Chronic antiepileptic drug use and functional network efficiency: A functional magnetic resonance imaging study

Pre- Transplant Ferritin Predicts Overall Survival and Non-Relapse Mortality in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Myelofibrosis

Considering Bone Marrow Blasts from Nonerythroid Cellularity Improves the Prognostic Evaluation of MDS in the Context of IPSS-R and Permits a Better Risk Assessment of MDS Patients Classified into the Intermediate Risk Category

Coronary Calcium Score Improves Classification of Coronary Heart Disease Risk in the Elderly: The Rotterdam Study

Background:Despite the overall good prognosis of follicular lymphoma (FL), approximately 20 to 30% of the cases experience early progression after first line therapy and suffer adverse survival (Casulo et al., 2015; Shi et al., 2017). Several efforts have been made to identify pre‐treatment factors useful to assess prognosis, however currently available parameters do not allow to accurately stratify patients before treatment. Lymphocyte to monocyte ratio (LMR) has been previously identified as an useful prognostic markers in diffuse large B‐cell lymphoma treated with Rituximab‐based chemotherapy (Rambaldi et al., 2013).Aims:In this study we aimed to evaluate the potential role of LMR in identifying patients with FL experiencing early progression after first line therapy.Methods:831 patients with a diagnosis of grade 1–3a FL were identified in the Bergamo Lymphoid Cancer Registry (NCT03131531) between 1983 to 2017. Cases managed with watchful observation after diagnosis (N = 145) or receiving local therapy (N = 121) or without adequate clinical information or follow‐up data (N = 117) were excluded from the analysis. The remaining patients (N = 448) with stage II‐IV disease and receiving first line chemotherapy at diagnosis were included in the study. The majority of the patients were treated with Rituximab‐based therapy (72%). Chemotherapy regimens included CHOP (N = 298), CVP (N = 76), Bendamustine (N = 22), Chlorambucil (N = 34) or others (N = 18). Rituximab maintenance was administered to 61 patients.Patients with early progression were defined as those with a PFS event before 30 months from first‐line treatment start (PFS30). Receiver operating characteristic (ROC) analysis was performed to assess the optimal cut‐off of LMR to predict PFS30. Kaplan‐Meyer curves, log‐rank tests and Cox models were used for survival analyses.Results:In the study population, 26% of the patients experienced early progression and were characterized by a shorter median OS compared to the other group (6.3 vs 17 years, P < 0.0001, Figure 1A). The optimal cut‐off of LMR to predict PFS30 was identified, with patients with LMR ≤2 or >5.2 (N = 176) being at higher risk for a PFS event compared to those with LMR >2 and ≤5.2 (N = 272) (Figure 1B). In multivariate analysis for PFS, LMR retained its significance independently from FLIPI (P = 0.0001). The simple addition of LMR to standard FLIPI permitted to refine patient prognosis in terms of PFS (Figure 1C) and OS (Figure 1D), with three groups identified i.e. low risk (FLIPI low and favorable LMR), intermediate risk (FLIPI low and unfavorable LMR; FLIPI int or high and favorable LMR) and high risk (FLIPI int or high and unfavorable LMR). Specifically, 57 (36%) patients with intermediate FLIPI were upgraded in the high risk category and 80 (54%) high risk FLIPI were downgraded into the intermediate one. Patients in the new high risk category were characterized by a 42% probability to have a PFS event before 30 months, compared to the 22% and 10% of the intermediate and low risk group, respectively. LMR was significantly associated with OS in univariate analysis (P = 0.047), but not in multivariate analysis with FLIPI (P = 0.11). The combined LMR and FLIPI index predicted survival with a 30‐months OS of 96%, 94% and 85% in the low, intermediate and high risk category, respectively (P = 0.0032).Summary/Conclusion:LMR is a significant prognostic factor for PFS in FL, independent from FLIPI and closely related to the use of Rituximab. The combination of LMR with currently available prognostic markers can be useful in identifying high patient before the start of first line treatment.image

BackgroundOncotype DX (ODx) is a 12-gene assay assessing the recurrence risk (high, intermediate, and low) of ductal carcinoma in situ (pre-invasive breast cancer), which guides clinicians regarding prescription of radiotherapy. However, ODx is expensive, time-consuming, and tissue-destructive. In addition, the actual prognostic meaning for the intermediate ODx risk category remains unclear.MethodsIn this work, we evaluated the ability of quantitative nuclear histomorphometric features extracted from hematoxylin and eosin-stained slide images of 62 ductal carcinoma in situ (DCIS) patients to distinguish between the corresponding ODx risk categories. The prognostic value of the identified image signature was further evaluated on an independent validation set of 30 DCIS patients in its ability to distinguish those DCIS patients who progressed to invasive carcinoma versus those who did not. Following nuclear segmentation and feature extraction, feature ranking strategies were employed to identify the most discriminating features between individual ODx risk categories. The selected features were then combined with machine learning classifiers to establish models to predict ODx risk categories. The model performance was evaluated using the average area under the receiver operating characteristic curve (AUC) using cross validation. In addition, an unsupervised clustering approach was also implemented to evaluate the ability of nuclear histomorphometric features to discriminate between the ODx risk categories.ResultsFeatures relating to spatial distribution, orientation disorder, and texture of nuclei were identified as most discriminating between the high ODx and the intermediate, low ODx risk categories. Additionally, the AUC of the most discriminating set of features for the different classification tasks was as follows: (1) high vs low ODx (0.68), (2) high vs. intermediate ODx (0.67), (3) intermediate vs. low ODx (0.57), (4) high and intermediate vs. low ODx (0.63), (5) high vs. low and intermediate ODx (0.66). Additionally, the unsupervised clustering resulted in intermediate ODx risk category patients being co-clustered with low ODx patients compared to high ODx.ConclusionOur results appear to suggest that nuclear histomorphometric features can distinguish high from low and intermediate ODx risk category patients. Additionally, our findings suggest that histomorphometric features for intermediate ODx were more similar to low ODx compared to high ODx risk category.

Background The management of asymptomatic intracranial meningiomas is controversial. Through the assessment of growth predictors, we aimed to create the basis for practicable clinical pathways for the management of these tumors. Material and Methods We volumetrically analyzed meningiomas radiologically diagnosed at our institution between 2003 and 2015. For this purpose, we used exclusively thin-layered MR images (i.e. ≤ 2mm slice thickness). The primary endpoint was tumor growth defined as a 14.35% increase in tumor volume. We identified predictive clinical and radiological characteristics and used the significant variables from a multivariable regression model to construct a decision tree based on the exhaustive Chi-squared Automatic Interaction Detection (exhaustive CHAID) algorithm. Results Of 240 meningiomas, 159 (66.3%) demonstrated growth during a mean observation period of 46.9 months. On multivariable logistic regression analysis, older age (OR=0.979 (0.958-1.000), p=0.048) and presence of calcification (OR=0.442 (0.224-0.872), p=0.019) had a negative predictive value for tumor growth, while T2-signal iso-/hyperintensity (OR=4.415 (2.056-9.479), p<0.001) had a positive predictive value. A decision tree model yielded three growth risk groups based on T2-signal intensity and presence of calcifications with a proportion of growing tumors of 34.1% in the low risk group, 60.0% in the intermediate risk group and 80.2% in the high risk group. Median tumor volume doubling time (Td) was 185.7 months in the low risk, 100.1 months in the intermediate risk and 51.7 months in the high risk group (p<0.001). While 0% of meningiomas in the low and intermediate risk group had a Td of ≤12 months, 8.9% in the high risk group did so (p=0.021). Conclusion Most meningiomas demonstrated growth during follow-up. The presence or absence of calcifications and the signal intensity on T2-weighted imaging allow a practical and simple stratification of meningiomas into low, intermediate and high risk tumors. Small tumors in the low or intermediate risk categories can be monitored with longer follow-up intervals, whereas in the high risk category proactive management decisions can be justified.

To describe the clinical features of a paediatric cohort affected by differentiated thyroid cancer (DTC) followed in a tertiary Department of Paediatric Endocrinology. Clinical data of 41 patients affected by DTC in the 2000-2020 period were reviewed. The main risk factor was autoimmune thyroiditis (39%). Cytological categories were TIR3b in 39%, TIR4 in 9.8%, TIR5 in 51.2%. After total thyroidectomy, radioiodine treatment was performed in 38 subjects (92.7%). ATA low-risk category was assigned in 11 (30.5%), intermediate-risk category in 15 (41.7%), and high-risk category in 10 patients (27.8%). Age at diagnosis was 15.1 ± 0.92 years in low-risk category, 14.7 ± 0.59 in intermediate-risk category, 11.7 ± 0.89 years in high-risk category (p = 0.01). TIR3b was manly observed in low-risk class (63.6%), while TIR5 was mainly reported in intermediate and high-risk class (60 and 80% respectively) (p = 0.04). Post-surgery stimulated thyroglobulin was increased in high-risk class (407.8 ± 307.1 ng/ml) [p = 0.04]. Tumour size was larger in high-risk category (42.6 ± 2.6 mm), than in low and intermediate-risk categories (19.4 ± 3.5 mm and 28.5 ± 3.9 mm, respectively) (p = 0.008). Patients in intermediate and high-risk categories displayed more tumour multifocality (60 and 90% respectively) (p < 0.005). Disease relapse was mainly observed in high risk category (40%, p = 0.04). DTC in childhood is more aggressive than in adults, but the overall survival rate is excellent. The therapeutic approach is still heterogeneous, especially in low-risk category. Further studies are needed to standardise management and reduce disease persistence in childhood.

ObjectivesClinical presentations of giant cell arteritis (GCA) are protean, and it is vital to make a secure diagnosis and exclude mimics for urgent referrals with suspected GCA. The main objective...

PD63-04 ALL HIGH-GRADE NMIBC IS HIGH RISK: BCG RESPONSE IN HIGH-GRADE TA TUMORS

Evaluation of The Society of Thoracic Surgeons Online Risk Calculator for Assessment of Risk in Patients Presenting for Aortic Valve Replacement After Prior Coronary Artery Bypass Graft: An Analysis Using the STS Adult Cardiac Surgery Database

In this study, we confirm the validity of the proposed Hammersmith score, which identifies three risk categories of patients and establish its strength on a large group of 128 chronic myeloid leukemia patients treated with second-generation tyrosine kinase inhibitors (TKIs) after being resistant to imatinib. Sixty-one patients were identified as good risk group, 27 patients as intermediate risk group, and 40 patients as poor risk group. The 1-year cumulative incidence of complete cytogenetic response was 73% in good risk patients, 40% in intermediate risk patients, and 22% in poor risk patients (P = 0.0001). Event-free survival at 3-year was 89% in good risk group, 70% in intermediate group, and 54% in poor risk group (P = 0.0001); the estimated 3-year progression-free survival was 95% in good risk category, 93% in intermediate risk category, and 87% in poor risk category (P = 0.05). Kaplan-Meier estimated that the 3-year overall survival was 100% in good risk category, 93% in intermediate risk category, and 82% in poor risk category (P = 0.04). In conclusion, some prognostic factors before starting second-generation TKIs might predict cytogenetic response and outcome. The so-called Hammersmith score was not yet validated in large series of patients: we demonstrated that this score is able to discriminate patients at high risk of failure and consequent progression before treatment with second-generation TKIs.

Can U.S. Prostate Brachytherapy Results be Reproduced in Europe?

BackgroundThe extent to which multiple cardiovascular and metabolic co‐morbidity and genetic factors combine or interact to increase dementia risk is unknown.MethodWe analysed 435 105 participants from the UK Biobank prospective cohort of European ancestry, aged 40 to 72 years, without dementia at baseline (2006‐2010), followed until 2021. A cardiometabolic multimorbidity index with a point given for co‐morbid stroke, diabetes and heart disease (myocardial infarction, atrial fibrillation or heart failure) was calculated for each participant along with a polygenic risk score for dementia with low (lowest quintile), intermediate (quintiles 2 to 4) and high (highest quintile) risk categories. The primary outcome was incident all‐cause dementia during follow‐up.ResultParticipants with both a high genetic risk and a cardiometabolic multimorbidity index of two or greater had an increased risk of developing dementia, hazard ratio of 5.01(95% confidence interval 3.35 ‐ 7.49), compared to those with a low genetic risk and no cardiometabolic conditions. The risk of developing dementia increased monotonically with increasing cardiometabolic morbidity. Crucially, there was no interaction between cardiometabolic multimorbidity and polygenic risk (P = 0.11).ConclusionCardiometabolic multimorbidity was independently associated with higher dementia risk, compared with genetic dementia risk. Addressing cardiometabolic multimorbidity may help to reduce dementia risk regardless of genetic risk.

ABSTRACTObjective : The reclassification of the risk according to the response to the initial treatment makes the treatment of differentiated thyroid cancer (DTC) vary in each individual. As the influence of age on this diagnostic strategy is unknown, we have decided to assess it in adults who are over 60 years of age.Subjects and methods : Ninety patients with DTC above 60 years old were enrolled, with total thyroidectomy plus radioiodine ablation, negative anti-thyroglobulin antibodies, follow-up ≥ 2 years and with clinical and pathological information to classify the risk of recurrence according to ATA (American Thyroid Association) and reclassify based on the response to initial therapy according to MSKCC (Memorial Sloan Kettering Cancer Center). The structural persistence at the end of the follow-up was the gold standard of our analysis.Results : The structural persistence in ATA low, intermediate and high risk categories was 0, 38, and 100%, respectively. In the intermediate group, none of those with an excellent response to the initial treatment showed structural persistence, whereas 39% of those with an incomplete/indeterminate response showed structural persistence (p < 0.01).Conclusions The re-stratification according to the response to the initial treatment in patients over 60 years of age with an ATA intermediate risk of recurrence allowed for the distinction of disease-free patients at the end of the follow-up from those with structural persistence and a worse clinical progression.

Background: Frailty and HF often co-exist identifying a population at increased risk for CV events. While perceived frailty may be a potential driver of clinical inertia, conventional HF therapy may reduce worsening HF and hospitalization which can lead to progressive frailty. Few contemporary data exist examining longitudinal patterns of GDMT use according to frailty status. Methods: In this retrospective nationwide cohort study, we identified 548, 841 patients with a new diagnosis of HFrEF in a 100% Medicare Fee for service sample with available data for Part D medication use between January 2016 to December 2023. Frailty was assessed using the Hospital Frailty Risk Score (HFRS) derived from ICD-10 codes and patients were categorized as low (HFRS&lt;5), intermediate (HFRS 5-15) and high (HFRS&gt;15) frailty risk. Optimal quadruple GDMT was defined as ≥ 50% of the target daily dose of beta blocker and ACEi/ARB or any dose of ARNI, MRA or SGLT2i. Time to optimal GDMT use according HFRS category was assessed using cumulative incidence curves. Results: Among 548, 841 patients with a new diagnosis of HFrEF, the mean age was 77 ± 11 years, 48% were women and the median HFRS was 77. 123,798(23%), 239,669 (44%) and 185,374 (34%) of patients were categorized as low, intermediate and high frailty risk, respectively. Compared to patients in the lowest frailty risk category, patients in the intermediate (HR 1.38; 95%CI: 1.35-1.41) and high risk(HR1.95; 95%CI: 1.90-2.00) categories experienced greater risk of mortality. The proportional use of optimal GDMT was lowest among patients with the highest levels of frailty at baseline (low: 7.7%; intermediate: 6.3%, high: 3.4%; P&lt;0.0001) and remained suboptimal at 12 months (low: 11.9%; intermediate: 9.2%, high: 5.4%; P&lt;0.0001); Figure 1 . Among patient not on optimal GDMT at baseline, patients with the highest frailty risk had a significantly lower probability of achieving optimal GDMT in follow up(P&lt;0.001); Figure 1 . Achievement of optimal GDMT in follow up was associated with a substantially lower risk of subsequent 1 year mortality (HR 0.50; 95%CI: 0.47-0.52) independent of frailty burden (P&lt;0.0001). Conclusion: In this nationwide cohort of newly diagnosed HFrEF, approximately 1 in 3 patients had high frailty risk. Such patients experienced worse outcomes and both the lowest proportional use and greatest time to optimal GDMT in follow up highlighting significant implementation gaps in this high-risk population.