Intermediate-risk Group Research Articles

Effectiveness of Mannheim's Peritonitis Index in Patients With Peritonitis Secondary to Hollow Viscus Perforation in a Tertiary Care Hospital in Jharkhand, India.

Introduction Peritonitis refers to the inflammation of the peritoneum and peritoneal cavity. Causes of peritonitis can be bacterial (gastrointestinal or non-gastrointestinal), chemical, traumatic, or ischemic. Peritonitis can be localized or diffuse, acute or chronic. Peritonitis can be primary, secondary, or tertiary, according to the pathogenesis. Peritonitis developed secondary to hollow viscus perforation is a life-threatening condition and a common cause of emergency surgery in India. The Mannheim peritonitis index (MPI) is a simple scoring system that can accurately predict the outcome of peritonitis.This study aimed to evaluate the effectiveness of MPI in predicting mortality risk or prognosis in patients with peritonitis due to hollow viscus perforation. Materials and methods This observational cross-sectional study at the Department of General Surgery, Rajendra Institute of Medical Sciences, Ranchi, involved 111 patients with peritonitis due to hollow viscus perforation from December 2021 to March 2022. Detailed history, clinical examination, relevant blood tests, and radiological investigations established a diagnosis of perforation peritonitis, followed by a score assessment. Data were analyzed using SPSS software (IBM Corp., Armonk, NY, USA). Results Patients >50 years had higher mortality (i.e., 18/43) than patients <50 years (i.e., 13/68). Overall mortality was 31, which included one in low risk, 12 in intermediate risk, and 18 in the high-risk group. Mortality was lowest in the low-risk group (i.e., 1/30), highest in the high-risk group (i.e., 18/40), and 12/41 in the intermediate-risk group; the p-value was <0.05, which was highly significant. Mortality was higher in patients presenting after 24 hours, having organ failure, and non-colonic sepsis. Conclusion The MPI scoring system is simple, easy to calculate, cost-effective, precise, and effective in assessing mortality and morbidity risk in patients with peritonitis due to hollow viscus perforation. It can also guide further management strategies.

Abstract PO4-11-01: Validation of a CARG-BC-based score for the prediction of therapy-induced toxicities in patients with metastatic breast cancer

Abstract Introduction Prediction of treatment-induced toxicities is important in order to tailor and adjust oncologic therapies. As limited tools exist to predict the risk of therapy-induced toxicities in patients with metastatic cancer, we aimed to develop and to validate a score for the prediction of therapy-induced toxicities in patients with metastatic breast cancer treated with chemotherapy and immunotherapy. The score was based on the Cancer and Aging Research Group-Breast Cancer early-stage breast cancer score for prediction of chemotherapy-induced toxicities. Methods All patients treated for metastatic breast cancer with chemotherapy and immunotherapy at the Department of Gynecology, Obstetrics and Reproductive Medicine at Saarland University Hospital between 01/2014 and 05/2022 were included in this retrospective study. Patient characteristics and therapy-relevant oncological parameters were recorded, as well as therapy-induced toxicities (recorded according to CTC), hospitalization rates, toxicity-related dose reductions and therapy discontinuations. In the first cohort (development cohort), a new score for the prediction of therapy-induced toxicities was developed using ROC analysis and multivariate analysis based on the CARG-BC score. In the second cohort (validation cohort), this was validated using Pearson’s correlation coefficient. Results Data from 32 patients were analyzed for the development cohort, and inclusion of 102 patients contributed to the validation cohort. The newly developed score consists of seven independent factors for the prediction of toxicities ≥ CTC III° and includes the parameters “presence of visceral metastases” (yes/no), “received previous lines of therapy” (yes/no), “limited mobility/able to walk less than one kilometer” (yes/no), “a fall in the last six months” (yes/no), “social interactions” (yes/no), “pretherapeutic change of transaminases” (yes/no) and “pretherapeutic change of hemoglobin” (hemoglobin &amp;lt;/&amp;gt; 10 g/dl). Based on the results, three risk groups were defined (low (0-2), medium (3-5) and high (6-15) risk). 28% of patients were in the low-risk group, 37% in the intermediate-risk group and 34% in the high-risk group. Overall, 49% of the patients had toxicities ≥ CTC III°. Distributed across the subgroups, these occurred in 14% in the low-risk group, 34% in the intermediate-risk group and in 52% in the high-risk group (p ≤ 0.01). Risk score results showed a correlation with treatment discontinuation and hospitalization rate (p ≤ 0.01), but not with dose reduction (p = 0.77). Conclusion The available data show a correlation between the risk score results and the occurrence of systemic therapy-induced toxicities in patients with metastatic breast cancer. The results can be used to further identify risk populations and to systematically apply preventive and supportive measures in order to approve quality of life in patients with metastatic breast cancer. Citation Format: Julia SM Zimmermann, Aylin Aygün, Askin Kaya, Marc P Radosa, Christoph G Radosa, Erich F Solomayer, Julia C Radosa. Validation of a CARG-BC-based score for the prediction of therapy-induced toxicities in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-11-01.

Abstract PO3-17-01: Brazilian Real-world data of HR+ HER2- early-stage Breast Cancer (BC) patients are poor when compared to control arms of recent adjuvant clinical trials

Abstract INTRODUCTION: In Brazil, BC is the most common neoplasm among women, with 73k new cases annually. Adjuvant hormone therapy (HT) options are evolving with personalized strategies based on risk stratification. Real-world data (RWD) plays a crucial role in understanding the outcomes in BC patients (pts) in low- and middle-income countries, where significant health disparities, access gaps, and barriers to the implementation of guidelines exist. This study aims to assess the epidemiologic profile, practice patterns, and real-world outcomes of pts with ER+ HER2- stage I-III BC treated in the largest network of private oncology services in Brazil and compare results with control arms of recent clinical trials evaluating CDK4/6 inhibitors in adjuvant setting. METHODS: Retrospective RWD study from Oncoclínicas Group with longitudinal EHR data from 2017 to 2022 merged in a platform where structured variables (demographics, tumor staging, pharmacy records) are integrated with unstructured data from physician notes and digitized pathology-molecular reports using technology-based abstraction performed by expert human curators that follow mCODE standards and predefined ontology. Treatment patterns and invasive disease-free survival (IDFS) outcomes were collected. Regarding risk stratification, pts were classified as high-risk (HR) if: (i) 4+ axillary lymph nodes (LN), or (ii) 1-3 LN and grade 3 and/or Ki620% and/or high-risk ODX/Mammaprint; intermediate-risk (IR) if: (iii) 1-3 LN with grade 1-2 and/or Ki67 &amp;lt; 20% and/or non-high-risk ODX/Mammaprint, or (iv) N0 with grade 2-3 and/or Ki67 &amp;gt;20% and/or high-risk ODX/Mammaprint; and low-risk (LR) if: (v) all other stages I and IIA not having the risk factors above. RESULTS: From over 30k BC pts in Oncoclínicas Database, 19k had HR+/HER2- early BC, 12k were treated in high-volume clinics, and 1,786 cases were selected for the study (diagnosis and first treatment in the last 6 years, complete histopathology and pharmacy registries). The median age was 57 years (27-96), 566 (32%) pts were premenopausal, 1052 (59%) had stage I disease, 372 (21%) stage IIA, 165 (9%) stage IIB and 197 (11%) stage III BC. Regarding risk stratification, 1,179 (66%) were LR, 351 (20%) IR, and 256 (14%) HR. In post-menopausal pts, aromatase inhibitor (AI) was used by 74% of pts with LR, 79% with IR and 83% with HR. In premenopausal pts, ovarian function suppression (OFS) – combined with tamoxifen or AI – was prescribed to 18% of LR pts, 15% of IR pts, and 48% of HR pts. Chemotherapy (CT) was offered to 32%, 38%, and 73% of postmenopausal pts in LR, IR, and HR groups. In premenopausal pts, 55%, 57%, and 78% received CT in LR, IR, and HR groups. The 3-year iDFS in the general population was 85%, reaching 80% in premenopausal and 86% in postmenopausal pts. The overall 3y iDFS was 87% in the LR, 86% in IR, and 72% in HR. Among premenopausal pts, the 3y iDFS was 81% in LR, 92% in IR, and 64% in the HR group. While the risk distribution of our cohort is similar to recent clinical trials, the 3y iDFS outcomes were numerically lower to those observed in the control groups of the pivotal trials evaluating adjuvant CDK4/6 inhibitors. In the HR group, the 3y iDFS was 72% (versus 84% 3y iDFS in the control arm of the MonarchE trial). Combining the IR/HR groups, the 3y iDFS was 80% (versus 87% in the control arm of NATALEE trial). CONCLUSION: In this large RWD cohort treated in a private setting in Brazil, most pts are diagnosed with stage I and LR BC. In this cohort, a significant proportion of premenopausal pts with IR/HR are not treated with OFS and do not receive CT. Real-world survival outcomes of Brazilian women with HR+ HER2- early BC treated in private clinic are inferior to those observed in recent clinical trials, especially in the premenopausal pts. In public healthcare system, where prevalence of HR disease is higher and access to essential treatments more limited, outcomes might even be worsened compared to the ones presented here. Citation Format: Aline Goncalves, Tomas Reinert, Max S. Mano, Heloisa Cruz, Cristiano Resende, Gustavo Bretas, Carlos Barrios, Matheus Costa e Silva, Rafael Paes, Guilherme Silva, Erika Martins, Fernanda Koyama, Bruno Ferrari, Carlos Gil Ferreira, Pedro Aguiar Junior, Rodrigo Dienstmann. Brazilian Real-world data of HR+ HER2- early-stage Breast Cancer (BC) patients are poor when compared to control arms of recent adjuvant clinical trials [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-17-01.

Abstract PO2-01-13: Clinico-Pathological and Molecular Characterization of Early Hormone Receptor-Positive Breast Cancer in Young Women

Abstract Introduction Premenopausal women diagnosed with hormone receptor-positive (HR+)/HER2-negative (HER2-) early breast cancer (EBC) face a significantly higher risk of cancer recurrence and mortality compared to older women, particularly those diagnosed under the age of 40. The underlying causes behind this disparity remain largely unknown. Material and methods We retrospectively select tumour samples from patients (pts) diagnosed with HR+/HER2- EBC at Hospital Clinic (Barcelona, Spain) from May 2014 to March 2020 who had a PAM50/Prosigna assay (Veracyte) previously performed. This assay examines the expression of 50 genes involved in important breast cancer signaling pathways, as well as the intrinsic subtypes (IS) and the Risk of Recurrence (ROR) score. Our primary objective was to compare the distinct clinicopathological and molecular characteristics of HR+/HER2- EBC between two age groups: patients under 40 years old (Young EBC or YEBC) and those 40 years old and above (Older EBC or OEBC). Disease-free survival (DFS) was defined as the time between diagnosis and the first recurrence. Comparisons between groups were carried out using chi-square tests (categorical variables). Additionally, we performed a two-class unpaired Significance Analysis of Microarrays (SAM) with a false discovery rate (FDR) less than 5% to identify genes with significantly different expression between YEBC and OEBC. The statistical significance level was set at less than 0.05. Results A total of 441 tumor samples from 420 patients were included in the analysis, with 5% (22/441) corresponding to YEBC. With a median follow-up of 64.5 months, there were 20 breast cancer (BC) recurrences (4.8%), 12 second cancers (2.9%) and 5 BC-related deaths (1.2%), all occurring in the OEBC group. Table 1 provides an overview of the main clinico-pathological and molecular characteristics. YEBC tended to have larger tumors, with 45.5% (10/22) measuring over 2 cm compared to 36.1% (151/419) in OEBC (p=0.376). YEBC also had a higher proportion of grade 3 tumors (18.18% versus 3.1% in OEBC, p=0.418) and lower expression of estrogen receptor (ER) as determined by immunohistochemistry (mean of 72.28% vs 88.36%, p=0.004). Regarding the PAM50 IS, there was a difference observed between YEBC and OEBC (p &amp;lt; 0.001). Specifically, YEBC patients exhibited a tendency towards a higher proportion of Luminal B tumors (54.6% versus 38.9% in OEBC, p=0.144), as well as non-Luminal subtypes such as Basal-like (18.2% versus 0.95% in OEBC, p&amp;lt; 0.001) and HER2E (4.6% versus 0.7% in OEBC, p=0.186). YEBC tended to have higher ROR (p=0.167), and to receive chemotherapy in a higher proportion, especially in the intermediate-risk group (p=0.004). In YEBC tumours, SAM analysis (p &amp;lt; 0.05) showed an overexpression of genes mainly related with proliferation (i.e., RRM2, MELK, MIK67), cell cycle progression (i.e., KNTC2, CDC20, MYBL2) and apoptosis inhibition (i.e., BIRC5). In OEBC there were an overexpression of genes related with the oestrogen receptor-signalling pathway (i.e., ESR1, NAT1, FOXA1, PGR). Luminal B tumours in YEBC showed an upregulation of genes related to proliferation, migration, and poor prognosis (i.e., KRT17, KRT5) compared to OEBC. However, since there were no recurrences in the YEBC group, differences in terms of DFS between the groups could not be calculated. Principio del formulario Final del formulario Conclusions YEBC exhibited a more advanced stage and a more aggressive intrinsic phenotype compared to OEBC. Additionally, these tumors showed a tendency to upregulate genes involved in proliferation, cell cycle progression, and survival, while downregulating genes related to hormone signaling pathways. These molecular characteristics may help explain the worse prognosis of YEBC compared to OEBC. However, further research is necessary to delve into the differential genomic characteristics that contribute to the unfavorable prognosis observed in patients diagnosed with HR+ EBC before the age of 40. Key clinical and molecular features in 441 biopsies Citation Format: Francisco Javier Muñoz-Carrillo, José Antonio Sola, Carme Crous, Esther Sanfeliu, Isabel Garcia-Fructuoso, Elia Seguí, Teresa Gorría, Raquel Gómez-Bravo, Barbara Adamo, Tomás Pascual, Olga Martínez-Sáez, Francesco Schettini, Pablo Rivera, Rosalía Cayuela, Montserrat Muñoz, Núria Chic, Maria Vidal. Clinico-Pathological and Molecular Characterization of Early Hormone Receptor-Positive Breast Cancer in Young Women [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-13.

Abstract PO3-29-05: Clinical risk score to predict overall survival and breast cancer recurrence in phase 3 TAILORx trial and the Surveillance, Epidemiology, and End Results (SEER) Database populations

Abstract Background: Overall survival (OS) is the gold standard and most relevant endpoint in oncology research and patient care. It underscores a need to develop methods to estimate the likelihood of mortality in breast cancer. Methods: We evaluated molecular and clinical measures that predicted mortality risk using multiple logistic regression and developed a clinical risk score (CS) in 8,905 patients from the phase 3 TAILORx trial. Association of CS with mortality in patients at low, intermediate, and high risks was analyzed by Kaplan-Meier and multivariable Cox proportional-hazards regression analyses. The score was validated in an independent population of 148,301 patients with node-negative, hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer in the SEER database. Likelihood ratio (LR) test and c-index were used to compare prognostic information provided by CS and a 21-gene recurrence score (RS) to OS, invasive disease-free survival (DFS), recurrence-free interval (RFI), and distant recurrence-free interval (dRFI). Results: The 10-year mortality rates in low-risk, intermediate risk, and high-risk groups were 3.9% (95% CI 3.1 to 4.8), 37.2% (95% CI 23.4 to 51.1), and 75.8% (95% CI 54.1 to 97.4), respectively (P&amp;lt; 0.0001). Compared with low-risk score, intermediate (adjusted HR 45.5, 95% CI 32.2 to 64.9) and high-risk scores (HR 2026, 95% CI 1194 to 3483) were associated with risk of mortality, independent of demographics, tumor grade, RS, tumor size, PR, and treatment factors. The algorithm also predicted DFS, dRFI, and RFI outcomes (P&amp;lt; 0.0001 each), outperforming RS by both LR test and c-index estimate. Its validity was corroborated in the SEER population (intermediate risk: HR 9.3, 95% CI 6.7 to 13.3 and high-risk: HR 125.9, 95% CI 85.2 to 189.6). Conclusions: Clinical risk score robustly predicts risk of mortality in early-stage breast cancer populations. It provides more prognostic information than RS to survival and breast cancer recurrences. Citation Format: Sherry Yang, John Yu, Ninet Sinaii. Clinical risk score to predict overall survival and breast cancer recurrence in phase 3 TAILORx trial and the Surveillance, Epidemiology, and End Results (SEER) Database populations [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-29-05.

Proposal of a Modified Classification of Hypertensive Crises: Urgency, Impending Emergency, and Emergency.

Systemic arterial hypertension (HTN) is the main cause of morbidity and mortality, and HTN crises contribute significantly to an unfavourable clinical course. For decades, HTN crises have been dichotomized into hypertensive emergency (HTN-E) and hypertensive urgency (HTN-U). The main difference between the two is the presence of acute hypertension-mediated organ damage (HMOD) - if HMOD is present, HTN crisis is HTN-E; if not, it is HTN-U. Patients with HTN-E are in a life-threatening situation. They are hospitalized and receive antihypertensive drugs intravenously (IV). On the other hand, patients with HTN-U are usually not hospitalized and receive their antihypertensives orally. We suggest a modification of the current risk stratification scheme for patients with HTN crises. The new category would be the intermediate risk group, more precisely the 'impending HTN-E' group, with a higher risk in comparison to HTN-U and a lower risk than HTN-E. 'Impending HMOD' means that HMOD has not occurred (yet), and the prognosis is, therefore, better than in patients with ongoing HMOD. There are three main reasons to classify patients as having impending HTN-E: excessively elevated BP, high-risk comorbidities, and ongoing bleeding/high bleeding risk. Their combinations are probable. This approach may enable us to prevent some HTNEs by avoiding acute HMOD using a timely blood pressure treatment. This treatment should be prompt but controlled.

Prognostic Value of Stress Myocardial Perfusion Imaging Across the Spectrum of Cardiovascular Risk

BackgroundSingle-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is widely used to identify ischemia. There is limited research to evaluate if there is a risk threshold below which SPECT-MPI may not add significant prognostic value. MethodsBetween January 1, 2012, and December 31, 2018, individuals who underwent SPECT-MPI were stratified into 4 risk groups. The primary outcome was acute myocardial infarction (MI) or death. Multivariable Cox proportional hazards regression analysis was used to calculated hazard ratios (HRs) with 95% confidence intervals (CIs). ResultsAmong 48,845 patients (52.3% male, median age 67 years), 8.5% were low risk, 4.8% borderline risk, 18.1% intermediate risk, and 68.6% high risk based on the American College of Cardiology pooled cohort equation. Ischemia was more commonly detected in the high-risk cohort (19.4% in high-risk vs 6.5% in low-risk). SPECT-MPI testing was associated with a significantly increased use of preventive medications such as statin therapy, regardless of stress test results. At a median follow-up of 4.2 years, there was no significant association between ischemia and death or MI in the low-risk cohort (adjusted HR, 1.91; 95% CI, 0.94-3.92) or the borderline-risk cohort (adjusted HR, 1.58; 95% CI, 0.79-3.15). Ischemia was associated with a higher risk of death or MI in the intermediate-risk (adjusted HR, 1.57; 95% CI, 1.24-1.99) and high-risk groups (adjusted HR, 1.54; 95% CI, 1.44-1.64). ConclusionsSPECT-MPI was less useful for risk stratification among low-risk patients because of their low event rates regardless of test results.

Deep learning image reconstruction of diffusion-weighted imaging in evaluation of prostate cancer focusing on its clinical implications.

Image-based assessment of prostate cancer (PCa) is increasingly emphasized in the diagnostic workflow for selecting biopsy targets and possibly predicting clinically significant prostate cancer (csPCa). Assessment is based on Prostate Imaging-Reporting and Data System (PI-RADS) which is largely dependent on T2-weighted image (T2WI) and diffusion weighted image (DWI). This study aims to determine whether deep learning reconstruction (DLR) can improve the image quality of DWI and affect the assessment of PI-RADS ≥4 in patients with PCa. In this retrospective study, 3.0T post-biopsy prostate magnetic resonance imaging (MRI) of 70 patients with PCa in Korea University Ansan Hospital from November 2021 to July 2022 was reconstructed with and without using DLR. Four DWI image sets were made: (I) conventional DWI (CDWI): DWI with acceleration factor 2 and conventional parallel imaging reconstruction, (II) DL1: DWI with acceleration factor 2 using DLR, (III) DL2: DWI with acceleration factor 3 using DLR, and (IV) DL3: DWI with acceleration factor 3 and half average b-value using DLR. Apparent diffusion coefficient (ADC) value, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured by one reviewer, while two reviewers independently assessed overall image quality, noise, and lesion conspicuity using a four-point visual scoring system from each DWI image set. Two reviewers also performed PI-RADSv2.1 scoring on lesions suspected of malignancy. A total of 70 patients (mean age, 70.8±9.7 years) were analyzed. The image acquisition time was 4:46 min for CDWI and DL1, 3:40 min for DL2, and 2:00 min for DL3. DL1 and DL2 images resulted in better lesion conspicuity compared to CDWI images assessed by both readers (P<0.05). DLR resulted in a significant increase in SNR, from 38.4±14.7 in CDWI to 56.9±21.0 in DL1. CNR increased from 25.1±11.5 in CDWI to 43.1±17.8 in DL1 (P<0.001). PI-RADS v2.1 scoring for PCa lesions was more agreeable with the DL1 reconstruction method than with CDWI (κ value CDWI, DL1; 0.40, 0.61, respectively). A statistically significant number of lesions were upgraded from PI-RADS <4 in CDWI image to PI-RADS ≥4 in DL1 images for both readers (P<0.05). Most of the PI-RADS upgraded lesions were from higher than unfavorable intermediate-risk groups according to the 2023 National Comprehensive Cancer Network guidelines with statistically significant difference of marginal probability in DL1 and DL2 for both readers (P<0.05). DLR in DWI for PCa can provide options for improving image quality with a significant impact on PI-RADS evaluation or about a 23% reduction in acquisition time without compromising image quality.

Application Value of NLR, PLR, LMR, HEART score, and POCT in Early Warning and Accurate Graded Diagnosis of High-Risk Chest Pain in Emergency Medicine

Objective: To evaluate the application value of neutrophils/lymphocytes (NLR), platelets/lymphocytes (PLR), lymphocytes/monocytes (LMR), HEART (history, electrocardiogram, age, risk factors, and troponin) score, and point-of-care testing (POCT) in the early warning and precise diagnosis of high-risk chest pain in emergency medicine. Methods: A total of 157 patients with acute chest pain who were admitted to the emergency department and chest pain treatment unit of our hospital between August 2022 and September 2023 were selected. Rapid testing of bedside myocardial markers (ultrasensitive troponin (hs-cTnI), myoglobin (MYO), creatine kinase isoenzyme (CK-MB), D-dimer (D-Dimer), and N-terminal B-type natriuretic peptide precursor (NT-proBNP)) was performed on the patients using a POCT device (ThermoKing BioMQ60proB). A HEART score was used to classify the patients into low (n = 53), intermediate (n = 59), and high-risk (n = 45) groups, and the NLR, PLR, and LMR were calculated. The NLR, PLR, and LMR values were compared among the three groups of patients, and the optimal cutoff values as well as sensitivity and specificity were determined based on receiver operating characteristic (ROC) analysis. Results: The HEART scores of patients in the low-risk, intermediate-risk, and high-risk groups were (2.72 ± 0.24), (4.75 ± 0.56), and (5.32 ± 0.73) respectively, and the differences were statistically significant (P &lt; 0.05). Compared with the low-risk group, the intermediate-risk group and high-risk group had a significantly higher NLR and PLR, and a significantly lower LMR; the high-risk group had higher NLR and PLR and lower values of LMR as compared to the other two groups, and the difference was statistically significant (P &lt; 0.05). The ROC curves suggested that the area under the curve, sensitivity, and specificity of the combined diagnosis of NLR, PLR, LMR, HEART score, and POCT were greater than those of LR, PLR, and LMR with HEART score and POCT alone. Conclusion: The combined application of NLR, PLR, LMR, HEART score, and POCT has significant application value in the early warning and precise diagnosis of emergency high-risk chest pain. It provides a more simple, easy-to-access, and efficient assessment index for the clinical prediction and treatment of emergency high-risk chest pain.

Comparison of outcomes between early-stage cervical cancer patients without high-risk factors undergoing adjuvant concurrent chemoradiotherapy and radiotherapy alone after radical surgery.

For patients with early-stagecervical cancer without high-risk factors, there is no consensus regarding the optimal postoperative treatment regimen and whether postoperative concurrent radiochemotherapy (CCRT) is superior to radiotherapy (RT) alone. The medical records of patients with stage I-IIA cervical cancer, who underwent radical surgery and postoperative RT or CCRT between June 2012 and December 2017, were retrospectively reviewed. Patients with any high-risk factors, including positive pelvic lymph node(s), positive resection margin(s), and parametrial invasion, were excluded. Patients with large tumors (≥ 4 cm), deep stromal invasion (≥ 1/2), and lymphovascular space involvement were categorized as the intermediate-risk group. Patients without intermediate-risk factors were categorized as the low-risk group. A total of 403 patients were enrolled and divided into 2 groups according to postoperative treatment: RT alone (n = 105); and CCRT (n = 298). For risk stratification, patients were also divided into 2 groups: intermediate-risk (n = 350); and low-risk (n = 53). The median follow-up was 51.7 months. Patients in the intermediate-risk group and those with multiple intermediate-risk factors were more likely to undergo CCRT. For patients who underwent RT alone or CCRT in the intermediate-risk group, 5-year overall survival (OS) rates were 93.4% and 93.8% (p = 0.741), and 5-year disease-free survival (DFS) rates were 90.6% and 91.4%, respectively (p = 0.733). Similarly, for patients who underwent RT alone or CCRT in the low-risk group, the 5-year OS rates were 100.0% and 93.5% (p = 0.241), and 5-year DFS rateswere 94.4% and 93.5%, respectively (p = 0.736). Adjuvant CCRT or RT were not independent risk factors for either OS or DFS. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those in the RT group (44.0% versus 11.4%, respectively; p < 0.001). There was no significant difference in grade ≥ 3 chronic toxicities of the urogenital and gastrointestinal systems between the CCRT and RT groups. There was no significant difference in 5-year OS and DFS rates between patients with early-stage cervical cancer without high-risk factors undergoing postoperative CCRT versus RT alone. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those who underwent RT alone.

Genetic mutations and immune microenvironment: unveiling the connection to AML prognosis

ABSTRACT Background: This study aims to investigate the correlation between NK and NKT cell proportion disparities and prognosis in patients with acute myeloid leukemia (AML). Methods: Forty-four cases of acute myeloid leukemia patients were selected, and flow cytometry was utilized to evaluate the expression of bone marrow NK and NKT cells. Next-generation sequencing technology was employed to detect genetic mutations in these 44 AML patients, and the rates of first induction remission and overall survival were recorded. Comparisons were made to analyze the respective differences in NK and NKT cell proportions among AML patients with various genetic mutations and risk stratifications. Results: The FLT-3-ITD+ group exhibited a significant increase in the proportion of NK cells compared to the normal control group and FLT3-ITD+/NPM1+ group, whereas the proportion of NKT cells was significantly decreased. Additionally, the CEBPA+ group showed an increased proportion of NKT cells compared to the TP53+ group and ASXL1+ group. The high-risk group had a higher proportion of NK cells than the intermediate-risk group, while the proportion of NKT cells was lower in the high-risk group compared to the intermediate-risk group.Patients achieving first induction remission displayed a higher proportion of NKT cells at initial diagnosis compared to those who did not achieve remission. The distribution of NK cells show significant differences among AML patients in different survival periods. Conclusion: This results implies that distinct genetic mutations may play a role not only in tumor initiation but also in shaping the tumor microenvironment, consequently impacting prognosis.

Integration of measurable residual disease by WT1 gene expression and flow cytometry identifies pediatric patients with high risk of relapse in acute myeloid leukemia.

Molecular testing plays a pivotal role in monitoring measurable residual disease (MRD) in acute myeloid leukemia (AML), aiding in the refinement of risk stratification and treatment guidance. Wilms tumor gene 1 (WT1) is frequently upregulated in pediatric AML and serves as a potential molecular marker for MRD. This study aimed to evaluate WT1 predictive value as an MRD marker and its impact on disease prognosis. Quantification of WT1 expression levels was analyzed using the standardized European Leukemia Network real-time quantitative polymerase chain reaction assay (qRT-PCR) among a cohort of 146 pediatric AML patients. Post-induction I and intensification I, MRD response by WT1 was assessed. Patients achieving a ≥2 log reduction in WT1MRD were categorized as good responders, while those failing to reach this threshold were classified as poor responders. At diagnosis, WT1 overexpression was observed in 112 out of 146 (76.7%) patients. Significantly high levels were found in patients with M4- FAB subtype (p=0.018) and core binding fusion transcript (CBF) (RUNX1::RUNX1T1, p=0.018, CBFB::MYH11, p=0.016). Following induction treatment, good responders exhibited a reduced risk of relapse (2-year cumulative incidence of relapse [CIR] 7.9% vs 33.2%, p=0.008). Conversely, poor responders' post-intensification I showed significantly lower overall survival (OS) (51% vs 93.2%, p<0.001), event-free survival (EFS) (33.3% vs 82.6%, p<0.001), and higher CIR (66.6% vs 10.6%, p<0.001) at 24 months compared to good responders. Even after adjusting for potential confounders, it remained an independent adverse prognostic factor for OS (p=0.04) and EFS (p=0.008). High concordance rates between WT1-based MRD response and molecular MRD were observed in CBF patients. Furthermore, failure to achieve either a 3-log reduction by RT-PCR or a 2-log reduction by WT1 indicated a high risk of relapse. Combining MFC-based and WT1-based MRD results among the intermediate-risk group identified patients with unfavorable prognosis (positive predictive value [PPV] 100%, negative predictive value [NPV] 85%, and accuracy 87.5%). WT1MRD response post-intensification I serves as an independent prognostic factor for survival in pediatric AML. Integration of WT1 and MFC-based MRD results enhances the reliability of MRD-based prognostic stratification, particularly in patients lacking specific leukemic markers, thereby influencing treatment strategies.

Prognostic Factors and Outcomes in World Health Organization Grade 1 and Grade 2 Intracranial Meningiomas—5-Year Institutional Experience

Meningiomas are the most frequent primary intracranial tumor. While histological grade and grade of excision are established predictors of recurrence, the predictive ability of other clinical features, such as the role of radical excision of dural attachment and postoperative radiation therapy in intermediate-risk groups, remains unknown. Clinical and radiological features and surgical details were analyzed in 451 World Health Organization (WHO) grade 1 intracranial meningiomas and 248 WHO grade 2 meningiomas operated on between 2010 and 2015. Outcomes were assessed in 352 WHO grade 1 and 208 WHO grade 2 meningiomas, studying the effect of extent of resection and use of radiation therapy. Kaplan-Meier analysis was used to determine differences in survival by extent of resection and use of postoperative radiation therapy in the treatment of the meningiomas. The mean age of the cohort was 46.3 years, with a female predominance. On univariate analysis, sex, WHO grade, and Simpson grade were significant predictors of recurrence. On multivariate analysis, WHO grade and Simpson grade remained significant predictors of recurrence. Recurrence was significantly associated with poor performance status and mortality. Postoperative radiation significantly improved progression-free survival among patients with grade 2 meningiomas who underwent gross total resection, but not among patients with grade 1 and grade 2 meningiomas who underwent subtotal resection. WHO grade and Simpson grade are independent predictors of recurrence in meningiomas. Regardless of WHO grade, gross total resection must be performed when possible, and postoperative radiation therapy may be recommended in grade 2 meningiomas.

Predicting post-stroke cognitive impairment using electronic health record data.

Secondary prevention interventions to reduce post-stroke cognitive impairment (PSCI) can be aided by the early identification of high-risk individuals who would benefit from risk factor modification. To develop and evaluate a predictive model to identify patients at increased risk of PSCI over 5 years using data easily accessible from electronic health records. Cohort study that included primary care patients from two academic medical centers. Patients were aged 45 years or older, without prior stroke or prevalent cognitive impairment, with primary care visits and an incident ischemic stroke between 2003 and 2016 (development/internal validation cohort) or 2010 and 2022 (external validation cohort). Predictors of PSCI were ascertained from the electronic health record. The outcome was incident dementia/cognitive impairment within 5 years and beginning 3 months following stroke, ascertained using International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) codes. For model variable selection, we considered potential predictors of PSCI and constructed 400 bootstrap samples with two-thirds of the model derivation sample. We ran 10-fold cross-validated Cox proportional hazards models using a least absolute shrinkage and selection operator (LASSO) penalty. Variables selected in >25% of samples were included. The analysis included 332 incident diagnoses of PSCI in the development cohort (n = 3741), and 161 and 128 incident diagnoses in the internal (n = 1925) and external (n = 2237) validation cohorts, respectively. The C-statistic for predicting PSCI was 0.731 (95% confidence interval (CI): 0.694-0.768) in the internal validation cohort, and 0.724 (95% CI: 0.681-0.766) in the external validation cohort. A risk score based on the beta coefficients of predictors from the development cohort stratified patients into low (0-7 points), intermediate (8-11 points), and high (12-23 points) risk groups. The hazard ratios (HRs) for incident PSCI were significantly different by risk categories in internal (high, HR: 6.2, 95% CI: 4.1-9.3; Intermediate, HR: 2.7, 95% CI: 1.8-4.1) and external (high, HR: 6.1, 95% CI: 3.9-9.6; Intermediate, HR: 2.8, 95% CI: 1.9-4.3) validation cohorts. Five-year risk of PSCI can be accurately predicted using routinely collected data. Model output can be used to risk stratify and identify individuals at increased risk for PSCI for preventive efforts. Mass General Brigham data contain protected health information and cannot be shared publicly. The data processing scripts used to perform analyses will be made available to interested researchers upon reasonable request to the corresponding author.

Nodal staging in high and high-intermediate risk endometrial cancer surgery: Which role in the molecular classification era?

ObjectivesNodal staging contributes to risk group definition and the indication to adjuvant treatment in endometrial cancer (EC) patients. However, the role of nodal assessment evolved and requires redefinition.Primary outcome of the study was to assess the impact of surgical nodal staging in defining high-risk (HR) EC. Secondary outcome was to evaluate the contribution of nodal assessment to the decision for adjuvant treatment in both high-risk and high-intermediate risk (HIR) patients submitted to surgery. MethodsClinical stage I-II EC patients with postoperative diagnosis of HR and HIR disease were included. The contribution of nodal staging in prognostic groups allocation was assessed by reviewing HR patients to identify those without any other feature of such class (non-endometrioid histology, p53abn immunohistochemistry, post-operative T3-T4 disease) and HIR cases to assess how nodal staging affected adjuvant treatment indication. Descriptive statistics were conducted to describe the two populations. ResultsFifty-seven patients were included, 46 with HR and 11 with HIR disease. Chemotherapy and external-beam radiotherapy (EBRT) were proposed in 40 HR patients. Considering histology, immunohistochemical profile and FIGO stage, high risk classification was exclusively relied on nodal involvement in 2/46 cases (4.3 %). Omitting retroperitoneal staging, one of them would have been classified in the intermediate risk group and the other as HIR: without nodal staging, chemotherapy and EBRT would have been omitted in 1/40 (2.5 %) case.Among HIR patients, chemotherapy was proposed in 7/11 cases and EBRT in all cases. Adjuvant chemotherapy was indicated in 5/6 (83.3 %) and omitted in 1/6 (16.7 %) pN0 patient (stage Ib G2, substantial LVSI). In HIRpN0 patients, omitting nodal staging could have changed adjuvant treatment indication in 1/6 (16.7 %) case. In HIRpNx patients, adjuvant chemotherapy was omitted in one patient (stage II, grade 2 and LVSI negative): nodal staging unavailability might have changed indication to chemotherapy in 1/5 (20 %) case, without changing indication to EBRT.Unavailable nodal staging could globally be related to omission of chemotherapy in 2/57 (3.5 %) patients and of EBRT in 1/57 (1.8 %) patient. ConclusionsIn this series, nodal staging had limited impact on definition of HR class and on the choice of adjuvant treatment in HR and HIR EC patients.

Validation of the 2022 European LeukemiaNet risk stratification for acute myeloid leukemia

This study aimed to validate the 2022 European LeukemiaNet (ELN) risk stratification for acute myeloid leukemia (AML). A total of 624 newly diagnosed AML patients from 1998 to 2014 were included in the analysis. Genetic profiling was conducted using targeted deep sequencing of 45 genes based on recurrent driver mutations. In total, 134 (21.5%) patients had their risk classification reassessed according to the 2022 ELN risk stratification. Among those initially classified as having a favorable risk in 2017 (n = 218), 31 and 3 patients were reclassified as having intermediate risk or adverse risk, respectively. Among the three subgroups, the 2022 ELN favorable-risk group showed significantly longer survival outcomes than the other groups. Within the 2017 ELN intermediate-risk group (n = 298), 21 and 46 patients were reclassified as having favorable risk or adverse risk, respectively, and each group showed significant stratifications in survival outcomes. Some patients initially classified as having adverse risk in 2017 were reclassified into the intermediate-risk group (33 of 108 patients), but no prognostic improvements were observed in this group. A multivariable analysis identified the 2022 ELN risk stratification, age, and receiving allogeneic hematopoietic cell transplantation as significant prognostic factors for survival. The 2022 ELN risk stratification enables more precise decisions for proceeding with allogeneic hematopoietic cell transplantation for AML patients.

A chest CT-based nomogram for predicting survival in acute myeloid leukemia

BackgroundThe identification of survival predictors is crucial for early intervention to improve outcome in acute myeloid leukemia (AML). This study aim to identify chest computed tomography (CT)-derived features to predict prognosis for acute myeloid leukemia (AML).Methods952 patients with pathologically-confirmed AML were retrospectively enrolled between 2010 and 2020. CT-derived features (including body composition and subcutaneous fat features), were obtained from the initial chest CT images and were used to build models to predict the prognosis. A CT-derived MSF nomogram was constructed using multivariate Cox regression incorporating CT-based features. The performance of the prediction models was assessed with discrimination, calibration, decision curves and improvements.ResultsThree CT-derived features, including myosarcopenia, spleen_CTV, and SF_CTV (MSF) were identified as the independent predictors for prognosis in AML (P < 0.01). A CT-MSF nomogram showed a performance with AUCs of 0.717, 0.794, 0.796 and 0.792 for predicting the 1-, 2-, 3-, and 5-year overall survival (OS) probabilities in the validation cohort, which were significantly higher than the ELN risk model. Moreover, a new MSN stratification system (MSF nomogram plus ELN risk model) could stratify patients into new high, intermediate and low risk group. Patients with high MSN risk may benefit from intensive treatment (P = 0.0011).ConclusionsIn summary, the chest CT-MSF nomogram, integrating myosarcopenia, spleen_CTV, and SF_CTV features, could be used to predict prognosis of AML.

Obesity Surgery Mortality Risk Score as a Predictor for Intensive Care Unit Admission in Patients Undergoing Laparoscopic Bariatric Surgery.

Background: Laparoscopic bariatric surgery provides many benefits including lower postoperative pain scores, reduced opioid consumption, shorter hospital stays, and improved quality of recovery. However, the anaesthetic management of obese patients requires caution in determining postoperative risk and in planning adequate postoperative pathways. Currently, there are no specific indications for intensive care unit (ICU) admission in this surgical population and most decisions are made on a case-by-case basis. The aim of this study is to investigate whether Obesity Surgery Mortality Risk Score (OS-MRS) is able to predict ICU admission in patients undergoing laparoscopic bariatric surgery (LBS). Methods: We retrospectively reviewed data of patients who underwent LBS during a 2-year period (2017-2019). The collected data included demographics, comorbidities and surgery-related variables. Postoperative ICU admission was decided via bariatric anaesthesiologists' evaluations, based on the high risk of postoperative cardiac or respiratory complications. Anaesthesia protocol was standardized. Logistic regression was used for statistical analysis. Results: ICU admission was required in 2% (n = 15) of the 763 patients. The intermediate risk group of the OS-MRS was detected in 84% of patients, while the American Society of Anaesthesiologists class III was reported in 80% of patients. A greater OS-MRS (p = 0.01), advanced age (p = 0.04), male gender (p = 0.001), longer duration of surgery (p = 0.0001), increased number of patient comorbidities (p = 0.002), and previous abdominal surgeries (p = 0.003) were predictive factors for ICU admission. Conclusions: ICU admission in obese patients undergoing LBS is predicted by OS-MRS together with age, male gender, number of comorbidities, previous abdominal surgeries, and duration of surgery.

Marginal zone lymphoma international prognostic index: a unifying prognostic index for marginal zone lymphomas requiring systemic treatment

Marginal zone lymphomas (MZL), comprised of three unique but related subtypes, lack a unifying prognostic score applicable to all the patients in need for systemic chemotherapy and/or immunotherapy. Patients from the prospective NF10 study (NCT02904577) with newly diagnosed MZL and receiving frontline systemic therapy at diagnosis or after observation were used to train a prognostic model. The primary endpoint was progression-free survival (PFS) from start of treatment. The model was externally validated in a pooled analysis of two independent cohorts from the University of Iowa and Mayo Clinic Molecular Epidemiology Resource and the University of Miami. We identified 501 eligible patients. After multivariable modeling, lactate dehydrogenase (LDH) above upper normal limit, hemoglobin <12g/dL, absolute lymphocyte count <1×109/L, platelets <100×109/L, and MZL subtype (nodal or disseminated) were independently associated with inferior PFS. The proposed MZL International Prognostic index (MZL-IPI) combined these 5 factors, and we defined low (LRG, 0 factors, 27%), intermediate (IRG, 1-2 factors, 57%) and high (HRG, 3+ factors, 16%) risk groups with 5-y PFS of 85%, 66%, and 37%, respectively (c-Harrell=0.64). Compared to the LRG, the IRG (Hazard Ratio [HR]=2.30, 95% CI 1.39-3.80) and HRG (HR=5.41, 95% CI 3.12-9.38) had inferior PFS. Applying the MZL-IPI to the pooled US cohort (N=353), 94 (27%), 192 (54%), and 67 (19%) patients were classified as LRG, IRG, and HRG, respectively, and the model was validated for PFS (log-rank test p=0.0018; c-Harrell=0.578, 95% CI 0.54-0.62). The MZL-IPI was also prognostic for OS in both the training and the external validation sets. MZL-IPI is a new prognostic score for use in all patients with MZL considered for systemic treatment. The MER was supported by P50 CA97274 and U01 CA195568.

Aspiration of thrombus for intermediate-risk subacute pulmonary embolism

Pulmonary embolism is the most common cardiovascular disease after myocardial infarction and stroke. Konstantinides (Eur Heart J 41(4):543–603, 2020) Current guidelines categorize patients with PE as being at low, intermediate, and high risk of early death, with the intermediate-risk group experiencing the greatest uncertainty regarding treatment recommendations. Rapid reduction of the thrombus load by thrombolysis significantly reduces symptoms and decreases mortality, but is accompanied by a high risk of bleeding. Meyer (N Engl J Med 370(15):1402-11, 2014) Mechanical thrombectomy (CDTE) have been proven safe and efficient, yet current ESC guidelines suggest the utilization of catheter interventions only for hypotensive patients with high bleeding risk, failed systemic thrombolysis, and cardiogenic shock or if a patient does not respond to conservative therapy Konstantinides (Eur Heart J 41(4):543–603, 2020). Here, we report a case of an intermediate-risk patient with pulmonary embolism who underwent thrombus aspiration and showed significant improvement in symptoms after treatment.