Additional Prognostic Information Research Articles

Optical genome mapping reveals additional prognostic information compared to conventional cytogenetics in AML/MDS patients.

Cytogenetic diagnostics play a crucial role in risk stratification and classification of myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), thus influencing treatment decisions. Optical genome mapping (OGM) is a novel whole genome method for the detection of cytogenetic abnormalities. Our study assessed the applicability and practicality of OGM as diagnostic tool in AML and MDS patients. In total, 27 patients with AML or MDS underwent routine diagnostics including classical karyotyping and fluorescence in situ hybridization (FISH) or real-time PCR analysis wherever indicated as well as OGM following a recently established workflow. Methods were compared regarding concordance and content of information. In 93%, OGM was concordant to classical karyotyping and a total of 61 additional variants in a predefined myeloid gene-set could be detected. In 67% of samples the karyotype could be redefined by OGM. OGM offers a whole genome approach to cytogenetic diagnostics in AML and MDS with a high concordance to classical cytogenetics. The method has the potential to enter routine diagnostics as a gold standard for cytogenetic diagnostics widely superseding FISH. Furthermore, OGM can serve as a tool to identify genetic regions of interest and future research regarding tumor biology.

Health-related quality of life in neuromyelitis optica spectrum disorder patients in an Argentinean cohort

BackgroundWe aimed to describe the health-related quality of life (HRQoL) in patients with neuromyelitis optica spectrum disorders (NMOSD), to compare HRQoL between NMOSD patients, multiple sclerosis (MS), and healthy controls (HC) and to study the associations between HRQoL and the clinical variables of the disease. MethodsA cross-sectional study was carried out. Patients with NMOSD seropositive, MS, and HC were enrolled and age-matched. The HRQoL was studied using the Argentinean validation of the SF-36 health questionnaire. Demographic and clinical characteristics were analyzed, as well as the EDSS and the total scores and subscales of the SF-36. Results243 individuals were included (NMOSD= 53, MS =100, and HC =90). The mean EDSS was 3.06 ± 2.01 in NMOSD and 2.67 ± 1.83 in MS with a mean of disease duration of 6.2 ± 4.4 and 6.3 ± 5.3 years, respectively. Significant statistical differences were observed in the total SF-36 score between both NMOSD and MS vs. HC (p < 0.01), but no differences were found when the total SF-36 score was compared between NMOSD vs. MS. Overall, NMOSD patients scored significantly lower in the total SF-36 and subscale scores compared to HC (p< 0.05). NMOSD patients also showed significant differences in bodily pain (58.8 ± 29.8 vs 75.1 ± 25.1, p < 0.01) and general health (44.4 ± 20.9 vs.31.9 ± 23.1, p < 0.01) when compared with MS, but no differences were found after comparing the rest of the subscales. We found that higher EDSS scores (β -1.28 p = 0.03) and disease duration (β 0.8, p = 0.02) were significantly associated to lower (worse) general health (dependent variable) score in NMOSD patients after having applied multiple linear regression analysis. Additionally, we observed that higher EDSS scores (β -10.2 p = 0.008) and the presence of relapses in the previous year (β -28.9, p = 0.02) were significantly associated to lower (worse) physical functioning (dependent variable) score. ConclusionPain seems to be a significant undertreated symptom in NMOSD patients that strongly impact on HRQoL. Patient-reported HRQoL scales scores provide comprehensive additional prognostic information beyond physical disability score.

Association of Plaque Location and Vessel Geometry Determined by Coronary Computed Tomographic Angiography With Future Acute Coronary Syndrome–Causing Culprit Lesions

Distinct plaque locations and vessel geometric features predispose to altered coronary flow hemodynamics. The association between these lesion-level characteristics assessed by coronary computed tomographic angiography (CCTA) and risk of future acute coronary syndrome (ACS) is unknown. To examine whether CCTA-derived adverse geometric characteristics (AGCs) of coronary lesions describing location and vessel geometry add to plaque morphology and burden for identifying culprit lesion precursors associated with future ACS. This substudy of ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a multicenter nested case-control cohort study, included patients with ACS and a culprit lesion precursor identified on baseline CCTA (n = 116) and propensity score-matched non-ACS controls (n = 116). Data were collected from July 20, 2012, to April 30, 2017, and analyzed from October 1, 2020, to October 31, 2021. Coronary lesions were evaluated for the following 3 AGCs: (1) distance from the coronary ostium to lesion; (2) location at vessel bifurcations; and (3) vessel tortuosity, defined as the presence of 1 bend of greater than 90° or 3 curves of 45° to 90° using a 3-point angle within the lesion. Association between lesion-level AGCs and risk of future ACS-causing culprit lesions. Of 548 lesions, 116 culprit lesion precursors were identified in 116 patients (80 [69.0%] men; mean [SD], age 62.7 [11.5] years). Compared with nonculprit lesions, culprit lesion precursors had a shorter distance from the ostium (median, 35.1 [IQR, 23.6-48.4] mm vs 44.5 [IQR, 28.2-70.8] mm), more frequently localized to bifurcations (85 [73.3%] vs 168 [38.9%]), and had more tortuous vessel segments (5 [4.3%] vs 6 [1.4%]; all P < .05). In multivariable Cox regression analysis, an increasing number of AGCs was associated with a greater risk of future culprit lesions (hazard ratio [HR] for 1 AGC, 2.90 [95% CI, 1.38-6.08]; P = .005; HR for ≥2 AGCs, 6.84 [95% CI, 3.33-14.04]; P < .001). Adverse geometric characteristics provided incremental discriminatory value for culprit lesion precursors when added to a model containing stenosis severity, adverse morphological plaque characteristics, and quantitative plaque characteristics (area under the curve, 0.766 [95% CI, 0.718-0.814] vs 0.733 [95% CI, 0.685-0.782]). In per-patient comparison, patients with ACS had a higher frequency of lesions with adverse plaque characteristics, AGCs, or both compared with control patients (≥2 adverse plaque characteristics, 70 [60.3%] vs 50 [43.1%]; ≥2 AGCs, 92 [79.3%] vs 60 [51.7%]; ≥2 of both, 37 [31.9%] vs 20 [17.2%]; all P < .05). These findings support the concept that CCTA-derived AGCs capturing lesion location and vessel geometry are associated with risk of future ACS-causing culprit lesions. Adverse geometric characteristics may provide additive prognostic information beyond plaque assessment in CCTA.

Physical activity and its trajectory over time and clinical outcomes in hemodialysis patients.

We examined whether physical activity measured at starting point and its trajectory over time were simultaneously associated with vital prognosis. This retrospective cohort study included 295 ambulatory maintenance hemodialysis patients (mean age 63.9years; 54.6% male). We measured physical activity at index date (starting point) and its change over 1year as predictors, and all-cause death and cardiovascular events were assessed as the outcomes. Two groups each of high versus low physical activity at starting point (based on 4000 steps per day) and no decline versus decline (based on a predicted mean slope) were created. Cox proportional-hazards regression and Fine-Gray proportional sub-distribution hazards model were used to examine associations between physical activity and its trajectory and clinical outcomes. Decline in physical activity over 1year was associated with a higher risk of all-cause death and cardiovascular events, irrespective of the physical activity at starting point. Furthermore, both lower physical activity at starting point and decrease in physical activity over time were independently associated with a higher risk of all-cause death and cardiovascular events in models in which each exposure was mutually adjusted. Compared to other groups that worsened in either exposure, the lowest risk for death/cardiovascular events was observed in the high at starting point/no decline over time group. Both physical activity at starting point and its change over time were independently associated with vital prognosis. The assessment of both exposures provides additional prognostic information for the assessment of each exposure.

Development and validation of a RNAseq signature for prognostic stratification in endometrial cancer

BackgroundDespite recent advances in endometrial carcinoma (EC) molecular characterization, its prognostication remains challenging. We aimed to assess whether RNAseq could stratify EC patient prognosis beyond current classification systems. MethodsA prognostic signature was identified using a LASSO-penalized Cox model trained on TCGA (N = 543 patients). A clinically applicable polyA-RNAseq-based work-flow was developed for validation of the signature in a cohort of stage I-IV patients treated in two Hospitals [2010–2017]. Model performances were evaluated using time-dependent ROC curves (prediction of disease-specific-survival (DSS)). The additional value of the RNAseq signature was evaluated by multivariable Cox model, adjusted on high-risk prognostic group (2021 ESGO-ESTRO-ESP guidelines: non-endometrioid histology or stage III-IVA orTP53-mutated molecular subgroup). ResultsAmong 209 patients included in the external validation cohort, 61 (30%), 10 (5%), 52 (25%), and 82 (40%), had mismatch repair-deficient, POLE-mutated, TP53-mutated tumors, and tumors with no specific molecular profile, respectively. The 38-genes signature accurately predicted DSS (AUC = 0.80). Most disease-related deaths occurred in high-risk patients (5-years DSS = 78% (95% CI = [68%–89%]) versus 99% [97%–100%] in patients without high-risk). A composite classifier accounting for the TP53-mutated subgroup and the RNAseq signature identified three classes independently associated with DSS: RNAseq-good prognosis (reference, 5-years DSS = 99%), non-TP53 tumors but with RNAseq-poor prognosis (adjusted-hazard ratio (aHR) = 5.75, 95% CI[1.14–29.0]), and TP53-mutated subgroup (aHR = 5.64 [1.12–28.3]). The model accounting for the high-risk group and the composite classifier predicted DSS with AUC = 0.84, versus AUC = 0.76 without (p = 0.01). ConclusionRNA-seq profiling can provide an additional prognostic information to established classification systems, and warrants validation for potential RNAseq-based therapeutic strategies in EC.

Prognostic value of the MELD-XI score in patients undergoing cardiac resynchronization therapy.

AimsMulti‐organ dysfunction was recently reported to be a common condition in patients with heart failure (HF). The Model for End‐stage Liver Disease eXcluding International normalized ratio (MELD‐XI) score reflects liver and kidney function. The prognostic relevance of this score has been reported in patients with a variety of cardiovascular diseases who are undergoing interventional therapies. However, the relationship between the severity of hepatorenal dysfunction assessed by the MELD‐XI score and the long‐term clinical outcomes of HF patients receiving cardiac resynchronization therapy (CRT) has not been evaluated.Methods and resultsClinical records of 283 patients who underwent CRT implantation between March 2003 and October 2020 were retrospectively evaluated (mean age 67 ± 12, 22.6% female). Blood samples were collected before CRT implantation. Patients were divided into three groups based on tertiles of the MELD‐XI score: first tertile (MELD‐XI = 9.44, n = 95), second tertile (9.44 < MELD‐XI < 13.4, n = 94), and third tertile (MELD‐XI ≥ 13.4, n = 94). The primary endpoint was all‐cause mortality. Compared with the other groups, the third tertile group exhibited significantly older age, higher prevalence of diabetes mellitus and hypertension, lower haemoglobin level, and higher N‐terminal pro‐brain natriuretic peptide level (all P < 0.05). The functional CRT response rate was also significantly lower in the third tertile group (P = 0.011). During a median follow‐up of 30 months (inter‐quartile range, 9–67), 105 patients (37.1%) died. Kaplan–Meier analysis revealed that patients with a higher MELD‐XI score had a greater risk of all‐cause mortality (log‐rank test: P < 0.001). Even after adjustment for clinically relevant factors and a conventional risk score, the MELD‐XI score was still associated with mortality (adjusted hazard ratio: 1.04, 95% confidence interval: 1.00–1.07, P = 0.014, and adjusted hazard ratio: 1.04, 95% confidence interval: 1.01–1.09, P = 0.005, respectively). A higher MELD‐XI score was associated with a greater risk of all‐cause mortality than a lower MELD‐XI score regardless of whether a pacemaker or defibrillator was implanted (log‐rank test: P = 0.010 and P < 0.001, respectively).ConclusionsImpaired hepatorenal function assessed by the MELD‐XI score was associated with older age, higher prevalence of multiple co‐morbidities, severity of HF, lower CRT response rates, and subsequent all‐cause mortality in HF patients undergoing CRT implantation. These results suggest that the MELD‐XI score can provide additional prognostic information and may be useful for improving risk stratification in this population.

Does exercise stress testing carry an incremental prognostic value beyond resting office blood pressure?

Does exercise stress testing carry an incremental prognostic value beyond resting office blood pressure?

TERT promotor status does not add prognostic information in IDH-wildtype glioblastomas fulfilling other diagnostic WHO criteria: A report of the RANO resect group.

Summary In IDH-wildtype glioblastomas which meet the histopathological or molecular diagnosis criteria, it remains unclear whether the presence of TERT promotor mutations provides additional prognostic information. Based on a multicenter cohort of 466 IDH-wildtype glioblastomas (including 396 with and 70 patients without TERT promotor mutations), we found that TERT promotor mutations were neither associated with progression-free survival nor overall survival. This held true in various treatment-based or molecular subgroups. This argues against standardized analysis for TERT promotor mutation status for the purpose of prognostic or therapeutic relevance in newly diagnosed IDH-wildtype glioblastoma that otherwise meets the histopathological and molecular diagnosis criteria.

Clinical Utility of Multigene Assays for Guiding Treatment Decisions in Early Breast Cancer Patients

The clinical management of invasive breast cancer has changed during the last decade with the use of molecular-based multigene assays (MGAs).They are increasingly used to gain additional prognostic and predictive information and guide adjuvant treatment decisions. Since 2004, several MGAs have become available but, four of them are the most widely used in clinical practice: the OncotypeDX® Breast Recurrence Score, the 70-gene signature MammaPrint®, the Prosigna® (PAM50) and the EndoPredict® (EP/EPclin Scores) assay. However, MGAs are not all the same and they do not provide interchangeable information. They differ in terms of the technological platform used for their development, the number and specific genes assessed, and the patient populations in which they were validated. Furthermore, although they are all validated for providing prognostic information, not all of them are supported with data from prospective randomised trials confirming the clinical value of their use in chemotherapy treatment decisions in certain groups of breast cancer patients; in this regard, so far there are published data only for OncotypeDX and MammaPrint, whilst PAM-50 (Prosigna) and EndoPredict assays are currently not supported by entirely prospective randomized trials evaluating their predictive value of chemotherapy benefit. As such, inclusion of these MGAs in major international treatment guidelines differs in indications for their use in clinical practice as prognosticators only or as predictors of chemotherapy benefit as well. Use of MGAs in clinical decision making can lead to de-escalation of chemotherapy recommendations and thus save a large number of patients from unnecessary side effects and decrease the cost of breast cancer treatment to National Health systems. This review provides an overview of the four most widely used MGAs in clinical practice, including basic information on their development and validation, as well as recent data on the information they can provide.

Neck Circumference Predicts Mortality in Hospitalized COVID-19 Patients

We aimed to determine whether neck circumference predicts mortality among hospitalized COVID-19 patients with respiratory failure. We performed a prospective multicenter (Italy and Brasil) study carried out from March to December 2020 on 440 hospitalized COVID-19 patients with respiratory failure. Baseline neck circumference was measured. The study outcome was 30- and 60-days mortality. Female and male participants were classified as “large neck” when exceeding fourth-quartile. Patients had a median age of 65 years (IQR 54–76), 68% were male. One-quarter of patients presented with grade-1 or higher obesity. The median neck circumference was 40 cm (IQR 38–43): 38 cm (IQR 36–40) for female and 41 cm (IQR 39–44) for male subjects. “Large neck” patients had a significantly higher prevalence of hypertension (63 vs. 48%), diabetes (33 vs. 19%), obesity (26 vs. 14%), and elevated C-reactive protein (CRP) (98 vs. 88%). The cumulative mortality rate was 13.1% (n = 52) and 15.9% (n = 63) at 30 and 60 days, respectively. After adjusting for age, BMI, relevant comorbidities, and high C-reactive protein to albumin ratio, “large neck” patients showed a significantly increased risk of death at 30- (adjusted HR 2.50; 95% CI 1.18–5.29; p = 0.017) and 60-days (adjusted HR 2.26; 95% CI 1.14–4.46; p = 0.019). Neck circumference is easy to collect and provides additional prognostic information to BMI. Among hospitalized COVID-19 patients with respiratory failure, those with large neck phenotype had a more than double risk of death at 30 and 60 days.

563 Different right ventricle maladaptation in patients with HFrEF and HFpEF: diagnostic and prognostic implications

Abstract Aims The prognostic impact of right ventricular (RV) dysfunction and of pulmonary hypertension (PH) in patients affected by heart failure (HF) is well known. More recently it has been demonstrated that the coupling between the afterload and the function of the right ventricle in terms of TAPSE/PAPS ratio, may provide additional prognostic information. In contrast, sparse and conflicting data have been published regarding the relevance of different echocardiographic features in patients with reduced or preserved ejection fraction. Additionally, RV function and ventricular-arterial coupling is poorly studied in acute setting. We planned a prospective monocentric study aimed at elucidating the role of PH and of RV structure and function, assessed by means of an echocardiographic examination in the early phase of hospital admission of patients with ADHF. We also compared different echo parameters in order to assess the prognostic role in patient affected by HF and reduced ejection fraction (HFrEF) vs. those with preserved ejection fraction (HFpEF). Methods and results we included 381 patients included in the study, 209 had HFrEF and 172 had HFpEF. All the examinations were performed by cardiologists according to the instructions provided by the American Society of Echocardiography. In all patients LV volumes and diastolic function analysis were performed. A detailed examination of RV dimension and function were achieved by the measurement of right ventricular diameter at basal level, Pulmonary systolic pressure (PAPS), Tricuspid anular peak systolic excursion (TAPSE) and s wave by TDI analysis at RV free wall basal level. Finally longitudinal function was measured at lateral RV wall by post processing strain analysis. Overall, the median TAPSE was 19 (16–21) mm, the median of RVEDD was 40 (36–45) mm, the median PASP was 45 (35–50) mmHg and the median s’ wave was 11 (7–14). Patients with HFrEF demonstrated a larger RVEDD compared to HFpEF (44 ± 6 vs. 38 ± 5 P &amp;lt; 0.05) and more reduced TAPSE (16 ± 4 vs. 20 ± 3 P &amp;lt; 0.05). Whereas PAPS values were similar in both groups (47 ± 10 vs. 45 ± 10 NS). Conversely, s’ wave was much more reduced in HFpEF (9 ± 3 vs. 12 ± 4 P &amp;lt; 0.05) RV longitudinal strain was reduced in both group but HFpEF population demonstrated more impaired values (−18 ± 5 vs. −22 ± 8; P &amp;lt; 0.01). TAPSE/PAPS was significantly reduced in HFrEF (0.38 ± 8 vs. 0.43 ± 5 P &amp;lt; 0.01). Conversely s’/PAPS was more pronounced in HFpEF group (0.25 ± 4 vs. 0.29 ± 7 P &amp;lt; 0.05). At univariate analysis several parameters were related to outcome: TAPSE ≤ 14 mm, [HR: 1.70 (1.14–2.52); P = 0.009], PASP≥ 40 mmHg [HR: 1.51 (1.05–2.17); P = 0.02], RVEDD &amp;gt; 38 mm [HR: 1.88 (1.36–2.61); P &amp;lt; 0.001], s wave &amp;lt; 9 [HR: 1.88 (1.3–2.4), P &amp;lt; 0.001], inferior vena cava diameter &amp;gt; 21 mm [HR: 1.90 (1.31–2.75); P = 0.001]. Therefore TAPSE/PAPS was associated with adverse event in HFrEF but not in HFpEF (HR: 1.75 and HR: 1.02). Whereas, s/PAPS was associated with more increased risk in HFpEF (HR: 1.8 and HR: 1.3). Conclusions Right ventricular dysfunction and maladaptation are associated with poor outcome in either HFrEF and HFpEF. However tissue excursion and longitudinal strain are much more impaired in HFpEF, whereas RV dilatation and reduced longitudinal function are closely related to HFrEF. Different prognostic values and evaluation may be comprised during the evaluation of HFrEF and HFpEF.

Feasibility of platelet marker analysis in ischemic stroke patients and their association with one-year outcome. A pilot project within a subsample of the Stroke Induced Cardiac Failure in Mice and Men (SICFAIL) cohort study

Patients with ischemic stroke (IS) are at increased risk of mortality and recurrent cerebro- or cardiovascular events. Determining prognosis after IS remains challenging but blood-based biomarkers might provide additional prognostic information. As platelets are crucially involved in the pathophysiology of vascular diseases, platelet surface proteins (PSP) are promising candidates as prognostic markers in the hyperacute stage. In this pilot study, feasibility of PSP analysis by flow cytometry (HMGB1, CD84, CXCR4, CXCR7, CD62p with and without ADP-stimulation, CD41, CD61, CD40, GPVI) was investigated in 99 (median 66 years, 67.5% male) acute IS patients admitted to Stroke Unit within a substudy of the Stroke-Induced Cardiac FAILure in mice and men (SICFAIL) cohort study. Association between PSP expression and unfavorable one-year outcome (cerebro- or cardiovascular event, all-cause mortality and care dependency defined as Barthel Index <60) was explored. PSP measurements were feasible. Several process- (e.g. temperatures, processing times) and patient-related factors (e.g. prestroke ischemic events, surgery, blood pressure, antiplatelet therapy) were identified to be potentially associated with PSP expression. Elevated CD40 levels above study population’s median were associated with unfavorable outcome. Standardized conditions during blood draw and processing within the hyperacute stroke unit setting are required and patient-related characteristics must be considered for valid measurements of PSP. Trial registration: German Clinical Trials Register (DRKS00011615).

Lymphocyte and macrophage infiltration in omental metastases indicates poor prognosis in advance stage epithelial ovarian cancer.

ObjectiveTo investigate the prognostic value of immune cells within omental metastases originating from advanced epithelial ovarian cancer (EOC).MethodsWe performed immunohistochemical analysis to determine the levels of CD4+/CD8+ tumor-infiltrating lymphocytes (TILs) and CD68+ tumor-associated microphages (TAMs) in omental specimens from 100 patients with advanced EOC. Significant prognostic factors, including immune cells and clinical parameters, were assessed by Kaplan–Meier survival analysis and Cox models.ResultsCox regression analysis showed that elevated levels of CD68+ TAMs and intra-islet CD4+ TILs in omental metastases were the main risk factors associated with worse survival outcomes for advanced EOC. Moreover, the survival analysis of relationships between omental immune cells and favorable clinical predictors revealed additional prognostic stratification information.ConclusionOmental immune cells (TAMs and TILs) provide alternative prognostic factors in advanced EOC. In contrast to markers of the EOC tumor microenvironment at the primary site, elevated CD68+ TAMs and intra-islet CD4+ TILs in omental metastases serve as negative prognostic markers in advanced EOC and imply an unfavorable outcome.

Association Between Dynamic Change of QT Interval and Long-Term Cardiovascular Outcomes: A Prospective Cohort Study.

Background: The prolongation or shortening of heart rate-corrected QT (QTc) predisposes patients to fatal ventricular arrhythmias and sudden cardiac death (SCD), but the association of dynamic change of QTc interval with mortality in the general population remains unclear.Methods: A total of 11,798 middle-aged subjects from the prospective, population-based cohort were included in this analysis. The QTc interval corrected for heart rate was measured on two occasions around 3 years apart in the Atherosclerosis Risk in Communities (ARIC) study. The ΔQTc interval was calculated by evaluating a change in QTc interval from visit 1 to visit 2.Results: After a median follow-up of 19.5 years, the association between the dynamic change of QTc interval and endpoints of death was U-shaped. The multivariate-adjusted hazard ratios (HRs) comparing subjects above the 95th percentile of Framingham–corrected ΔQTc (ΔQTcF) (≥32 ms) with subjects in the middle quintile (0–8 ms) were 2.69 (95% CI, 1.68–4.30) for SCD, 2.51 (1.68–3.74) for coronary heart disease death, 2.10 (1.50–2.94) for cardiovascular death, and 1.30 (1.11–1.55) for death from any cause. The corresponding HRs comparing subjects with a ΔQTcF below the fifth percentile (<-23 ms) with those in the middle quintile were 1.82 (1.09–3.05) for SCD, 1.83 (1.19–2.81) for coronary heart disease death, 2.14 (1.51–2.96) for cardiovascular death, and 1.31 (1.11–1.56) for death from any cause. Less extreme deviations of ΔQTcF were also associated with an increased risk of death. Similar, albeit weaker associations also were observed with ΔQTc corrected with Bazett's formula.Conclusions: A dynamic change of QTc interval is associated with increased mortality risk in the general population, indicating that repeated measurements of the QTc interval may be available to provide additional prognostic information.

Association of Tumor-Associated Collagen Signature With Prognosis and Adjuvant Chemotherapy Benefits in Patients With Gastric Cancer

The current TNM staging system provides limited information for prognosis prediction and adjuvant chemotherapy benefits for patients with gastric cancer (GC). To develop a tumor-associated collagen signature of GC (TACSGC) in the tumor microenvironment to predict prognosis and adjuvant chemotherapy benefits in patients with GC. This retrospective cohort study included a training cohort of 294 consecutive patients treated between January 1, 2012, and December 31, 2013, from Nanfang Hospital, Southern Medical University, People's Republic of China, and a validation cohort of 225 consecutive patients treated between October 1, 2010, and December 31, 2012, from Fujian Provincial Cancer Hospital, Fujian Medical University, People's Republic of China. In total, 146 collagen features in the tumor microenvironment were extracted with multiphoton imaging. A TACSGC was then constructed using the least absolute shrinkage and selection operator Cox proportional hazards regression model in the training cohort. Data analysis was conducted from October 1, 2020, to April 30, 2021. The association of TACSGC with disease-free survival (DFS) and overall survival (OS) was assessed. An independent external cohort was included to validate the results. Interactions between TACSGC and adjuvant chemotherapy were calculated. This study included 519 patients (median age, 57 years [IQR, 49-65 years]; 360 [69.4%] male). A 9 feature-based TACSGC was built. A higher TACSGC level was significantly associated with worse DFS and OS in both the training (DFS: hazard ratio [HR], 3.57 [95% CI, 2.45-5.20]; OS: HR, 3.54 [95% CI, 2.41-5.20]) and validation (DFS: HR, 3.10 [95% CI, 2.26-4.27]; OS: HR, 3.24 [95% CI, 2.33-4.50]) cohorts (continuous variable, P < .001 for all comparisons). Multivariable analyses found that carbohydrate antigen 19-9, depth of invasion, lymph node metastasis, distant metastasis, and TACSGC were independent prognostic predictors of GC, and 2 integrated nomograms that included the 5 predictors were established for predicting DFS and OS. Compared with clinicopathological models that included only the 4 clinicopathological predictors, the integrated nomograms yielded an improved discrimination for prognosis prediction in a C index comparison (training cohort: DFS, 0.80 [95% CI, 0.73-0.88] vs 0.78 [95% CI, 0.71-0.85], P = .03; OS, 0.81 [95% CI, 0.75-0.88] vs 0.80 [95% CI, 0.73-0.86], P = .03; validation cohort: DFS, 0.78 [95% CI, 0.70-0.87] vs 0.76 [95% CI, 0.67-0.84], P = .006; OS, 0.78 [95% CI, 0.69-0.86] vs 0.75 [95% CI, 0.67-0.84], P = .002). Patients with stage II and III GC and low TACSGC levels rather than high TACSGC levels had a favorable response to adjuvant chemotherapy (DFS: HR, 0.65 [95% CI, 0.43-0.96]; P = .03; OS: HR, 0.55 [95% CI, 0.36-0.82]; P = .004; dichotomized variable, P < .001 for interaction for both comparisons). The findings suggest that TACSGC provides additional prognostic information for patients with GC and may distinguish patients with stage II and III disease who are more likely to derive benefits from adjuvant chemotherapy.

MRI-based radiomics and ADC values are related to recurrence of endometrial carcinoma: a preliminary analysis

BackgroundTo identify predictive value of apparent diffusion coefficient (ADC) values and magnetic resonance imaging (MRI)-based radiomics for all recurrences in patients with endometrial carcinoma (EC).MethodsOne hundred and seventy-four EC patients who were treated with operation and followed up in our institution were retrospectively reviewed, and the patients were divided into training and test group. Baseline clinicopathological features and mean ADC (ADCmean), minimum ADC (ADCmin), and maximum ADC (ADCmax) were analyzed. Radiomic parameters were extracted on T2 weighted images and screened by logistic regression, and then a radiomics signature was developed to calculate the radiomic score (radscore). In training group, Kaplan–Meier analysis was performed and a Cox regression model was used to evaluate the correlation between clinicopathological features, ADC values and radscore with recurrence, and verified in the test group.ResultsADCmean showed inverse correlation with recurrence, while radscore was positively associated with recurrence. In univariate analyses, FIGO stage, pathological types, myometrial invasion, ADCmean, ADCmin and radscore were associated with recurrence. In the training group, multivariate Cox analysis showed that pathological types, ADCmean and radscore were independent risk factors for recurrence, which were verified in the test group.ConclusionsADCmean value and radscore were independent predictors of recurrence of EC, which can supplement prognostic information in addition to clinicopathological information and provide basis for individualized treatment and follow-up plan.

Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures

Chronic lymphocytic leukemia (CLL) is one of the most frequent types of leukemia. It typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that interfere with the regulation of proliferation and of apoptosis in clonal B-cells. The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen as well as typical B-cell markers. The clinical staging systems provide prognostic information by using the results of physical examination and blood counts. Various biological and genetic markers provide additional prognostic information. Deletions of the short arm of chromosome 17 (del[17p]) and/or mutations of the TP53 gene predict resistance to chemoimmunotherapy and a shorter time to progression with most targeted therapies. The CLL international prognostic index integrates genetic, biological, and clinical variables to identify distinct risk groups of patients with CLL. Only patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. When treatment is indicated, several therapeutic options exist: a combination of the B-cell lymphoma 2 (BCL2) inhibitor venetoclax with obinutuzumab, monotherapy with inhibitors of Bruton tyrosine kinase (BTK) such as ibrutinib and acalabrutinib, or chemoimmunotherapy. At relapse, the initial treatment may be repeated, if the treatment-free interval exceeds 3 years. If the disease relapses earlier, therapy should be changed using an alternative regimen. Patients with a del(17p) or TP53 mutation are usually resistant to chemotherapy and should, therefore, be treated with targeted agents. Combinations of targeted agents are now being investigated to create efficient, potentially curative therapies of CLL with fixed duration. One of the most relevant questions currently addressed in clinical trials is the comparison of monotherapies with BTK inhibitors with fixed duration combination therapies. Moreover, the optimal sequencing of targeted therapies remains to be determined. Alternative therapies are needed for patients with BTK and BCL2 inhibitor double-refractory disease.

Abstract 13335: Elevated Protease Inhibitor SERPINA3 is Associated With Increased Mortality and Improves Prognostic Stratification in a de novo or Worsened Heart Failure

Introduction: Overexpression of serpin peptidase inhibitor, clade A member 3 (SERPINA3) has been associated with poor prognosis in cancer. Hypothesis: SERPINA3 in a de novo or worsened heart failure (HF) bears a prognostic information alone and in addition to established biomarkers NT-proBNP and ST2 or clinical risk factors. Methods: Circulating SERPINA3 levels were examined in HFpatients who died within 5 years (n=44) and compared with age- and hemodynamically matched survivors (n=39). Prognostic value of circulating SERPINA3 levels alone and in combination with ST2 and NT-proBNP was then analyzed in an independent cohort with a de novo or worsened HF (n=384). Results: Plasma SERPINA3 levels were significantly higher in HF non-survivors compared to survivors (334.7 ± 138.7 vs 228.2 ± 83.1 μg/mL, p&lt;0.01). In the spline curve analysis,SERPINA3 level of 316 μg/mL emerged as optimal cut-off value for mortality. In the validation cohort with a de novo or worsened HF (n=384), circulating SERPINA3 levels &gt;316 μg/mL were associated with increased all-cause mortality (HR (95% CI): 2.4 (1.5-3.9), p=0.0002) and its composite with unplanned cardiac admission (HR (95% CI): 2.0 (1.2-3.3), p=0.004). In a multivariate analysis, including established clinical risk factors and ST2 and NT-proBNP, SERPINA3 remained independent predictor of all-cause mortality together with age, ST2, glomerular filtration and pulmonary capillary wedge pressure. Conclusions: Elevated SERPINA3 appears to provide additional prognostic information in models incorporating clinical, hemodynamic and laboratory risk including ST2 and NT-proBNP by identifying a subgroup of heart failure patients at increased mortality risk.

The prognostic nutritional index predicts the biochemical recurrence of patients treated with robot-assisted laparoscopic radical prostatectomy.

To evaluate the prognostic nutritional index (PNI) in predicting the biochemical recurrence (BCR) of patients treated with robot-assisted laparoscopic radical prostatectomy (RALP). The clinical data of 136 patients treated with RALP in the Department of Urology, The Third Xiangya Hospital of Central South University were retrospectively analyzed. The endpoint of observation was BCR. The area under the receiver operating characteristic (ROC) curve was evaluated to determine the optimal cutoff value of PNI. The correlation of the PNI with BCR was estimated using Kaplan-Meier analysis and Cox proportional hazards model. The optimal cutoff value of the PNI was 46.03 according to the ROC curve. (95% confidence interval: 0.604-0.805, Youden index = 0.401, sensitivity = 82.5%, specificity = 57.6%, p < 0.01). Multivariate Cox analysis showed that clinical staging, prostate-specific antigen, and PNI were independent prognostic factors for predicting BCR in patients treated with RALP. PNI is an independent prognostic factor for predicting BCR in patients treated with RALP. The incorporation of the PNI into risk assessments may provide additional prognostic information.

Status epilepticus heralding thymomatous paraneoplastic multifocal cortical encephalitis in Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune disorder involving the neuromuscular junction characterized by fatigable weakness of the striated muscles [1]. It is primarily mediated by autoantibodies against the acetylcholine receptors (AChR) on post-synaptic membrane of the motor end plate and are present in the serum of 85% of MG patients [1]. Recently, antibodies recognizing other skeletal muscle components have been detected which have provide additional diagnostic and prognostic information [2]. Anti-titin antibodies fall under this category and are found in 20–40% of anti-AChR antibody positive patients.