 2022. We considered only patients with a post-ROSC 12-lead ECG and all the variables for UB-ROSC calculation available. The PROGRESS score considers age, sex, number of segments with ST elevation, QRS width, and Brugada pattern and from 0 to 26 identifies three categories of risk of death at 30 days (low: 0-4; intermediate: 5-7; high: 8-26). The UB-ROSC score considers age, aetiology, location, witnessed OHCA, bystander cardiopulmonary resuscitation (CPR), emergency medical service (EMS) arrival time and type of presenting rhythm. The performance of the PROGRESS score, in terms of discriminatory power of calibration, was tested both alone and after correction for UB-ROSC score. Results We considered 940 OHCAs of whom 63.9% were males with a median age of 70 [59.5-79]. 30-day survival was 37.9%, 63.1% and 64.5% in high, intermediate, and low risk groups respectively. PROGRESS score was shown to discriminate high-risk patients from low-risk ones [HR 1.97 (95% CI 1.42-2.73), p-value <0.001], (Harrel-C= 0.58). After correction for UB-ROSC score both calibration and discrimination improved (Harrel-C = 0.70). Conclusions The PROGRESS score was confirmed to predict the risk of death at 30 days in patients resuscitated from an OHCA and its discriminatory power was increased by correction for the UB-ROSC score. The use of this two scores in the field allows risk stratification during resuscitation manoeuvres and in post-ROSC care, which is essential to guide resource allocation.

Scoring System to Personalize Management of Emphysematous Pyelonephritis.

Emphysematous pyelonephritis (EPN) is a life-threatening condition that requires prompt diagnosis and treatment. The prognosis of EPN is variable, and there is no single treatment that is universally effective. In this study, we developed a scoring system to predict the prognosis of EPN and to guide management. The scoring system was developed based on a retrospective analysis of 91 patients with EPN. Nineteen risk factors for emphysematous pyelonephritis were assessed with univariate and multivariate analysis. Seven factors were found significant on analysis. The scoring system was developed by including these 7 risk factors: renal stone disease, leukocytosis, raised creatinine, EPN grade, and septic shock. The score ranged from 1 to 18, with a higher score indicating a worse prognosis. The scoring system was able to stratify patients into three risk groups: good risk, intermediate risk, and poor risk. The scoring system can be used to personalize the management of EPN. Patients in the good-risk group may be managed with conservative treatment, while patients in the intermediate-risk and poor-risk groups may require intervention, such as DJ stenting, percutaneous nephrolithotomy or nephrectomy. The scoring system is a valuable tool for predicting the prognosis of EPN and guiding management. It can help clinicians to tailor treatment to the individual patient and to improve outcomes. The prognostic score helps identify patients who are at high risk. This score helps in the selection of appropriate management options.

Safety and outcomes with use of FlowTriever for mechanical thrombectomy i n acute pulmonary embolism

Objectives: Mortality in the pulmonary embolism (PE) risk categories has historically been reported between 30% and 40% in high-risk and <15% in intermediate-risk group. In those who survive, there is a high rate of morbidity with dyspnea and exercise intolerance. Advanced therapies with a favorable safety profile have the potential to improve outcomes. We present the largest single-center data set studied to-date for safety, mortality, and outcomes post-mechanical thrombectomy including functional assessment 3 months post-discharge. Material and Methods: We analyzed retrospective database of patients with PE undergoing catheter directed mechanical thrombectomy (CDMT). We report clinical characteristics and outcomes stratified by PE risk categories. Comparison in the groups has been made using analysis of variance method. Results: A total of 365 patients were evaluated in the CDMT group. Among these 81 (22%) presented with high-risk and 261 (71%) with intermediate-risk PE. The average age at diagnosis was 61 ± 17 years with male-to-female distribution ratio of 1.2. Most common risk factors being reduced mobility (18%), malignancy (15%), recent surgery (13%), and hormonal therapy (12%). Mortality within 30 days of PE diagnosis was 8.6% (7/81) in high-risk, 1.7% (4/230) in intermediate-high-risk groups. There were no deaths in intermediate-low and low-risk group post-CDMT. Before thrombectomy, 349 (95%) patients had right heart strain, 307 (84%) had elevated troponin, and 197 (54%) had elevated B-type natriuretic peptide. Post-procedure echocardiogram at 3 month revealed improvement in the right ventricular (RV) fractional area change (27.53 ± 10.38% to 39.73 ± 8.3%, P < 0.01), tricuspid annular plane systolic excursion (10.9 ± 8.3 mm to 21.81 ± 4.75 mm), and RV systolic pressure (43.96 ± 14.48 mmHg to 28.47 ± 7.88 mmHg, P < 0.01). At 3 months post-thrombectomy, the majority (74%) of the patients fell into non-to-negligible functional limitation. Conclusion: We present a descriptive analysis of outcomes including improved mortality, and functional assessment of patients undergoing CDMT.

Clinical study of immune-targeting combined with attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma

Objective: To evaluate the efficacy and safety of brentuximab vedotin (BV) combined with rituximab and attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma (cHL). Methods: A prospective, non-randomized, risk-assigned study. Clinical data (including age, gender, B symptoms, bulky disease, CD30 and Epstein-Barr virus-encoded RNA(EBER) expression, clinical stage, risk stratification, etc.) of 28 intermediate to high-risk cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2022 to May 2024 were collected. Immuno-targeted combined with attenuated chemotherapy was administered based on risk stratification and early treatment response. The patients were followed up until May 1st, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 28 patients, there were 22 males and 6 females, the age was 12 (5,16) years, 16 cases (57%) presented with bulky disease and 10 cases (36%) with B symptoms. The most common pathological type was nodular sclerosis (14 cases, 50%). There were 7 cases of stage Ⅱ, 14 cases of stage Ⅲ and 7 cases of stage Ⅳ according to the Ann Arbor staging system. There were 5 cases in the intermediate-risk group and 23 cases in the high-risk group. EBER was positive in 20 cases (71%) and negative in 6 cases (21%), and CD30 antigen was expressed in tumor cells of all enrolled children. Treatment duration: 5 cases (18%) received 4 courses of treatment, 21 cases (75%) received 6 courses of treatment, and 2 cases (7%) received 8 courses of treatment, 25 cases (89%) achieved complete metabolism response (CMR) through early assessment after 2 courses of chemotherapy. The CMR rates were 100% in intermediate-risk group and 87% in high-risk group, respectively. Four patients (14%) finally received residual field radiotherapy. Toxicities included grade Ⅰ-Ⅱ myelosuppression, early infusion reaction and mild peripheral neuropathy, only one case of grade 3 adverse events was recorded and did not affect sequential treatment. At the end of treatment and 3 months of follow-up, the levels of IgA, IgG and IgM were all decreased compared with the baseline before chemotherapy, and the total B cell count began to be lower than the level before chemotherapy at the early stage of treatment (after 2 courses). The total B cell count monitored during treatment was 50 (0, 101)×106/L and was 12 (0, 25)×106/L at the end of treatment. The follow-up time was 6 (3, 13) months, all 28 children had event-free survival and all achieved complete remission. At 6 and 9 months of follow-up, IgA, IgG, IgM and total B cell counts returned to pre-chemotherapy baseline levels, respectively. Conclusion: BV combined with rituximab attenuated chemotherapy has demonstrated efficacy and a tolerable safety profile in the treatment of cHL in children, and significantly reduce radiation rate.

PRODIGY score predicts respiratory depression in the post-anesthesia care unit: A post-hoc analysis.

Surgical patients who experience respiratory depressive episodes (RDEs) during their post-anesthesia care unit (PACU) admission are at a higher risk of developing subsequent respiratory complications in general care wards. A risk assessment tool for PACU RDEs has not been previously assessed. The PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) score is an assessment tool that uses baseline patient variables to categorize patients into low, intermediate, or high risk groups for RDEs in general care wards. This study assessed whether PRODIGY groups are associated with PACU RDEs. This analysis utilized data from a previous observational trial of PACU RDEs detected by capnography. PRODIGY scores were retrospectively calculated, and the number and duration of respiratory alerts were compared among PRODIGY groups. Twenty-six (29.9%) patients were classified as low risk, 29 (33.3%) as intermediate risk, and 32 (36.8%) as high risk. A total of 3,580 alerts were recorded in the PACU, 47% of which were apnea episodes lasting ≥ 10 seconds. The total number and duration of alerts were highest in high risk group patients (median 56 [IQR 12 - 87] alerts per patient vs 22 [9 - 37] in low risk and 26 [13 - 42] in intermediate risk patients, P = 0.035; 303 [123 - 885] seconds vs 177 [30 - 779] in low risk and 301 [168 - 703] in intermediate risk patients, P = 0.042). Poisson regression analysis indicated that the rate of RDEs in the high PRODIGY risk group was higher than in the intermediate (rate ratio estimate = 2.01 [95% CI 1.86 - 2.18], P < 0.001) and low (rate ratio estimate = 2.25 [95% confidence interval 2.07 - 2.45], P < 0.001) risk groups. This analysis suggests that the PRODIGY score may be useful in assessing the risk of PACU RDEs. Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT02707003.

Development and validation of a lung cancer polygenic risk score incorporating susceptibility variants for risk factors.

Incorporating susceptibility genetic variants of risk factors has been reported to enhance the risk prediction of polygenic risk score (PRS). However, it remains unclear whether this approach is effective for lung cancer. Hence, we aimed to construct a meta polygenic risk score (metaPRS) of lung cancer and assess its prediction of lung cancer risk and implication for risk stratification. Here, a total of 2180 genetic variants were used to develop nine PRSs for lung cancer, three PRSs for different histopathologic subtypes, and 17 PRSs for lung cancer-related risk factors, respectively. These PRSs were then integrated into a metaPRS for lung cancer using the elastic-net Cox regression model in the UK Biobank (N = 442,508). Furthermore, the predictive effects of the metaPRS were assessed in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial (N = 108,665). The metaPRS was associated with lung cancer risk with a hazard ratio of 1.33 (95% confidence interval: 1.27-1.39) per standard deviation increased. The metaPRS showed the highest C-index (0.580) compared with the previous nine PRSs (C-index: 0.513-0.564) in PLCO. Besides, smokers in the intermediate risk group predicted by the clinical risk model (1.34%-1.51%) with the intermediate-high genetic risk had a 6-year average absolute lung cancer risk that exceeded the clinical risk model threshold (≥1.51%). The addition of metaPRS to the clinical risk model showed continuous net reclassification improvement (continuous NRI = 6.50%) in PLCO. These findings suggest the metaPRS can improve the predictive efficiency of lung cancer compared with the previous PRSs and refine risk stratification for lung cancer.

Clinical Utility of Genetic Variants in PNPLA3 and TM6SF2 to Predict Liver-Related Events in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Fibrosis-4 (FIB-4) index and genetic polymorphisms have been used in assessing the risk of liver-related events (LRE) in metabolic dysfunction-associated steatotic liver disease (MASLD). To establish a more efficient prediction strategy for LRE, we investigated a combined approach that uses the FIB-4 index and genetic polymorphisms. We enrolled 1304 Japanese patients with biopsy-proven MASLD in this longitudinal multicenter cohort study. PNPLA3, TM6SF2, GCKR and MBOAT7 genotypes were genotyped, and polygenic risk score high fat content (PRS-HFC) were calculated. During the follow-up period of 8.1 year, 96 LRE occurred and 53 patients died. PNPLA3, TM6SF2 and GCKR genotypes were associated with LRE development. We divided patients into three groups based on the FIB-4 index and PNPLA3 and TM6SF2 genotype. The cumulative LRE development rate in each group was 2.1%/28.9%/53.5%, respectively, at 10 years. Multivariate analysis revealed hazard ratios (HRs) for LRE of 10.72 in the high-risk group and 4.80 in the intermediate-risk group. Overall survival in each group was 98.8%/85.2%/72.4%, respectively, at 10 years. HRs for prognosis were 8.74 in the high-risk group and 5.62 in the intermediate-risk group. Patients with FIB-4 index > 2.67 and high PRS-HFC had HR of 6.70 for LRE development and HR of 6.07 for prognosis compared to patients with FIB-4 ≤ 2.67. The approach of measuring the FIB-4 index first followed by assessment of genetic polymorphisms efficiently detected patients at high risk of developing LRE. Therefore, this two-step strategy could be used as a screening method in large populations of patients with MASLD.

Prognostic factors and risk-stratification model of recurrent or metastatic head and neck squamous cell carcinoma treated with cetuximab containing regimen

BackgroundIn recent years, the addition of cetuximab to chemotherapy has improved treatment outcomes for patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In this study, we present the real-world survival data of R/M HNSCC patients who received cetuximab-containing regimens from thirteen medical centers in Taiwan, as well as a three-level risk stratification model for this patient population.MethodsThis study enrolled R/M HNSCC patients from thirteen medical centers in Taiwan who received cetuximab-containing regimens from January 1, 2017 to June 6, 2022. The cases were divided into a training cohort and a validation cohort based on the start of treatment. Overall survival (OS) was evaluated in both cohorts and exploratory analysis was performed to identify associated adverse clinical and laboratory factors. The results of the exploratory analysis were used to construct a three-level risk stratification prediction model for OS.ResultsA total of 1434 patients with R/M HNSCC were enrolled in this study and received cetuximab-containing regimens. The overall population had a median OS of 8.57 months (95% CI: 8.07 – 9.08). Multivariate analysis of the training cohort identified poor ECOG performance status, heavy alcohol consumption, and prior adjuvant CCRT or lack of prior RT as adverse prognostic factors. Comparison of laboratory data between patients with OS≦6 and OS > 6 also revealed unfavorable factors, including increased white blood cell count, decreased hemoglobin level, increased platelet count, increased absolute neutrophil count, decreased absolute lymphocyte count, and increased neutrophil-to-lymphocyte ratio. Using forward prediction, a three-level risk stratification prediction model was constructed using the variables of ECOG performance status, alcohol consumption, skin metastasis, modality of radiation therapy, hemoglobin level, and neutrophil-to-lymphocyte ratio. The median OS in the low-risk, intermediate-risk, and high-risk groups were 12.02 months (95% CI 10.44–13.61), 7.5 months (95% CI 7.33–8.17), and 4.01 months (95% CI 3.94–4.08), respectively, with a log-rank test p-value < 0.001.ConclusionThis study presents a three-level risk stratification model with strong prediction ability for OS in R/M HNSCC patients who received cetuximab-containing regimens. The results are based on real-world data and may provide valuable information for clinicians in treatment planning and future drug development.

CDKN2A Homozygous Deletion Is a Stronger Predictor of Outcome than IDH1/2-Mutation in CNS WHO Grade 4 Gliomas.

Background: We primarily investigated the prognostic role of CDKN2A homozygous deletion in CNS WHO grade 4 gliomas. Additionally, we plan to examine traditional prognostic factors for grade 4 gliomas and validate the findings. Materials: We conducted a retrospective analysis of the glioma cohorts at our institute. We reviewed medical records spanning a 15-year period and examined pathological slides for an updated diagnosis according to the 2021 WHO classification of CNS tumors. We examined the IDH1/2 mutation and CDKN2A deletion using NGS analysis with ONCOaccuPanel®. Further, we examined traditional prognostic factors, including age, WHO performance status, extent of resection, and MGMT promoter methylation status. Results: The mean follow-up duration was 27.5 months (range: 4.1-43.5 months) and mean overall survival (OS) was 20.7 months (SD, ±1.759). After the exclusion of six patients with a poor status of pathologic samples, a total of 136 glioblastoma cases diagnosed by previous WHO classification criteria were newly classified into 29 (21.3%) astrocytoma, IDH-mutant, and CNS WHO grade 4 cases, and 107 (78.7%) glioblastoma, IDH-wildtype, and CNS WHO grade 4 cases. Among them, 61 (56.0%) had CDKN2A deletions. The high-risk group with CDKN2A deletion regardless of IDH1/2 mutation had a mean OS of 16.65 months (SD, ±1.554), the intermediate-risk group without CDKN2A deletion and with IDH1/2 mutation had a mean OS of 21.85 months (SD, ±2.082), and the low-risk group without CDKN2A deletion and with IDH1/2 mutation had a mean OS of 33.38 months (SD, ±2.946). Multifactor analysis showed that age (≥50 years vs. <50 years; HR 4.645), WHO performance (0, 1 vs. 2; HR 5.002), extent of resection (gross total resection vs. others; HR 5.528), MGMT promoter methylation, (methylated vs. unmethylated; HR 5.078), IDH1/2 mutation (mutant vs. wildtype; HR 6.352), and CDKN2A deletion (absence vs. presence; HR 13.454) were associated with OS independently. Conclusions: The present study suggests that CDKN2A deletion plays a powerful prognostic role in CNS WHO grade 4 gliomas. Even if CNS WHO grade 4 gliomas have mutant IDH1/2, they may have poor clinical outcomes because of CDKN2A deletion.

Two simple modifications to the World Falls Guidelines algorithm improves its ability to stratify older people into low, intermediate and high fall risk groups.

We conducted a secondary analysis of a cohort study to examine the World Falls Guidelines algorithm's ability to stratify older people into sizable fall risk groups or whether minor modifications were necessary to achieve this. Six hundred and ninety-three community-living people aged 70-90years (52.4% women) were stratified into low, intermediate and high fall risk groups using the original algorithm and a modified algorithm applying broader Timed Up and Go test screening with a >10-s cut point (originally >15s). Prospective fall rates and physical and neuropsychological performance among the three groups were compared. The original algorithm was not able to identify three sizable groups, i.e. only five participants (0.7%) were classified as intermediate risk. The modified algorithm classified 349 participants (50.3%) as low risk, 127 participants (18.3%) as intermediate risk and 217 participants (31.3%) as high risk. The sizable intermediate-risk group had physical and neuropsychological characteristics similar to the high-risk group, but a fall rate similar to the low-risk group. The high-risk group had a significantly higher rate of falls than both the low- [incidence rate ratio (IRR) = 2.52, 95% confidence interval (CI) = 1.99-3.20] and intermediate-risk groups (IRR = 2.19, 95% CI = 1.58-3.03). A modified algorithm stratified older people into three sizable fall risk groups including an intermediate group who may be at risk of transitioning to high fall rates in the medium to long term. These simple modifications may assist in better triaging older people to appropriate and tailored fall prevention interventions.

The relationship between sarcopenia and metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and the prognostic value of sarcopenia in early-stage non-small cell lung cancer.

Patients with lung cancer face a heightened risk of developing sarcopenia. Despite this known risk, the impact of sarcopenia on the long-term prognosis of lung cancer patients, specifically concerning progression-free survival (PFS) and overall survival (OS), remains unclear. The primary objective of our study was to examine the correlation between metabolic parameters derived from 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and sarcopenia, as well as the prognostic value of sarcopenia in patients with surgically resected early-stage non-small cell lung cancer (NSCLC). In this retrospective cross-sectional study, we analyzed 187 NSCLC patients who underwent 18F-FDG PET/CT at the First Affiliated Hospital of Soochow University between March 2019 and October 2023. Patients were divided into two groups based on the presence (n=46) or absence (n=141) of sarcopenia. The correlation between sarcopenia, metabolic parameters, and patient characteristics was evaluated using chi-square and Mann-Whitney U tests. Survival analyses, including PFS and OS, were conducted using Kaplan-Meier analysis and Cox proportional hazards regression. Based on sarcopenia, metabolic parameters and patient characteristics, patients were classified into high-risk (n=28), intermediate-risk (n=121), and low-risk (n=38) groups. Our analysis identified gender, body mass index (BMI), psoas Hounsfield unit (HU), and maximum standardized uptake value of the psoas major muscle (SUVmax-Muscle) as independent predictors of sarcopenia (P<0.05 for all). A nomogram model, utilizing these parameters, was constructed to predict sarcopenia. Survival analysis further demonstrated that total lesion glycolysis [hazard ratio (HR) =2.499; 95% confidence interval (CI): 2.014-3.267; P=0.016], sarcopenia (HR =3.323; 95% CI: 1.748-6.316; P<0.001), and programmed death ligand-1 (PD-L1) expression (HR =0.093; 95% CI: 0.012-0.698; P=0.021) emerged as independent predictors of OS in early-stage NSCLC. Notably, patients categorized as high-risk, characterized by elevated total lesion glycolysis, presence of sarcopenia, and PD-L1 positivity, exhibited a significantly poorer prognosis compared to the intermediate-risk (P<0.05) and low-risk groups (P<0.05). Our findings indicated an inverse relationship between SUVmax-Muscle or psoas HU with the incidence of sarcopenia in NSCLC patients. Additionally, total lesion glycolysis, sarcopenia, and PD-L1 expression were identified as independent prognostic factors for OS in early-stage NSCLC. The risk stratification model, incorporating total lesion glycolysis, sarcopenia, and PD-L1 expression, assumed a pivotal role in guiding personalized therapy decisions and post-treatment monitoring.

Predictive utility of a combination of the modified caprini risk assessment score and D-dimer for the evaluation and management of lower extremity venous thrombosis after lung cancer surgery

ObjectiveThe objective of this study was to examine the utility of a combination of the modified Caprini score and D-dimer levels for the evaluation and management of lower extremity venous thrombosis following lung cancer surgery. The purpose was to offer insights for developing clinical intervention programs.MethodsThe study sample consisted of 224 patients who underwent surgery for lung cancer at the First Central Hospital of Baoding City. General patient data and D-dimer levels on the first day post-surgery were collected. The modified Caprini risk assessment score was calculated. All patients underwent ultrasonography of the lower limb veins before and after surgery to identify venous thrombosis in the lower limb veins. Differences in lower extremity venous thrombosis and D-dimer levels among patients in various modified Caprini score groups were compared and analyzed.ResultsBased on the modified Caprini risk assessment score, all patients were categorized into three groups: the low-risk, medium-risk, and high-risk groups. The groups did not differ significantly in terms of age, but the differences in the rates of lower extremity venous thrombosis in the low, intermediate, and high-risk Caprini risk groups (16.5%, 19.2%, and 37.1%, respectively) were statistically significant. Out of the total 224 patients, 47 (21%) were diagnosed with venous thromboembolisms post-surgery, and all of them had thrombosis of the intermuscular veins of the lower extremity. The difference in the modified Caprini risk assessment score between patients with and without lower extremity venous thrombosis was statistically significant (P = 0.035), as were the postoperative D-dimer levels (1.28 ± 1.64 vs. 2.69 ± 2.77, respectively; P < 0.05) between these two groups of patients. The modified Caprini risk assessment score showed an association with lower extremity venous thrombosis (r = 0.15, P = 0.56) with an area under the receiver operating characteristic curve (AUC) of 0.59.ConclusionIn this study, we found that combining the modified Caprini risk assessment score with D-dimer measurements enhanced the accuracy of assessing the severity of deep vein thrombosis (DVT). This combination can be beneficial in evaluating thrombosis risk post-lung cancer surgery and holds significant clinical utility.

Effect of hemoglobin, albumin, lymphocyte, and platelet score on prognosis in intermediate-risk endometrial cancer according to molecular-based classification.

The aim of this study is to compare the relationship between molecular classification and HALP score in endometrial cancer (EC). Patients who were operated with the diagnosis of EC 2014 and 2024 were included in our study. 150 patients were included in the study. We divided the patients into three groups in terms of molecular classification; group 1 was the patients with POLE mutation, group 2 was the patients with MMRd and NSMP (intermediate prognosis), and group 3 was the patients with p53 mutation. Group 2 participants were divided into two groups, a low HALP score group and a high HALP score group, according to the HALP score cut-off value. Using the value with the highest Youden's index (0.306) as a basis, it was demonstrated that the HALP score with a cut-off value of 33.735 has a sensitivity of 61.86% and a specificity of 68.75% in intermediate-risk EC. The 5-year overall survival (OS) was found to be 75.4% in intermediate-risk EC patients with low HALP scores and 91.5% in intermediate-risk EC patients with high HALP scores (p = 0.008). The 5-year progression-free survival (PFS) was found to be 86% in intermediate-risk EC patients with low HALP scores and 94.4% in intermediate-risk EC patients with high HALP scores (p = 0.089). MMR deficiency and NSMP have been considered intermediate-risk groups for endometrial cancer and are a heterogeneous group. Although the use of the HALP score to reduce this heterogeneity is successful in predicting OS, it is not sufficient for PFS.

Impact of 18FDG PET/CT on Clinical Management, Cost Effectiveness, and Radiation Exposure in Newly Diagnosed Breast Cancer Patients.

For the initial staging of breast cancer (BC), 18FDG PET/CT is recommended by professional guidelines in stage III (except T3N1) and inflammatory BC (T4d) and optional when conventional imaging is equivocal or suspicious. However, growing evidence also supports its role in the staging of intermediate-risk groups (IIA, IIB, T3N1 of IA). This study aimed to compare the impact of 18FDG PET/CT with conventional imaging (CT-chest+abdomen+pelvis and bone scan; CT-CAP+BS) in staging, cost-effectiveness, and radiation exposure in the initial staging of BC. A retrospective study (April 2020 2024) included 115 biopsy-proven BC patients who had CT-CAP+BS and 18FDG PET/CT for initial staging. Data were analyzed to see the impact of 18FDG PET/CT on change in staging, cost-effectiveness, and radiation exposure compared to CA-CAP+BS. Out of 115 patients (113 female and 02 male), 110 had unilateral and 5 had bilateral BC (Invasive Ductal Ca. 107; Non-IDC: 08) with non-significant laterality. The overall upstaging rate for regional nodal and/or distant metastases was 36% (24/66; excluded 49 with stage IV). The overall upstaging rate due to unsuspected higher nodal metastases was 20% (predominantly stage IIA, and IIB). Upstaging rate to stage IV was seen in 17% (11/66; predominantly in IIIA-C). The overall concordance (no change in staging) was seen in 64% (42/66) while no downstaging was found in any patient. In patients with stage-IV disease (n = 49), 18FDG PET/CT identified a higher number of hypermetabolic lesions in 18 (37%), lesser in 07 (14%), and similar in 24 (49%) cases. The estimated cost in Pak rupees for CT-CAP+BS and PET/CT was 139000 and 106000 respectively. The mean effective dose imparted by 18FDG PET/CT was 8.85 mSv compared to the reported 26.6 mSv by CT-CAP+BS. We conclude that in the initial staging of BC, 18FDG PET/CT compared with CT-CAP+BS has a significant impact on decision-making by upstaging the disease in stage II and III and detecting more metastatic lesions in stage-IV disease. Furthermore, 18FDG PET/CT is more cost-effective and imparts significantly lower radiation exposure as compared with CT+CAP+BS. These findings support the inclusion of 18FDG PET/CT in the initial staging of stage II-IV BC.

Prognostic model for second progression-free survival and overall survival in patients with high-risk metastatic hormone-sensitive prostate cancer treated with abiraterone acetate and androgen deprivation therapy.

To develop and validate a prognostic risk model for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with upfront abiraterone acetate (ABI). This retrospective multicenter study involved 233 high-risk mHSPC patients who received upfront ABI, developed by three academic centers. The model was externally validated with an independent cohort of 282 patients. To identify independent prognostic factors for second progression-free survival (PFS2) and develop the best-fitted model, Cox proportional hazards regression, followed by the Akaike information criterion, was used. Patients were categorized into three groups based on their risk scores. PFS2 and overall survival (OS) were evaluated according to the risk groups in the discovery and validation cohorts. The median age was 72 (range 51-89) years, with a median follow-up duration of 27 months. Independent factors linked to PFS2 included an Eastern Cooperative Oncology Group performance status ≥2, a primary Gleason score of 5, an extent of disease score of ≥3 or liver metastasis, and lactate dehydrogenase >220 U/L. Median PFS2 for favorable-, intermediate-, and poor-risk groups were not reached, 43 months, and 16 months, respectively. The median OS was 29 months in the poor-risk group, whereas it was not reached in the favorable- and intermediate-risk groups. The 2-year OS rates in the favorable-, intermediate- and poor-risk groups were 94.5%, 80.1%, and 60.3%, respectively. The validation cohort confirmed the risk model's relationship with PFS2 and OS. The median PFS2 and OS in the high-risk group were 21 months and 32 months, respectively. Our prognostic model, including five clinical factors, is useful for patient care and treatment selection in high-risk mHSPC patients treated with ADT plus ABI. The developed model could provide more accurate information, guide treatment decisions, or classify patients in future clinical trials.

Comprehensive Risk Assessment in Patients With Pulmonary Arterial Hypertension Referred for Lung Transplantation.

Whether comprehensive risk assessment predicts post-referral outcome in patients with pulmonary arterial hypertension (PAH) referred for lung transplantation (LT) in Japan is unknown. We retrospectively analyzed 52 PAH patients referred for LT. Risk status at referral was assessed using 3- and 4-strata models from the 2022 European Society of Cardiology and European Respiratory Society guidelines. The 3-strata model intermediate-risk group was further divided into 2 groups based on the median proportion of low-risk variables (modified risk assessment [MRA]). The primary outcome was post-referral mortality. During follow-up, 9 patients died and 13 patients underwent LT. There was no survival difference among 3-strata model groups. The 4-strata model classified 33, 16, and 3 patients as low intermediate, high intermediate, and high risk, respectively. The 4-strata model identified high-risk patients with a 1-year survival rate of 33%, but did not discriminate survival between the intermediate-risk groups. The MRA classified 15, 28, 8, and 1 patients as low, low intermediate, high intermediate, and high risk, respectively. High intermediate- or high-risk patients had worse survival (P<0.001), with 1- and 3-year survival rates of 64% and 34%, respectively. MRA high intermediate- or high-risk classification was associated with mortality (hazard ratio 12.780; 95% confidence interval 2.583-63.221; P=0.002). Patients classified as high intermediate or high risk by the MRA after treatment should be referred for LT.

Efficacy of postoperative radioactive iodine therapy for patients with low and intermediate risk papillary thyroid carcinoma.

This study aimed to evaluate the efficacy of postoperative radioactive iodine (RAI) and its impact on recurrence rates and survival benefits in low- to intermediate-risk papillary thyroid carcinoma (PTC). This retrospective study involved the examination of 1286 patients diagnosed with low- to intermediate-risk PTC who underwent total thyroidectomy with or without neck dissection, supplemented with postoperative RAI therapy or not between the years 2000 and 2021. From the patient pool, 589 (45%) were classified as low-risk and 697 (55%) as intermediate-risk according to the 2015 American Thyroid Association guidelines. Among the low-risk group, 375 (63.7%) underwent postoperative RAI, while in the intermediate-risk group, 566 (82.2%) underwent the procedure. The overall survival and disease-free survival rates were not statistically different between the groups that received RAI and those that did not, in both the low- and intermediate-risk categories. In a subgroup analysis, within the intermediate-risk category, postoperative RAI was significantly correlated with decreased recurrence in two subgroups: patients over 55 years with pN1b disease (hazard ratio 0.043, 95% confidence interval 0.004-0.500, p = 0.012) and patients over 55 years with five or more metastatic lymph nodes (hazard ratio 0.060, 95% confidence interval 0.005-0.675, p = 0.023). Our findings suggest that, while post-total thyroidectomy RAI does not substantially influence recurrence or survival rates in most low-risk and intermediate-risk PTC patients, it may be beneficial in specific subgroups, particularly patients over 55 with pN1b disease or those presenting with five or more metastatic lymph nodes.