Group Stratification Research Articles

The RAS-signaling-pathway-mutation-related prognosis in B-cell acute lymphoblastic leukemia: A report from South China children's leukemia group.

The next-generation sequencing technologies application discovers novel genetic alterations frequently in pediatric acute lymphoblastic leukemia (ALL). RAS signaling pathway mutations at the time of relapse ALL frequently appear as small subclones at the time of onset, which are considered as the drivers in ALL relapse. Whether subclones alterations in the RAS signaling pathway should be considered for risk group stratification of ALL treatment is not decided yet. In this work, we investigate the RAS signaling pathway mutation spectrum and the related prognosis in pediatric ALL. We employed an NGS panel comprising 220 genes. NGS results were collected from 202 pediatric ALL patients. 155 patients (76.7%) harbored at least one mutation. The incidences of RAS signaling pathway mutations are different significantly between T-ALL and B-ALL. In B-ALL, the RAS pathway is mostly involved, and NRAS (17.6%), KRAS (22.7%), and PTPN11 (7.7%) were the three most frequently mutated genes. Co-occurring mutations of CREBBP and NRAS, FLT3, or PTPN11 (p=0.002, p=0.009, and p=0.003, respectively) were found in this cohort. The 3-year RFS rates for the RAS signaling pathway mutation-positive and negative cases was 76.5 % versus 89.7 % (p=0.012). Four cases relapsed in the lately 3years were RAS signaling pathway mutation-positive. RAS signaling pathway mutation is an important biomarker for poorer relapse-free survival in pediatric B-ALL patients despite good early MRD levels.

Clustering patients with late-life depression by blood glutathione-dependent enzymatic activities for stratification of a heterogeneous group

IntroductionWe have previously found significant alterations in activities of glutathione dependent enzymes in blood cells of patients with late-life depression (LLD) compared with age-matched controls.ObjectivesThe revealing subgroups of LLD patients by glutathione-metabolism enzymes’ activities in blood cells using cluster analysis.Methods LLD patients (n=101) of 60-86 age (69 patients with recurrent depression (RD), 23 with bipolar disorder (BD) and 9 patients with a single depressive episode (DE)) were assessed by Hamilton depression rating scale (HAMD-17), and Hamilton Anxiety Rating Scale (HARS). Activity levels of glutathione reductase (GR) and glutathione S-transferase (GST) were determined in patients’ platelets (-pl) and erythrocytes (-er). The control group consisted of 51 peoples 55-84 years old without mental pathology. Cluster analysis module of the STATISTICA software was used for clustering the patients by baseline blood parameters.Results Three clusters of patients were obtained: C1, n=39, C2, n=31, C3, n=31, differing significantly in all biochemical parameters (Kruskal-Wallis test, p<0.001), except GST. When compared with control group by Mann-Whitney test, GST-pl, GST-er, and GR-er were significantly decreased in C1; GST-er was significantly increased in C2; GST-pl, GR-pl, and GR-er were significantly decreased in C3. Several significant correlations were found between the measured parameters and scores by HDRS or HAMD-17. In C1, baseline activity of GST-er correlated with total scores by HAMD-17 (R=0.335, p=0.043) after treatment. In C2, baseline activity of GR-er correlated with total scores by HARS (R=-0.376, p=0,037) after treatment and GR-pl correlated with delta scores by HAMD-17 under the treatment (R=0.484, p=0.006). No significant correlations were found in C3. Patients with BD distributed significantly unevenly between C1, C2, and C3, with significantly more BD patients clustering in C1 (61%) compared with C2 and C3 (Yetes-corrected Chi-square =7.73, p=0.0054), whereas patients with RD and DE distributed evenly.Conclusions Patterns of activity levels for glutathione-dependent enzymes in patients with BD differ from those in patients with RD and DE. Significant correlations of the measured biochemical parameters with scores by HDRS or HAMD-17 assessed after the treatment and evidenced for the treatment efficacy seem to be promising biomarkers for further evaluation of the treatment efficacy in heterogeneous group of LLD patients using the proposed approach to their stratification into subgroups.Disclosure of InterestNone Declared

The Dilemma of Lithium Discontinuation in Bipolar Disorder During Pregnancy Planning: A Case Report and Literature Review

IntroductionLithium is considered the gold standard mood stabiliser for bipolar disorder, yet its use during pregnancy remains controversial, demanding careful consideration of potential risks and benefits. Classically, it has been associated with an increased risk in congenital heart defects, however, recent studies point towards a much lower absolute risk than was previously believed. Furthermore, discontinuation of lithium before or during pregnancy poses a high risk of destabilisation and lithium has been shown to reduce the risk of relapse both in pregnancy and in the postpartum period. Hence, treatment planning is of the upmost importance in this patient group and individual risk stratification should be undertaken for patients to make informed decisions about their treatment.ObjectivesTo describe the case of a patient with bipolar disorder who discontinued lithium treatment while attempting to conceive and subsequently presented with a manic episode and to expand the scientific knowledge on this topic.MethodsCase report and brief literature review.Results A 41-year-old patient with a diagnosis of bipolar disorder, previously on lithium 900mg/day, was admitted to the emergency department with symptoms suggestive of a manic episode. One month prior, the patient had discontinued treatment with lithium due to her desire to pursue pregnancy and interrupt treatment while trying to conceive. The patient had a history of postpartum psychosis followed by various depressive and manic episodes with psychotic symptoms, leading to a bipolar disorder diagnosis and commencing treatment with lithium. Her consultant psychiatrist had informed her of the individualised risks of interrupting treatment with lithium and had advised to continue treatment alongside frequent follow-up due to the high-risk of relapse. Despite her consultant’s recommendation, she decided to interrupt treatment and hence a personalised lithium tapering regime and advice to continue treatment with quetiapine 200mg/day was given. During the ED stay, treatment with olanzapine was introduced which helped to stabilise her symptoms. Lithium levels were subtherapeutic (lithium serum level 0.11 mmol/L). Inpatient psychiatric admission was avoided due to rapid symptom improvement, strong social support in the community and her preference for ambulatory care. Lithium was gradually reintroduced and antipsychotic treatment was adjusted at follow up appointments, which ultimately led to the resolution of symptoms and stabilisation.ConclusionsThis case highlights the significance of considering continuing lithium treatment in bipolar disorder during pregnancy planning. Decisions about medication in pregnancy are multifaceted, making appropriate risk stratification imperative in order to inform individualised care plans to minimise the risk of relapse in these patients.Disclosure of InterestNone Declared

Flow cytometric minimal residual disease measurement accounting for cytogenetics in children with non-high-risk acute lymphoblastic leukemia treated according to the ALL-MB 2008 protocol.

Quantitative measurement of minimal residual disease (MRD) is the "gold standard" for estimating the response to therapy in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Nevertheless, the speed of the MRD response differs for different cytogenetic subgroups. Here we present results of MRD measurement in children with BCP-ALL, in terms of genetic subgroups with relation to clinically defined risk groups. A total of 485 children with non-high-risk BCP-ALL with available cytogenetic data and MRD studied at the end-of-induction (EOI) by multicolor flow cytometry (MFC) were included. All patients were treated with standard-risk (SR) of intermediate-risk (ImR) regimens of "ALL-MB 2008" reduced-intensity protocol. Among all study group patients, 203 were found to have low-risk cytogenetics (ETV6::RUNX1 or high hyperdiploidy), while remaining 282 children were classified in intermediate cytogenetic risk group. For the patients with favorable and intermediate risk cytogenetics, the most significant thresholds for MFC-MRD values were different: 0.03% and 0.04% respectively. Nevertheless, the most meaningful thresholds were different for clinically defined SR and ImR groups. For the SR group, irrespective to presence/absence of favorable genetic lesions, MFC-MRD threshold of 0.1% was the most clinically valuable, although for ImR group the most informative thresholds were different in patients from low-(0.03%) and intermediate (0.01%) cytogenetic risk groups. Our data show that combining clinical risk factors with MFC-MRD measurement is the most useful tool for risk group stratification of children with BCP-ALL in the reduced-intensity protocols. However, this algorithm can be supplemented with cytogenetic data for part of the ImR group.

Long Non-Coding RNA RP11-252C15.1 Is a Potential Biomarker of Prognosis and Hallmark for Leukemogenesis in Children with B-Cell Precursor Acute Lymphoblastic Leukemia

Introduction: Improved understanding of the prognostic biomarkers associated with childhood acute lymphoblastic leukemia (ALL) is needed for accurate risk group stratification. This study aimed to identify potential long non-coding RNA (lncRNA) markers and evaluate their prognostic value in children with ALL. Methods: We selected 50 children with newly diagnosed ALL and 20 age-matched patients with idiopathic immune thrombocytopenia (controls). RNA sequencing was performed to identify differentially expressed lncRNAs between the ALL and control groups. Correlation analysis was performed to determine the relationships between candidate lncRNAs, clinical features, and the risk of leukemogenesis. Results: A total of 1,019 differentially expressed lncRNAs were identified between the ALL and control groups. Reverse transcriptase (RT-qPCR) revealed that lncRNA RP11-252C15.1 and lncRNA RP11-701P16.2 were significantly upregulated in patients with ALL. Furthermore, correlation analysis showed that lncRNA RP11-252C15.1 and lncRNA RP11-701P16.2 represent potential predictors of leukemogenesis; however, only lncRNA RP11-252C15.1 was associated with clinical features and outcome in children with B-cell precursor ALL (BCP-ALL). In vitro experiments confirmed that lncRNA RP11-252C15.1 was significantly overexpressed in BCP-ALL cell lines and promoted proliferation and repressed apoptosis in MHH-CALL-3 cells. Conclusion: lncRNA RP11-252C15.1 is a potential oncogene in BCP-ALL pathogenesis and a prognostic biomarker in children with BCP-ALL.

Abstract 3463: Beyond staging systems in cutaneous squamous cell carcinoma: Validation of two thresholds for a model-estimated metastatic risk

Abstract Background: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, therefore causing a death toll comparable to that of melanoma, despite its low propensity to metastasize (2-5%). We recently developed a clinicopathological (CP) model that predicts absolute metastatic risk in cSCC patients. We have recently shown that, in a nationwide Dutch cohort, the model enhances the risk stratification provided by the American Joint Committee on Cancer, eighth edition (AJCC) and the Brigham and Women's Hospital (BWH) staging systems. The current study aims to evaluate the refined risk stratification and designed risk thresholds in an independent, nationwide UK cohort. Methods: In the Dutch cohort, we defined patients at increased risk within the low-risk group (AJCC: T1-T2, BWH: T1-T2a) as those with an estimated risk above 1%; and in the high-risk group (AJCC: T3-T4, BWH: T2b-T3), as those with a risk above 3.5%. Both risk thresholds were evaluated in the nested case-control (NCC) cohort (n=696), sampled from the nationwide UK cohort (n=31981). The CP model was applied to the NCC cohort and results were binarized as CP Low-Risk or CP High-Risk. Weighted metrics were computed to adjust for the difference in proportion of cases and controls between NCC and nationwide cohorts. Results: In the low-risk group as per AJCC (T1-T2) and BWH (T1-T2a), the metastatic risk is respectively 0.93% and 1.07%. Within this group, CP High-Risk patients represent respectively 1.69% and 6.11% of the AJCC and BWH groups and have increased metastatic risk of 7.54% in AJCC and 5.36% in BWH. In the high-risk group as per AJCC (T3-T4) and BWH (T2b-T3), the metastatic risk is respectively 7.79% and 13.80%. Within this group, CP High-Risk patients represent respectively 7.42% and 24.40% of the AJCC and BWH groups. They have an increased metastatic risk of 27.92% in AJCC and 24.07% in BWH. Conclusions: This study validates the designed risk thresholds in an independent nationwide cohort. Differences in performance compared to the Dutch cohort can be explained by the exclusion of patients with multiple missing variables and worse annotation of pathological features in the UK cohort. Additionally, this study confirms that our risk model can enhance cSCC staging systems by a refined risk stratification in both low-risk and high-risk groups. Specifically, the CP High-Risk subgroup within the staging systems' low-risk group might benefit from heightened surveillance and diagnostic screening, such as lymph node ultrasonography. Similarly, the CP High-Risk subgroup within the staging systems’ high-risk group could be considered for intensified surveillance and (adjuvant) treatment. In conclusion, adding the CP model to current cSCC staging systems would enable more personalized decisions about follow-up and treatment, while also facilitating the management of healthcare resources. Citation Format: Olivia FM Steijlen, Lara Pozza, Barbara Rentroia-Pacheco, Celeste. J. Eggermont, Domenico Bellomo, Sheril Alex, Jvalini Dwarkasing, Antien L. Mooyaart, Loes M. Hollestein, Marlies Wakkee. Beyond staging systems in cutaneous squamous cell carcinoma: Validation of two thresholds for a model-estimated metastatic risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3463.

Autotaxin is a potential predictive marker for the development of veno-occlusive disease/sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation.

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT), and stratification of the high-risk group before transplantation is significant. Serum autotaxin (ATX) levels have been reported to increase in patients with liver fibrosis caused by metabolic inhibition from liver sinusoidal endothelial cells. Considering that the pathophysiology of VOD/SOS begins with liver sinusoidal endothelial cell injury, an increase in serum ATX levels may precede the onset of VOD/SOS. A retrospective study with 252 patients, including 12 patients with VOD/SOS, who had received allo-HCT was performed. The cumulative incidence of VOD/SOS was higher in the group with serum ATX levels before conditioning (baseline ATX) above the upper reference limit (high ATX group, p < 0.001), and 1-year cumulative incidences were 22.7% (95% confidence interval [95%CI], 3.1-42.4%) and 3.5% (95%CI, 1.1-5.8%), respectively. In the multivariate analysis, elevated baseline ATX was identified as an independent risk factor for VOD/SOS development and showed an additive effect on the predictive ability of known risk factors. Furthermore, the incidence of VOD/SOS-related mortality was greater in the high ATX group (16.7% vs. 1.3%; p = 0.005). Serum ATX is a potential predictive marker for the development of VOD/SOS.

Predictive Value of Multiparametric Magnetic Resonance Imaging in Risk Group Stratification of Prostate Adenocarcinoma

The aim of this study was to further assess the clinical utility of multiparametric magnetic resonance imaging (MP-MRI) in prostate cancer (PC) staging following 2023 clinical guideline changes, both as an independent predictor of high-stage (>T3a) or high-risk PC and when combined with patient characteristics. The present study was a retrospective review of 171 patients from 2008 to 2018 who underwent MP-MRI before radical prostatectomy at a single institution. The accuracy of clinical staging was compared between conventional staging and MP-MRI-based clinical staging. Sensitivity, specificity, positive predictive value, and negative predictive value were compared, and receiver operating characteristic curves were generated. Linear regression analyses were used to calculate concordance (C-statistic). Of the 171 patients, final pathology revealed 95 (55.6%) with T2 disease, 62 (36.3%) with T3a disease, and 14 (8.2%) with T3b disease. Compared with conventional staging, MP-MRI-based staging demonstrated significantly increased accuracy in identifying T3a disease, intermediate risk, and high/very-high-risk PC. When combined with clinical characteristics, MP-MRI-based staging improved the area under the curve from 0.753 to 0.808 (P = .0175), compared with conventional staging. MP-MRI improved the identification of T3a PC, intermediate-risk PC, and high- or very-high-risk PC. Further, when combined with clinical characteristics, MP-MRI-based staging significantly improved risk stratification, compared with conventional staging. These findings represent further evidence to support the integration of MP-MRI into prostate adenocarcinoma clinical staging guidelines.

Genetics and Age-Related Macular Degeneration: A Practical Review for Clinicians.

Age-related macular degeneration (AMD) is a multifactorial genetic disease, with at least 52 identifiable associated gene variants at 34 loci, including variants in complement factor H (CFH) and age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase-1 (ARMS2/HTRA1). Genetic factors account for up to 70% of disease variability. However, population-based genetic risk scores are generally more helpful for clinical trial design and stratification of risk groups than for individual patient counseling. There is some evidence of pharmacogenetic influences on various treatment modalities used in AMD patients, including Age-Related Eye Disease Study (AREDS) supplements, photodynamic therapy (PDT), and anti-vascular endothelial growth factor (anti-VEGF) agents. However, there is currently no convincing evidence that genetic information plays a role in routine clinical care.

Questionnaire as a stratification method in organizing colorectal cancer screening

The purpose of the study: to compare the efficacy of questionnaires and fecal immunochemical tests in stratification of risk groups during colorectal cancer screening. A non-randomized comparative study was conducted to evaluate the effectiveness of two stratification methods for colorectal cancer screening as part of pilot projects in the regions of the Central Federal District of the Russian Federation. In the first group, the stratification method was the original questionnaire, and in the second group — the fecal immunochemical test (FIT). All participants included in the first and second groups underwent colonoscopy at the second stage of screening. A total of 250 respondents participated in the study, 128 in the questionnaire group and 122 in the FIT group. In the questionnaire group, a high risk of colorectal cancer was found in 91 (71.1 %) individuals, while 37 (28.9 %) respondents had a low risk. Based on colonoscopy results, colorectal cancer and colorectal polyps were diagnosed in 65 (50.8 %) participants, and no significant pathology was found in 63 (49.2 %). In the FIT group, 102 (83.6 %) participants tested positive (FIT+) and 20 (16.4 %) tested negative (FIT-). According to the results of the performed colonoscopy, colorectal cancer and colon polyps were diagnosed in 75 (61.5 %) individuals, while no significant pathology was detected in 47 (38.5 %) participants. The sensitivity of the questionnaire was 86.2 % (95 % CI 75.3–93.5 %) and specificity was 44.4 % (95 % CI 31.9–57.5 %); the predictive value of a positive result was 61.5 % (95 % CI 50.7–71.6 %), and the predictive value of a negative result was 75.7 % (95 % CI 58.8–88.2 %). The FIT sensitivity was 86.7 % (95 % CI 76.8–93.4 %), the specificity was 21.3 % (95 % CI 10.7–35.7 %), the predictive value of a positive result was 63.7 % (95 % CI 53.6–73.0 %), and the predictive value of a negative result was 50.0 % (95 % CI 27.2–72.8 %). In conclusion, the questionnaire method in the colorectal cancer screening model is comparable in sensitivity and specificity to those of the FIT. It is essential to emphasize that questionnaires, along with ease of implementation, do not entail significant economic costs.

Risk Factors Affecting Clinical Outcomes of Low-risk Early-stage Human Papillomavirus-Associated Endocervical Adenocarcinoma Treated by Surgery Alone: Application of Silva Pattern.

This study aimed to report the clinical outcomes and risk factors for survival of patients with low-risk early-stage human papillomavirus-associated (HPVA) endocervical adenocarcinoma (EAC) treated with surgery alone. This retrospective study obtained the clinicopathological data of patients with early-stage HPVA EAC who underwent surgery between 2012 and 2018. The Silva pattern of invasion was determined by reviewing pathology slides. Locoregional recurrence-free survival (RFS), RFS, and overall survival were calculated, and the risk factors for survival were analyzed. One hundred seventeen patients with a median follow-up of 5.2 years (0.5-9.7yr) were included. The most common histologic type was usual (94/117, 80.3%). The Silva pattern was A in 79 patients (67.5%), B in 30 (25.6%), and C in 8 (6.8%). The 5-year locoregional RFS, RFS, and overall survival rates were 92.4%, 87.8%, and 97.2%, respectively. The presence of intermediate-risk factors and Silva pattern C were significantly associated with worse survival. Based on these findings, patients were categorized into 2 groups: Group 1 (Silva pattern A or Silva pattern B without intermediate-risk factors) and Group 2 (Silva pattern B with intermediate-risk factors or Silva pattern C ). Group 2 showed significantly worse outcomes than Group 1, including the 5-year locoregional RFS (98.6% vs 68.0%), RFS (96.4% vs 54.6%), and overall survival (100.0% vs 86.5%). In conclusion, surgery alone for early-stage HPVA EAC resulted in favorable outcomes. Consideration of the Silva pattern, in addition to well-known risk factors, could help in precise risk group stratification of low-risk, early-stage HPVA EAC.

Viable tumor cell density after neoadjuvant chemotherapy assessed using deep learning model reflects the prognosis of osteosarcoma

Prognosis after neoadjuvant chemotherapy (NAC) for osteosarcoma is generally predicted using manual necrosis-rate assessments; however, necrosis rates obtained in these assessments are not reproducible and do not adequately reflect individual cell responses. We aimed to investigate whether viable tumor cell density assessed using a deep-learning model (DLM) reflects the prognosis of osteosarcoma. Seventy-one patients were included in this study. Initially, the DLM was trained to detect viable tumor cells, following which it calculated their density. Patients were stratified into high and low-viable tumor cell density groups based on DLM measurements, and survival analysis was performed to evaluate disease-specific survival and metastasis-free survival (DSS and MFS). The high viable tumor cell density group exhibited worse DSS (p = 0.023) and MFS (p = 0.033). DLM-evaluated viable density showed correct stratification of prognosis groups. Therefore, this evaluation method may enable precise stratification of the prognosis in osteosarcoma patients treated with NAC.

Up-regulated mRNA expression of VEGFA receptors (FLT1 and KDR) in placentas after assisted reproductive technology fertilization

Placental angiogenesis is a pivotal process for feto-maternal circulation and ensures efficient development of the placenta throughout pregnancy. Many factors during in vitro fertilization and embryo transfer procedures may affect placental gene expression and fetus development. The present study aimed to identify differences in angiogenesis-related gene (VEGFA, FGF2, FLT1, and KDR) expression profiles in placentas after assisted reproductive technology fertilization and natural conception in healthy women. In a case-control study, term placentas were collected from Caucasian women after assisted reproductive technology fertilization (N = 20) and after natural conception in women with uncomplicated pregnancy (N = 9). The mRNA expression in placentas was examined for VEGFA, FGF2, FLT1, and KDR genes by real-time quantitative polymerase chain reaction (RT-qPCR). Group stratification was performed for comparison of investigated genes between the type of embryo transferred (fresh/frozen), place of tissue donation (center/margin), and newborns’ gender (male/female). In the ART placentas, significant down-regulation of VEGFA gene (p = 0.016) and up-regulation of FLT1 (p = 0.026) and KDR (p < 0.001) gene receptors were observed. Genes encoding VEGFA receptors were up-regulated in both fresh (ET) and frozen (FET) embryo transfer groups compared to controls. For the FLT1 gene, a statistically significant difference was observed between the frozen embryo transfer group and the controls (p = 0.032). Relative expression of KDR was significantly higher for both embryo transfer groups compared to controls (p < 0.001) and between ET and FET (p = 0.002). No statistically significant differences were observed between placental expression in different places of tissue donation and newborns’ gender. We observed differences in the placental expression of VEGFA and its receptors FLT1 and KDR in pregnancies after assisted reproductive technology compared to naturally conceived pregnancies. More research is needed to clarify these alterations that may affect placental development and fetal health.

Abstract A112: Liquid biopsy shows distinctive proteome of long-term recurrence free survivors after PDAC resection

Abstract Pancreatic ductal adenocarcinoma (PDAC)patients have a 5-year survival rate of less than 10%, partly due to 80% developing recurrence within 2 years after curative intent surgery. As surgical resectability criteria expand and techniques progress, better understanding of tumor biology regarding post-resection prognosis is needed to improve patient outcomes. Our study therefore investigated usefulness of liquid biopsy and proteomics analysis for stratification of post-resection risk groups. Patients undergoing standardized follow-up after resection of PDAC at the European Pancreas Center (Heidelberg, Germany) donated blood samples and clinical data after giving informed consent. Outcomes were extracted from the institutional database or Electronic Health Records and documented retrospectively. From all included patients (n=101) 7mL serum was drawn at different follow-up time points. Overall, 139 samples were collected. Protein expression values of 2953 proteins were determined via antibody microarrays. For analysis and statistics, GenePix 6.0, R and GraphPad Prism were used. First, a principal component analysis was performed on the complete data set. Then the data set was split in a training and test set and A subgroup of 43 patients experienced recurrence of PDAC within 24 months post resection (median: 11.39 months), classified as “early recurrence” (ER). Furthermore, 23 patients experienced recurrence between 26 and 144 months and were termed “late recurrence” (LR). 32 patients had a follow up &amp;gt; 26 months after resection and 6 months after sampling and remained recurrence-free; those were termed “long-term recurrence free survivors” (LT-RFS). Principal component analysis of protein microarray data revealed distinct clustering of LT-RFS together along the primary axis. Contrarily, all of the samples taken at time of recurrence were exclusively found in other quadrants, as were all samples but one of the ER subgroup preceeding diagnosis of recurrence. Samples of the LR subgroup appeared to shift from clustering with LT-RFS samples towards samples from ER and post-recurrence. Lasso regression yielded a panel of 10 proteins, with a specificity of 98.0%/90.9% and a sensitivity of 89.4%/65.0% (training/test set), for identification of samples from LT-RFS. The findings of our protein microarray analysis on PDAC recurrence monitoring suggest a distinct proteome of patients with RFS of &amp;gt;2a post resection. Furthermore, we found hints that the post-resection proteome undergoes a dynamic shift from recurrence-free phenotype towards a phenotype of recurrence. These data need validation in prospective cohorts to determine clinical relevance, however, they point towards opportunities offered by liquid biopsy for sophisticated disease monitoring post resection and for novel insights into mechanisms of disease in PDAC. A protein panel predictive of long-term RFS might enable personalized follow-up pathways and have a positive impact on frequency and invasiveness of post-resection diagnostic testing for PDAC patients. Citation Format: Teresa Colbatzky, Fawaz N. Al-Shaheri, Andrea S. Bauer, Nathalia Giese, Jörg D. Hoheisel, Ulrike Heger. Liquid biopsy shows distinctive proteome of long-term recurrence free survivors after PDAC resection [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A112.

The Association Between the Albumin-Bilirubin Score and Contrast-Associated Acute Kidney Injury in Patients Undergoing Elective Percutaneous Coronary Intervention.

The albumin-bilirubin (ALBI) score is considered an effective and convenient scoring system for assessing liver function. We hypothesized that the ALBI score was predictive of contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). We retrospectively observed 5629 patients undergoing elective PCI. Contrast-associated acute kidney injury is defined as a 50% or 0.3mg/dl increase in baseline serum creatinine levels within 48 h of contrast exposure. The incidence of CA-AKI was 6.2% (n = 350). After adjusting for potential confounding factors, multivariate analysis showed that the ALBI score was an independent predictor of CA-AKI (P = .002). A restricted cubic spline analysis confirmed approximately linear relationships between the ALBI score and risks of CA-AKI. Furthermore, at a median follow-up of 2.8years, multivariate Cox regression analysis indicated that the ALBI score was an independent risk factor for long-term mortality (P < .001). The ALBI score was closely related to the occurrence of CA-AKI and long-term mortality in patients who underwent elective PCI. This score might be useful for risk stratification in high-risk patient groups to predict CA-AKI.

Serum Raman spectroscopy: Evaluation of tumour load variations in experimental carcinogenesis.

Several serum Raman spectroscopy (RS) studies have demonstrated its potential as an oral cancer screening tool. This study investigates influence of low tumour load (LTL) and high tumour load (HTL) on serum RS using hamster buccal pouch model of experimental oral carcinogenesis. Sera of untreated control, LTL, and HTL groups at week intervals during malignant transformation were employed. Serum Raman spectra were subjected to multivariate analyses-principal component analysis, principal component-based linear discriminant analysis (for stratification of study groups), and multivariate curve resolution-alternating least squares (MCR-ALS) (to comprehend biomolecular differences). Multivariate analysis revealed misclassifications between LTL and HTL at all week intervals. MCR-ALS components showed statistically significant abundances between control versus LTL and control versus HTL, but could not discern LTL and HTL. MCR-ALS components exhibited spectral mixtures of proteins, lipids, heme and nucleic acids. Thus, these findings support use of serum RS as a screening tool as varying tumour load is not a confounding factor influencing the technique.

Magnitude of Diabetes Mellitus in Upper Gastrointestinal Hemorrhage

Objective: To determine the frequency of diabetes mellitus in patients presenting with upper gastrointestinal hemorrhage.&#x0D; Methodology: This descriptive cross-sectional study was conducted at Department of Gastroenterology, Isra University Hospital, Hyderabad, from February, 2020 to August, 2020. All individuals aged 18 to 60 years, of both genders, and those experiencing upper gastrointestinal bleeding were enrolled. A 5ml blood sample was taken to evaluate the blood sugar level. DM was defined as fasting plasma glucose &gt; 7 mmol/I (126 mg/dl), or 2 hours post prandial plasma glucose &gt;11 mmol/I (200mg/dl). All the collected information was entered into the predesigned proforma. Data was analyzed using SPSS v. 23.0.&#x0D; Results: The mean age was 42.1 ± 11.2 years, and the mean body mass index (BMI) was 26.4 ± 6.1 kg/m². Among 184 patients, 73 (39.7%) were male, and 111 (60.3%) were female. Diabetes mellitus was found in 21 (11.4%) patients. Stratification of age groups, gender, BMI, and socioeconomic status with DM among individuals with upper gastrointestinal hemorrhage found to be statistically insignificant (p &gt;0.05).&#x0D; Conclusion: Upon investigation of the prevalence of Diabetes Mellitus in cases of Upper Gastrointestinal Hemorrhage, notable results were found, revealing an observed incidence of DM at 11.4%. This emphasizes a significant presence of DM within this cohort, so prompt additional investigation into the connection between DM and Upper Gastrointestinal Hemorrhage are recommended.

Treatment of follicular lymphoma with a focus on radiotherapy

PurposeTo describe the overall treatment patterns of follicular lymphoma (FL) in a single tertiary institution, with a focus on the outcomes of radiotherapy treatment in this group of patients. Methods and materialsRetrospective analysis on 177 patients with FL registered from 1996 to 2011 and followed up to October 2017. Diagnosis was confirmed by histology and staging by clinical examination and imaging with positron emission tomography (PET) or computed tomography (CT) scan. Demographics, clinicopathological characteristics, treatment details and clinical outcomes were reviewed. ResultsFifty-five patients (31%) had early stage and 122 (69%) had advanced stage FL. Median follow-up was 7 years and 7.5 years for early and advanced FL respectively. For advanced stage, median overall survival (OS) was 12.9 years, 5-year and 10-year OS were 77% and 63%, and 5-year and 10-yr PFS were 57% and 40% respectively. In multivariable model, moderate FLIPI, palliative RT and anti-CD20 targeted therapy were significantly associated with OS when comparing with those with high FLIPI score, no RT and no anti-CD20 targeted therapy respectively. For early stage, median OS has not reached, 5-year and 10-year OS were 79% and 74% and 5-year and 10-year progression free survival (PFS) were 64% and 52% respectively. Stage 2 non-contiguous disease had significantly poorer survival than stage 1 patients in multivariable (HR 8.19, 95%CI 1.86 – 35.98) analysis. Overall, 49 of 177 patients (27.7%) had any form of radiotherapy as part of their treatment for FL. There were no in-field alone relapses seen in all cases treated with RT. 10% in early FL had G3-4 acute toxicities with RT whilst there was no G3-4 late toxicities. In advanced FL, there were no G3-4 acute toxicities with consolidation RT and 1 G3 with salvage RT. ConclusionFL has effective response rates to RT both in early and advanced FL. We demonstrated that: 1) stage 2 disease has poorer outcomes than stage 1 disease with stage 2 non-contiguous disease having the poorest outcomes, indicating the need for more aggressive treatment strategies for this group of patients; 2) there were no in-field alone relapses seen in all cases treated with RT; 3) overall, there is a general under-utilization of RT concurring with the literature. New prospective studies are therefore warranted to shed light on improving the utility of RT for patients with FL. With advances in molecular medicine, imaging and treatment approaches, there is potential for better stratification of different patient groups for more localized versus systemic treatments.

Активность теломеразы, гиперлипидемия и особенности атеросклеротического поражения брахиоцефальных артерий у бессимптомных пациентов трудоспособного возраста с субклиническим гипотиреозом

Aim. To study telomerase activity, lipidemia and to assess the severity of atherosclerotic lesions of the brachiocephalic arteries in asymptomatic patients of working age with subclinical hypothyroidism. Design. A cross-sectional cohort study. Materials and methods. Data on 131 patients of working age (32 men and 99 women) with different hormonal status of the thyroid gland (thyroid) without clinical signs of chronic cerebral circulatory insufficiency were analyzed. Based on the assessment of the hormonal status of the thyroid gland, 2 groups of patients were formed: 87 with laboratory-confirmed hypertension (thyroid-stimulating hormone level &gt; 4.0 mMU/l with normal characteristics of free fractions of thyroid hormones) and 44 patients without thyroid dysfunction. The groups formed were comparable in age, gender composition, presence and severity of hypertension, aggravated family history of early cardiovascular events, and smoking. All patients underwent ultrasound examination of the brachiocephalic arteries, determination of the lipid spectrum and telomerase concentration. The processing of the obtained data was carried out using statistical packages Excel, Statistica v. 10.0. The data obtained were interpreted as reliable, and the differences between the indicators were considered significant when the error-free prediction value was equal to or greater than 95% (p &lt; 0.05). Results. In the group of people with hypothyroidism, the proportion of people with multivessel atherosclerotic lesion was higher (34.5% (n = 30) vs. 13.6% (n = 6) (χ2 = 6.37; p &lt; 0.05)), one or a combination of several signs of instability of atherosclerotic plaque (41.4% (n = 36) vs. 18.2% (n = 8) (χ2 = 7.05; p &lt; 0.01)). In patients with subclinical hypothyroidism, precerebral atherosclerosis occurs against the background of atherogenic type IIa secondary hyperlipidemia (67.8% (n = 59) vs. 34.1% (n = 6) (χ2 = 13.52; p &lt; 0.001) in combination with insufficiency of antiatherogenic high density lipoproteins (74.7% (n = 65) vs. 45.5% (n = 20) (χ2 = 10.98; p &lt; 0.001)), lower values of telomerase concentration in comparison with the group of people without thyroid dysfunction: (8.2 (7.4–9.5) vs. 10.8 (10.1–12.2) ng/ml (p &lt; 0.001)). The relationship between the level of telomerase activity (r = –0.72; p &lt; 0.05) and the presence of subclinical hypothyroidism, atherosclerotic lesions of the precerebral bed in patients (r = –0.33; p &lt; 0.05) was established. Conclusion. In clinically healthy patients of working age with newly diagnosed, medically uncorrected subclinical hypothyroidism, the proportion of persons with ultrasound signs of multivessel atherosclerotic lesions of the brachiocephalic arteries is higher, and precerebral atherosclerosis occurs against the background of atherogenic type IIa secondary hyperlipidemia in combination with insufficiency of antiatherogenic high density lipoproteins, lower values of telomerase activity in comparison with the group of persons without thyroid dysfunction. Etiopathogenetic mechanisms of "early vascular aging", the criteria for stratification of risk groups for atherosclerosis-associated cardiovascular disease, the choice of diagnostic algorithms for visualizing preclinical stages of atherogenesis, and timely antiatherogenic tactics in asymptomatic patients with comorbid thyroid pathology require further study. Verification of a stenosing hemodynamically significant or non-hemodynamically significant atherosclerotic lesion of the coronary basin, regardless of the clinical component, is a factor of high cardiovascular risk requiring immediate correction of hyperlipidemia. Keywords: thyroid gland, hypothyroidism, hyperlipidemia, atherosclerosis, precerebral (brachiocephalic) arteries, telomerase activity, comorbid pathology.

Association between Leukemic Evolution and Uncommon Chromosomal Alterations in Pediatric Myelodysplastic Syndrome.

Pediatric myelodysplastic syndrome (pMDS) is a group of rare clonal neoplasms with a difficult diagnosis and risk of progression to acute myeloid leukemia (AML). The early stratification in risk groups is essential to choose the treatment and indication for allogeneic hematopoietic stem cell transplantation (HSCT). According to the Revised International Prognostic Scoring System, cytogenetic analysis has demonstrated an essential role in diagnosis and prognosis. In pMDS, abnormal karyotypes are present in 30-50% of the cases. Monosomy 7 is the most common chromosomal alteration associated with poor prognosis. However, the rarity of specific cytogenetic alterations makes its prognosis uncertain. Thus, this study aimed to describe uncommon cytogenetic alterations in a cohort of 200 pMDS patients and their association with evolution to AML. The cytogenetic analysis was performed in 200 pMDS patients by G-banding and fluorescence in situ hybridization between 2000 to 2022. Rare chromosome alterations were observed in 7.5% (15/200) of the cases. These chromosome alterations were divided into four cytogenetic groups: hyperdiploidy, biclonal chromosomal alterations, translocations, and uncommon deletions representing 33.3%, 33.3%, 20%, and 13.3%, respectively. Most of these patients (10/15) were classified with advanced MDS (MDS-EB and MDS/AML) and the initial subtype was present in five patients (RCC). The leukemic evolution was observed in 66.66% (10/15) of the patients. Most patients had poor clinical outcomes and they were indicated for HSCT. The study of uncommon cytogenetic alterations in pMDS is important to improve the prognosis and guide early indication of HSCT.